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THE SOUTH AFRICAN JOURNAL OF

Diabetes vascular Disease OBESITY

LIPIDAEMIA DYS

IN RESISTANCE INSUL

HYPERTENSION

In association with the British Journal of Diabetes & Vascular Disease

ETES & DIAB

V

AS

ATH EROSCLEROSIS

CUL

AR DISEASE

HYPER INSULINAEMIA THROMBOSIS

HYP

ERGLYCAE MIA

Volume 6 Number 2

June 2009

GI VE AW AY

Featured in this issue Need for a diabetes charter Constitutional rights in management of chronic diseases Diabetes strategy Treatment of hypertension Triglycerides Patient information leaflet Diabetes management made easier Patients in a resource-constrained environment


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OBESITY IPIDAEMIA DYSL

ISSN 1811-6515 HYPERTENSION

IN RESISTANC E INSUL

DIABETES &

ATH EROSCLEROSIS

CULA

Diabetes & vascular disease

S

E

V

AS

R DISEA

THE SOUTH AFRICAN JOURNAL OF

HYPER INSULINAEMIA

in association with the British Journal of Diabetes & Vascular Disease

THROMBOSI S HYP

E R G L Y C AE MI A

VOLUME 6 NUMBER 2 • JUNE 2009

Corresponding Editor PROF WF MOLLENTZE

Head of the Department of Internal Medicine, University of the Free State, Bloemfontein Consulting Editors PROF J-C MBANYA PROF AJ BRINK Assisant Editor: Special Assignments JULIA AALBERS Production Editor SHAUNA GERMISHUIZEN National Editorial Board DR A AMOD

CONTENTS Editorials 47

FA Mahomed

48

Centre for Diabetes, Endocrinology and Metabolic Diseases, Life Healthcare, Chatsmed Gardens Hospital, Durban PROF F BONNICI

Emeritus Professor, Faculty of Health Sciences, University of Cape Town and President of Diabetes South Africa PROF R DELPORT

Department of Family Medicine, University of Pretoria DR L DISTILLER

Director of the Centre of Diabetes and Endocrinology, Houghton, Johannesburg

50

International Editorial Board PROF IW CAMPBELL

Physician, Victoria Hospital, Kircaldy, Scotland, UK

A diabetes strategy for (South) Africa: regaining momentum WF Mollentze

Reviews 52

Treatment of hypertension in diabetic patients: the ASH position paper provides valuable insights J Aalbers

55

PROF YK SEEDAT

Emeritus Professor of Medicine and Honorary Research Associate, University of Natal, Durban

Patient’s constitutional rights regarding the management of chronic diseases in South Africa E Klinck

PROF KAREN SLIWA

Associate Professor of Medicine and Cardiology, Baragwanath Hospital, University of the Witwatersrand, Johannesburg

The need for a diabetes charter in South Africa

Triglycerides: making sense of the forgotten lipid fraction J Morrell

Patient Information Leaflet 59

Taking aspirin for the prevention of cardiovascular disease

PROF PJ GRANT

Professor of Medicine and head of Academic Unit of Molecular Vascular Medicine, Faculty of Medicine and Health, University of Leeds; honorary consultant physician, United Leeds Teaching Hospitals NHS Trust, UK

Hands On 61

JA Kok

PROF J-C MBANYA

Professor of Endocrinology, Faculty of Medicine and Biomedical Sciences, University of Yaounde I, Cameroon and President-Elect, International Diabetes Federation (2006−2009) PROF N POULTER

Professor of Preventive Cardiovascular Medicine, Imperial College, School of Medicine, London, UK DR H PURCELL

Senior Research Fellow in Cardiology, Royal Brompton National Heart and Lung Hospital, London, UK

Diabetes management made easier: insulin delivery devices

Diabetes Personality 64

Overcoming the challenges of a resource-poor environment to deliver quality diabetes care in a public-sector clinic D Tupy


Assistant Editor: Special Assignments JULIA AALBERS

TEL: (021) 976-4378 FAX: 086 610 3395 e-mail: jaalbers@icon.co.za

Roundtable Discussion 66

WF Mollentze

Production Editor SHAUNA GERMISHUIZEN

TEL: (021) 785-7178 FAX: 086 628 1197 e-mail: shaunag@xsinet.co.za

Management of the diabetic patient in a resource-constrained environment

Drug Trends in Diabetes 75

News from the 2009 SEMDSA Congress

TEL/FAX: (021) 976-8129 e-mail: cvjsa@cvjsa.co.za

Report from Sanofi Aventis diabetes cardio-thrombosis meeting

Production Co-ordinator WENDY WEGENER

Novo Nordisk Diabetes Update Symposium: April 2009

Incretin therapy: a new treatment modality in the fight against the worldwide diabetes epidemic

Testosterone: the missing link in the treatment of type 2 diabetes

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Diabetes News

Editorial Assistant and Circulation ELSABÉ BURMEISTER

TEL: (021) 976-4378 e-mail: wendy.icon@wol.co.za

The South African Journal of Diabetes and Vascular Disease is published four times a year for Clinics-Cardive Publishing Co. by Martingraphix and printed by Durbanville Commercial Printers. Articles in this Journal are sourced as per agreement with the British Journal of Diabetes and Vascular Disease

All correspondence to be directed to: THE EDITOR PO BOX 1013 DURBANVILLE 7551 or cvjsa@cvjsa.co.za TEL/FAX: (021) 976-8129 INT: 2721 976-8129

The editorial team regrets the early publication of the insulin pump guidelines in our November 2008 issue. The error was bona fide.

Front cover photographs from left to right: Sampling blood to determine lipid levels; a vital aspect of care for all diabetic patients (page 58) Helping Life for a Child Foundation provide diabetes care to children in the poorest countries around the world (page 88) Enter our giveaway to win ofGeneric two South African Colorone profile: CMYK printer profilecookbooks with delicious recipes Default screen suitable for all diabeticsComposite (page 65)

The opinions, data and statements that appear in any articles published in this journal are those of the contributors. The publisher, editors and members of the editorial board do not necessarily share the views expressed herein. Although every effort is made to ensure accuracy and avoid mistakes, no liability on the part of the publisher, editors, the editorial board or their agents or employees is accepted for the consequences of any inaccurate or misleading information.

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SA JOURNAL OF DIABETES & VASCULAR DISEASE

EDITORIAL

The need for a diabetes charter in South Africa

D

iabetes is increasingly becoming a major problem in South Africa. In rural areas, overall age-adjusted prevalence of diabetes is 3.9%,1 but in other subgroups, for example in South Africans of Indian origin, up to 16.2% of the population may have diabetes.2 Very little work is being done in South Africa on standards of care, socio-economic impact, burden of disease and complications in clinics and hospitals. South Africa also has a poorly regulated private sector. Although guidelines for diabetes care are available on professional bodies’ websites,3 there are no clear monitoring mechanisms and no corrective procedures in place. The main role of a charter is that of patient advocacy. It sets out the rights and responsibilities of patients, healthcare workers and politicians. Its aim is to provide people with diabetes with a good-quality healthcare service, but more importantly, it gives them some measure of control, rather than being passive recipients of healthcare. Other countries have already set out diabetes charters and New Zealand is a good example.4 Elements of a charter include the following. The right to: • see a doctor once every six months • see a podiatrist, dietician, diabetes nurse educator, ophthalmologist or optometrist • have information about diabetes, its complications and its therapy, including the demonstration of the correct insulin injection technique, in a language they can fully understand • have regular examination of blood pressure, eyes, feet, kidneys and the heart • have access to self-monitoring equipment • have access to medical staff who are suitably trained in diabetes care • have access to an ombudsman to report substandard care • have access to a public-health campaign to educate the population about diabetes and its prevention Correspondence to: FA Mahomed Department of Endocrinology, Grey’s Hospital, Pietermaritzburg Tel: +27 (0) 33 897 3000 e-mail: fazmah@hotmail.com S Afr J Diabetes Vasc Dis 2009; 6: 47.

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FA Mahomed

• have school, work and prison environments that are capable of handling diabetes routine care, as well as diabetic complications. This includes a clinic area, suitable equipment, suitably trained staff and access to referral medical centres. It has become imperative that patients, medical staff and politicians all take responsibility for diabetes care in South Africa. A diabetes charter provides a framework for setting adequate standards of healthcare in diabetes in South Africa.

References 1. Motala AA, Esterhuizen T, Gouws E, Pirie FJ, Omar MA. Diabetes and other disorders of glycemia in a rural South African community: prevalence and associated risk factors. Diabetes Care 2008; 31(9): 1783–1788. 2. Motala AA, Pirie FJ, Gouws E, Amod A, Omar MA. High incidence of type 2 diabetes mellitus in South African Indians: a 10-year follow-up study. Diabet Med 2003; 20(1): 23–30. 3. SEMDSA Guidelines for Diagnosis and Management of Type 2 Diabetes Mellitus for Primary Health Care – 2009. Guideline Committee SEMDSA. http://www.semdsa.org.za/files/SEMDSA_DM_Guide_2009. pdf. Accessed 7/5/2009. 4. Patient Charter. Diabetes New Zealand. http://www.diabetes.org.nz/ resources/patient_charter Accessed 7/5/2009.

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Patient’s constitutional rights regarding the management of chronic diseases in South Africa The right of access to healthcare he South African Constitution awards every person the right of access to healthcare and simultaneously places a duty on government to realise these rights progressively:1 ● Everyone has the right to access to: – healthcare services, including reproductive healthcare – sufficient food and water – social security, including, if they are unable to support themselves and their dependants, appropriate social assistance. • The state must take reasonable legislative and other measures, within its available resources, to achieve the progressive realisation of each of these rights. • No one may be refused emergency medical treatment. It should be noted that this right applies to everyone (not only citizens) and that it includes access to social security. Social security could take the form of social insurance (e.g. medical scheme cover and/or national health insurance) or social assistance (e.g. care provided for free at public facilities to pregnant women and children under the age of seven).

T

Realisation of the right of access to healthcare Section 7(2) of the Constitution creates a general duty on government in that ‘the state must respect, protect, promote and fulfill the rights in the Bill of Rights.’ The fulfillment of rights is an important constitutional imperative. Section 27(2) provides more detail on the fulfillment of access to healthcare services. It obliges the state to: • ‘take reasonable measures’ • ‘progressively realise’ health rights • undertake such realisation ‘within available resources’. This means that these constitutional duties go beyond policy making and the setting of guidelines. It also means that ‘resource constraints’ should not be used as an ‘excuse’ for non-delivery of services, but rather that the constitutional duty requires careful consideration of how the state will ‘progressively’ realise health rights, within available resources. The Department of Health, in its most recent strategic plan acknowledges that there is, among others, lack of leadership, poor management, poor-quality services and subsequent poor Correspondence to: Elsabé Klinck Principal Consultant, Benguela Health, Pretoria Tel: +27 (0) 12 664-5959, +27 (0) 11 326-2185 e-mail: elsabe@benguelahealth.com S Afr J Diabetes Vasc Dis 2009; 6: 48–50.

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Elsabé Klinck

health outcomes, i.e. ‘inadequate outputs for the resources allocated … from the national fiscus’.2 De Waal et al.3 summarises the burden placed on the state to make things work within its resource constraints, as follows: ‘The fact that the full realisation … can only be achieved progressively does not alter the obligation on the state to take those steps that are within its power immediately and other steps as soon as possible. The burden is on the State to show that it is making progress toward the full realisation of the rights.’ Even when resources are scarce the obligation remains on the state to ‘strive to ensure the widest possible enjoyment of the relevant rights under the prevailing circumstances’. Given the contention that it is perhaps not only an issue of resources in the health sector (allocations from the fiscus may be sufficient), the how and where resources are spent may be of greater importance in the current debates. The Roadmap to Health4 (widely regarded as the basis from which the health sector has to proceed to address its numerous challenges) refers to the 2000 Burden of Disease survey. The survey shows that non-communicable diseases such as stroke, asthma and diabetes are the leading causes of disability-adjusted life years (DALY), accounting for 33% of this burden. This means that priority should be afforded to the realisation of such clearly identified needs. Such a prioritisation should bear in mind that conditions such as diabetes place financial constraints on other parts of society,

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whether in the form of early disability, unemployment, or downstream costs in the form of hospitalisation. ‘Resource constraints’ should therefore not be seen as only relating to the capacity to treat certain conditions in a basic manner within a certain line item (e.g. medicines). An investigation into ‘available resources’ should therefore entail an analysis of the implications of resource choices and access to healthcare from a wider perspective. As health budgets are often separated into ‘medicines’, ‘human resources’, ‘infrastructure’, ‘primary care’ and ‘hospital care’, the interrelated nature of the impact on resources is often understated or not considered at all. According to Olivier et al.5 the constitutional duty entails ‘devising, formulating, funding and implementing, as well as constant review of comprehensive, co-ordinated and welltargeted programmes. Issues such as staff shortages at top level in the National Department of Health6 may indeed play a role in whether programmes to address access to healthcare are ‘co-ordinated’ and ‘well-targeted’. A recent case where lack of co-ordination has resulted in decreased access is the re-scheduling of some of the vaccines. This now requires nurses to be in possession of permits in terms of the Nursing Act of 2005, which has not been fully operationalised (i.e. permits cannot lawfully be issued). It also requires a prescription to be obtained from a medical practitioner (who may not be available in many primary-care settings, or only available at an additional cost, of travel and practitioner fees, to the patient).

Case law on socio-economic rights Healthcare, social security, education and housing are all referred to as ‘socio-economic rights’,7 i.e. these rights are social or societal in nature and require financial and other resources for their fulfillment. A number of decisions by the Constitutional Court, discussed below, provide guidance as to how these rights are to be interpreted and therefore implemented. How budgets are set and resources allocated Perhaps the most notable case in relation to access to healthcare is that of Mr Soombramoney.8 He had kidney failure, but according to the guidelines applicable at the particular health facility, did not qualify for access to the dialysis programme, which (for reasons of limited resources) only took on patients who qualified for kidney transplants. Although Mr Soombramoney did not get the relief he sought, the case still places important criteria on resource allocations and constraints: • The particular province has overspent its budget in order to attempt to realise the rights of as many patients as possible, i.e. if there are unspent resources (whether from treasury or donors, for example) in a particular health department, such department would not be able to use resource unavailability as a defense. • Budgets must be set rationally and bona fide, i.e. the

VOLUME 6 NUMBER 2 • JUNE 2009

EDITORIAL

courts will not intervene if there are ‘better’ plans to realise the rights, where the existing programmes and budget allocations are proven to be underpinned by sufficient information, analyses and projections to be ‘rational’ and not arbitrary, or by considering inappropriate factors or failing to consider appropriate factors. The Soobramony case also serves as a reminder of the inter-relatedness of constitutional issues and various policy programmes. Had there been more kidney donors and more kidney transplants, the extent to which transplant patients would require dialysis could be less, possibly freeing up dialysis resources for persons not qualifying for transplants.

‘Reasonable’ programmes In the Grootboom case,9 the Court interpreted what was meant by ‘reasonable’ measures: ‘To be reasonable, measures cannot leave out the degree and extent of the denial of the right they endeavour to realise ... If the measures, though statistically successful, fail to make provision for responding to the needs of those most desperate, they may not pass the test of reasonableness.’ This means that limiting the standard of care, for example, for diabetes patients requires consideration of the impact of such a programme on these patients. The additional criteria for reasonableness can be summarised as follows:10 • The context of the deficiencies in the system that the specific measures aim to address, i.e. an analysis of how services have been provided, or not sufficiently provided in the past, and the impact on various communities. For example, the identification of specific districts for intervention in the strategic plan would be one manifestation of the fulfillment of this requirement. • The institutional capacity to implement the programme; for example, a failure to ensure sufficient oversight and coordination of non-communicable disease programmes and related units, such as pharmaceutical planning and hospital programmes. • Whether the programme is balanced, flexible and open to review, which implies regular reviews of aspects such as treatment guidelines, funding and the manner in which healthcare is delivered and an openness to criticism and input from stakeholders. • Addressing short-, medium- and long-term needs, such as, in the case at hand, relating, among others, to how diseases progress, and the resource needs to address such progression. • Whether the programme is inclusive. • Whether the programme and measures ensure that larger numbers of people and a wider range of people benefit, as time progresses. • The programme must clearly allocate responsibilities and tasks to certain positions. In the Soombramoney case, the programme was reasonable as it was carefully designed to help as many patients as

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possible who required dialysis. It chose patients who would optimise the resources of the dialysis unit.

The importance of medical expertise The so-called Nevirapine case11 highlighted the importance of medical expertise within the context of realising healthcare rights, with reference to the existence of specific conditions that would facilitate access to the specific treatment (emphasis provided): ‘Where counseling and testing facilities exist, the administration of nevirapine is well within the available resources of the state and, in such circumstances the provision of … nevirapine … where medically indicated is a simple, cheap and potentially lifesaving intervention.’ It is therefore not only ethically required that medical practitioners participate in decisions relating to the care required, and the implications of not providing such care, but indeed a constitutional imperative. Conclusion This article briefly examined some of the constitutional issues relating to the right of access to healthcare, and the duties placed not only on policymakers and programme managers, but also on medical practitioners to ensure compliance with the criteria set by the Constitution. It should also be borne in mind that many other human rights support the right of access to healthcare, most notably

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the right to administrative justice (that decision makers make reasonable decisions, while considering all relevant factors and acting in a procedurally fair manner), the rights of children and the right of equal protection and benefit of the law. These rights, coupled with the right of access to healthcare and the right of access to social security, should protect and fulfill the rights of South African patients to an increasing extent.

References 1. Section 27, Constitution of the Republic of South Africa, 1996 (‘the Constitution’). 2. Department of Health Strategic Plan. 2009/10 – 2011/12 2009 2-3 available at http://www.doh.gov.za/docs/strategic09-11-f.html. 3. De Waal, Currie, Erasmus. The Bill of Rights Handbook. Cape Town: Juta, 2000: 403. 4. Development Bank of Southern Africa, www.dbsa.org. 2008: 6. 5. Olivier, Smit, Kalula. Introduction to Social Security. Durban: LexisNexis, 2004: 73. 6. Department of Health Organogram, available at http://www.doh.gov. za/department/index.html. 7. De Waal, Currie, Erasmus. The Bill of Rights Handbook. Cape Town: Juta, 2000: 398. 8. Soobramoney v. Minister of Health (KwaZulu-Natal) 1997 12 BCLR 1969 CC. 9. Government of RSA v. Grootboom and others 2000 11 BCLR 1169 CC. 10. Olivier, Smit, Kalula. Introduction to Social Security. Durban: LexisNexis, 2004: 73. 11. Minister of Health and others v. Treatment Action Campaign 2002 BCLR 10 1033 CC.

A diabetes strategy for (South) Africa: regaining momentum

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 e historic 19th meeting of the International Diabetes h Federation (IDF) in Cape Town in December 2006 put diabetes mellitus in Africa, and South Africa in particular, under the spotlight. This meeting will be remembered for the launch of the African Diabetes Declaration,1 which was also signed by the South African Minister of Health. The purpose of the declaration is to raise community and political awareness about diabetes and to improve diabetes care by working through a coalition of individuals, communities, corporations and governments. The main objectives of the declaration are summarised in table 1.

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A few days after the conclusion of the IDF meeting in Cape Town, the United Nations adopted its Resolution on Diabetes, declaring 14 November (previously known as World Diabetes Day) as a United Nations day to be observed every year, starting in 2007.2 The UN resolution encourages member states to develop national policies for the prevention, treatment and care of diabetes. Within two years of the African Diabetes Declaration and the UN resolution, diabetes care in the public sector in South Africa is adversely affected by the current downturn in the economy. It is not uncommon for patients to report shortages of essential medication and consumables, including insulin

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and syringes, at some primary healthcare clinics in various provinces.3 To address these issues a roundtable meeting was convened between key role-players at the Wanderers Club in Johannesburg on the eve of the recent SEMDSA annual meeting. Diabetes care in a resource-constrained environment was the main topic for discussion. The full report of this roundtable discussion appears on page 66. The main conclusions and recommendations of this discussion are summarised as follows: • Diabetes along with the other non-communicable diseases (cancer, hypertension and obesity) remain a major public health concern in South Africa. • The management of diabetes is sub-optimal at all levels of care across the board in the public service. • Basic medication such as insulin, oral hypoglycaemic and antihypertensive agents along with insulin syringes are often not available at supply points. • Healthcare systems at primary healthcare (PHC) level differ vastly from province to province and even between PHC clinics in the same province. • There is a need for basic research on healthcare systems to identify deficiencies and improve the supply chain of basic medication and consumables. • Policy regarding care of non-communicable diseases in South Africa is determined by the national Department of Health while it is up to individual provinces to implement policy. • Excellent policy documents are available but implementation lags behind. • Resources (human and infrastructure) are limited at all levels of care and it is highly unlikely that it will improve in the foreseeable future. • The main challenge is to think out of the box and develop new healthcare strategies to utilise limited resources more efficiently. • A standard of care based on IDF policies and documents needs to be developed. • A standardised patient data-capture form should be developed and implemented as widely as possible – this may be the first step towards the auditing of diabetes care. • A standardised undergraduate diabetes curriculum needs to be developed. DESSA should be commended in this regard for taking the initiative towards a standardised training programme for diabetes educators.

Correspondence to: Prof WF Mollentze Department of Internal Medicine, University of the Free State, Bloemfontein Tel: +27 (0) 51 405-3154 Fax: +27 (0) 51 444-3138 e-mail: wfm@mweb.co.za S Afr J Diabetes Vasc Dis 2009; 6: 50–51.

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EDITORIAL

Table 1. The Declaration – a call to action.4 • • • •

• • • • •

Adequate, appropriate and affordable medications and supplies for people with diabetes Earlier detection and optimal quality of care of diabetes Effective efforts to create healthier environments and prevent diabetes Identification and dissemination of information, education and communication to empower people with diabetes to access appropriate diabetes services and improve self care Equitable access to care and prevention services for people with or at risk of diabetes Awareness of diabetes in the community and among healthcare providers A truly integrated approach which utilises the whole health workforce to address infections and non-communicable diseases simultaneously Government commitment to reducing the personal and public health burden of diabetes Partnership and collaboration within and between government and private sectors, non-governmental organisations and communities to create community and workplace environments that promote better health.

• There is a need to establish a task team in each province to assume responsibility for the implementation and monitoring of a diabetes strategy. This team must be multidisciplinary and should ideally include academics, members of SEMDSA, DESSA, DSA and officials from the provincial Departments of Health. These task teams will need full buy-in and support from the national Department of Health. This should go a long way to ensure that the UN resolution and the IDF diabetes strategy get implemented. • A need exists for a patient advocacy group similar to the Treatment Action Campaign for HIV/AIDS. • The special needs of children, adolescents and women at risk of or with diabetes in pregnancy need to be recognised and addressed. • The problems facing diabetes care in Lesotho are similar to those in South Africa – we need more formal interaction at this level between the two countries. Diabetes care is at a crossroads in South Africa. Are we heading towards the high road or the low road? I believe this roundtable discussion will add new impetus to regain the momentum that was lost after the IDF meeting, Declaration for Africa and UN resolution two years ago.

References 1. Diabetes Declaration and Strategy for Africa: A call to action. http:// www.idf.org/node/1355?unode=14A26179-13DD-4220-A8656576D4D417FB. Accessed 3 Jun 2009. 2. The UN Resolution on Diabetes. http://www.worlddiabetesday.org/ en/the-campaign/unite-for-diabetes/the-un-resolution-on-diabetes. Accessed 3 Jun 2009. 3. Incident reports on file with author. 4. The Diabetes Declaration and Strategy for Africa: a call to action and plan of action to prevent and control diabetes and related chronic diseases. http://www.idf.org/webdata/docs/Diabetes%20Declaration% 20&%20Strategy%20for%20Africa_full.pdf. Accessed 3 June 2009.

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Treatment of hypertension in diabetic patients: the ASH position paper provides valuable insights

T

he American Society for Hypertension (ASH) has published a position paper (2008) with a very useful algorithm for treating hypertension in diabetic patients (figure 1).1 Incorporating many of the most recent trials until July 2008, the position paper notes that while the basic approach to achieving blood pressure control in persons with diabetes has not changed appreciably from the JNC VII guidelines, some important new considerations have emerged. Stressing lifestyle modification (weight reduction, dietary sodium reduction, increased physical activity, smoking cessation and moderate alcohol use) as a first step, all patients with diabetes and blood pressure > 130/80 mmHg should be started on a once-daily renin–angiotensin–aldosterone system (RAAS) blocker and the dose should be maximised within the first month if the target of < 130/80 mmHg is not reached. If blood pressure is more than 20/10 mmHg above goal then combination therapy with an RAAS blocker and either a low-dose thiazide-like diuretic (if kidney function is appropriate) or a calcium channel blocker (CCB) should be initiated. If the estimated glomerular filtration rate (eGFR) is below 50 ml/min, a loop diuretic should be used (once-daily torsemide or twice-day furosemide). Chlorthalidone can also be used if eGFR is below 40 ml/min. The authors of the guidelines noted the need to reduce target-organ damage (cardio-renal risk) which requires a multifactorial approach (table 1).

The role of combination therapy The importance of encouraging patient compliance and effectively lowering blood pressure by using combination treatment is stressed in the position paper. Strong consideration should be given to either an RAAS/diuretic or an RAAS/ CCB. The combination of an ACEI and ARB should be avoided in diabetic patients, except those with advanced nephropathy. In order to simplify patient medication and improve compliance, combining a blood pressure-lowering agent with a statin in a single tablet could be of particular value in type 2 diabetic patients who need to take multiple medications. Even with up-titration of blood pressure-lowering drugs to their maximum tolerated dose, other medications may well be required to bring the patient’s blood pressure to target levels. Vasodilating β-blockers are better tolerated and are especially useful in persons with an elevated pulse rate. Correspondence to: Julia Aalbers South African Journal of Diabetes & Vascular Disease Tel: +27 (0) 21 976-4378 e-mail: jaalbers@icon.co.za S Afr J Diabetes Vasc Dis 2009; 6: 52.

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Figure 1. Algorithm for treating hypertension in diabetic patients.

If blood pressure > 130/80 mmHg in diabetes (eGFR ≥ 50 ml/min)∧ (If systolic BP ≥ 20 mmHg above goal) Start with ACEI or ARB + thiazide diuretic* or CCB Recheck within 2–3 weeks If BP still not at goal (130/80 mmHg)

(If systolic BP < 20 mmHg above goal) Start ARB or ACE inhibitor, titrate upwards

Add CCB OR β-blocker** Recheck within 2–3 weeks If BP still not at goal (130/80 mmHg)

Add long-acting thiazide diuretic* or CCB

Consider an aldosterone receptor blocker If CCB used, add other subgroup of CCB (ie, amlodipine-like agent if verapamil or dilitiazem already being used and vice versa) OR could add alpha-blocker if not using vasodilating beta-blocker with alpha effects Recheck within 4 weeks If BP still not at goal (130/80 mmHg) Refer to a clinical hypertension specialist A suggested approach to achieve blood pressure goal in patients with diabetes. ^Represents kidney function (estimated glomerular filtration rate: eGFR), which generally responds well to thiazide diuretics. *Chlorthalidone is the suggested thiazide-like diuretic since this is the diuretic used in clinical trials and forms the basis for the cardiovascular outcome data. **Vasodilating beta-blockers have a better tolerability profile and less metabolic consequences compared to older agents such as atenolol.

Combination of a non-dihydropyridine CCB (verapamil or dilatiazem) in moderate doses, together with a dihydropyridine CCB has additive effects and will also help achieve target blood pressure levels. An important fourth-line strategy is the use of aldosterone blockade (spiranolactone), particularly in patients with sleep apnea and central obesity. This agent’s blood pressure lowering is similar in African-American and Caucasian individuals. The authors stressed the need to watch for hyperkalaemia in patients treated with spironolactone and other agents, while pointing to the valuable role that avoiding high potassiumcontaining foods and substances that cause hyperkalaemia (e.g. NSAIDS) can play with regard to keeping potassium levels within the normal range.

Reference 1.

Bakris GL, Sowers JR, on behalf of the American Society of Hypertension writing group. ASH position paper: Treatment of hypertension in patients with diabetes – an update. J Clin Hypertens 2008; 10:707–713.

Table 1. • • • • • •

Approach needed to maximally reduce cardio-renal risk*

Lifestyle modifications Achieve BP < 130/80 mmHg Achieve LDL < 70 mg/dl Achieve glycaemic control (< 7% HbA1c)* Antiplatelet therapy: low-dose aspirin 75–162 mg/day In those with albuminuria or proteinuria: reduce by > 30% after starting treatment within 6 months.

*Based on ADA guidelines, AACE guidelines indicates < 6.5% HbA1c.

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Providing Synergy , Prolonging Time 1

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Triglycerides: making sense of the Prevention inMAKING Practice TRIGLYCERIDES: SENSE OF sometimes forgotten lipid fraction THE SOMETIMES FORGOTTEN LIPID

FRACTION TRIGLYCERIDES: MAKING SENSE OF THE SOMETIMES FORGOTTEN LIPID FRACTION

Jonathan morrell Dr Jonathan Morrell GP and GPwSI in Cardiology, Beaconsfield Road Surgery and Conquest Hospital, Hastings

© iStock.com/Justin Sneddon© iStock.com/Justin Sneddon

Dr Jonathan Morrell GP and GPwSI in Cardiology, Beaconsfield Road Surgery and Conquest Hospital, Hastings S Afr J Diabetes Vasc Dis 2009; 6: 55–58

T T

he importance of lowering total and LDL cholesterol (LDL-C) in the prevention of cardiovascular disease (CVD) is so firmly established that it has, in only a short time, become part of everyday practice for all primary care health professionals. Lipids, of course, come in multiple forms, which include fatty acids, the different forms of cholesterol and triglycerides. Most practitioners have only a sketchy idea of what triglycerides he importance of lowering total and LDL cholesterol (LDL-C) in the prevention of are, what they do and how important they are. Few understand the intricacies of measurement, cardiovascular disease (CVD) is so firmly established that it has, in only a short time, diagnosis and interpretation, and when – and how – to manage them. The story is complex and become part of everyday practice for all primary care health professionals. Lipids, of involves difficult biochemical and metabolic concepts, so we should begin at the beginning. course, come in multiple forms, which include fatty acids, the different forms of cholesterol and triglycerides. Most practitioners have only a sketchy idea of what triglycerides Fatty acids (saturated and unsaturated) are the building blocks from which are, what they do and how important they are. Few understand the intricacies of measurement, other fats in the body are made. After the process of digestion, three fatty acids diagnosis and interpretation, and when – and how – to manage them. The story is complex and attach themselves to a glycerol backbone (in a process called esterification) involves difficult biochemical and metabolic concepts, so we should begin at the beginning. forming a triglyceride. Dietary triglycerides are complemented by synthesis in other tissues, particularly in the liver, but also in adipose tissue and muscle. Fatty acids (saturated arelength the building blocksoffrom which Because fatty acidsand differunsaturated) in their chain and degree saturation, other fats in the body are made. After the process of digestion, three fatty acids there are multiple different triglycerides and that is why they are always attach themselves to a glycerol backbone (in a process called esterification) referred to in the plural. Although glycerol is soluble, fatty acids are insoluble forming a triglyceride. Dietary triglycerides are complemented synthesis in and the resulting triglycerides have to be carried in larger, morebycomplex other particularly in the liver, We but are alsofamiliar in adipose and muscle. carriertissues, molecules called lipoproteins. withtissue cholesterol being Because fatty acids differ in their chain length and degree of carried in the same way in low- or high-density lipoproteins (LDL-Csaturation, and HDL-C). there are multiple different triglycerides and that is why they are always WHY WEtheNEED referredDO to in plural.TRIGLYCERIDES? Although glycerol is soluble, fatty acids are insoluble The primary role of triglycerides is energy storage.inAdipose cells complex consist of a and the resulting triglycerides have to be carried larger, more droplet of triglycerides surrounded by a thin rim of cytoplasm. When look at carrier molecules called lipoproteins. We are familiar with cholesterolyou being fat on the butcher’s counter you are mostly looking at triglycerides. Each gram carried in the same way in low- or high-density lipoproteins (LDL-C and HDL-C). of triglycerides yields about 9 kcal and as adipose tissue is about 10% WHY DO WE cytoplasm, eachNEED gram ofTRIGLYCERIDES? adipose tissue yields about 8 kcal. When glycogen is The primary role of triglycerides energy storage. Adipose stored in liver or muscle there is ismuch more cytoplasm andcells eachconsist gram ofof a droplet of triglycerides surrounded by a thin rim of cytoplasm. When you look at glycogen stored yields only about 1 kcal. fat Itonmakes the butcher’s you are mostlyenergy looking triglycerides. gram biologicalcounter sense, then, to store as at triglycerides, andEach a healthy, of triglycerides yields about 9 kcal and as adipose tissue is about 10% non-obese 70 kg man usually has about 15 kg adipose tissue, representing cytoplasm, each gram ofenergy adipose tissue yields about 8 kcal. When glycogen is 140,000 kcal of stored (compared to about 900 kcal in stored glycogen). stored in liver or muscle there is much more cytoplasm and each gram of Different species use triglycerides with different melting points to ensure they glycogen only aboutFor 1 kcal. stay liquidstored at bodyyields temperature. example, fish use triglycerides with longerIt makes biological sense, then, to storeliquid energy triglycerides, and a healthy, chain unsaturated fatty acids, which stay at as lower temperatures, non-obese 70 kg man usually has about 15 kg adipose tissue, representing maintaining flexibility and cushioning. Storage triglycerides also contribute to 140,000 kcal of stored energy and (compared to about 900 kcal in stored thermoregulation by insulation rapid heat production in brown fat. glycogen). Different species use triglycerides with different melting points to ensure they stay liquid at body temperature. For example, fish use triglycerides with longerchain unsaturated fatty acids, which stay liquid at lower temperatures, maintaining flexibility and cushioning. Storage triglycerides also contribute to thermoregulation by insulation and rapid heat production in brown fat.

Most studies have shown a relationship between moderately � elevated triglycerides and CHD, and some have shown increased risk for stroke� Most studies have shown a relationship between moderately � elevated triglycerides and CHD, and some have shown increased risk for stroke�

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Figure 1:

8

HDL TG

10

C

LIVER 4

ARTERY

9

VLDL 5

TG

IDL

3 6

C 1

BLOOD TGs 2

FATTY ACIDS INTESTINE

ENERGY

STORAGE

窶天E

C LDL

7

ATHEROMA

TISSUES +VE

GROWTH REPAIR HORMONES VITAMIN D

Key VLDL: very low-density lipoprotein LDL: low-density lipoprotein HDL: high-density lipoprotein IDL: intermediate-density lipoprotein TG: triglycerides C: chylomicrons

HANG ON FOR A 10-POINT JOURNEY THROUGH TRIGLYCERIDE METABOLISM! 1. In the enterocytes of the gut wall, triglycerides (assembled from absorbed dietary fatty acids) are added to cholesterol, phospholipids and a specific protein (apo-B48) to form chylomicrons. Chylomicrons are secreted into the lymphatic system and thereafter into venous blood. 2. An enzyme called lipoprotein lipase (LPL) in peripheral tissues breaks down triglycerides into free fatty acids, which can be used for immediate energy supply or re-synthesised into triglycerides for storage. 3. What remains of the chylomicron is called a remnant and is removed by the liver. 4. The liver makes its own triglycerides (as well as cholesterol) and secretes them together as VLDL (very low-density lipoprotein). 5. LPL breaks down triglycerides in VLDL producing IDL (intermediate-density lipoprotein). Surface components are liberated which help mature HDL (high-density lipoprotein). It is this that causes the strong linkage between levels of triglycerides and HDL. When triglycerides are high, HDL tends to be low. We will see the clinical relevance of this later.

6. LPL also acts on IDL, producing LDL (low-density lipoprotein), which we know as the main cholesterol carrier of the body, and by now contains few triglycerides. 7. LDL delivers cholesterol to tissues for its various functions. About half of it is unused and recycled to the liver but excess cholesterol can deposit in arterial walls as atheroma. 8. HDL can remove excess cholesterol from tissues and either offload it to other lipoproteins, eg VLDL, or return it to the liver. 9. In some conditions, such as abdominal obesity, glucose intolerance and type 2 diabetes, liver synthesis of triglyceride-rich VLDL is increased. In addition the breakdown cascade is more sluggish. Higher, and more persistent, levels of triglyceride-rich lipoproteins mean that cholesterol in LDL and HDL is exchanged with triglycerides in VLDL. 10.The resulting triglyceride-rich LDL and HDL are then acted on by hepatic lipase, which removes triglycerides, leaving smaller and denser lipoproteins. Small, dense LDL-C is much more toxic than ordinary LDL-C and small, dense HDL-C may be less cardioprotective.

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BACKGROUND, WHAT DOEStoo! In I’m afraid the epidemiology is difficult EPIDEMIOLOGY TELL US? contrast to the situation with cholesterol, debate I’m afraid the epidemiology is difficult too! In about the risk of triglycerides is still raging, nearly contrast to the situation with cholesterol, debate 50 years after the first case-control study showed about the risk of triglycerides is still raging, nearly increased triglyceride levels in CHD patients. 50 years after the first case-control study showed Mostincreased studies have shownlevels a relationship triglyceride in CHD patients. between moderately elevated triglycerides and Most studies have shown a relationship CHD, and some moderately have shown increased risk for and between elevated triglycerides stroke. CHD, A meta-analysis in 1996 convincingly and some have shown increased risk for showedstroke. an increased risk of CHD (32% for men A meta-analysis in 1996 convincingly showed an increased risk of CHD (32% for men and 76% for women) in people with moderately and 76% for women) in people with moderately raised triglycerides. When statistically adjusted for triglycerides. When statistically HDL-C,raised however, the association was moreadjusted than for the that association halved. HDL-C, Critics however, pointed out single was more than halved. Critics pointed out that single measurements of triglycerides used in the surveys measurements of triglycerides used in the surveys were unreliable as they vary (by up to 20%) on a were unreliable as they vary (by up to 20%) on a daily basis. In addition, women were underdaily basis. In addition, women were underrepresented in the studies and, therefore, the represented in the studies and, therefore, the apparent extra risk for women was unreliable. apparent extra risk for women was unreliable. More fundamentally, they questioned whether it it More fundamentally, they questioned whether was appropriate to adjust for HDL-C at all when was appropriate to adjust for HDL-C at all when (as we (as havewejust seen) levels levels of triglycerides and and have just seen) of triglycerides HDL-C HDL-C are so are closely linked.linked. so closely What isWhat clearisisclear that isthe of moderately thatpattern the pattern of moderately raised triglycerides and cholesterol with an raised triglycerides and cholesterol with an associated lower level of HDL-C is the commonest associated lower level of HDL-C is the commonest lipoprotein pattern seen in patients with myocardial lipoprotein pattern seen in patients with myocardial infarction. onlybut that,it but it is commonly also commonly infarction. Not onlyNotthat, is also seen in people with abdominal obesity, impaired seen in people with abdominal obesity, impaired glucose regulation (as part of the metabolic glucose regulation (as part of the metabolic syndrome), type 2 diabetes, renal insufficiency and syndrome), type 2 diabetes, renal insufficiency and HIV – all states of high cardiovascular risk. HIV – all states of high cardiovascular risk.

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Box 1: The definition of metabolic syndrome

Box 1: The definition of metabolic Thesyndrome diagnosis is made when three or more of the following are present:

National Cholesterol Education Program, Adult Treatment Panel III (2001)

NOW WE UNDERSTAND THE BACKGROUND, WHAT DOES NOW WE UNDERSTAND EPIDEMIOLOGY TELL US? THE

National Cholesterol Education Program, Adult Treatment Panel III (2001)

SA JOURNAL OF DIABETES & VASCULAR DISEASE

The diagnosis is made when three or more of 1. Waist measurement: men >102 cm, women the following are present:

>88 cm

1. Waist measurement: men >102 cm, women 2. Serum >1.7 mmol/L >88triglycerides cm

3. HDL-C <1.0 mmol/L (men), <1.2 mmol/L 2. Serum triglycerides >1.7 mmol/L (women) 3. HDL-C <1.0 mmol/L (men), <1.2 mmol/L 4. Blood pressure >130/85 mmHg (women) 4. Bloodglucose pressure>6.1 >130/85 mmHg 5. Fasting mmol/L. 5. Fasting glucose >6.1 mmol/L.

The metabolic syndrome, while controversial in syndrome, some The eyes,metabolic has become one ofwhile the controversial major publicin some eyes, has worldwide. become oneItsofutility the major health challenges is to public help health challenges worldwide. Its utility is to identify individuals at high risk of developinghelp type 2 identify individuals at high risk of developing type 2 diabetes and CVD. Dyslipidaemia (raised diabetes and CVD. Dyslipidaemia (raised triglycerides and low HDL-C) is a key component triglycerides and low HDL-C) is a key component of definitions of the syndrome (eg Box 1). It often of definitions of the syndrome (eg Box 1). It often co-exists with abnormal glucose handling and co-exists with abnormal glucose handling and abdominal obesity and abdominal obesity andconfirms confirmsthe theposition position of of raised triglycerides as a marker for increased raised triglycerides as a marker for increased CV risk. CV risk.

HOW COULD TRIGLYCERIDES HOW COULD TRIGLYCERIDESLEAD LEAD TO TO INCREASED CARDIOVASCULAR INCREASED CARDIOVASCULARRISK? RISK? While cholesterol contentofofVLDL VLDLand andIDL IDL isis While thethe cholesterol content potentially atherogenic in itself, the major adverse potentially atherogenic in itself, the major adverse effects of raised triglyceride-containinglipoproteins lipoproteins effects of raised triglyceride-containing are to lower protective HDL-C and increase the are to lower protective HDL-C and increase the amounts of small, dense (and therefore potentially amounts of small, dense (and therefore potentially more atherogenic) LDL-C. This seems to occur at more atherogenic) LDL-C. This seems to occur at triglyceride levels between 1.7 and 5.0 mmol/L and triglyceride levels between 1.7 and 5.0 mmol/L and is the reason why many guidelines now accept is the reason why many guidelines now accept

1.7 mmol/L as the upper limit of normal for triglycerides. There are additional effects of raised 1.7 mmol/L asontheendothelial upper limitfunction of normaland for triglycerides triglycerides. There are additional effects of raised thrombogenesis. triglycerides on endothelial function and thrombogenesis. WHAT OTHER PROBLEMS CAN RAISED

TRIGLYCERIDES CAUSE?

WHAT OTHER PROBLEMS CAN RAISED Very high levels of triglycerides (even over TRIGLYCERIDES CAUSE? 100 mmol/L) are sometimes seen. over Levels above Very high levels of triglycerides (even 1.7 mmol/L indicate raised VLDL and 100 mmol/L) are sometimes seen. Levelslevels aboveabove 11 mmol/L, raised chylomicrons. the above levels climb 1.7 mmol/L indicate raised VLDL andAs levels further, chylomicrons predominate andlevels the blood 11 mmol/L, raised chylomicrons. As the climblooks milky (cow’s milk consists of chylomicrons with a further, chylomicrons predominate and the blood looks milky (cow’s content milk consists chylomicrons with aof the triglyceride of 45ofmmol/L). Because triglyceride of 45 of mmol/L). Because of the cholesterolcontent component VLDL and IDL, total cholesterol component of VLDL and IDL, total cholesterol is also increased (about 1 mmol/L for cholesterol is alsoofincreased (about 1 mmol/L for every 5 mmol/L triglycerides). every 5 mmol/L of triglycerides). Interestingly, the risk to patients here is of acute Interestingly, the risk to patients here is of acute pancreatitis not cardiovascular disease. Confusingly, pancreatitis not cardiovascular disease. Confusingly, some patients are very resistant to pancreatitis, some patients are very resistant to pancreatitis, even at high triglyceride levels, whereas others can even at high triglyceride levels, whereas others can be affected at much lower levels. Pancreatitis is be affected at much lower levels. Pancreatitis is more likely likelywith withtriglyceride triglyceridevalues values over mmol/L. more over 11 11 mmol/L. When triglycerides triglyceridesexceed exceed2020 mmol/L When mmol/L theythey cancan produce eruptive skin xanthomata on the extensor produce eruptive skin xanthomata on the extensor surfacesofofthe thearms armsand andlegs, legs, buttocks back. surfaces buttocks andand back. Fattyinfiltration infiltrationofofthetheliver liver is seen in degrees all degrees Fatty is seen in all of transaminase of hypertriglyceridaemia hypertriglyceridaemiaand andliver liver transaminase enzymes Rarely, a fatty enzymes(ALT, (ALT,AST) AST)may maybeberaised. raised. Rarely, a fatty liver may progress to the more serious nonliver may progress to the more serious nonalcoholic alcoholicsteatohepatosis steatohepatosis(NASH). (NASH). MEASUREMENT MEASUREMENTISSUES ISSUES

Unlike serum cholesterol (total and HDL cholesterol), Unlike serum cholesterol (total and HDL cholesterol), the concentrations of triglycerides are affected by the concentrations of triglycerides are affected by meals. As we have learned, our diet is a major meals. As we have learned, our diet is a major source of triglycerides and post-prandial source of triglycerides and post-prandial Prevention_in_practice 1/20/09since4:08 PM of Page 4 chylomicrons have been observed the days chylomicrons have been observed the days of blood-letting in the 18th century. Mostsince healthy blood-letting the 18th century. Most healthy people stabiliseintheir triglyceride levels in about 6-8 people stabilise their triglyceride levels in about 6-8 hours but those with abnormal triglyceride hours but those withlonger abnormal triglyceride metabolism may take and for this reason the full lipoproteinmay profile checkedand after 12-14 hour the metabolism takeis longer fora this reason fast (water allowed). full lipoprotein profile is checked after a 12-14 hour the full profile helps the clinician to fastDetermining (water allowed). make a more complete of the an clinician to Determining the fullassessment profile helps individual’s lipoprotein abnormality and diagnosis. make a more complete assessment of an Triglyceride levels are not useful for Framinghamindividual’s lipoprotein abnormality and diagnosis. based CV risk assessment, where the non-fasting Triglyceride levels are not useful for Framinghamtotal to HDL-C ratio can be used alone but, as we based CV risk assessment, where the non-fasting have seen, they are a useful indicator of those at total to HDL-C ratio can be used alone but, as we greater cardiovascular risk. In addition, if we want to 17 work out LDL-C levels using the Friedewald equation 17 (Box 2), we need full fasting profiles. It is important to 57 remember that the Friedewald equation is only accurate for triglyceride levels up to 4.5 mmol/L.

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Box 2: The Friedewald equation LDL-C (mmol/L) =


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triglycerides � Abdominal obesity � Glucose intolerance and type 2 diabetes � Pregnancy � Excess alcohol � Abdominal obesity � Drugs – beta-blockers, steroids, oestrogens, Box 3: Secondary causes of raised Glucose intolerance and&type 2 diabetes SA�JOURNAL OF DIABETES VASCULAR DISEASE

eg HRT, anti-psychotics, eg olanzapine, triglycerides � Excess alcohol

have seen, they are a useful indicator of those at greater cardiovascular risk. In addition, if we want to work out LDL-C levels using the Friedewald equation have seen, they are a useful indicator of those at (Box 2), we need full fasting profiles. It is important to greater cardiovascular risk. In addition, if we want to remember that the Friedewald equation is only work out LDL-C levels using the Friedewald equation accurate for triglyceride levels up to 4.5 mmol/L. (Box 2), we need full fasting profiles. It is important to remember that equation only at have theythe areFriedewald a useful indicator ofis those Boxseen, 2: The Friedewald equation accurate for triglyceride levels up to 4.5 mmol/L. greater cardiovascular risk. In addition, if we want to LDL-C (mmol/L) = work out LDL-C levels using the Friedewald equation Totalseen, cholesterol Triglycerides Box 2: The equation have theyFriedewald are– aHDL-C useful–indicator of those at (Box 2), we need full fasting profiles. It is important to 2.19 greater cardiovascular risk. In addition, if we want to have seen, theythe are=Friedewald a useful indicator LDL-C (mmol/L) remember that equationofis those only at work out LDL-C levels using the Friedewald equation greater cardiovascular risk. addition, we want to Total cholesterol – HDL-C Triglycerides accurate fortrials, triglyceride levelsIn–have up to been 4.5 ifmmol/L. In most triglycerides measuredto (Box needlevels full fasting It is important work 2), outwe LDL-C using profiles. the Friedewald equation 2.19 in the fasting state.Friedewald Recently, studies haveonly remember that equation Box2),2:weThe Friedewald equation (Box needthe full fasting profiles. It isisimportant to suggestedforthat non-fasting triglyceride levels are accurate triglyceride levels up to 4.5 mmol/L. In most trials, triglycerides have been measured remember that the =Friedewald equation is only LDL-C (mmol/L) more predictive of CVD risk than fasting levels. This in Total the fasting state.–Recently, accurate for triglyceride levels studies up to 4.5have mmol/L. cholesterol HDL-C Triglycerides Box 2: The Friedewald equation seems to make sense, as the– fasting level is not suggested that non-fasting triglyceride levels are normal and we spend more of equation our 2.19 lives in the postBox 2: The Friedewald LDL-C (mmol/L) more predictive of =CVD risk than fasting levels. This prandial state. Total cholesterol Triglycerides seems to make as the–have fasting levelmeasured is not LDL-C (mmol/L) =– HDL-C In most trials,sense, triglycerides been normal andSENSE westate. spend more our 2.19 lives in theOF postMAKING OF RAISED LEVELS Total cholesterol –Recently, HDL-C –ofstudies Triglycerides in the fasting have prandial state. TRIGLYCERIDES 2.19 levels are suggested that non-fasting triglyceride In most trials, have been measured In practice, mostoftriglycerides ofCVD the risk patients see in primary more predictive thanwe fasting levels. MAKING SENSE OF RAISED LEVELS OFThis in the fasting state. Recently,levels studies have In most trials, triglycerides have been measured care with raised triglyceride have values in seems to make sense, as the fasting level is not TRIGLYCERIDES suggested that non-fasting triglyceride levels are in the fasting state. Recently, studies have the range mmol/L. Inofmost cases, the postnormal and1.7-5.0 we spend our lives In practice, most themore patients we see in in the primary more predictive ofofCVD risk than fasting suggested that non-fasting levels areThis hypertriglyceridaemia will betriglyceride secondary tolevels. another prandial state. care with raised triglyceride levels have values in seems to make sense, as the fasting level is not more predictive of CVD This underlying problem, withrisk thethan vastfasting majoritylevels. of people the 4range 1.7-5.0 mmol/L. Inofmost cases, theOF PM Page MAKING SENSE OFmore LEVELS normal and we spend our lives in the postseems make sense, asRAISED the fasting level is not having to abdominal obesity, impaired glucose hypertriglyceridaemia will be secondary to another TRIGLYCERIDES prandial state. normal and spend(metabolic more of oursyndrome), lives in theorposttolerance or we diabetes underlying problem, with the vastwemajority people PM Page 4 In practice, most of the patients see in of primary prandial state. issues with SENSE alcohol. However, there LEVELS are other OF MAKING OF RAISED having abdominal obesity, impaired glucose care with raised triglyceride levels have values in situations that can cause raised triglyceride levels, TRIGLYCERIDES MAKING SENSE OF RAISED LEVELS tolerance diabetes (metabolic syndrome), orOF the range or 1.7-5.0 mmol/L. In most cases, the including pregnancy and liver disease (see Box 3). In practice, most of the patients we see in primary TRIGLYCERIDES issues with alcohol. However, there are other hypertriglyceridaemia will be secondary to another Rarely, specific defects canhave result care with raised triglyceride levels values in In practice, most ofgene the see in in primary situations that can cause raised triglyceride levels, underlying problem, withpatients the vastwe majority of people families prone to hypertriglyceridaemia. About one in the range 1.7-5.0 mmol/L. In most cases, the care with raised triglyceride levels have values including pregnancy and liver disease (see Box in3). having abdominal obesity, impaired glucose ahypertriglyceridaemia million people have LPL deficiency and even rarer willdefects beInsecondary to in another the range or 1.7-5.0 mmol/L. most cases, the Rarely, specific gene can result tolerance diabetes (metabolic syndrome), or is a deficiency of apoprotein C-II, the activator of underlying problem, with the vast majority of hypertriglyceridaemia will be secondary to another familieswith prone to hypertriglyceridaemia. Aboutpeople one in issues alcohol. However, there are other LPL. Some familiesobesity, have aimpaired partial LPL deficiency having glucose underlying problem, with vasttriglyceride majority oflevels, people a millionabdominal people have LPLthe deficiency and even rarer situations that can cause raised and the tendency for hypertriglyceridaemia isor tolerance or diabetes (metabolic syndrome), having abdominal obesity, impaired glucose is a deficiency of apoprotein C-II, the activator of including pregnancy and liver disease (see Box 3). broughtwith out alcohol. by another provoking factor such as the issues However, there aredeficiency other tolerance diabetes (metabolic syndrome), LPL. Someor families have a partial LPL Rarely, specific gene defects can result in or metabolic syndrome or excess alcohol. Most of situations that canfor cause raised triglyceride issues alcohol. However, there are other and thewith tendency hypertriglyceridaemia islevels, families prone to hypertriglyceridaemia. About one in e at these situations show veryliver high levels of Box including pregnancy and disease (see 3).the situations that can cause raised triglyceride levels, brought out by another provoking factor such as want to a million people have LPL deficiency and even rarer triglycerides with pancreatitis and skin Rarely, specific gene defects can result in including pregnancy and liverC-II, disease (see metabolic syndrome or excess alcohol. MostBox ofof3). e at is a deficiency of apoprotein the activator quation manifestations. families prone to hypertriglyceridaemia. About one in Rarely, specific gene defects can result in theseSome situations show verya high want to LPL. families have partiallevels LPL of deficiency rtant to The genes behind familial combined atriglycerides million people have LPL deficiency and even rarer families prone to hypertriglyceridaemia. About with pancreatitis and skin quation and the tendency for hypertriglyceridaemia is one in hypercholesterolaemia are unknown, but the is a deficiency of apoprotein C-II, the activator of millionout people have LPL deficiency andsuch evenasrarer manifestations. rtant to abrought by another provoking factor the /L. condition affects about 1 ainpartial every 200activator people and LPL. Some families have LPL deficiency is a deficiency of apoprotein C-II, the The genes behind familial combined metabolic syndrome or excess alcohol. Most ofof presents with a mixed pattern of raised cholesterol, and the tendency forhave hypertriglyceridaemia LPL. Some families partial LPLbut deficiency hypercholesterolaemia area unknown, theis /L. these situations show very high levels of raised triglycerides and a strong family history of brought out by another provoking factor such and the tendency for hypertriglyceridaemia is as condition affects 1 in every andthe triglycerides with about pancreatitis and 200 skin people metabolic syndrome excess ofaslife brought bypicture provoking factor such the CVD. Theout full usually emerges inMost middle presents with aanother mixedor pattern ofalcohol. raised cholesterol, 18 manifestations. these situations show very high levels of metabolic syndrome or excess alcohol. Most of especially when drawn out by accompanying raised triglycerides and a strong family history of The genes behind familial combined triglycerides with pancreatitis andlevels skinin these situations show very high of middle CVD. The picture usually emerges features offull the metabolic hypercholesterolaemia aresyndrome. unknown, but the life manifestations. 18 triglycerides with pancreatitis and skin especially when drawn out by accompanying Hypertriglyceridaemia seen200 in remnant sured condition affects aboutis1also in every people and The genes behind familial combined manifestations. features of the metabolic syndrome. hyperlipidaemia, another rare condition, where presents with a mixed pattern of raised cholesterol, hypercholesterolaemia are unknown, but theup The genes behind familial combined Hypertriglyceridaemia is also seen in remnant sured defective liver receptors are unable to take are raised triglycerides and a strong family history of condition affects about are 1 rare inunknown, every 200but people hypercholesterolaemia the and hyperlipidaemia, another condition, where chylomicron remnants. s. This presents with areceptors mixed of raised cholesterol, affects about 1are in every 200 people and defective liver unable take upand are 18 condition In primary care it is pattern reasonable totoidentify not 58 raised triglycerides and a strong family history of presents withcommon, a mixed simple patterncauses of raised chylomicron remnants. This manage the of cholesterol, es.post-

CVD. The full picture usually emerges in middle life especially when drawn out by accompanying features of the metabolic syndrome. CVD. The full picture usually emerges in middle life Hypertriglyceridaemia is also seen in remnant especially when drawn out by accompanying hyperlipidaemia, another rare condition, where features of the metabolic syndrome. defective liver receptors are unable to take up Hypertriglyceridaemia is also seen in remnant chylomicron remnants. hyperlipidaemia, another rareemerges condition, CVD. The full picture usually in where middle life In primary care it is reasonable to identify and defective liver arebyunable to take up especially whenreceptors drawn out accompanying manage the common, simple causes of chylomicron remnants. features of the metabolic syndrome. hypertriglyceridaemia, but theemerges more difficult cases CVD. The full care picture in middle life In primary it isusually Hypertriglyceridaemia isreasonable also seen to in identify remnantand should be referred to, and managed by, specialist especially when drawn out byemerges accompanying CVD. Thethe full picture usually middle life manage common, simple ofin where hyperlipidaemia, another rare causes condition, centres. ofwhen features the metabolic syndrome. especially drawn out by accompanying hypertriglyceridaemia, more to difficult cases defective liver receptorsbutaretheunable take up Hypertriglyceridaemia is also seen in by, remnant features of the metabolic syndrome. should be referred to, and managed specialist HOW DO WE TREAT chylomicron remnants. hyperlipidaemia, anotheralso rare seen condition, where Hypertriglyceridaemia in identify remnant centres. HYPERTRIGLYCERIDAEMIA? In primary care it is isreasonable to and defective liver receptors are to take up hyperlipidaemia, another rareunable condition, where The key to controlling hypertriglyceridaemia is often manage the common, simple causes of HOW DO WE TREAT chylomicron defective liverremnants. receptors to take(Box up the identification and control ofmore its causes 3). hypertriglyceridaemia, butaretheunable difficult cases HYPERTRIGLYCERIDAEMIA? In primary care it is reasonable to identify and chylomicron remnants. Lifestyle measures include weight loss aided by should referred to, hypertriglyceridaemia and managed by, specialist The keybeto controlling is often manage the common, ofon sensible In primary care itactivity is simple reasonable to identify and increased physical andcauses advice centres. the identification and control ofmore its causes (Box 3). hypertriglyceridaemia, but the difficult cases manage the common, simple causes of drinking. In moderate hypertriglyceridaemia, the diet Lifestyle measures include weight loss aided by HOW DO WE TREAT should managed by, specialist hypertriglyceridaemia, but difficult cases should be be referred the sameto,asand thethe dietmore to lower cholesterol, increased physical activity and advice on sensible HYPERTRIGLYCERIDAEMIA? centres. should to, andfatmanaged by,by specialist namely be lowreferred in saturated substituted monodrinking. moderate hypertriglyceridaemia, diet The key toIn controlling hypertriglyceridaemia istheoften centres. and poly-unsaturates or complex (low glycaemic HOW DO WE TREAT should be Secondary the same the diet to of lower cholesterol, the identification andascontrol of its causes (Box 3). Box 3: causes raised index) carbohydrates according to energy balance. HYPERTRIGLYCERIDAEMIA? HOW DO WE TREAT namely low in saturated fat substituted by monoLifestyle measures include weight loss aided by Astriglycerides triglycerides approach 11 mmol/L and higher, The key to controlling hypertriglyceridaemia is often HYPERTRIGLYCERIDAEMIA? and poly-unsaturates or complex (low glycaemic Box 3: physical Secondary causes of raised increased activity and advice on sensible the�identification need tocontrolling reduce demands very lowthe andchylomicrons control of its causes balance. (Box 3). Pregnancy The key toIn hypertriglyceridaemia istheoften index) carbohydrates to energy triglycerides drinking. moderate according hypertriglyceridaemia, diet fat diets and specialist advice is required. Lifestyle measures include weight loss aided by3). Abdominal obesity the identification and of its causes (Box As�triglycerides approach mmol/L and higher, should be the same ascontrol the11diet to lower cholesterol, Technically, the clinical trial evidence forsensible Pregnancy increased activity andtype advice on Glucose intolerance and 2loss diabetes Lifestyle measures include aided by lowthe�need tophysical reduce chylomicrons demands very namely low in saturated fat weight substituted by monopreventing CVD by lowering triglycerides is � Abdominal obesity drinking. In moderate hypertriglyceridaemia, the Excess alcohol increased physical activity andisadvice sensiblediet fat diets and specialist required. and poly-unsaturates oradvice complex (low on glycaemic inconclusive but, as we have seen, it is hard to diet � Glucose intolerance and type 2 diabetes should beInthe same ashypertriglyceridaemia, thetrial diet to lower cholesterol, Drugs –moderate beta-blockers, steroids, oestrogens, drinking. the Technically, the clinical evidence index) carbohydrates according to energyforbalance. isolate triglyceride changes from the other � Excess alcohol namely lowthe in saturated fat diet substituted byismonoeg be HRT, anti-psychotics, eg toolanzapine, should same as the lower preventing CVD by lowering As triglycerides approach 11triglycerides mmol/L andcholesterol, higher, lipoproteins. Inbeta-blockers, the majority of cases, raised levels of � poly-unsaturates Drugs – steroids, oestrogens, and or complex (low glycaemic retinoids, cyclosporine, protease inhibitors, namely low in saturated fat substituted monoinconclusive but, aschylomicrons we have seen,demands it is by hard to lowthe need to reduce very triglycerides indicate higher CV risk and statins are eg HRT, anti-psychotics, eg olanzapine, index) carbohydrates according to energy balance. interferon and poly-unsaturates or complex (low glycaemic isolate triglyceride changes from the other fat diets and specialist advice is required. the mainstay of treatment. By reducing liver retinoids, cyclosporine, protease inhibitors, As approach and balance. higher, �triglycerides Endocrine disorders –11 hypothyroidism, index) carbohydrates according to energy lipoproteins. In the the majority ofmmol/L cases, raised Technically, clinical trial evidence for levels of synthesis of reduce cholesterol, statins also reduce VLDLinterferon the need to chylomicrons demands very lowCushing’s disease As triglycerides approach 11 mmol/L and triglyceridesCVD indicate higher CV risk and statins preventing by lowering triglycerides ishigher,are lowering triglycerides roughly inis proportion to their �diets Endocrine disorders – hypothyroidism, fat and specialist advice required. Liver disease the need to reduce chylomicrons demands very mainstaybut, of treatment. Byseen, reducing inconclusive as we have it is liver hard to lowLDL-C-lowering capacity. Therefore, higher-intensity Cushing’s disease Technically, the clinical trial evidence for � Renal disease fat dietstriglyceride and specialist advice isalso required. synthesis of cholesterol, statins isolate changes from the reduce other VLDLstatins, such as atorvastatin and rosuvastatin, lower � Liver disease preventing CVDthe by lowering triglycerides is to their Lipodystrophies. Technically, trial evidence for lowering triglycerides roughly proportion lipoproteins. In the clinical majority of incases, raised levels of triglycerides more. � Renal disease inconclusive but,by aslowering we have seen, ithigher-intensity is hard preventing CVD triglycerides is to are LDL-C-lowering capacity. Therefore, triglycerides indicate higher CV risk and statins � Lipodystrophies. isolate triglyceride changes from the other inconclusive but, as we have seen, it is hard statins, suchand as atorvastatin rosuvastatin, Fibrates acid are also used the mainstay of nicotinic treatment. Byand reducing liver totolower lipoproteins. In the majority of cases, raised levels of isolate the reduce other VLDLtriglycerides more. changes reduce triglyceride triglycerides eitherstatins asfrom monotherapy synthesis of cholesterol, also triglycerides indicate higher CV risk and statins lipoproteins. In the majority raised levels Fibrates and nicotinic acid are also used to (particularly when statins areof not tolerated) or inareof lowering triglycerides roughly incases, proportion to their the mainstay of treatment. By reducing liver triglycerides indicate higher CV risk and statins reduce triglycerides eitherTherefore, as monotherapy combination withcapacity. a statin. Fibrates reduce VLDLare LDL-C-lowering higher-intensity synthesis of cholesterol, statins also reduce the mainstay of treatment. By reducing liver (particularly when statinstissue areand not tolerated) in synthesis and LPL, thereby orVLDLstatins, such asincrease atorvastatin rosuvastatin, lower lowering triglycerides roughly in proportion toVLDLtheir synthesis of cholesterol, statins also reduce combination with a statin. Fibrates reduce VLDL increasing HDL-C and reducing triglycerides. triglycerides more. LDL-C-lowering capacity. Therefore, higher-intensity lowering triglycerides proportion synthesis and increase tissue LPL, thereby Fenofibrate should be roughly used toin avoid liver to their statins, such as atorvastatin and rosuvastatin, lower LDL-C-lowering capacity. Therefore, higher-intensity increasing triglycerides. cytochromeHDL-C issuesand withreducing simvastatin and triglycerides more. statins, such as atorvastatin and rosuvastatin, Fenofibrate be acid usedalso to avoid liverVLDL lower atorvastatin.should Nicotinic reduces

raised triglycerides a strong family history of In primary care itand is but reasonable todifficult identify and not hypertriglyceridaemia, the more cases 18 manage common, simple causesby, of specialist e postshould bethereferred to, and managed OF 18 hypertriglyceridaemia, but the more difficult cases centres. should be referred to, and managed by, specialist

triglycerides more. cytochrome with simvastatin and to secretion butissues has historically been difficult atorvastatin. Nicotinic acid also reduces tolerate due to skin flushing. LaropiprantVLDL is a secretion but has antidote historically difficult to and newly discovered forbeen this side-effect tolerate due to skin flushing. Laropiprant is a

retinoids, cyclosporine, protease inhibitors,

� Pregnancy Drugs – beta-blockers, steroids, � Box 3: Secondary causes of oestrogens, raised interferon eg HRT, anti-psychotics, eg olanzapine, � Abdominal obesity triglycerides Box 3: Secondary of raised � Endocrine disorders causes – hypothyroidism, retinoids,intolerance cyclosporine, inhibitors, � Glucose andprotease type 2 diabetes triglycerides Cushing’s disease � Pregnancy interferon � Excess alcohol � Abdominal Liver disease � obesity – hypothyroidism, � Pregnancy � Endocrine disorders � Drugs – beta-blockers, steroids, oestrogens, � Renal disease � Abdominal Glucose intolerance type 2 diabetes � obesity and eg Cushing’s disease eg HRT, anti-psychotics, olanzapine, � Excess Lipodystrophies. � alcohol � Glucose intolerance and type 2 diabetes � retinoids, Liver disease cyclosporine, protease inhibitors, � –alcohol beta-blockers, steroids, oestrogens, � Excess � Drugs Renal disease

interferon

eg HRT,–and anti-psychotics, eg � Drugs beta-blockers, steroids, Fibrates nicotinic acid areolanzapine, alsooestrogens, used to � Lipodystrophies. � Endocrine disorders – hypothyroidism,

retinoids, cyclosporine, inhibitors, eg HRT, anti-psychotics, eg olanzapine, reduce triglycerides either asprotease monotherapy Cushing’s disease interferon retinoids, cyclosporine, protease inhibitors, (particularly when statins are not tolerated) or in � Liver disease Fibrates and nicotinic acid are also used to � Endocrine disorders – hypothyroidism, interferon combination with a statin. Fibrates reduce VLDL � Renal disease reduce triglycerides either as monotherapy disease � Cushing’s Endocrine disorderstissue – hypothyroidism, synthesis and increase LPL, thereby � Lipodystrophies. (particularly when statins are not tolerated) or in � Liver disease Cushing’s disease increasing HDL-C and reducing triglycerides. combination with a statin. Fibrates reduce VLDL � disease � Renal Liver disease Fenofibrate should be used to avoid liver synthesis and LPL,also thereby Fibrates andincrease nicotinictissue acid are used to � Lipodystrophies. � Renal disease cytochrome issues with simvastatin and increasing HDL-C and reducing triglycerides. reduce triglycerides either as monotherapy � Lipodystrophies. atorvastatin. Nicotinic acid also reduces VLDL Fenofibrate should be used avoid liver or in (particularly when statins aretonot tolerated) secretion but has historically difficult Fibrates and nicotinic acid been are also usedtoto cytochrome issues with simvastatin and combination with a statin. Fibrates reduce VLDL tolerate due to skin flushing. Laropiprant is ato reduce triglycerides either as monotherapy Fibrates and nicotinic acid are also used atorvastatin. Nicotinic acid also reduces VLDL synthesis and increase tissue LPL, thereby newly discovered antidote for thistolerated) side-effector and (particularly when statins are not reduce triglycerides either as been monotherapy secretion but has historically difficult to in increasing HDL-C and reducing triglycerides. a(particularly combination of extended-release nicotinicVLDL acid combination with a statin. Fibrates reduce when aretoLaropiprant not tolerated) tolerate dueshould to skinstatins flushing. a in Fenofibrate be used avoid liver is or and laropiprant will be launched soon in the UK. synthesis andwith increase tissue LPL,side-effect therebyVLDL combination statin. Fibrates reduce newly discovered for this and cytochrome issuesaantidote with simvastatin and In severe hypertriglyceridaemia, high-dose omegaincreasing HDL-C and reducing triglycerides. synthesis and increase tissue LPL, thereby a combinationNicotinic of extended-release nicotinic atorvastatin. acid also reduces VLDLacid 3 fish oil capsules (2 gused twicetodaily) will also Fenofibrate should be avoid liver increasing HDL-C and reducing triglycerides. and laropiprant will be launched soon in secretion but has historically been difficultthetoUK. reduce triglycerides, especially in combination cytochrome issues be with simvastatin and Fenofibrate should used toLaropiprant avoid liver is omegaIn severedue hypertriglyceridaemia, high-dose tolerate to skin flushing. a with other drugs. atorvastatin. Nicotinic acid also reduces VLDL cytochrome issues with simvastatin and 3newly fish oil capsules (2 g twice daily) will also discovered antidote for this side-effect and secretion butNicotinic has historically been difficult to atorvastatin. acid also VLDL reduce triglycerides, especially inreduces combination aSUMMARY combination of extended-release nicotinic acid tolerate due tohas skinhistorically flushing. Laropiprant is a secretion but beensoon with laropiprant other drugs. Raised triglycerides arelaunched common indifficult patients and will be in thetowith UK. newly discovered antidote for this side-effect tolerate to skintheir flushing. a and CVD anddue through relatedLaropiprant effects on is LDL-C, In severe hypertriglyceridaemia, high-dose omegaSUMMARY anewly combination of extended-release nicotinic discovered antidote for should this side-effect and and other risk be also seenacid as 3HDL-C fish oil capsules (2are gfactors twice daily) Raised triglycerides common in will patients with and laropiprant will be launched soon in the UK. areduce combination of extended-release nicotinic acid an indicator of increased CV risk. Common especially in combination CVD andtriglycerides, through their related effects on LDL-C, In severe hypertriglyceridaemia, high-dose and laropiprant will be launched soon in theomegaUK. secondary causes of hypertriglyceridaemia should with other drugs. HDL-C and other risk factors should be seen as 3In fish oil capsules (2 g twice daily) will also hypertriglyceridaemia, omegabesevere identified and treated. If, afterhigh-dose lifestyle and an indicator of increased CV risk. Common SUMMARY reduce in combination 3statin fish treatment, oiltriglycerides, capsulestriglycerides (2especially g twice daily) willa also remain problem secondary causes of hypertriglyceridaemia Raised triglycerides are common in patientsshould with with other drugs. reduce triglycerides, especially in combination there is a role for combination treatment using be identified and treated. If, after lifestyle and CVD and through their related effects on LDL-C, with other drugs. acid fibrates, nicotinic or fish oils. SUMMARY statin treatment, remainbe a problem HDL-C and other triglycerides risk factors should seen as Raised triglycerides are common in patients with SUMMARY there is a roleof for combination treatment using an indicator increased CV risk. Common CVD and through their related effects on LDL-C, Raised with fibrates,triglycerides nicotinic orcommon fish oils.in patientsshould secondary causesacid ofare hypertriglyceridaemia HDL-C and other risk factors should beonseen as CVD and through their related effects LDL-C, be identified and treated. If, after lifestyle and an indicator of increased CV risk. Common HDL-C and other risk factors should seen as statin treatment, triglycerides remainbe a problem Triglycerides. Heart Foundation secondary causes ofBritish hypertriglyceridaemia should an indicator of increased CV risk. Common • there is a role for combination treatment using Factfile be identified and treated. If, after lifestyle and No.4. July 2008. secondary causes of hypertriglyceridaemia should fibrates, nicotinic acid or fish oils. statin treatment, triglycerides remain a problem Reckless J and Morrell J. Lipid Disorders. be • and treated. after Foundation lifestyle and Triglycerides. BritishIf,Heart •identified there istreatment, a role fortriglycerides combination treatment using Your Questions Answered . Churchill statin remain a problem Factfile No.4. July 2008. fibrates, acid Livingstone 2005or fish oils. there isReckless anicotinic role for combination treatment using J and Morrell J. Lipid Disorders. • fibrates, nicotinic acid or fish oils. Your Questions Answered. Churchill Livingstone 2005 British Heart Foundation • Triglycerides.

• • • • •

Factfile No.4. July 2008. Reckless J and Morrell J. Lipid Disorders. Triglycerides. British Heart Foundation Your Questions Answered. Churchill Factfile No.4. British July 2008. Triglycerides. Heart Foundation Livingstone 2005 Reckless J and Morrell Factfile No.4. July 2008.J. Lipid Disorders. Your Questions Churchill Reckless J and Answered Morrell J..Lipid Disorders. Livingstone 2005 Your Questions Answered . Churchill VOLUME 6 NUMBER 2 • JUNE 2009 Livingstone 2005


SA JOURNAL OF DIABETES & VASCULAR DISEASE

Patient information leaflet

Keep and Copy Series

T AKING ASPIRIN FOR THE PREVENTION OF CARDIOVASCULAR DISEASE

"

S Afr J Diabetes Vasc Dis 2009; 6: 59

Why has my doctor prescribed aspirin? Your doctor has assessed your risk for heart disease and stroke and is prescribing aspirin daily to reduce the risk of these life-threatening events. Heart attacks and ischaemic stroke (strokes) occur when blockages in the blood vessels that supply the heart or brain cut off blood supply long enough to damage parts of these organs. Aspirin decreases the chances of a heart attack or stroke in patients who have had heart attacks or strokes, and newer evidence suggests that aspirin is also beneficial in certain people who have not had a heart attack or stroke. This is particularly true for diabetic patients. Aspirin can cause uncommon but serious complications, such as bleeding in the digestive tract or brain. Enteric-coated aspirin can reduce the occurrence of this bleeding. The dose of aspirin for prevention should not be more than 150 mg/day and a dose of approximately 75 mg/day is as effective as higher dosages, which are associated with more bleeding complications. Evidence shows that aspirin decreases the incidence of heart attacks in men aged 45 to 79 years and strokes in women aged 55 to 79 years, who are at increased risk for these events but have not yet had either of these problems. Aspirin also prevents more heart attacks and strokes in people with several risk factors for cardiovascular disease. However, taking aspirin does increase a person’s chances of bleeding in the stomach, intestine or brain (called haemorrhagic stroke). Your doctor will have carefully looked at this benefit–risk relationship.

How do I know what my risk levels are? For men, patients and doctors should consider age, blood pressure and cholesterol level, and whether he is a smoker or a diabetic when deciding whether to use aspirin to prevent heart attacks. (A tool to calculate your risk as a man for a heart attack is available at http://healthlink.mcw. edu/article/923521437.html.) For women, patients and doctors should consider age, blood pressure, whether she is a diabetic or a smoker, has abnormal heart rhythms, an enlarged heart or has a history of other cardiovascular disease. (A tool for estimating your stroke risk is available at www.westernstroke.org/PersonalStrokeRisk1.xls.) Men aged 45 to 79 years should take aspirin if the chances of preventing heart attack outweigh the chances of bleeding in the digestive tract. Women aged 55 to 79 years should take aspirin if the chances of reducing ischaemic stroke outweigh the chances of bleeding in the digestive tract. Men younger than 45 years and women younger than 55 years who have not previously had a heart attack or stroke should not take aspirin for prevention. It is unclear whether the benefits of aspirin outweigh the risks for patients 80 years or older. What are the cautions to aspirin usage? Always follow the advice of your doctor/nurse. Take your medication regularly as prescribed. If you are taking other medication, tell your healthcare provider. Read the package insert of the medicine carefully.

Source Aspirin for the prevention of cardiovascular disease: US Preventive Services Task Force. Ann Int Med 2009; 150: 396–404.

VOLUME 6 NUMBER 2 • JUNE 2009

59


It's the shell that makes R

safer.

Safety-Coated R

81mg The ORIGINAL low dose aspirin for optimum cardio-protection pH

Each tablet contains Aspirin 81mg. Reg.No.: 29/2.7/0767 Pharmafrica (Pty) Ltd, 33 Hulbert Road, New Centre, Johannesburg 2001 Under licence from Goldshield Pharmaceuticals Ltd. U.K.


SA JOURNAL OF DIABETES & VASCULAR DISEASE

Hands on DIABETES MANAGEMENT MADE EASIER: INSULIN DELIVERY DEVICES Dr JA Kok Union Hospital, Alberton, Gauteng e-mail: jakok@mweb.co.za

S Afr Diabetes Vasc Dis 2009; 6: 61–62.

S

o uth Africa is one of the major consumers of insulin pen devices in the world. For those patients who need to use multiple injections per day, making insulin injections easier and more comfortable assists them in complying with a treatment plan. This article discusses the delivery devices available and some of the advantages of each.

In whichever way insulin is delivered, the physiological action of insulin remains the same but the dosage must be delivered accurately, effectively and safely. Apart from the well-known insulin syringes and needles, there are now many other injection devices available. Spring-loaded and jet-injection devices, insulin pens and injection ports are discussed.1 Recently, several pump centres were accredited in South Africa for continuous subcutaneous insulin injection (CSII), which offers another option. Insulin vials, syringes and needles Syringe choices can make a difference but economics may limit the choice available. This is especially true in the public sector. There are 3/10, 5/10 and 1-cm3 syringe sizes, the last being the most widely used. Needles come in 28–32 gauge and different lengths. This is important when matching the size of the patient with the length of the needle. For example, a child would require a much shorter needle compared to an overweight adult with a body mass index above 35 kg/m2. The smaller syringe allows for more accurate dosing but is not widely available. Not all insulins are available in vials. Insulin pens Over time, various companies have vastly improved the accuracy, ease of use and safety of insulin pens. Disposable devices are increasingly being used as they are accurate, convenient and can be used anywhere. Reusable devices in pen form with insulin cartridges are also available and at a lower cost. The

VOLUME 6 NUMBER 2 • JUNE 2009

desired dose is administered by turning the dose selector at the end of the pen. Once the dosage has been selected, the amount will be reflected in a window on the pen. The dose is administered by pushing the end of the pen. Disposable devices are easy to administer, can be carried in a pocket, handbag or briefcase and eliminate the need to draw up the insulin into a syringe.1 You need to discuss your patient’s treatment plan with him/her and decide on the appropriate insulin. The physiological profile and the effect you desire must match, for example, are you targeting fasting or postprandial glucose levels. The device chosen will depend on the reimbursement policies and formulary of the funder in private practice and may not always be ideal. Remember that if you do use the formulary agent and it does not improve the patient’s control, you can motivate for alternatives without attracting a co-payment or levy as per the Medical Schemes Act of 2004. Novo Nordisk2 This company recently launched the new-generation FlexPen which requires significantly less pressure to inject; 30% less than the previous disposable FlexPen, and on average 18 to 45% less that the competitor devices. Levemir (insulin detemir) and NovoRapid (insulin aspart) pens are colour coded to avoid confusion. These devices are therefore easier to use. The FlexPen is numbered in two-unit increments and each turn can be felt, as well as making an audible click for those who cannot see well. The dose indicator gives a clear dosage level and can be dialled back to

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SA JOURNAL OF DIABETES & VASCULAR DISEASE

Hands on zero if the patient makes a mistake the first time. There are five pens in a box, each containing 300 units per pen. Protaphane and NovoMix 30 are also available in the new FlexPen devices but are not colour coded. NovoPen 3 is a device that takes cartridges of the various insulins of Novo Nordisk and is numbered in one-unit increments. The NovoPen Junior is numbered in 0.5-unit increments for ease of dosage adjustment. The pen needles are also disposable, Novo or BD needles can be used, and gauges available are 29 to 32 cm3, again depending on the morphology of your patient. The new insulins are very stable and the pen can be kept out of the refrigerator for 30 to 35 days after first use, depending on the ambient temperature. A very useful device for people with a needle phobia is the NovoPen 3 penmate. Sanofi aventis2 This company launched the SoloStar disposable pens a few months ago, a major improvement on their first-generation Autopen and Optipenset. These pens contain Lantus (glargine) and Apidra (glulisine) insulin, with five pens in a box, each pen containing 300 units of insulin. The same principle of palpable and audible clicks enables poorly sighted patients to administer accurate dosages. The human insulin Insuman 30/70 cartridges in the Autopen were launched more recently. This was for economic reasons as it is less expensive and the pen device performs well. BD needles are preferred for the Sanofi aventis insulins as the insulin may crystallise with Novo needles. In a study presented as a poster at EASD 2007 (currently not published), Pfützner directly compared the accuracy of insulin delivery pens by means of a standardised laboratory protocol. The results suggested that the FlexPen was more reliable when delivering insulin detemir than the SoloStar delivering insulin glargine.3 Eli Lilly2 Although the first company to market insulin, their pen devices have developed slowly. The recent Miriopen is the best of their pens available at present and although a bit bulky, it is a major improvement on past products. The various insulins available include Humalog, Humulin N, Humulin 30/70, Humalog Mix 25, Humalog Mix 50 and Humulin R. Not all of these are available in the Miriopen. Pen fills are available for most. The dosage indicator on these devices is much smaller and the pressure required to inject is significantly more but no direct comparisons with other devices exist, therefore it is a subjective observation. These pens are also in 300 units per pen and boxes of five. They can use both BD and Novo needles.

62

csii This method of insulin administration is for the motivated and capable patient only. It requires extra resources and may provide some improvement in diabetic control versus conventional regimes such as basal-bolus therapy. It is mentioned here for completeness but requires an article on its own to do it justice. spring-loaded and Jet-inJection devices These are not available to my knowledge in South Africa. With springloaded devices, the patient places a conventional insulin syringe in the device, activates it and then allows the device to inject the insulin. Jet devices supply a subcutaneous spray of insulin. This is facilitated by forcing the insulin with compressed air into the subcutaneous space.1 conclusion To be able to spend time with patients, demonstrating the safe and appropriate administration of mixed insulin injections with vial and syringe may be difficult in this era of scarce human resources. Pen-delivery devices have without a doubt revolutionised the ease of initiation of insulin therapy in clinics. It has also been shown to improve patient compliance, adherence to therapy and control of diabetes. There is also reduced likelihood of hypoglycaemic events. The biggest barrier to their use is the medical funding industry. The funders need to understand the benefits of insulin pen devices, particularly accurate, safe dosing, especially in poorly sighted patients, and improved control, which is the ultimate objective. These devices have the additional benefit that they are easy to use and the patient can be educated in their use in a short space of time.4,5

References 1. 2. 3. 4.

5.

Liebovitz H. In: Klingensmith GJ, ed. Intensive Diabetes Management. 3rd edn. American Diabetes Association Inc, 2003. Literature and data from Novo Nordisk, Sanofi Aventis and Eli Lilly. Pfützner A, et al. Prefilled insulin device with reduced injection force: patient perception and accuracy. Curr Med Res Opin 2008; 24(9): 2545–2549. Lee WC, Balu S, Cobden D, et al. Medication adherence and the associated health– economic impact among patients with type 2 diabetes mellitus converting to insulin pen therapy. Clin Therap 2006: 28: 1712–1725. Rubin R, Peyrot M. Quality of life, treatment satisfaction and treatment preference associated with use of a pen device delivering a premixed 70/30 insulin as part suspension versus alternative treatment strategies. Diabetes Care 2004; 27: 2495–2497.

VOLUME 6 NUMBER 2 • JUNE 2009


It gets patients the insulin they need without getting in the way of life Advanced patient-friendly Technology

Easy to learn, easy to use1 Low, smooth injection force1 Light weight1

Killian Webb 1272

Eli Lilly (S.A.) (Pty) Ltd. Reg No. 1957/000371/07. 1 Petunia Street, Bryanston, 2021 Private Bag X1119, Bryanston, 2021 Telephone: (011) 510 9300 A1717 Jan 09

S3 Humalog Solution. 29/21.1/0785. S3 Humalog Mix25. 33/21.1/0073. S3 Humalog Mix50. 33/21.1/0074.

References: 1. Lilly Data on File. For full prescribing information refer to the current approved package insert.


SA JOURNAL OF DIABETES & VASCULAR DISEASE

Diabetes Personality OVERCOMING THE CHALLENGES OF A RESOURCEPOOR ENVIRONMENT TO DELIVER QUALITY DIABETES CARE IN A PUBLIC-SECTOR CLINIC Dr Dana Tupy Diabetes Clinic, Hillbrow Community Health Centre, Johannesburg Tel: +27 (0) 11 694-3778 e-mail: tupy@yebo.co.za

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S Afr J Diabetes Vasc Dis 2009; 6: 64–65.

T

o manage patients with a chronic disease like diabetes, it is essential first and foremost to earn their trust. Once you achieve that, understanding them and knowing what’s on their minds, you will be able to treat them properly. This is the view of Dr Dana Tupy, who runs the diabetes clinic at Hillbrow Community Health Centre. She has been involved with it for 14 years and, in recent years, has been the lone doctor there, assisted only by two ‘excellent and dedicated nursing sisters’. ‘Being foreign, earning that trust was especially difficult for me’, says the Slovakian-born Dr Tupy, ‘but after so many years with these people who I’ve come to love, I think I can say with confidence that they love me too.’ Love for and commitment to her patients are what keep Dr Tupy working in a public-sector facility, with its challenges and obstacles related to lack of resources, both human and otherwise. A specialist physician and diabetologist, her specialist qualifications are not recognised in South Africa, where she is employed by the state as a general practitioner – even though the services she offers go far beyond those of one. ‘I still don’t understand why this is so’, she says. ‘I could walk into a specialist facility anywhere in the European Union, so why does a developing country with a serious shortage of specialists not accredit my qualifications?’ When Dr Tupy joined the clinic at what was then Hillbrow Hospital in 1995, the clinic was fairly small, she recalls. At that time there were two doctors and each of them saw perhaps 20 to 25 patients a day. ‘But gradually the numbers began to increase, something that was accelerated by Johannesburg Hospital clos-

ing its diabetic polyclinic. All those patients reverted to us, and today I’m probably seeing 60 to 70 patients per day, and in the region of 100 on days immediately before public holidays.’ The incidence of diabetes is increasing rapidly worldwide, and developing countries are bearing the brunt of this burgeoning epidemic. In South Africa, the number of people with diabetes is expected to double in the next 15 years. Dr Tupy estimates that she’s currently serving in the region of 6 500 patients in total, some of whom come from as far afield as Rustenburg, Witbank and even KwaZulu-Natal. And that number continues to grow with two or three new patients arriving every day. Ideally, every one of these patients should be seen once a month, but this is a task beyond the capability of one lone doctor, no matter how dedicated. ‘But I’m glad to say that the majority of my patients are very well controlled, allowing me simply to give repeat prescriptions every month without a consultation.’ To achieve this level of control and patient compliance requires a great investment in educating patients on exactly what a chronic disease is, on dietary and lifestyle changes, and the importance of compliance with insulin or other therapies. Dr Tupy describes herself as a very strict teacher. ‘New patients are like children, and it’s important not to allow them to take liberties.’ With the assistance of her two nursing sisters, Dr Tupy therefore lays it on thick. The majority of her patients already have advanced disease by the time she first sees them, given that the nurses who staff the satellite clinics where these patients will initially have

VOLUME 6 NUMBER 2 • JUNE 2009


SA JOURNAL OF DIABETES & VASCULAR DISEASE

Diabetes Personality presented, are unable or reluctant to introduce insulin therapy. ‘There is often no time to lose in initiating therapy and it’s imperative to overcome patient resistance to needles, given that insulin is still the best option. Unlike private practitioners who might be reluctant to offend a patient for fear of losing their business, I don’t try to be subtle. I make it clear that this is a chronic disease and that without insulin, they will die! It may be necessary to repeat the message and re-educate at intervals if there is initial non-compliance, but once patients begin to trust me and really believe that I have their best interests at heart, it’s very rewarding to see the change in their attitude, along with a desire to please and their gratitude at feeling better. I’m also very conscious of praising compliance and improvement in their condition in order to keep them motivated.’ Dr Tupy has some strong feelings about hospital protocols, which apply a ‘once size fits all’ approach to a diverse patient population. She believes in individualising treatment and, as a physician, employs a cross-disciplinary holistic approach. (She acknowledges the support she gets from the podiatrist at Hillbrow Community Health Centre when it comes to managing diabetic foot complications.) ‘Even though I may be paid as a general practitioner, I cannot separate my knowledge, and I believe in using all my skills to treat patients to the very best of my ability. This includes, for example, being aware of and treating cardiac and other complications, such as ketoacidosis. Many of my patients are HIV positive or have tuberculosis, and I need to be aware of this too and factor it into my care.’

From left to right: Fahiul Josepha Fischer, Sr Lanele Mthimkhulu, Dr Daniela Tupy, podiatrist, Helen Versfeld.

In addition to the demanding work of running the clinic, Dr Tupy has also been involved in research at the Wits Donald Gordon Medical Centre for the past three years. The money she earns doing this is used to buy equipment for her clinic that the state is unable to provide. In addition, she also teaches students/interns, making them aware of the challenges involved in treating diabetics. ‘You can do anything if you really want to’, she concludes.

South African Cookbook for Diabetes and Insulin Resistance 1: Hilda Lategan (R175)

H

ilda Lategan is a registered dietician and well-known author from Pretoria, who specialises in the dietary treatment of people with diabetes and insulin resistance. The South African Cookbook for Diabetes and Insulin Resistance 1 promotes good blood sugar control and optimal health. It enables one to affordably prepare easy, nutritious meals, follow a healthy diet while still enjoying one’s favourite treats, and choose from more than 230 tested recipes made with readily available

VOLUME 6 NUMBER 2 • JUNE 2009

ingredients. The comprehensive introduction includes important information such as the differences between type 1 and 2 diabetes, and glycaemic index (GI) and glycaemic load (GL), general information on meal planning, and tips for handling special occasions, for example, hiking trips, functions and children’s parties. This cookbook is ideal for diabetics and specialists working with people with diabetes. It is available at most bookstores or can be ordered from the dis-

tributors on 086 1668 368 or orders@onthedot.co.za The South African Journal of Diabetes & Vascular Disease and Tafelberg together are giving away two cookbooks, one each in English and Afrikaans. To win one of these, simply e-mail Wendy on wendy.icon@wol. co.za with your name, specialty, address and language preference. The draw will take place on 1 August 2009 and winners will be contacted by e-mail.

GI VE AW AY

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Management of the diabetic patient in a resourceconstrained environment Chairperson: Prof WF Mollentze

Panel members Prof NS Levitt: (SA representative, IDF, Africa region) Prof R Delport: (Dept Family Medicine, University Pretoria) Prof DG van Zyl: (Dept Medicine, Kalafong Hospital, Tshwane) Dr F Mahomed: (Dept Medicine, Grey’s Hospital, Pietermaritzburg) Dr M Monyamane: (Specialist physician, Maseru, Lesotho) Ms A Croasdale: (Deputy Director, Chronic Diseases, Dept Health) Dr A Spitaels: (Paediatrician, Red Cross Children’s Hospital, Cape Town) Ms A Went: (Chairperson: Diabetes Educator’s Society of South Africa) Prof Mollentze: Sub-Saharan Africa faces a quadruple burden of disease: it is still struggling with age-old infectious diseases such as tuberculosis, and parasitic diseases such as malaria, while non-communicable diseases like diabetes and hypertension are emerging at a rapid rate alongside injuries from violence. In addition, sub-Saharan Africa is bearing the brunt of the global HIV/AIDS epidemic. A century ago diabetes was virtually unknown in Africa.1 Currently 10 million people are living with this disease in Africa and the number is predicted to double by 2025. Type 2 diabetes accounts for 85 to 95% of all cases in the region. The main factors responsible for the rapid increase in the prevalence of diabetes in sub-Saharan Africa are an aging population, unhealthy diet, overweight and obesity, and a sedentary lifestyle, closely related to rapid urbanisation of the population in the region. According to the International Diabetes Federation, the global diabetes epidemic has devastating human, social and economic effects.2 In sub-Saharan Africa, people with diabetes face the stark reality of premature death. In the poorest countries of the region, people with diabetes and their families bear almost the entire cost of whatever medical care they can access and afford. A person requiring insulin for survival in Zambia will live an aver-

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age of 11 years, in Mali 30 months and in Mozambique 12 months. Although the plight of people living with diabetes in South Africa is undoubtedly less severe than in neighbouring countries, the challenges facing our healthcare system are huge. The two most important and immediate challenges, for example in the Free State Province, are a lack of capacity, especially at primary healthcare level, and financial constraints. In the Free State with its population of 2.7 million, 7% or 93 000 individuals in the age group 25 years and older are suffering from diabetes, of whom only half or 46 500 are aware of the fact that they have the condition.3 Another 13% in the same age group have pre-diabetes and are at risk of developing diabetes. Hypertension is present in 27% (i.e. 355 000) of the adult population. Added to this, another 281 258 individuals in the 15- to 49-year age group are HIV positive. Of the 14 000 patients enrolled into the HAART programme in 2003–2004, almost 3% had active tuberculosis. It is common knowledge that patients accessing our primary healthcare system tend to present with more advanced disease, often requiring medical care beyond the level and expertise available at entry points. I have estimated that in a typical health district in the Free State, at least 85 000 patients with diabetes, hypertension or HIV/AIDS are dependent for their care on 43 primary healthcare clinics. From this it follows that each clinic is responsible for approximately 2 000 patients with one or more of these disorders per clinic catchment area. These patients have to collect their medication at least monthly and must be evaluated at three- to six-month intervals. This is over and above other services such as mother and child healthcare that these clinics are responsible for. The staff at these clinics is further stretched by the National Department of Health’s Comprehensive Care, Management and Treatment of HIV and AIDS Programme aiming for a horizontal antiretroviral-rollout programme. Serious concerns exist that HIV/AIDS may result in the crowding out of patients in need of care

for non-communicable diseases, as well as burnout of medical and support staff. Dr Mahomed: The same applies across the board. I think all of us are facing similar constraints. Ms Croasdale: We visit clinics in the rural nodes and we find that even within a health area in the district, one clinic is vastly different from the others. These are not even provincial differences. Much has to do with the clinic manager and his/her commitment and focus. If the focus is HIV then you will find that non-communicable diseases (NCDs) are totally overlooked. Prof van Zyl: In addition, I think a big problem is that service delivery is dependent on one individual working in a small area. If nobody is driving the programme in a clinic, nothing happens. There are no feedback or control mechanisms to report on what the clinic is doing and what it should be doing. So, there is no accountability of the people working in that clinic. Take the example of down-referrals from hospitals to clinics. If drugs are not ordered by the clinic and therefore are not available for patients down-referred, the clinic staff just shrug their shoulders and say: ‘Sorry, go back to the hospital’. One of our major problems is down-referral of patients who have diseases that should actually be a primary healthcare problem but now have to be managed at a higher level. Prof Delport: I would like to report on diabetes care at primary healthcare level, with specific reference to whether we are meeting the challenges in South Africa. To address these challenges, healthcare providers probably need to be as resilient as their patients, who have to face the daunting effects this disease has on their lives. Bradshaw et al.4 reported an incidence of 5.5% for diabetes in South Africans aged 30 and older, and calculated that about 14% of the ischaemic heart disease burden, 10% of stroke, 12% of hypertensive disease and 12% of the renal disease burden in adult males and females (30+ years) were attributable to diabetes.

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For my discussion I would like to start off by setting a standard for practice against which one could measure current primary healthcare initiatives in South Africa. Guaranteed minimum services for improved diabetes management in South Africa,5 as defined by Larry Distiller, could be used for such a purpose. These services include: • consultation with a health professional trained in diabetes management no less than twice per year – more if required • full initial and ongoing individual and group diabetes education, as specified in the guidelines • an initial interview with a dietician followed by an annual visit – more if required • a minimum of one visit per year to a podiatrist • appropriate laboratory investigations, including but not limited to HbA1c determinations every six months; annual monitoring of blood lipid levels and kidney function • one annual consultation for retinopathy and glaucoma screening with a specialist ophthalmologist • all diabetes medication, including blood sugar testing meters and strips • all hospitalisation for diabetes emergencies, including diabetic ketoacidosis and hypoglycaemia • a 24-hour telephone hotline to facilitate the management of home-treatable diabetes emergencies. Although targets at the primary healthcare level of prevention, detection and treatment of complications are clearly stated, and guidelines are available, these do not appear to be implemented in general,6,7 as is evident from the following quote. ‘Care and control of diabetes in this rural community is sub-optimal. There is a need for primary-care staff to focus on modifying prescriptions in the face of poor blood glucose control and/or uncontrolled hypertension.’7 In Mpumalanga, primary healthcare physicians reportedly experience great difficulty in providing diabetes care. At primary healthcare clinics, only urine glucose testing is performed for monitoring purposes, and target organ evaluation or body mass index measurements are not done. The primary healthcare nurses are perceived as poorly trained, records are poorly kept, and audits are not done for quality assurance purposes. Dietary advice is lacking and if provided, patients often experience the advice as culturally unacceptable. Lifestyle adjustment is poor due to lack of patient education.

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Medication is unavailable in most primary healthcare clinics in this area. The cost of blood glucose-monitoring strips is prohibitively high and attrition of monitors is a regular phenomenon. Blood glucose monitoring occurs monthly and that of HbA1c three- to six-monthly with < 7% as treatment goal and > 8% as an indication for additional treatment being prescribed. The reliability of laboratory methods and devices available for metabolic monitoring in resource-poor settings may be an additional matter of concern, as reported.8 It is obvious that the challenges in diabetes care are currently overwhelming. As a solution, Levitt8 proposes that ‘A concerted multisectoral effort will be critical to ensuring improvement in healthcare delivery for people with diabetes in the region’. A review by Beran and Yudkin on diabetes care in sub-Saharan Africa9 provides a list of key areas to be addressed if diabetes is to be tackled in sub-Saharan Africa, as identified by the International Insulin Foundation. These are: • organisation of the health system • prevention • data collection • diagnostic tools and infrastructure • drug procurement and supply • accessibility and affordability of medicines and care • training and availability of healthcare workers • adherence issues • patient education and empowerment • community involvement and diabetes associations • positive policy environment. Addressing these key issues may be regarded as idealistic but successful concerted multisectoral efforts will eventually provide positive outcomes in the long run. There is evidence of successful endeavours in primary healthcare following Alma-ATA,10 and of the ‘Composite lessons learned from countries that are progressing’, the one that should encourage us is: ‘Building coverage of care and comprehensive health systems with time. Although a single right way does not exist, key factors in these countries include prioritisation of high-effect interventions to start with, integrated service delivery and building on each programme, moving from selective primary healthcare to an effective continuum of care in a comprehensive health system. Increase in human resources and skills levels with time and a willingness to innovate, including delegation to com-

munity and extension workers, and short training courses (e.g. accelerated midwifery training) followed by in-service upgrading of skills. Attention to essential drugs and appropriate technology for health, development of local generics when feasible.’ Prof van Zyl: The most important reason for managing diabetes is to prevent disability and complications. Patients who are still socio-economically active should be kept active. I find often the system fails the patient, so it becomes impossible for them to continue working. Clinic times are only in the morning. Patients are allowed to receive only one month of treatment at a time. Therefore they have to take 12 days a year off from work just to have access to treatment. Furthermore, the infrastructure is there but the staff are overburdened or have no interest in diabetes management. Often the sisters and even the doctors are suffering from compassion fatigue. They just do not care any more because they are overwhelmed with patients. Diabetes care is based on four pillars: hypertension management, glucose management, lipid management, and screening for complications. The first three are aimed at preventing complications. Screening is to identify patients at risk for complications and to intervene more intensively at an early stage to prevent further problems. Amputations should not happen, although we often see patients having amputations because no screening is done early on to identify feet at risk. Foot care in South Africa is horrific because podiatrists are not available. We train podiatrists but they leave the country. Dieticians only work in hospitals and very few are available in the community. Perhaps a bigger problem is that because diabetes is often not symptomatic until very late in the disease, we fail to identify patients. Patients are diagnosed late, especially type 2 patients, and often already have complications at diagnosis. Our biggest task is making the population aware of diabetes. Much manpower is wasted by healthcare workers not working according to a plan or structure in the management of diabetes. That is why I want to emphasise a structured approach to diabetes management, where the healthcare worker can actually see results and measure success. I feel that all patients should be managed in a structured way according to a scientifi-

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cally based guideline and an implementation strategy that can be measured. Clinic performance can be measured by the use of process measures (e.g. how many patients in your clinic had eye and foot examinations? How many had blood pressure checked at each visit? How many patients have a glucometer?), and outcome measures (e.g. the proportion of patients achieving glycaemic and blood pressure control). Blood tests are often not available at the clinics, for example determination of HbA1c levels. Clinic staff therefore rely on one blood glucose measurement once a month or even once every three months to assess glycaemic control. I think our healthcare workers are often not empowered with the necessary skills to manage diabetes; they may know what to do, but they just do not have the time to fit in the diabetes patient between all the other patients. The diabetic patientâ&#x20AC;&#x2122;s consultation is not a quick one where the glucose and blood pressure are measured, a prescription is given and the patient is on his/her way. It requires training and education of the patient, which takes time. Ms Croasdale: There are so many tools available to address these issues and it is just a problem of getting the people to use the tools. Prof van Zyl: I think the bottom line at this stage is a financial constraint and a manpower problem. Prof Levitt: We need to embrace the fact that there is a manpower problem. It is not going to go away, and we can either hide behind that for the next 20 years or we can see it as a challenge. How can we use the manpower that we have in a different way? It requires active engagement with them and for them to be part of the process. Then you diminish the burnout and the sense of disaffection and you create a totally different dynamic within the clinical situation. Dr Mahomed: I agree with Prof Levitt that there are positive things we can do. I have six points that I would like to discuss. One of the problem areas is in the hospital environment. The standard of care practised by medical staff nationally is highly variable. Patients get different health messages from different levels of care and they become totally confused. One of my suggestions is to have a standard diabetes clinic proforma that is used in

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every clinic and hospital in the country, but there are pros and cons to this. I have a copy of the proforma we have been using in KwaZulu/Natal for the past two years. It is a single page with patient identification, pharmacy and examination records, and it is a simple checklist. If we use this across our healthcare facilities, then we can standardise diabetes assessment. The second thing is to have a standard syllabus of core knowledge in diabetes care that can be taught to undergraduates and postgraduates and does not have to be limited to internal medicine. Consideration should be given to adding the syllabus to a CME programme. The Department of Health could make it a mandatory requirement for CME for doctors and other healthcare workers. The third point is to have proper auditing of diabetes care. Prof van Zyl alluded to that earlier. We need to know the standard of our care. The private sector should not escape this kind of auditing. One also has to limit the bureaucracy. What I would recommend is to choose a small number of core statistics, for example how many diabetics there are, how many have complications, how many are on insulin or are non-insulin dependent; because those kind of statistics have implications for healthcare planning and delivery. My next comment is about proper use of the multi-disciplinary approach. We have all mentioned the importance of involving the following staff in diabetes care: podiatrists, dieticians, diabetes nurse educators, ophthalmology services, pharmacists and nephrologists. Because we have such low staff numbers, my suggestion to overcome that problem is to have a system where we train healthcare workers to do basic assessments. So, instead of having a podiatrist at every level of care, the podiatrist could focus on just the higher level of care. He/ she could train five or six healthcare workers to do basic assessments and just refer a limited amount of highly specialised work through to him/her. That is the best use of a limited resource such as the podiatrist. Access to a multi-disciplinary team does not necessarily mean having a dietician or ophthalmologist in each facility but the medical staff in every facility should have access to a service through a referral system. We need to revisit the referral systems to see if people actually do have access, and that can be audited as well. My next point is about availability of medication: we need to re-look at medica-

tion and the supply chain, especially insulin. Prof Mollentze mentioned the issue of insulin supplies sometimes running out. Blood tests: when to do them, how many to do, and what to do. This has tremendous cost implications. I think that medics can advise the Department of Health about a safe minimum number of blood tests that can be done, so that it is affordable, yet still effective. Another big problem is self-testing and this includes the cost of meters and sticks. I think it is false economy to not spend money on this because it helps improve glycaemic control and thus reduces complications. It also assists in guiding safe and appropriate therapy. We also need greater co-operation between the Department of Health and academic institutions. Academics can supply information and they can also guide costeffective use of facilities and resources. The Department of Health should accept the protocols and guidelines that are published by South African expert associations. Better co-operation includes better communication, encouragement of staff, as well as regular visits to health facilities by senior Department of Health staff. This will help with the implementation of the national health policy. Patient advocacy can be achieved with the setting up of a patient charter. I have an example of this. The patient, the healthcare worker and the Department of Health each have rights and responsibilities. There should be an independent assessment of the healthcare service that is linked to a corrective process. My last comment is that we have nongovernmental organisations that have expertise in certain areas and can take over some of the educational programmes that are required. The Department of Health should consider outsourcing some of the duties to them. Prof Mollentze: Many of these points are common to the various areas in which we function and an important one is the mixed messages going out. Standards of care are also important. Ms Croasdale: I think from your perspective, it seems as though the Department of Health sits on the sidelines and is not involved, but we are currently intimately involved with the people. I was involved with the SEMDSA guideline and we are aligning ours with the SEMDSA guideline.

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We are working with the people we know and we expect the chairperson of an organisation like SEMDSA to pass the information on to their members, so that we can get comprehensive input from them. But this is very difficult. We can only work through a few people, but we do expect the base numbers to be broadened.

African healthcare environment.

Dr Mahomed: I accept that, but what I would like is greater participation between our healthcare facilities and the local Department of Health personnel who are tasked with chronic diseases. We would welcome a two-way process on that.

Prof Mollentze: Ms Croasdale, we are looking forward to an update on what the Department of Health has on the agenda for diabetes care in South Africa.

Prof Mollentze: We must distinguish between the national Department of Health and their initiatives and what is happening in the provinces. The Free State Department of Health welcomes participation and input from clinicians. I was recently invited to address top management about this very issue and to put forward a basic strategy that could be followed to improve diabetes care in the Free State, and this was welcomed. Our unit is now developing a protocol for structured diabetes care in a particular health district in the Free State. We are optimistic that if this proves to be successful, the Free State Department of Health would buy in and consider expanding the programme to other health districts. It is a two-way process and maybe we need more visibility and support from the provincial Department of Health. We also need to make use of what is available. Dr Levitt: I would like to support Prof Mollentze. The National Department of Health does wonderful things. It produces all these documents but none of them get implemented because of the total breakdown in the way healthcare is organised. However, I can speak from our experience in the Western Cape where we have fantastic relationships with the Cape Town metropolitan area and the Western Cape Department of Health with regard to chronic diseases. We meet with them, we are engaged in workshops with them, and we develop audit tools in multiple aspects. It is a matter of finding somebody that you can talk to because that makes a huge difference, and once you have that, you will see substantial progress. Prof Mollentze: It boils down to one important issue, and that is communication, both vertically and horizontally. This is in need of serious attention in the South

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Ms Croasdale: It is all very well talking about communication but if you do not know exactly who is responsible for a particular programme, it is very difficult to find out. I am happy to pass on my immediate contacts in the provincial offices.

Ms Croasdale: I will discuss the diabetes implementation strategy for the public sector in South Africa. This strategy was developed by Ms Kotzenberg, the cluster manager for non-communicable diseases (NCDs) in the National Department of Health, after due consultation. She was requested to develop an implementation plan for the Diabetes Declaration and Strategy for Africa, which was ratified at the IDF Conference in December 2006. Mrs Kotzenberg was originally opposed to this because she did not want to focus on specific diseases, but rather address risk factors that are common to the primary NCDs. This document to hand is the final document and I will give you copies. To achieve improved management of diabetes, specific areas of action have been highlighted in the strategy. The activities have been placed under 10 major headings, these being risk-factor prevention/reduction; early detection of diabetes; empowering people with diabetes; clinical management and follow-up of diabetes patients; early detection and management of complications and disabilities; health workforce capacity development; support services or partnerships; resource allocation; monitoring and evaluation; and research. The kind of research we want is research that will inform the policies that we are developing, be they treatment policies or total management care policies. The improved management of diabetes does not just hinge on this implementation strategy alone, but will also make use of other NCD management tools that have been developed. The guideline, Non-Communicable Diseases – A Strategic Vision (I will give you a copy) explains the long-term care model in detail and highlights the fact that collaboration between the community and the health system is essential. The six interdependent areas, community resources and policies, and the five health system areas – organi-

sation of healthcare, self-management support, delivery system design, decision support, and clinical information systems – must be addressed. We need to know how to get the statistics; we need the information systems that will provide them. The guideline also details all aspects of dedicated services – a requirement of the long-term care model, and includes national record keeping and patient file management. I like the patient records example that you have given me (from KwaZulu/Natal). We also have a very good example from Western Cape. I think what we need to do is take all of these and make one document. Western Cape has found that theirs works very well. For effective long-term care we need a coordinated and comprehensive continuum of care, and people with NCDs should have access to dedicated services because they will be attending the clinic over a long period of time. We talk about a reasonable patient–healthcare provider ratio and we know that is not the situation currently, but we need to think differently on how to make best use of our human and other resources. The Department held a collaborative workshop with the World Health Organisation in November 2008, during which a framework for the implementation of longterm care was finalised. This user-friendly implementation framework will be utilised by provinces, districts, and health facilities to establish where they are in terms of implementation. We have provisionally filled in some of the columns to give them an idea of where we think they are at this point. They will use it within their own context. I have done training in Gauteng only, and we will have to expand on the training. At the workshop we also finalised the standardised Chronic Diseases Management Register, to comply with national record keeping, as mentioned in the Strategic Vision document. Provinces wanted a standardised register. The register will be printed and implemented in the 18 priority districts over the next two years. Input to the section Chronic Diseases and Geriatrics in the Primary Healthcare Supervision Manual was also finalised. This cross references the chronic diseases care being rendered by the clinics in terms of the long-term care model and monitors the appropriateness of the care and the availability of medicine and equipment. The Manual actually falls under the directorate of Quality Assurance at national level, with Dr Louis Claassens. Everything is up to date

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and all documents are in agreement. Other tools include the disease-specific clinical management guidelines (containing non-drug and drug management). This is the diabetes hospital-level guideline (I will give you a copy). The primary healthcare guideline is being updated. I was waiting for the SEMDSA guideline to be finalised. There are departmental strategic plans, operational plans, the 18 priority districts (identified by senior managers), and the district health information system. I have recently had access to the raw data but you cannot use it because in a particular month one may have 2 000 patients on register, and in the next month it is only 1 000. When I questioned them about what happened to the other 1 000, they did not know. Data are being collected but are not being used and are not informing decisions. The 18 priority districts are defined as the most disadvantaged districts in the country. Within these 18, of the total of 52 I think it is, the most deprived sub-districts have been identified. Eastern Cape for example has six identified districts, with a number of sub-districts. One of the key strategic objectives of the Department of Health is to improve the management of NCDs. The above diabetes strategy, together with the many generic tools and non-communicable disease-specific clinical management guidelines will certainly put this objective within reach, provided that the available products are utilised by the various health facilities at district and provincial levels. Prof Mollentze: This is very useful information. Thank you for representing the Department of Health at this discussion. It is appropriate to be reminded of the many policy documents, guidelines and strategies that are available. It remains, however, a question of disseminating this information, creating awareness and deciding how these policies could be implemented. I think SEMDSA and allied organisations should play a definite role in that. Prof Levitt: I agree. One of the major challenges is how can we move on. There are so many isolated groups of individuals working in parallel, often in isolation, and nobody knows what the next person is doing. There are so many wonderful initiatives both within and outside the Department of Health. What we need to do as a society is hold the Department of Health to account. We

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must make sure that what they promise actually comes about, so that the people with diabetes have a better outcome. I think we have to be very assertive in this. Dr Mahomed: I suggest that SEMDSA set up provincial committees and take the lead in co-ordinating people such as the Department of Health, DESSA (Diabetes Education Society of South Africa), dieticians, podiatrists and so on to look specifically at implementation. Prof Mollentze: Many initiatives are ongoing but not in a coherent way. Dr Mahomed’s proposal is an excellent one that should be raised at the proper forum. Prof Delport: I am thinking of all the data that could be generated to influence decision-making. I would like to suggest that it be captured in digital format if possible as it may get lost otherwise. Furthermore, I would like to applaud what you are doing. Ms Croasdale: May I just say, from the National Department of Health’s point of view, we are the advocacy support. We are not the implementing organisation. So, implementation then falls to the provincial Departments of Health and that is where we get stuck with staff shortages, which everybody hides behind. ‘We do not have to do much because we do not have enough staff.’ But if we start thinking out of the box and looking at alternative suggestions then we can make use of the tools that are available and get the necessary information. Prof van Zyl: I agree with that. We underutilise the resources we have because we do not have a strategy to achieve our objectives. We waste a lot of time repeating the same tests, and neglect to do other equally important tests because we do not work according to a plan. Dr Spitaels: Many of these problems are exactly the same ones we encounter in paediatrics. If children are not in a children’s hospital or in a child service they get lost among the adults because there are so many more adults. The issues around children specifically do not always get recognised. I think this is across the board in private and hospital practise. Protocols that have been set up for adults get applied to children. So children land up at a day hospital and get given Atraphane and not told how

to use it. We are now using Protophane. They may also be told: ‘you are too late, come and fetch your insulin tomorrow’, because there is no understanding that you do not do that to a type 1 diabetic. Or they get one box of strips when they are three years old and they need four. Ms Went: That’s where we find people start falling through the cracks – when they are adolescents. They may be staying out in the townships and they go into diabetic ketoacidosis during the night. Sometimes they end up in one of those primary or secondary health clinics or a private hospital. They sit there for a while before they are referred to tertiary institutions and that is a real problem for our adolescents. Dr Spitaels: Where a 14-year-old lands up is very different from province to province and from hospital to hospital. The hospital system says that you are an adult when you turn 13 but it is not true. Also they are long-term patients. The other thing I did want to mention was that the reasons to use more expensive insulins in children are slightly different from adults. So, if we are trying to motivate for that, it is a specialised need. Dr Monyamane: As we all know, Lesotho is a land-locked country of 30 000 km2. It is defined by the World Bank as one of the poorest countries. The population is 1.8 million, the literacy rate is 85%, but only 11% of the population live in the highlands. There is only about 8% arable land, as most of Lesotho is mountainous. Many people work in South Africa as miners. There are about 6 million in South Africa and 1.8 million living in Lesotho. Public healthcare in Lesotho is provided by 18 health service areas and each is headed by a hospital. Sometimes it is a district, a political district on a political map, because the public sector is a mixture of church-owned and government-owned facilities. Each hospital is supported by 10 to 15 clinics, and below the clinics we have health posts. Starting at the bottom, the health posts are staffed by nurses, sisters and village health workers. The clinics are staffed by professional nurses, and at the hospitals we have doctors and professional nurses. Tertiary care we get from the Free State. Diabetes care is currently accessed in hospitals. Both in the minds of the patients and the Minister of Health, diabetes is a spe-

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cialist disease. Unfortunately in all hospitals there is only one day a week for seeing diabetic patients, and if the patient has diabetes and hypertension, he will be attending different clinics on different days. In our clinics, consultations and treatment are free. In the hospital it is R15.00 and you get a month’s prescription and two repeats for that. Despite that we still have many challenges. The first challenge is access to healthcare because of the topography of the country. It is difficult for patients to get to the clinics and once there, they find that there is no insulin or oral hypoglycaemic medicines because these are seen as dangerous drugs only to be prescribed by a doctor. Fifteen per cent of the people are not working, so it is difficult to get from their homes to the centre of care. The waiting time at the clinics is very long. As you can imagine, with 100 to 200 patients having to be seen in a clinic, people arrive at 3 am and leave at 5 pm, because doctors have tea and lunch breaks in between. There is no appointment system. If we book 20 patients, about 50 will arrive. The second challenge is the quality of care. The contact time with the patients is a big problem. The doctors just repeat the previous prescription, even if the patient is poorly controlled. There is no time for education or physical examination. Examination of the eyes and feet is not done. Monitoring of haemoglobin A1c is not done – not even in the referral hospital laboratory because it is expensive. The accuracy of information given to patients is also a problem. Patients get confused because we have doctors from all over the world, speaking different languages. We have Chinese and Cuban doctors, as well as doctors from the DRC and Zimbabwe. Ninety per cent of our doctors are expatriates from the African continent, Cuba and other places. Local doctors are limited to about 60 registered private practitioners, but there is no relationship between the private doctors and the public facilities. Patients go to their private doctor or family physician for diagnosis and initiation of treatment only. Patients will then migrate to the nearest hospital because the fee is affordable or the service is free. After a year or two, patients will turn up at the private doctor again but now they have complications. As far as nutrition is concerned, patients are still told not to eat starch. This happens in spite of a ‘Train the Trainer’ programme

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provided by partners such as the University of the Free State, Novo-Nordisk and Life Scan. However, if you listen to patients sitting outside clinics they tell one another: ‘no you do not have to eat starch’. If patients do eat starch it is the white sorghum pap. Follow-up is a further problem. Patients have the perception that they only need to go and see their doctor if they are not well or if they run out of medicine. The knowledge of the professional staff is also quite a challenge because there is no continuing medical education. There is also no induction despite a very high turnover of staff. Supply-chain management is a big challenge, since the pharmacy, technicians and the supply department do not order in time, especially for patients who are using insulin. Patients are given six syringes, and if they are lucky, 15 syringes, because syringes are perceived to be expensive. In reality syringes cost about 10 cents each. What can we do with what we have? I would suggest that we have integrated care at the point of contact, whether it is at a clinic or a village post. If ordinary people can be trained to do HIV testing and counselling as lay counsellors at clinic level, why can we not empower the same group to check blood pressure and manage patients with diabetes, because diabetes is a chronic disease and has to be integrated into the primary healthcare model. We can also enter into partnerships with patient associations. They are very enthusiastic and good at training, teaching and volunteering to check blood sugar and educate the patients. The nurses would then be relieved to perform other duties. Staff induction or in-house training would also improve the attitude and knowledge of the staff because diabetes patients tend to be thrown about if they are in hospital. Skills are lacking to take care of diabetic patients if they are in a surgical ward and patients tend to stay longer in hospital, escalating costs. It is also important that hospital staff including doctors, nurses, pharmacists and dieticians function as a team. Access to self-monitoring is also a challenge. Patients will visit clinics once in three months to be tested or they do not go at all. A child may even be sent to pick up the medicine from the clinic. Even though pharmaceutical companies have donated glucose meters, test strips are not provided since it is too expensive. Finally, the prevalence of HIV/AIDS in Lesotho is 23.2% and contrary to diabetes care, a lot of money is channelled into AIDS

care. In many ways diabetes is no different from AIDS and people still die from diabetes. As a donor-dependent country, I think we have the culture of entitlement and needing to be helped, although we can do a lot ourselves. The roles of general practitioners or family doctors have been limited to hospitals to perform caesarean sections and fix broken bones. We should empower them to help at the clinics, and also engage them in training so that the patients they see are managed in a better way. Dr Mahomed: In terms of the AccuChek or GlucoMeter sticks, maybe it applies to us as well – can we not negotiate a good price for it if you are buying in bulk? Prof Levitt: The national tender now requires the companies to tender both on the machine and the strips. Dr Monyamane: Since Lesotho is regarded as an international country, prices for drugs and consumables are higher than in South Africa. Ms Went: DESSA is an organisation of diabetes educators. We have large branches in the Western Cape, KwaZulu/Natal and Gauteng. There is a sprinkling of members in other areas. As you can, see you have a concentration of highly trained health professionals in certain areas and not out in the more rural areas. We are looking specifically at training for standardisation purposes and we have been doing ad hoc training over the years. In each centre the staff do a number of training courses each year, but now we are developing a manual to standardise it across the board. It is presently approaching completion and SEMDSA are in the process of having it edited by Dr Delport. Hopefully once we have that, we can offer standardised courses in specific areas throughout South Africa. We would be very grateful for help from the Department of Health in implementing these courses. Things need to be standardised and I think DESSA has a large role to play here. We are dealing with both healthcare professionals and patients. We need one qualified diabetes educator and several other educators in each support group system. Tomorrow at the DESSA workshop they are doing a conversations map. Each diabetes educator will be presented with a box of conversations maps, which he/she will

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take back to his/her respective area. These are maps of pictures, which stimulate discussion around the table, and patients are encouraged to take responsibility for themselves and to help others, so not just one person does all the work. Obviously DESSA is very important for networking. We are often seen as a link between the doctors and patients. It is wonderful to have a diabetes education centre in Cape Town where everything is available. Patients come in and it is a one-stop shop. They are seen, examined, receive their medication, have their microalbuminuria done, their blood work is done routinely, their HbA1c is done in six minutes and off they go. This is an unusual situation. Ms Went: They get their three boxes or the 30 syringes, but despite that, we still have people with diabetes who do not actually take responsibility for their disease. They are not motivated within themselves. Our aim is to motivate these patients to take responsibility, and to empower themselves. Dr Monyamane: How can we access or link with DESSA? I feel you are doing a wonderful job, because there is no education in our public clinics in Lesotho. Ms Went: One possibility is to become a member of SEMSDA. I do not know if Lesotho has members in SEMDSA. You could send representatives to our meetings and workshops. We have a website and we are contactable through the SEMDSA website on the DESSA link. Take my details and somebody will get hold of you and let you know when things happen. Prof Levitt: I represent IDF, Africa because I am the Southern African representative on this regional board. IDF is merely the sum of its member organisations. Our country differs because we actually have two member organisations of IDF: SEMSDA and Diabetes South Africa. IDF Africa represents subSaharan Africa. Northern Africa actually falls within the Northern African Mediterranean region. The major impact that the IDF has had in the recent past is the UN Resolution, and subsequent to that, there have been regional workshops to try and ensure that the UN Resolution and the Africa Declaration are implemented. There was a workshop in Nairobi in December where 15 countries were represented. We have been waiting for six

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months for the report. The question is how can we make sure as an organisation that we improve the lot of people with diabetes in the region. The first issue is actually political buy-in at the level of the Department of Health and the Ministry of Health. No country in Africa is going to achieve anything unless we achieve political buy-in. Jean-Claude Mbanya from Cameroon is the current president of the IDF, and Africa needs to utilise the fact that we have a president from Africa to promote the process of improved diabetes healthcare in our region. A letter is due to go out to the ministers of health emphasising this and asking them to take the lead. There also needs to be a committee set up in each country to represent Government, the health professionals and the people with diabetes, as well as the pharmaceutical industry, in order to ensure that the UN Resolution and the Africa Declaration is implemented. Our country is way ahead of many other countries in subSaharan Africa. We have had interaction with the Department of Health with regard to the implementation. The second need is to create a committee to hold Government responsible. The third is to make sure that diabetes care becomes a primary healthcare responsibility. In South Africa, diabetes care is rendered at a primary healthcare level but in many other countries in Africa it is not primary healthcare. Patients have to go to the district hospital in order to get diabetes healthcare. A further challenge is to improve the care for pregnant women with diabetes. What is IDF doing about this? Firstly, there is the Africa Declaration and secondly, as part of the Africa Declaration there are implementation documents. For example, the region developed clinical practise guidelines for the management of diabetes, which are available. Secondly, an educational manual was developed by participants right across the region. These are the tools that have been provided for the individual countries to implement. The region acquired some funding through World Diabetes Foundation to develop these documents and to implement them in about eight countries. Honestly, the countries where you see success are where the Department of Health is driving it. For example, in Mozambique there has been a wonderful initiative. Dr Carla Silva-Matos in the Department of Health had these documents translated into Portuguese and they have had numer-

ous workshops around many parts of the country to make sure that the guidelines are implemented and that the infrastructure is improving. I think the IDF would like to work with all of its member associations in order to achieve these objectives. I was asked by the IDF Africa office who they can contact in Lesotho for the Diabetes Association. Prof Delport: You identified diabetes in pregnancy as an area of initiative where you can achieve maximum effects, but in your paper that was published in Heart recently, you referred to Nayaran’s paper,11 focusing on HbA1c and hypertension. Prof Levitt: In fact Nayaran’s paper identified three things that are cost effective and accessible across all developing areas and you are quite right, it is HbA1c, high blood pressure and foot care. Dr Spitaels: Being able to do an HbA1c test or lower the values? Prof Levitt: No, lower HbA1c below 9% and improve high blood pressure. It is interesting that at that time the cut-off blood pressure value was 160/90 mmHg. The third was to improve foot care. In fact, attention to pregnant women fell into the next category. So, it was cost effective and cost saving, but not fully accessible across all regions or developing countries that were identified in Narayan’s paper. This was an issue that was hotly debated. What the document says is make diabetes part of primary healthcare, and identify and screen pregnant women. You are not going to be able to do this in most countries but it is something to work towards and try to implement by about 2011. These were targets more than anything else. Prof Delport: What I really like is the fact that one targets ones initiatives. The outcomes are measurable, which in turn would increase motivation and make it cost effective. Ms Croasdale: Here in South Africa with the former Minister of Health there was absolute buy-in because her own close family members were diabetic. That is why they emphasised an implementation strategy even though Mrs Kotzenburg objected to it. I am pleased to say there is buy-in in South Africa.

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Prof Mollentze: The former president, President Mbeki, was also a signatory to the Africa Declaration. Prof Mollentze: There was definite buy-in and we must now try to keep the momentum. Prof Levitt: In fact it is really interesting, every single member state of the UN signed. They have no excuse, but it is incumbent upon us to actually make sure that they implement the changes needed. Prof van Zyl: Can I ask whether any timelines were set? When can we expect to see a reduction in HbA1c levels and blood pressure – in 10 years’ time? Clearly, an implementation strategy with realistic timelines is needed. Lastly, whose responsibility is it going to be? Prof Levitt: At this implementation meeting I tried to push the cluster manager, Kristel Kotzenberg, to create an implementation group that could oversee this, and her response was that this needs to be done on a provincial level because the National Department of Health has no access. It is dependent upon the provinces to implement. Prof Levitt: The National Department of Health develops the strategies but they need to be implemented by the provinces and by the local authorities. She suggested that an implementation programme or group be set up for each province and maybe that is something that could be considered, although I do believe that there needs to be a national drive to make sure that each province is doing their bit. Ms Croasdale: Although the Department of Health’s strategic plan was drawn up by the national office, all departments have to adhere to it. Implementation of this is starting in the current year, as of April 2009, and the timeframes that we have put to it are that nine of the priority districts must implement the plan this year, and the following year all 18 of the priority districts must have done so. We give them a bit of time to do it, but the fact is if they do not have the financial resources and cannot do the necessary training, it is not going to happen. We are not in a position to instruct provinces because of the political autonomy that has been given to them. So, we can just advise and say this is where we should

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be going, and they can say: ‘yes we agree with you but we cannot do it for the next 10 years because we do not have the capacity to do it, and our focus is on HIV and AIDS or maternal and child health’ or wherever the focus is, and that is the problem. We do put timeframes to it, but we cannot force them or coerce them, we can only ask them to do it. Prof van Zyl: Should we not follow the example of the HIV/AIDS action group. They had an action campaign that eventually pushed so hard that a strategic plan was formulated and implemented. Is it not time for us to recruit champions for diabetes care to highlight the problems and to put pressure on the provinces to start implementing a strategy to improve diabetes care? Ms Croasdale: We want to empower the patients to the point that the services are patient driven. They will come into the service and say ‘you have not checked my feet, you must do it. I need to go for an eye check, you have to do it’. It will take time because there is unfortunately a culture of ‘the doctor knows everything’ and you cannot question the doctor. That still exists, especially in older or less educated people, who would not challenge the seniority of a doctor. Prof van Zyl: Perhaps that is where SEMDSA and DESSA can play a role and be more visible. The lay press can also be involved to educate patients with diabetes to request the minimum required care. If patients do not receive this they should ask their doctor or healthcare worker why not. Prof Levitt: Because I am involved with Diabetes South Africa (DSA), and I do not know why they are not here, I want to speak on their behalf as well. Prof Mollentze: You can speak on their behalf. You may wear two hats. Prof Levitt: I do feel quite strongly about DSA. I can speak for our region where DSA is doing very good work and multiple support groups meet regularly, empowering patients, doing assessments of feet, checking on blood glucose levels, and measuring blood pressure. I think that SEMSDA, DSA and DESSA need to create a movement for diabetes that will really work. Prof Mollentze: At the end of this round-

table discussion I am the first to confess that I underestimated the difficulties facing diabetes care in southern Africa. On the positive side, however, I was impressed by the overwhelming enthusiasm and commitment of each of the participants to improve diabetes care in our region. I wish to thank each of you not only for making yourselves available for this roundtable discussion but also for your preparation and lively interaction. A number of issues were identified that necessitate further reflection. If the only outcome of this event is to emphasise the pressing need for a concerted effort to improve diabetes care in our region, we can declare this roundtable discussion a resounding success. 1. Diabetes Declaration and Strategy for Africa: A Call for Action. http://www.idf. org/node/1355?unode=14A26179-13DD4220-A865-6576D4D417FB. Accessed 1 June 2009. 2. The Human, Social and Economic Impact of Diabetes. http://www.idf.org/human-socialand-economic-impact-diabetes. Accessed 1 June 2009. 3. Mollentze WF, Koning JMM. Where have all the diabetics gone? S Afr Med J 2007; 97(6): 444–445. 4. Bradshaw D, Norman R, Pieterse D, Levitt NS, South African Comparative Risk Assessment Collaborating Group. Estimating the burden of disease attributable to diabetes in South Africa in 2000. S Afr Med J 2007; 97(8 Pt 2): 700–706. 5. Distiller L. Improved diabetes management in South Africa: the case for a capitation model. Diabetes Voice 2004; 49(2): 16–18. 6. Steyn K, Levitt NS, Patel M, Fourie J, Gwebushe N, Lombard C, Everett K. Hypertension and diabetes: poor care for patients at community health centres. S Afr Med J 2008; 98(8): 618–622. 7. Rotchford AP, Rotchford KM. Diabetes in rural South Africa – an assessment of care and complications. S Afr Med J 2002; 92(7): 536–541. 8. Levitt NS. Diabetes in Africa: epidemiology, management and healthcare challenges. Heart 2008; 94(11): 1376–1382. 9. Beran D, Yudkin JS. Diabetes care in sub-Saharan Africa. Lancet 2006; 368: 1689–1695. 10. Rohde J, Cousens S, Chopra M, Tangcharoensathien V, Black R, Bhutta ZA, Lawn JE. 30 years after Alma-Ata: has primary health care worked in countries? Lancet 2008; 372(9642): 950–961. 11. Nayaran KMV, Zhang P, Kanaya AM, et al. Diabetes: the pandemic and potential solutions. In: Jamison DT, Breman JG, Measham AR, et al, eds. Disease Control Priorities in Developing Countries. 2nd edn. Washington: Oxford University Press and The World Bank, 2006: 591–603.

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Drug Trends News from the 2009 SEMDSA Congress

T

 e major development at h the Society of Endocrinology, Metabolism and Diabetes of South Africa (SEMDSA) congress was the publication of the new South African guidelines for the management of type 2 diabetes.1 The expert committee (details below) and sponsors provided clear guidelines on the aspects of glycaemic control, as well as blood pressure and lipid treatment recommendations. The latter two aspects will likely provoke further debate. Guideline committee: Naomi (Dinky) Levitt, Aslam Amod, Brynne Ascott-Evans, Steve Delport, Kenneth Huddle, Pankaj Joshi, Hilton Kaplan, Willie Mollentze, Ayesha Motala, MAK Omar, Fraser Pirie, Derick Raal, Paul Rheeder, Jacobus van Dyk, Danie van Zyl.

The scientific substantiation as referenced for the guidelines have been derived from the American Diabetes Association, the International Diabetes Federation, the European Societies of Cardiology and Diabetes, and the Canadian Diabetes Association guidelines and comment.

Self-monitoring of blood glucose (SMBG) The key involvement of the patient in managing his diabetes is particularly recognised in the following guidelines: • SMBG results must be used for the purpose of attaining and maintaining glycaemic targets, by guiding self and practitioner adjustment of therapy and to provide evidence on hypoglycaemia. • SMBG should be carried out three or more times daily for patients using multiple (≥ two) daily injections of insulin.

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• SMBG should be carried out up to once daily for patients using a single daily injection of insulin either alone or in combination with oral agents. • SMBG can be considered in patients using oral agents (e.g. for assessing if additional Rx is required; to confirm hypoglycaemia if symptomatic), but NOT regularly and indefinitely. • Perform SMBG more frequently in setting of: – acute illness – periods of poor glycaemic control – frequent hypoglycaemic episodes – pregnancy – any adjustment to therapy.

Metformin usage in type 2 diabetes The South African guidelines also follow the well-validated core therapy in the consensus guidelines of the ADA and EASD of early introduction of metformin. The South African guidelines are clearer in their recommendation on dosage and the approach of escalating therapy to a maximum of 2 550 mg over a period of one to two months to minimise gastrointestinal (GI) side-effects. The value of extended-release tablets to minimise GI effects is acknowledged. Metformin is also recommended at the time of diagnosis in all patients; both overweight and of normal weight. This is in line with research showing similar glycaemic response to metformin in non-obese and obese patients.2 While acknowledging that metformin may be contra-indicated in some patients, the

South African guidelines do not include the more specific guidance from the ADA/EASD consensus statement concerning renal dysfunction. The ADA/EASD guidelines note: ‘Renal dysfunction is considered a contra-indication to metformin use because it may increase the risk of lactic acidosis, an extremely rare (less than one case per 100 000 treated patients) but potentially fatal complication.3 However, recent studies have suggested that metformin is safe unless the estimated glomerular filtration rate falls to below 30 ml/min.’4 The possibility of metformin interfering with vitamin B12 absorption is not mentioned; although the effect is well documented.5 The drop in vitamin B12 levels is rarely associated with anaemia.

The South African guidelines are aimed at clear guidance for primary-care practitioners and also note that metformin can be continued even when other classes of anti-diabetic agents, including insulin are added. The South African algorithm is provided (figure 1) together with the recent ADA/EASD guidelines for clinical comparison. 1. SEMDSA guidelines. J Endocrin Metab Diabetes S Afr 2009; 14(1): 55–58. 2. Donnelly LA, Doney ASF, Hattersley AT, Morris AD, Pearson ER. Diabetic Med 2006; 23(2): 128–133. 3. Salpeter S, Greyber E, Pasternak G, Salpeter E. Cochrane Syst Rev 2006; 1: CD002967. 4. Shaw JS, Wilmot RL, Kilpatrick ES. Diabetic Med 2007; 24: 1160–1163. 5. Bailey CJ, Turner RC. N Engl J Med 1996; 334: 574–583.

Fig. 1. The South African algorithm and the recent ADA/EASD guidelines for clinical comparison. STEP 1 AT DIAGNOSIS: LIFESTYLE MODIFICATION + METFORMIN Initiate metformin at diagnosis and titrate dose up to 2 550 mg over 1–2 months HbA1c > 7% after 3 months or if metformin is contraindicated STEP 2a ADD SULPHONYLUREA ADD BASAL INSULIN • Especially if HbA1c • Especially if HbA1c ADD < 8.5% > 8.5% PIOGLITAZONE • Use glibenclamide • Start 10 U at • Not preferred OR only if serum creati- OR bedtime except under nine is normal • Titrate by 2 U/ special circum• Titrate to maximum week until fasting stances tolerated dose over 3 glucose < 7.0 months mmol/l STEP 2b

HbA1c > 7% after ≥ 3 months ADD A 3RD DRUG FROM STEP 2 I.e. choose a 3rd as yet unused agent from STEP 2a HbA1c > 7% after ≥ 3 months

STEP 3 START BIPHASIC INSULIN • When intensive insulin therapy is not feasible

REFER FOR INTENSIVE INSULIN THERAPY I.e. basal + prandial insulin therapy

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Report from Sanofi Aventis diabetes cardio-thrombosis meeting Modern strategies to optimise blood glucose in type 2 diabetes

D

iabetes is a disease with chronic consequences. It is therefore crucial to make the newly diagnosed patient aware of these, and the fact that over the years many organs of the body will potentially be affected if blood glucose levels are not properly controlled. These organs include the eyes, feet, kidneys and cardiovascular system. This is the view of Prof Geremia Bolli of the Department of Internal Medicine, Endocrinology and Metabolism at the University of Perugia in Italy. He was speaking at a diabetes cardio-thrombosis meeting hosted by Sanofi Aventis. ‘Often a patient is asymptomatic and therefore does not understand the need to take the long view to initiate appropriate treatment for diabetes before complications set in. There is no motivation to implement the dietary and lifestyle changes required or ensure compliance with drug treatment. It must therefore be emphasised that diabetes is a risk condition that adds to other risks, making a huge difference to the prognosis in respect of mortality. The epidemiological evidence for this is impressive. The OASIS study showed us that the risk of myocardial infarction (MI) in a newly diagnosed diabetic is equivalent to that of someone who has suffered a previous MI.’1 The UKPDS study showed that lowering of HbA1c levels reduced the risk of complications, regardless of how this was achieved.2 Even relatively small reductions were associated with marked benefits, notably in microvascular complications. Where macrovas-

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cular complications such as MI were concerned, the picture was less clear until late 2008, when important 10-year follow-up data showed an unequivocal decrease in risk for all diabetes-related endpoints, including MI, macrovascular disease and all-cause mortality.3 ‘We’d been waiting for a long time for this evidence that good glycaemic control is rewarding for both micro- and macrovascular complications’, said Prof Bolli. ‘What we now know is that the macrovascular complications just take longer to manifest.’ Intensive treatment should

therefore be initiated immediately at diagnosis to protect against later complications. Most patients in the UK and USA are off target in respect of their blood glucose levels. ‘We’ve been too tolerant in the past’, continued Prof Bolli, ‘sometimes taking years to prescribe drugs, while all the time the HbA1c is going up, predisposing patients to complications.’ He attributes this to ‘a combination of patient and clinician inertia’. A change of approach is therefore required; clinicians need to be more aggressive in fighting hyperglycaemia earlier in the disease process.

It is the consensus of both the American Diabetes Association and European Association for the Study of Diabetes, that metformin be initiated along with lifestyle changes at diagnosis (figure 1).4 ‘We should not wait to see its effects; HbA1c levels should be checked again at three months and if still above 7.0%, we need to introduce a second oral drug or maybe consider the early use of a basal insulin.’ Regardless of the initiating drug, good effects are usually seen in the first years of treatment. Prof Bolli cautions, however, that slowly over time,

Figure 1. Algorithm for the metabolic management of type 2 diabetes. Reinforce lifestyle interventions at every visit. Check HbA1c every three months until HbA1c is < 7% and then at least every six months. The interventions should be changed if HbA1c is ≥ 7%. *Sulfonylureas other than glibenclamide (glyburide) or chlorpropamide. **Insufficient clinical use to be confident regarding safety.

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SCHEDULING STATUS: S3 PROPRIETARY NAME AND DOSAGE FORM: APIDRATM solution for injection. COMPOSITION: 1 ml contains 3,5 mg insulin glulisine, corresponding to 100 U human insulin. REGISTRATION NUMBER: A38/21.1/0506 NAME AND BUSINESS ADDRESS OF THE HOLDER OF THE CERTIFICATE OF REGISTRATION: sanofi-aventis south africa (pty) ltd, 2 Bond Street, Midrand, 1685. Reg. No. 1996/10381/07. SCHEDULING STATUS: S3 PROPRIETARY NAME (and dosage form): LANTUS 速 (solution for injection). COMPOSITION: Each ml of the solution for injection contains 3.64 mg of the active ingredient insulin glargine, corresponding to 100 U human insulin. REGISTRATION NUMBER: 34/21.1/0248. NAME AND BUSINESS ADDRESS OF THE APPLICANT: sanofi-aventis south africa (pty) ltd, 2 Bond Street, Midrand, 1685. Reg. No. 1996/10381/07. APPLICANT: sanofi-aventis south africa (pty) ltd, 2 Bond Street, Midrand, 1685. Reg. No. 1996/10381/07.

ZA.GLA.09.04.13


DRUG TRENDS

a rebound effect becomes evident as HbA1c levels begin to rise again. ‘This is the socalled secondary failure of oral drugs.’ He feels that even the newer drugs, for which data are still lacking, will ultimately fail, making insulin necessary. ‘Insulin should now be used early, and not as a last resort when hyperglycaemia is severe. It’s now seen as a “friendly treatment” that can safely and effectively keep HbA1c levels at target, preserving beta-cell function and preventing apoptosis over the years.’

How should insulin be initiated? There are no definite rules when it comes to the initiation of insulin, only opinions and experiences. ‘The pre-mix insulin regimens are the most popular worldwide’, said Prof Bolli, ‘but there is little science behind them. This means we need to revisit their usefulness

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and assess it in terms of scientific data. Pre-mixes are, in my opinion, no good for optimising blood glucose in type 2 diabetics. When used aggressively to lower HbA1c levels to target, they cause frequent episodes of hypoglycaemia, which can be potentially dangerous for the brain and cardiovascular system. In addition, hypoglycaemia works against patient compliance. Non-compliance in turn results in elevated HbA1c values and sub-optimal blood glucose control.’ The modern approach, based on scientific data, is rather to introduce a basal insulin. Fasting hyperglycaemia is more important than postprandial hyperglycaemia in increasing mean daily blood glucose and HbA1c levels, so it makes sense to introduce a basal insulin to reduce and possibly normalise the fasting blood glucose level, and then add a bolus later if required. Treatment with a basal insulin, whether NPH

or a newer analogue such as glargine or detemir, has been validated in scientific studies, which have shown that when the drug is successfully titrated, it is possible to reach target HbA1c with a single daily injection, usually in the evening. What are the advantages of the newer long-acting analogues over NPH? ‘With the long-acting analogues, there is much less risk of nocturnal hypoglycaemia. This means that while they’re comparable to NPH in respect of achieving target HbA1c levels, their ability to protect against hypoglycaemia makes them safer and therefore superior.’5 Where the fasting glucose level is controlled, but the postprandial glucose level is not and HbA1c remains above 7.0%, a bolus of rapid-acting insulin analogue should be introduced. Prof Bolli reiterated his view that this does not mean reverting to a pre-mix regimen, but rather using a bolus insulin

at the time of the main meal. If this is insufficient, a second or even a third injection at other mealtimes may be introduced. It is very important to titrate until targets are reached. In fact, this is the indication in the consensus algorithm by the American Diabetes Association and the European Association for the Study of Diabetes.

Conclusion Summing up, Prof Bolli stated that insulin needs to be used more than is currently the case. It must be initiated earlier, and there should be greater use of the newer analogues. Both fasting and postprandial blood glucose need to be treated to target. ‘Despite the evidence, doctors still remain reluctant to put patients on insulin’, he concluded. ‘We need to remember that it’s not a drug – rather, it’s a natural hormone present in all healthy humans, but missing in diabetics!’

Differences in insulin preparations/models: do they matter?

S

 eaking at the recent Sanofi p Aventis-sponsored diabetes cardio-thrombosis meeting, Prof Geremia Bolli opened his talk spotlighting different insulins with a brief history of the use of insulin in treating diabetes. ‘From 1922 until 1950, the only insulin available to us was rapid acting, meaning that multiple daily injections were routine, until Hagedorn’s work brought us the delayed-release insulin, NPH. But doctors in the 1950s thought insulin was like any other hormone and started combining short-acting and delayed-release preparations with no real insight into how human physiology works. This paved the way for the introduction of the pre-mix insulins, which I consider to have been

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an injudicious move. They can work against human physiology by causing high peaks in blood glucose after meals and at the same time the risk of hypoglycaemic episodes or “hypos” before the next meal.’ At their most extreme, hypos can result in diabetic coma, a phenomenon Prof Bolli said was unknown prior to the advent of insulin. ‘This means it’s actually an iatrogenic event. We need to be mindful of physiology and copy nature when we institute insulin therapy. Pre-mix insulins should therefore not be used either in type 1 or type 2 diabetes when the goal of treatment is lowering HbA1c levels to prevent and/or delay late vascular complications.’

Prof Bolli pointed out that his views on pre-mixes are not universally held and that their use is defended by others. ‘In the INITIATE study, Raskin and colleagues found that more of their type 2 patients reached their HbA1c target of 7.0% with a pre-mix twice daily than with insulin glargine once daily. But this study minimised the data on hypoglycaemic side effects. The pre-mix doses were increased to a point where those patients taking them experienced a higher percentage (3–400%) of minor hypos relative to those on glargine.’ (Minor hypoglycaemia was defined as a documented plasma glucose value less than 56 mg/dl, with or without symptoms).6

According to Prof Bolli, it’s a fallacy that hypos are rare in type 2 diabetes. They entail a decrease in arterial blood glucose below the level of activation of hormone counter-regulation. When this counter-regulation kicks in in a recurrent manner, patients experience a dangerous complication, the loss of their diabetic symptoms, further to the brain’s adaptation to frequent mild hypoglycaemic episodes. Those who’ve lost symptoms, and hence awareness, are therefore at much greater risk of severe hypos and coma than others. The harmful consequences can include brain dysfunction and vascular events. Turning to the ACCORD trial, Prof Bolli observed that

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Figure 1. Harmful effects of hypoglycaemia.

intensive treatment to an HbA1c target of 6.5% rather than 7.5% was associated with worse outcomes in respect of mortality. ‘Hypoglycaemia was probably the most important factor here, with a 300% increase in severe episodes in the intensively treated patients. This is yet more evidence that non-physiological treatment resulting in hypoglycaemia is bad for patients.’7

NPH vs newer analogues The introduction of NPH insulin was consequent on a study involving a single patient in 1936. ‘It’s taken us 70 years to fully understand it’, said Prof Bolli. ‘It’s not an ideal basal insulin as it lacks the “flat” action profile required. A cloudy suspension of not entirely soluble crystals, its absorption over 24 hours can vary from 100% to as little as 30%. How can one

DRUG TRENDS

rely on such an insulin?’ The new long-acting analogues, glargine and detemir, are clear, soluble suspensions and more reproducible. While their reduction in HbA1c levels is comparable to what can be achieved with NPH, their flatter profile mitigates the risk of nocturnal hypos in both type 1 and type 2 diabetics. Detemir frequently requires two daily injections rather than one in many patients, which may have negative implications in respect of both cost and compliance. Concluding, Prof Bolli reiterated that an insulin regimen needs to mimic nature as closely as possible, and that a basal/bolus regimen achieves this far more successfully than the use of a pre-mix preparation. He underscored too that hypoglycaemia is a serious

complication and frequent episodes can have serious longterm consequences. Clinicians need to be mindful of this and the effects of glucose counterregulation. 1. Malmberg K, Jusu FS, Grstein HC, et al. Circulation 200; 102(9): 1014–1019. 2. UK PDS group (1998). Lancet 1998; 352: 854–865. 3. Holman RR, et al. N Engl J Med 2008; Sept 10:10.1056/NEJMoa 0806470. 4. Consensus Statement from the ADA and AESD. Diabetologia DOI 10.1007/s 00125-0081157-y. 5. Zammitt NN, et al. Diabetes Care 2005; 28: 2948–2961. 6. Raskin P, Allen E, Hollander P, et al. Diabetes Care 2005; 28: 260–265. 7. The ACCORD study group. N Engl J Med 2008; 358: 2545– 2559.

Novo Nordisk Diabetes Update Symposium: April 2009

T

 is well-attended sympoh sium set the scene for the annual SEMDSA meeting, which followed at the Wanderers Club, Johannesburg. This report summarises the major points of the interesting reviews from both local and overseas experts.

Incretin hormones: what do we know and are they the future of diabetes management? Prof Mary Ann Banerji, State University of New York The incretin hormones are released in the body while eating, creating the so-called ‘incretin effect’. This effect is diminished in type 2 diabetics. Speaking at the Novo Nordisk Diabetes Update Symposium, Prof Mary Ann Banerji, profes-

VOLUME 6 NUMBER 2 • JUNE 2009

sor of medicine at SUNY, New York, posed the question, ‘Can we use the incretin effect to benefit patients? She went on to review the American experience with incretin analogue therapies, which are soon to be available in South Africa. ‘There are a number of incretin hormones, but the most important for type 2 diabetics is GLP-1. Patients with impaired glucose tolerance or type 2 diabetes show decreased levels of postprandial GLP-1 as well as decreased incretin effect. The infusion of a GLP-1 analogue in diabetics is associated with increased secretion of insulin. Near normalisation of blood glucose improves the potentiating effect of GLP-1. As glucose normalises, the incretin effect wears off, meaning that unlike with insulin, incretin

therapy does not carry the risk of hypoglycaemia’, she said. A problem is that the incretin effect is inactivated quickly. However, this can be remedied by continuous infusion or modification of the analogue with an enzyme that increases the drug’s half-life. There are two types of incretin-based treatments: dipeptidyl peptidase-4 (DPP-4) inhibitors and GLP-1 receptor agonists (also called incretin mimetics). Exenadin 4, the most important member of the latter class, was originally isolated as a 39-amino acid peptide from the saliva of the Gila monster and has a partial amino acid overlap with GLP-1. Exenatide is a synthetic analogue of exenadin 4 that has been shown to improve plasma glucose and glucagon in diabetics.

‘Many short-term trials have shown that when combined with standard treatments, it gets 30 to 40% of patients to a goal HbA1c of < 7%. The main adverse effect is nausea, but this is dose-dependent and decreases over time’, said Prof Banerji. ‘Exenatide lowers both fasting and postprandial glucose, avoiding the postprandial peaks associated with insulin. Exenatide is safe in patients with long-standing diabetes and is also associated with significant weight reduction in 25% of patients, in marked contrast to biphasic insulins and insulin glargine, which are associated with weight gain when introduced in patients suboptimally treated with sulphonylureas and metformin. In addition because GLP-1 is

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References 1. Estimated number of patients using FlexPen®, based on worldwide sales in number of packs sold, IMS world wide data Q4'07 and Daily Defined Dosage (DDD) for insulin as issued by WHO. IMS Data Q4 2007. 2. Asakura T et al. Dosing accuracy of two insulin pre-filled pens. Curr Med Res Opin 2008;24(5):1429-1434. 3. Hänel H et al. Differences in the Dose Accuracy of Insulin Pens. J Diabetes Sci Technol 2008;2(3): 478-481. 4. Pfützner A et al. Prefilled insulin device with reduced injection force: patient perception and accuracy. Curr Med Res Opin 2008;24(9):2545-2549. 5. Rissler J et al. Evaluation of the injection force dynamics of a modified prefilled insulin pen. Expert Opin Pharmacother 2008;9(13):2217-2222.

Proprietary Name: NovoMix® 30. Scheduling Status: S3 Composition: soluble insulin aspart/protamine crystallised insulin aspart 100 U/ml in the ratio of 30/70. Registration Number: 35/21.1/0031. For full prescribing information refer to package insert approved by the medicines regulatory authority. Proprietary Name: NovoRapid®. Scheduling Status: S3 Composition: Insulin aspart 100 units/ml. Registration Number: 34/21.1/0160. For full prescribing information refer to package insert approved by the medicines regulatory authority. Proprietary Name: Levemir®. Scheduling Status: S3 Composition: Insulin detemir 100 units /ml. Registration Number: 38/21.1/0084. For full prescribing information refer to package insert approved by the medicines regulatory authority. Novo Nordisk (Pty) Ltd. Reg No. 1959/000833/07. 10A Achter Road, Paulshof, Sandton, 2056. Tel: (011) 202 0500 Fax: (011) 807 7989 www.novonordisk.co.za NN/DUO2965/12/08/ver1

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SA JOURNAL OF DIABETES & VASCULAR DISEASE

associated with a decrease in the number of apoptotic betacells, stimulating it also suggests benefit in respect of a preservation effect.’ An extended, once-weekly version of the drug called exenatide LAR has shown even better results than the original, which required administration twice daily. It also has other potential applications, for example in Crohn’s disease. Because DPP-4 rapidly degrades endogenous GLP-1, the rationale behind the DPP4 inhibitors is that inhibiting this process can be beneficial. Studies of sitagliptin, the most prominent and well studied of the DPP-4 inhibitors, have shown a positive effect in respect of raising GLP-1 and lowering plasma glucose levels. Sitagliptin improves HbA1c levels over 24 weeks, both as monotherapy and in combination with other treatments. It is generally well tolerated and adverse events are rare. As is the case with exenatide, it has a built-in safety mechanism insofar as the lower the HbA1c levels, the lower the effect of the drug, so there is virtually no risk of hypoglycaemic episodes. A number of other GLP-1 agonists and DPP-4 inhibitors are also under investigation and showing promising results. Notable among them, the incretin mimetic liraglutide has shown robust effects in respect of getting patients to target HbA1c levels (around 50%). It has a greater homology with native GLP-1 relative to exenatide, and in direct comparison with the latter has shown greater benefit with comparable weight reduction and less nausea. Concluding, Prof Banerji noted that while both the DPP-4 inhibitors and the GLP1 agonists have shown robust effects on postprandial glucose and glucagon in head-to-head

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comparison, the effects are slightly higher with the latter class. ‘Incretin-based treatments offer us new therapeutic options for diabetic patients’, she said. However, their final role is yet to be established as not all patients respond. There are also some issues of cardiovascular safety that remain to be addressed.

Blood pressure and its management in type 2 diabetes Prof Joe Veriava, University of the Witwatersrand, Johannesburg ‘Hypertension can kill.’ This was the stark message conveyed by Prof Joe Veriava. ‘It can lead to terminal cardiovascular disease (including myocardial infarction and stroke) and renal failure. In South Africa, with limited resources, many patients may not be able to access the dialysis or cardiac transplants they might require as a consequence of hypertension.’ Prof Veriava noted that it is important not to think only of blood pressure when treating hypertension. Its interplay with diabetes, dyslipidaemia and obesity must always be borne in mind. Hypertensives have a greater tendency to become diabetic than normotensives. The prevalence of hypertension in diabetics is 48% in the absence of albuminuria, rising to 68% when albuminuria is present. This figure increases to 85% when there is overt nephropathy. ‘By 2025, there will be 300 million diabetics worldwide, 75% of them in developing countries with limited resources’, he said. That 140/90 mmHg is still perceived as a ‘safe’ blood pressure is something he finds worrying. Today’s ‘normal’ is 130/85 mmHg, and that is not the same as ‘optimal’, which in diabetics is 120/80 mmHg. So-called ‘high-normal’ blood

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pressure is associated with an increased risk of cardiovascular events over 12 years in diabetics and each additional complication of diabetes is associated with a significant increase in morbidity if there is associated hypertension, a phenomenon Prof Veriava termed ‘double jeopardy’. ‘Cardiovascular mortality is worse when diabetes and hypertension are both present, and as blood pressure increases, morbidity increases with it.’ Diabetics also experience an increase in pulse pressure, leading to the earlier development of atherosclerosis. Increased systolic blood pressure allied to decreased diastolic pressure places an additional load on the heart. Diabetics tend to have a greater prevalence of nocturnal hypertension. Normotensives’ blood pressure tends to dip at night – with a greater risk of target-organ damage. Diabetics also experience a greater increase in blood pressure during exercise and are more prone to episodes of orthostatic hypertension. ‘We need to intervene at a blood pressure of 130/85 mmHg in diabetic patients’, continued Prof Veriava. ‘Protecting against further escalation will help prevent future cardiac events.’ Lifestyle modification remains key, including exercise, weight loss and decreased salt intake. There is evidence that delaying the onset of hypertension can prevent or delay progression to overt disease in patients at risk for diabetes. Lifestyle changes alone can delay the onset of diabetes in those with impaired glucose tolerance but where blood pressure reduction requires medication, this needs to take priority. ‘Based on the MICROHOPE study, the indications are compelling for the use of ACE inhibitors in diabetics or, where

patients are ACE-intolerant, angiotensin receptor blockers.’ As to how low can one go, Prof Veriava noted that the HOT study showed that lowering diastolic blood pressure below 80 mmHg was associated with a 51% decrease in cardiovascular events. ‘We therefore need to get diabetics to a blood pressure of 120/80 mmHg. This may require several drugs and, when we are unable to treat to target, we may need to settle for the benefits of some lowering’, he said. ‘That said, the STENO-2 study, which evaluated conventional multi-factorial treatment versus intensified target-driven therapy showed lots of cardiovascular benefit with the latter strategy. Intervention with multiple drug combinations was sustained in type 2 diabetics. The co-existence of hypertension and type 2 diabetes results in more cardiovascular mortality than either of them alone. Prevention and delay of both are possible – and worth striving for.’

Exercise as the cornerstone of diabetes management Dr David Segal, Centre for Diabetes and Endocrinology, Johannesburg Some pertinent quotes provide a vivid sketch of this stimulating talk. ‘Exercise is a form of medication and therefore requires a prescription.’ ‘Patients prefer pills to putting in the effort required by diet and lifestyle changes.’ ‘Lifestyle modification is twice as effective as drugs – but it’s a hard sell to patients.’ ‘To be effective, exercise must be combined with a lowcalorie diet. It’s not effective alone.’ ‘Fear of hypoglycaemic episodes is what concerns most

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diabetics and prevents their participation in exercise.’ ‘When it comes to exercise, doctors need to talk to patients individually and tailor a plan that is safe for them.’ Five rules: • eat breakfast – otherwise your body will think you’re trying to starve it • don’t take in calories from drinks • exercise for 30 minutes to an hour per day • don’t take weekends off from your diet and exercise plan • weigh yourself every week.

Please Take A Special Interest In Foot Care Prof Paul Rheeder, University of Pretoria, Pretoria ‘Clinicians must examine the high-risk diabetic patient’s feet at every visit’, was the special appeal from Prof Paul Rheeder, incumbent of the Medihelp Chair of Clinical Epidemiology at the University of Pretoria and Head of the Diabetes Clinic at the Steve Biko Academic Hospital. • Ulceration is precipitated by incorrect shoes Please is denoted as the main precipitating cause of ulcers; inappropriate shoes. Evaluate and talk to your patient about appropriate shoes. • Type of neuropathy Take the time to identify the presence and type of neuropathy; which is chiefly of a vascular nature (85%), and sometimes of mixed origin. • Assess arterial supply so that the patient can be referred appropriately to a vascular surgeon.

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• Special – use a simple staging system. In the past mainly Wagners’ system was used. Now a newer staging system from the University of Texas1 allows one to define the lesion in terms of infection and degree of ischaemia, as well as the depth of the lesion. • Interest – Involve the podiatrist and the vascular surgeon early in order to prevent amputations. Debridement must be done thoroughly and the debrided lesion appropriately dressed.2 • In – be innovative and use your imagination to develop cost-effective methods of offloading. ‘Walking on an ulcer ensures that healing cannot take place’. In India, they utilise locally derived appropriate solutions to offload in circumstances where the gold standard of a total contact cast is not possible. Vacuum-assisted closure3 is very effective with excellent results in more than 40% of patients after a 100-day period. • Don’t forget to treat the whole patient; manage his glucose levels and cardiovascular risk appropriately to ensure that more patients avoid the micro- and macrovascular consequences of diabetes.

Landau. ‘Type 2 diabetes is corrected completely by bariatric surgery and responds significantly to dietary intervention. For this reason we must make a serious attempt to introduce effective and early lifestyle management’, he noted. ‘The UKPDS series of trials has placed metformin at the primary-prevention level as it achieves both macrovascular (over the long term) and microvascular benefits. Also, these studies have shown that metformin and glibenclamide do make a difference to the progression of the type 2 disease. Metformin, even after the results of recent trials of other newer oral agents, still forms the basis of therapy and there is sound evidence for this agent’s upfront use’, Dr Landau said. ‘We do need to individualise our patients’ treatment and accept that currently there is no holy grail in reducing HbA1c levels. The early addition of insulin when HbA1c levels are not stable at below 7% is also a well-validated approach’, Dr Landau noted.

Oral agents: their role and positioning in the management of type 2 diabetes

The ‘wait for failure’ approach before introducing insulin in type 2 diabetes is no longer the optimal standard of care following the recent publication of the consensus statement from the American Diabetes Association (ADA) and the European Association for the study of Diabetes (EASD).4 Prof F Pirie of the University

Dr Stanley Landau, Centre for Diabetes and Endocrinology, Johannesburg. ‘Any disease curable by diet alone should not be treated otherwise’, stressed Dr Stanley

Apply more aggressive insulin-titration approaches in type 2 diabetes Prof F Pirie, University of KwaZulu-Natal, Durban

of KwaZulu-Natal pointed this out to delegates attending the Novo Nordisk symposium prior to the Society for Endocrinology, Metabolism and Diabetes (SEMDSA) meeting at the Wanderers’ in April. This approach is also reflected in the new SEMDSA guidelines, which recommended the addition of basal insulin, especially if the HbA1c remains above 8.5% and the fasting plasma glucose is above 7.2 mmol/l. Reflecting on the need to titrate more aggressively, Prof Pirie’s views resonate with the EASD/ADA guidelines where the authors stated there is no maximum dose of insulin beyond which a therapeutic effect will not occur. They noted that relatively large doses of insulin (≥ 1 U/kg) may be needed to overcome the typical insulin resistance of type 2 diabetic patients. The insulin algorithm should be based on simple increases and research has shown that a patient-led titration model is more effective than a clinicianled approach. A recent study5 in the Netherlands over a long period of 18 months has shown that self-titration of biphasic insulin aspart 30/70 improves glycaemic control and allows easy intensification in a Dutch clinical practice. 1. Armstrong DG, Lavery LA. Am Fam Physician 1998; 57(6): 1325–1332; 1337–1338. 2. Hinchliffe RJ, Valk GD, Apelgvist J, et al. Diabetes Metab Res Rev 2008; Suppl 1: 5119–5144. 3. Blume PA, Walters J, Payne W, et al. Diabetes Care 2008; 31(4): 631–636. 4. Nathan D, et al. Diabetolgia 10.1007/s 00125-008-1157g. 5. Ligthelm RJ. Prim Care Diabetes 2009 March 12; e-publication.

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DRUG TRENDS

Incretin therapy: a new treatment modality in the fight against the worldwide diabetes epidemic

Prof Jeff Wing, Johannesburg

T

 e launch in South Africa h of the first incretin mimetic, exenatide (Byetta, Lilly), offers local clinicians a first-in-a-class new option for treating type 2 diabetic patients who are not yet insulin dependent. Speaking at the Johannesburg launch, Prof Jeff Wing quoted Intel’s Andy Grove that the advent of incretin therapy marks an ‘inflection point’ in the fight against the worldwide diabetes epidemic. ‘The incidence of diabetes is increasing worldwide and it is the largest epidemic man-

kind has ever seen. Developing countries are worst affected. In South Africa, eight to 12% of urban dwellers have diabetes and we’re expecting the number of patients to double in the next 15 years.’ Diabetes is currently ranked as the sixth most common cause of death in South Africa. According to Prof Wing, in North America, 63% of diabetics are not controlled and outcomes are ‘horrendous’. In South Africa too, based on public-sector data, approximately two-thirds of patients are poorly controlled with HbA1c levels above 7%. ‘We’re therefore facing big challenges when it comes to glycaemic control, and most of our problems are related to type 2 diabetes and its co-morbidities associated with the metabolic syndrome, especially obesity.’ Prof Wing observed ‘it’s clear that completely different strategies are needed, and to persist with the same ones we’ve been using is not going to work. We need to control both fasting and postprandial glucose levels and reduce the

Figure 1. GLP-1 effects in humans: understanding the glucoregulatory role of incretins.

VOLUME 6 NUMBER 2 • JUNE 2009

incidence of beta-cell failure. Therefore we need to look at pre-diabetes differently, identifying patients earlier and introducing metformin in addition to lifestyle changes much earlier than is currently the case in patients under 60 years. A second strategy is to use disease-modifying measures that are are able to re-establish normal physiology.’ By the time type 2 diabetes is diagnosed, patients have already lost a significant amount of their beta-cell reserves and usually progress to requiring insulin in a period of five to 10 years. ‘We need to initiate treatment to attenuate the curve of progressive betacell loss, and incretin therapy can achieve this.’ It is important to achieve an HbA1c of close to 7% – but with current therapies, there are two major constraints to achieving target: weight gain and the risk of inducing hypoglycaemia. ‘Most agents induce weight gain, and maintaining weight with lifestyle measures is near impossible. Also, the tighter the glycaemic

control achieved, the greater the risk of hypoglycaemia, which evokes reactive eating and more gain. It’s a vicious circle – can we break it?’ The era of incretins holds the promise that this can be achieved. ‘Of all the gut hormones, GLP-1 is the most important when it comes to obesity and insulin resistance. Endogenous GLP-1 amplifies insulin secretion and betacell sensitivity, and increases insulin synthesis and beta-cell mass while decreasing glucagon secretion (figure 1). This is the so-called incretin effect – but it only takes over when blood sugar levels are rising. It’s therefore important to realise that GLP-1 agonists have multiple direct incretin effects on human physiology. ‘The incretin model is very interesting in obese type 2 diabetics’, continued Prof Wing. ‘We know that the incretin effect is lost in type 2 diabetics and that obesity blunts it further. Exenatide has a peptide sequence with a 53% homology with GLP-1 and an incretin effect nearly identical to GLP-1.

Figure 2. Change in HbA1c levels and weight over three years of Byetta treatment.

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As the first incretin mimetic commercially available, it’s set to play a key role in the future treatment of type 2 diabetes.’ Because it mimics the effect of GLP-1, it is a perfect pharmacological treatment (table 1). It reduces blood glucose without without causing hypoglycaemia. This is because it has a built-in safety mechanism, with the incretin effect switching off automatically as glucose levels normalise. In addition, incretin mimetics show promise for retarding and even reversing beta-cell failure. In animal models, exenatide was shown to reduce the rate of beta-cell apoptosis and even encourage islet neogenesis from dormant stem cells resident in the pan-

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creatic ducts. ‘This evidence of beta-cell recovery is very encouraging’, said Prof Wing. Another crucial property of exenatide is that unlike with other diabetes therapies, patients actually lose weight. ‘The results are impressive in that in the region of three-quarters of patients on exenatide maintain their target HbA1c levels and lose weight. Current therapies usually achieve targeted glucose lowering but at the expense of weight gain. Incretin mimetics can address this.’ Prof Wing cautioned that most diabetics would ultimately reach a state of insulin dependence, but those with some beta-cell reserves will

Table 1. Byetta mimics five key actions of a pharmacological dose of continuously infused GLP-1.

Figure 3. Initiating treatment with Byetta.

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benefit from exenatide prior to this. However, exenatide is not an insulin replacement and is not indicated in type 1 diabetics or those with advanced insulin-dependent type 2 diabetes. ‘In the right patients, however, it improves glucose control in a sustained way,

without hypoglycaemia, and with weight loss rather than gain. The weight loss is usually accompanied by meaningful reduction in lipids and blood pressure and, very importantly, these metabolic improvements are sustained.

Optimally using exenatide: when and in which patient Dr Aslam Amod, senior endocrinologist from Durban, spoke at the Cape Town launch of Byetta and reviewed the attributes of the exenatide injection. Focusing on recent guidelines of SEMDSA and ADA/ EASD, Dr Amod pointed out that therapies must be introduced earlier in type 2 diabetic patients. ‘As doctors, we must overcome therapeutic inertia and use combination therapies earlier. Of course, the principal of “first do no harm” is paramount, but newer strategies are needed if we are to attain better outcomes. We need a decade of change, with earlier diagnosis and initiation of therapy, using agents that address multiple pathophysiologies, and have the lowest potential for hypoglycaemia.’ Byetta has been approved for use as an adjunctive therapy to improve glycaemic control in type 2 diabetic patients who are taking either metformin or sulphonylureas or both, and who have not achieved glycaemic control. The type of patient most likely to benefit from this incretin mimetic, Dr Amod noted, is the patient who has not achieved glycaemic control with maximum tolerated levels of other oral anti-diabetic agents, who is overweight and is willing to introduce injectable therapy, but is concerned about further weight gain. ‘In these patients, you now have a new class of agents that can offer equivalent glu-

Dr Aslam Amod, Durban

cose control with weight loss. This is important as all insulin regimens improve glycaemic control, but achieve this most often with weight gain’, Dr Amod noted (figure 2). A current clinical trial, CHOICE, is investigating changes in treatment and outcomes in patients with type 2 diabetes initiating injectable therapy, either exenatide or an insulin in usual clinical practice, and will provide valuable insights. The study is European based and will follow outcomes in patients for two years; results are expected in 2011 (source: www.clinicaltrials.gov.com). The most common adverse events for Byetta are gastrointestinal related. Lilly is introducing a patient support programme to help with initiation of therapy and management of any adverse events. Byetta initiation schedule is provided (figure 3).

VOLUME 6 NUMBER 2 • JUNE 2009


Now, with BYETTA, HbA1c reduction and weight loss are both achievable goals

ADA/EASD GLP-1 agonists (BYETTA) are now included in the ADA/EASD algorithm for the metabolic management of type 2 diabetes1 CONSENSUS STATEMENT

“I take pills for my diabetes, but it’s still progressing and I continue to gain weight.” “Isn’t there something that can help me gain control of both?”

BYETTA is indicated for treatment of type 2 diabetes mellitus in combination with metformin, and/or sulphonylureas in patients who have not achieved adequate glycaemic control on maximally tolerated doses of these oral therapies

HbA1c

Sustained HbA1c reductions2

Progressive weight loss2

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Weight ÊM Dose twice daily, within 1 hour before the 2 main meals

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ÊM Minimally invasive needle ÊM 1 pen lasts for a full month ÊM After 1st month, switch to 10-mcg pen

5

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mcg

10 mcg

For the duration of therapy

S3 Byetta 5 µg, 10 µg. Reg. No. 41/34/0068, 41/34/0069. 0.25 mg exenatide per ml. For full prescribing information refer to the latest approved package insert. References: 1. Nathan DM, Buse JB, Davidson MB, et al. Medical management of hyperglycaemia in type 2 diabetes: A consensus algorithm for the initiation and adjustment of therapy. Diabetes care. 2008;31(12):1-11 2. Klonoff DC, Buse JB, Nielsen LL, Guan X, Bowlus CL, Holcombe JH, Wintle ME, Maggs DG. Exenatide effects on diabetes, obesity, cardiovascular risk factors and hepatic biomarkers in patients with type 2 diabetes treated for at least 3 years. Curr Med Res Opin. 2008;24(1):275-286. Eli Lilly (S.A.) (Pty) Ltd. Reg. No. 1957/000371/07. Private Bag X119, Bryanston, 2021 Telephone: (011) 510 9300 A1783 May 09


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Testosterone: the missing link in the treatment of type 2 diabetes

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reating male diabetic patients with testosterone corrects hypogonadal symptoms and leads to reduced waist circumference, increased muscle mass and insulin sensitivity, and lower lipid and blood pressure levels.1,2 When testosterone treatment is combined with lifestyle and dietary changes, these benefits are even more significant with diabetic patients achieving even greater reductions. These include a drop of 1% in HbA1c and a reduction of some 15 cm in waist circumference, which significantly reduces the risk factors that contribute to cardiovascular morbidity and mortality.2 Presenting these studies at the recent SEMDSA meeting held in Johannesburg, Prof Michael Zitzmann from the Centre for Reproductive Medicine and Andrology, Münster, Germany, noted that the results of a double-blind, randomised, cardiac outcome study of testosterone treatment in newly diagnosed diabetics and in men with impaired glucose tolerance (IGT) would be available early next year. ‘This will contribute to the increasing evidence that correcting low testosterone levels in diabetic men reduces overall cardiac risk and the number of cardiovascular events’, he noted. Symptoms of hypogonadism are not only related to erectile dysfunction, but also include symptoms of depression, fatigue, reduced libido and impaired cognitive ability as well as a reduction in muscle mass, anaemia and osteo-

86

porosis. ‘This is particularly important in the ageing male patient where psychosomatic complaints should be taken into account when deciding on whether to introduce testosterone therapy’, Prof Zitzmann said.3 Of particular interest, in a presentation on polymorphisms of the androgen receptor gene, Prof Zitzmann pointed out that there are ethnic factors influencing the range of normal testosterone levels. ‘In African men, the gene structure consists of fewer repeating codes, leading to the hypothesis that lower testosterone levels could be both normal and effective in this population group. This certainly warrants further study and clinicians should be aware of this and base their treatment not only on achieved testosterone levels, but also on overall improvement of hypogonadal symptoms’, he noted. The relationship between testosterone and luteinising hormone (LH) levels is important; a drop in testosterone levels and an increase in LH should lead to careful evaluation of pituitary and hypothalamic functioning. ‘However, there is a mixed picture of a lower testosterone level and normal to high-normal LH levels, which is indicative of a disturbed feedback mechanism and mixed hypogonadism’, he pointed out. In different countries, there are different thresholds at which therapy is initiated. However, research has substantiated the general levels of testosterone at which symp-

toms occur.3 Testosterone deficiency is not a rare condition and frequently is associated with obesity, diabetes, hypertension and hyperlipidaemia.4 Traditional risk factors are amplified in a low testosterone environment. ‘In a study where risk factors in patients with a normal testosterone levels were set at an arbitrary level of one, declining testosterone levels were associated with an increased cardiovascular risk, with a 1.39 relative risk for hypertension, 1.37 for diabetes, 1.35 for cardiovascular disease and 1.30 for the metabolic syndrome’, Prof Zitsmann explained.5 The relationship between testosterone levels and insulin sensitivity is an important arena for diabetologists to consider when treating diabetic patients. ‘A laboratorybased study has shown that stem cells under the influence of testosterone are increasingly differentiated to muscle cells rather than fat cells. This reduces visceral obesity and improves insulin sensitivity’, Prof Zitzmann noted. The longer-acting ester of testosterone, testosterone undecanoate should be used, with loading doses at initiation, six weeks and 12 weeks, to reach a testosterone level of 10–15 nmol/l.6 Thereafter, injection intervals are every three months to maintain target levels. An absolute prerequisite to the initiation of therapy is a prostate examination and PSA determination. ‘The PSA level does not significantly increase with testosterone treatment in

younger and older men’, Prof Zitzmann stressed.7 ‘There is no evidence that testosterone increases the risk of prostate cancer; there is therefore no obvious disadvantage to testosterone treatment. Clinicians can be confident that testosterone therapy reverts hypogonadal symptoms and improves the cardiovascular risk profile of the diabetic patient’, Prof Zitzmann concluded. 1. 2.

3.

4.

5.

6.

7.

Heufelder A, et al. Endocrine Society Abstract 2007. Kapoor D, et al. Androgen deficiency as a predictor of metabolic syndrome in aging men: an opportunity for intervention. Drugs Aging 2008; 2008: 25(5): 357-369. Zitzmann M, Faber S, Nieschlage E. Association of specific symptoms and metabolic risks with serum testosterone in older men. J Clin Endocrin Metab 2006; 91(911); 43354343. Mulligan T, Frick MF, Zuraw QC, Sternhagen A, McWhirter C. Prevalence of hypogonadism in males aged at least 45 years: the HIM study. Int J Clin Pract 2006; 60(7): 762–769. Laughlin GA, Barrettt-Connor E, Bergstrom J, et al. Low serum testosterone and mortality in older men. J CEM 2008; 93(1): 68–75. Behre HM, AbshagenK, Oettel M, et al. Intramuscular injection of testosterone undeconoate for the treatment of hypogonadism: phase I studies. Eur J Endocrinol 1999; 140(5): 414–419. Marks LS, Mozer NA, Mostagel E, et al. Effect of testosterone replcemnt therapy on prostate tissue in men with late-onset hypogonadism: a randomised controlled trial. J Am Med Assoc 2006: 296(19); 2351–2361.

VOLUME 6 NUMBER 2 • JUNE 2009


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1. Male Hypogonadism or Testosterone Deficiency Syndrome: Implications and Management. BMJ 2008, Supplement, pg 14. 2. Miner M et al. Vardenafil in men with stable statin therapy and dyslipidemia. J Sex Med. 2008; 5(6):1455-67. 3. Rosenberg MT et al. Improvement in duration of erection following phosphodiesterase type 5 inhibitor therapy with vardenafil in men with erectile dysfunction: the ENDURANCE study. Int J Clin Pract 2009; 63(1):27-34. 4. Yassin A, Huebler D and Saad F et al. Long-acting testosterone undecanoate for parenteral testosterone therapy. Therapy 2006; 3(6):709-721. S4 LEVITRA 5, 10, 20 (Tablets). LEVITRA 5: contains 5 mg vardenafil. LEVITRA 10: contains 10 mg vardenafil. LEVITRA 20: contains 20 mg vardenafil. PHARMACOLOGICAL CLASSIFICATION: A. 7.1.5 Vasodilators - peripheral. INDICATION: Treatment of erectile dysfunction. REGISTRATION NUMBERS: LEVITRA 5: 36/7.1.5/0515, LEVITRA 10: 36/7.1.5/0516, LEVITRA 20: 36/7.1.5/0517. S5 NEBIDO (Oily solution for injection). Each ampoule contains 1000 mg testosterone undecanoate in a 4 ml solution for injection (250 mg testosterone undecanoate/ml). PHARMACOLOGICAL CLASSIFICATION: A 21.7 Male sex hormones. INDICATION: Testosterone replacement in primary and secondary male hypogonadism. REGISTRATION NUMBER: A38/21.7/0641. HOLDER OF THE CERTIFICATES OF REGISTRATION: Bayer (Pty) Ltd, Reg. No.: 1968/011192/07, t/a Bayer Schering Pharma, 27 Wrench Road, Isando, 1609. Tel: (011) 921-5052. Fax: (011) 921-5041. For full information, please refer to the package insert approved by the Medicines Regulatory Authority (MCC). ZA.GM.MHC.05-2009.0042 **Fisher WA, et al. J Sex Med 2005; 2:699-708.*** Bhasin S, et al. J Clin Endoc & Metabs 2006; 91(6): 1995-2010.

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2ESTORETHELEVELS LEVELS*** 2ESTORETHEPERFORMANCE


DIABETES NEWS

SA JOURNAL OF DIABETES & VASCULAR DISEASE

Diabetes News SEMDSA News

T

 e 2009 SEMDSA congress h at the Wanderers Club was well attended by members of the Society of Endocrinology, Metabolism and Diabetes of South Africa (SEMDSA), the Diabetes Educators’ Society of South Africa (DESSA), the Lipid and Atherosclerosis Society of

South Africa (LASSA) and the Paediatric Diabetic Society of South Africa (Paeds-SA). Well supported by the pharmaceutical industry, the conference was attended by some 300 delegates from South Africa, Namibia and Botswana.

At Abbott’s stand, Ruth Field, product manager deals with delegates' queries. Abbott’s patient education leaflets on care of the eyes and feet are easy to understand and can help clinics and doctors achieve the new SEMSDA guidelines for patient education. For your supply of patient leaflets, e-mail Ruth at ruth.field@abbott.com.

Sanofi Aventis emphasises how diabetic patients can enjoy challenging sport and have an active life while on medication.

The Novo Nordisk stand was busy and well staffed. William Modiba, training manager and Zella Young, product manager enjoy a quieter third day of the congress.

Donation to Life for a Child programme

E

li Lilly and Company recently announced it intends to donate more than 800 000 vials of insulin to the International Diabetes Federation’s Life for a Child programme, providing free life-saving medicine to as many as 24 000 children who currently have no access to diabetes treatment. The initial focus of the donations will be to help children with diabetes in sub-Saharan

88

Africa. This donation will allow the International Diabetes Federation (IDF) to expand its work meaningfully over the next four years in at least nine of the poorest countries on the continent. Lilly’s donation is the largest corporate insulin donation to the Life for a Child programme. The Life for a Child programme provides access to care, education and life-saving medicines and supplies, to sup-

port children with diabetes in some of the poorest countries around the world. It also aims to raise awareness of the plight of children with diabetes in these countries and encourages governments to establish appropriate care to safeguard the future of children with diabetes.

Children at the Fundación Aprendiendo a Vivir con Diabetes in Ecuador

For more information on the Life for a Child programme, visit www.lifeforachild.org.

VOLUME 6 NUMBER 2 • JUNE 2009


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SAJDVD Volume 6, Issue 2  

Need for a diabetes charter Constitutional rights in management of chronic diseases Diabetes strategy Treatment of hypertension Triglyceride...

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