EASD - Clinical Updates on Congenital and Acquired Lipodystrophy

Clinical Updates on Congenital and Acquired Lipodystrophy Translating Research Into Practice Dates: 16–19

September 2014

This activity is jointly sponsored by Global Education Group and Integritas Communications.

This activity is supported by an educational grant from AstraZeneca.

CME/MEDICAL COMMUNICATIONS INQUIRIES info@integritasgrp.com integritasgrp.com

Clinical Updates on Congenital and Acquired Lipodystrophy

Translating Research Into Practice

FACULTY David B. Savage, MD Wellcome Trust Senior Clinical Fellow Department of Clinical Biochemistry University of Cambridge Metabolic Research Laboratories Cambridge, United Kingdom

Dr. Savage is a Wellcome Trust Senior Clinical Fellow at Institute of Metabolic Science at Cambridge University. The principal focus of his laboratory is to understand the molecular and physiological basis of insulin resistance in humans. He has a keen interest in rare genetic disorders characterized by extreme insulin resistance, particularly lipodystrophy, and has worked in this area for the past 14 years.

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TARGET AUDIENCE The educational design of this activity addresses the needs of endocrinologists and other health care providers involved in the management of the heterogeneous group of lipodystrophy syndromes.

STATEMENT OF NEED/PROGRAM OVERVIEW Lipodystrophies are a heterogeneous group of disorders characterized by pathologic loss and redistribution of fat tissue as well as reduced levels of adipocyte-derived hormones, such as leptin and adiponectin.1,2 Affected patients may present with a range of metabolic complications, which often include severe insulin resistance, diabetes, hypertriglyceridemia, and hepatic steatosis.3,4 Unfortunately, varied manifestations and unfamiliar etiologies delay diagnosis and appropriate treatment.2 Even experienced endocrinologists may miss lipodystrophy as they focus on the growing problem of obesity-related insulin resistance and type 2 diabetes.5 Moreover, most therapies that are used to treat the associated metabolic issues have not been studied in individuals with lipodystrophy, and the prospects for benefit vary depending on the type of lipodystrophy and patient-specific presentation.6 This Interactive Professor™ program will discuss key features suggestive of a lipodystrophy disorder, clinical clues to a differential diagnosis of underlying causes, and recommendations on employing the available treatment armamentarium, including treatment approaches that target specific underlying pathophysiologic mechanisms.7

REFERENCES 1. Garg A. Lipodystrophies. Am J Med. 2000;108(2):143-152.

2. Handelsman Y, Oral EA, Bloomgarden ZT, et al. The clinical approach to the detection of lipodystrophy—an AACE consensus statement. Endocr Pract. 2013;19(1):107-116.

3. Garg A, Agarwal AK. Lipodystrophies: disorders of adipose tissue biology. Biochim Biophys Acta. 2009;1791(6):507-513.

4. Fiorenza CG, Chou SH, Mantzoros CS. Lipodystrophy: pathophysiology and advances in treatment. Nat Rev Endocrinol. 2011;7(3):137-150.

5. Ovalle F. Clinical approach to the patient with diabetes mellitus and very high insulin requirements. Diabetes Res Clin Pract. 2010;90(3):231-242.

6. Garg A. The Physician’s Guide to Lipodystrophy Disorders. Danbury, CT: National Organization for Rare Disorders, 2012.

7. Brown RJ, Cochran E, Gorden P. Metreleptin improves blood glucose in patients with insulin receptor mutations. J Clin Endocrinol Metab. 2013;98(11):E1749-E1756.

Clinical Updates on Congenital and Acquired Lipodystrophy

Translating Research Into Practice

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EDUCATIONAL OBJECTIVES After completing this activity, the participant should be better able to: • Describe the etiologic causes and pathophysiologic mechanisms of congenital and acquired lipodystrophies • Differentially diagnose various types of lipodystrophy based on the degree and pattern of adipose tissue loss, other clinical features, and appropriate laboratory testing • Discuss evidence supporting pharmacologic treatment of lipodystrophy and associated metabolic disorders • Tailor multimodal therapeutic regimens for lipodystrophy to address pathologic changes in fat distribution and associated metabolic disturbances

PHYSICIAN ACCREDITATION STATEMENT This activity has been planned and implemented in accordance with the Essential Areas and Policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint sponsorship of Global Education Group (Global) and Integritas Communications, LLC. Global is accredited by the ACCME to provide continuing medical education for physicians.

PHYSICIAN CREDIT DESIGNATION Global Education Group designates this live activity for a maximum of 0.5 AMA PRA Category 1 Credit™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Global Contact Information For information about the accreditation of this program, please contact Global at +1 303 395-1782 or inquire@globaleducationgroup.com.

Instructions to Receive Credit In order to receive credit for this activity, the participant must complete the evaluation form and application for credit.

Fee Information & Refund/Cancellation Policy There is no fee for this educational activity.

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DISCLOSURE OF CONFLICTS OF INTEREST Global Education Group (Global) requires instructors, planners, managers, and other individuals and their spouses/life partners who are in a position to control the content of this activity to disclose any real or apparent conflict of interest they may have as related to the content of this activity. All identified conflicts of interest are thoroughly vetted

by Global for fair balance, scientific objectivity of studies mentioned in the materials or used as the basis for content, and appropriateness of patient care recommendations.

The faculty reported the following financial relationships or relationships to products or devices they or their spouses/life partners have with commercial interests related to the content of this CME activity: David B. Savage, MD Consultant to Aegerion Pharmaceuticals, Inc. and AstraZeneca The planners and managers reported the following financial relationships or relationships to products or devices they or their spouses/life partners have with commercial interests related to the content of this CME activity: Ashley Marostica, RN, MSN

Nothing to disclose

Amanda Glazar, PhD

Nothing to disclose

Andrea Funk

Nothing to disclose

Jim Kappler, PhD

Nothing to disclose

DISCLOSURE OF UNLABELED USE This educational activity may contain discussion of published and/ or investigational uses of agents that are not indicated by the FDA. Global Education Group (Global) and Integritas Communications, do not recommend the use of any agent outside of the labeled indications.

The opinions expressed in the educational activity are those of the faculty and do not necessarily represent the views of any organization associated with this activity. Please refer to the official prescribing information for each product for discussion of approved indications, contraindications, and warnings.

Clinical Updates on Congenital and Acquired Lipodystrophy

Translating Research Into Practice

DISCLAIMER Participants have an implied responsibility to use the newly acquired information to enhance patient outcomes and their own professional development. The information presented in this activity is not meant to serve as a guideline for patient management. Any procedures, medications, or other courses of diagnosis or treatment discussed in this activity should not be used by clinicians without evaluation of patient conditions and possible contraindications on dangers in use, review of any applicable manufacturer’s product information, and comparison with recommendations of other authorities.

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Clinical Updates on Congenital and Acquired Lipodystrophy

Translating Research Into Practice

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Clinical Updates on Congenital and Acquired Lipodystrophy

Translating Research Into Practice

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Clinical Updates on Congenital and Acquired Lipodystrophy

Translating Research Into Practice

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Clinical Updates on Congenital and Acquired Lipodystrophy

Translating Research Into Practice

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Clinical Updates on Congenital and Acquired Lipodystrophy

Translating Research Into Practice

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Clinical Updates on Congenital and Acquired Lipodystrophy

Translating Research Into Practice

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Clinical Updates on Congenital and Acquired Lipodystrophy

Translating Research Into Practice

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Clinical Updates on Congenital and Acquired Lipodystrophy

Translating Research Into Practice

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Clinical Updates on Congenital and Acquired Lipodystrophy

Translating Research Into Practice

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Clinical Updates on Congenital and Acquired Lipodystrophy

Translating Research Into Practice

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Clinical Updates on Congenital and Acquired Lipodystrophy

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GUIDELINES The Clinical Approach to the Detection of Lipodystrophy—A Consensus Statement From the American Association of Clinical Endocrinologists A consensus statement from the American Academy of Clinical Endocrinologists about the classification, detection, and diagnosis of various types of lipodystrophy.

The expert task force of clinical practitioners and leaders in lipodystrophy research aims to increase awareness of these underdiagnosed disorders and provide a framework for future diagnostic criteria.

Handelsman Y, et al. Endocr Pract. 2013;19(1):107-116.

LINK: https://www.aace.com/files/lipodstrophy-cs.pdf

American Diabetes Association’s Standards of Medical Care in Diabetes—2014 The American Diabetes Association’s Standards of Care provide clinicians, patients, researchers, payers, and other interested individuals with the components of good diabetes management, general treatment goals, and tools to evaluate the quality of care. Importantly, these recommendations should be adjusted based on individual preferences, comorbidities, and other patient-related factors.

American Diabetes Association. Diabetes Care.

2014;37(suppl 1):S14-S80.

LINK: http://care.diabetesjournals.org/content/37/ Supplement_1/S14.full.pdf

American Association of Clinical Endocrinologists’ Comprehensive Diabetes Management Algorithm 2013 This algorithm from the AACE outlines a complicationscentric approach to diabetes care and recommendations on evidence-based treatment approaches. The document contains sections on managing obesity, prediabetes, hyperglycemia, hypertension, and hyperlipidemia, as well as other risk-reduction strategies.

Garber AJ, et al. Endocr Pract. 2013;19(2):327-336.

LINK: https://www.aace.com/files/aace_algorithm.pdf

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TOOLS Lipodystrophy Resource Center at The Endocrine Society The Endocrine Society has created a variety of educational materials covering the pathophysiology, clinical presentations, and treatment of lipodystrophies.

Particular emphasis is placed on the connections between generalized or partial adipose tissue loss and their often severe metabolic complications, including severe insulin resistance, type 2 diabetes, and hypertriglyceridemia.

LINK: http://www.endocrine.org/education-and-practicemanagement/continuing-medical-education/lipids-and-obesity/ lipodystrophy-resource-room-slide-series

My Lipodystrophy Web Site This Web site contains information and resources for patients with lipodystrophy and their families. In addition to helping people better communicate with health care providers, the Web site also provides access to communities of people living with lipodystrophy.

LINK: http://mylipodystrophy.com

SUGGESTED READING Ectopic lipid storage and insulin resistance: a harmful relationship.

BorĂŠn J, et al. J Intern Med. 2013;274(1):25-40.

LINK: http://onlinelibrary.wiley.com/doi/10.1111/joim.12071/pdf

Clinical classification and treatment of congenital and acquired lipodystrophy.

Chan JL, Oral EA. Endocr Pract. 2010;16(2):310-323.

LINK: http://www.ncbi.nlm.nih.gov/pubmed/20061300

Clinical effects of long-term metreleptin treatment in patients with lipodystrophy.

Chan JL, et al. Endocr Pract. 2011;17(6):922-932.

LINK: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3498767/pdf/nihms410897.pdf

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Lipodystrophy: pathophysiology and advances in treatment.

Fiorenza CG, et al. Nat Rev Endocrinol. 2011;7(3):137-150.

LINK: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3150735/pdf/nihms313106.pdf

Lipodystrophies: genetic and acquired body fat disorders.

Garg A. J Clin Endocrinol Metab. 2011;96(11):3313-3325.

LINK: http://press.endocrine.org/doi/pdf/10.1210/jc.2011-1159

Lipodystrophy: metabolic insights from a rare disorder.

Huang-Doran I, et al. J Endocrinol. 2010;207(3):245-255.

LINK: http://joe.endocrinology-journals.org/content/207/3/245.full.pdf

Leptin and the central nervous system control of glucose metabolism.

Morton GJ, Schwartz MW. Physiol Rev. 2011;91(2):389-411.

LINK: http://physrev.physiology.org/content/91/2/389.full-text.pdf+html

Exploring the pathophysiology behind the more common genetic and acquired lipodystrophies.

Nolis T. J Hum Genet. 2014;59(1):16-23.

LINK: http://www.nature.com/jhg/journal/v59/n1/pdf/jhg2013107a.pdf

Rationale for leptin-replacement therapy for severe lipodystrophy.

Oral EA, Chan JL. Endocr Pract. 2010;16(2):324-333.

LINK: http://aace.metapress.com/content/e2n14628x168001n/

How to diagnose a lipodystrophy syndrome.

Vantyghem MC, et al. Ann Endocrinol (Paris). 2012;73(3):170-189.

LINK: http://www.ncbi.nlm.nih.gov/pubmed/22748602

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NOTES

Clinical Updates on Congenital and Acquired Lipodystrophy

Translating Research Into Practice

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