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Association of Obesity and Dyslipidemia with the severity of Diabetic retinopathy in Type 2 Diabetes mellitus patients. Nalini. M.1,3 M.Pharm, Saroj Kumar Raul3, Dr. A. Annapurna1, Dr. P. Avinash2 AU College of Pharmaceutical Sciences, Andhra University, Vishakhapatnam. Department of Retina and Vitreous, L.V. Prasad Eye Institute, GMR Varalakshmi campus, Vishakhapatnam. Maharajaha’s College of Pharmacy, Phoolbaugh, Vzianagaram .

Abstract

Introduction

Aim: To investigate the association of obesity and dyslipidemia with the risk and severity of diabetic retinopathy (DR) in type 2 diabetes mellitus patients and normal healthy subjects. Materials and Methods: Data of randomly selected (n=150) type 2 diabetic patients were collected from the Outpatient Department of LVPEI, Vishakhapatnam. Retinopathy grading was done after a detailed clinical examination by an Ophthalmologist using Ophthalmoscope according to Wilcoson’s Early Treatment Diabetic Retinopathy Study. Demographic, anthropometric parameters were recorded. Serum lipid profile were measured in different groups. Results: Risk of retinopathy, was found to have statistically significant association with duration of diabetes (p=0.0001), HbA1c (p=0.001) and BMI () on multivariate analysis. On univaraite analysis BMI was found to be positively associated with the serum triglycerides (p=0.002), total cholesterol (p=0.032), LDL levels (0.04) and negatively associated with HDL levels (). Conclusion: Obesity and dyslipidemia showed a significant association with the severity of diabetic retinopathy. Obesity causing impaired insulin function is responsible for the risk of diabetic retinopathy in type 2 diabetic patients. Reduced BMI and serum lipids and maintaining normal glycemic condition may help in reducing the vision loss due to diabetic retinopathy in type 2 diabetic patients. Keywords: Obesity, Dyslipidemia, Diabetic retinopathy

➢ Diabetic retinopathy (DR) is a microvascular complication of diabetes and is the major cause of vision loss in diabetic patients. ➢ The risk of diabetic retinopathy increases with age and duration of diabetes. In developing countries like India the risk of diabetic retinopathy was increasing due to urbanization, lifestyle and food habits. ➢ Prevalence rises to 40 - 50% after 10 years of Diabetes mellitus. Type 1 - all Type 2- 60% ➢ Accurate data on risk factors involved in the development of Diabetic retinopathy and the role of inflammatory cytokines involved in the progression of Diabetic retinopathy is still lacking. ➢ Screening and early treatment can prevent substantial visual loss. ➢ The present study is aimed to assess the risk of BMI and body fats in the progression and severity of diabetic retinopathy.

Methods and Materials The present study is an observational study conducted in the LV Prasad Eye Institute, GMR Varalakshmi campus, Vishakhapatnam, Andhra Pradesh, India and Andhra University, Visakhapatnam, A.P., India. The study included n=150 type 2 diabetic patients and were selected on the basis of inclusion and exclusion criteria. The study subjects are randomly selected from the hospital after detailed clinical examination by an Ophthalmologist and after obtaining informed consent from the patients. Two stages of diabetic retinopathy grading are included in the study based on Wilcoson’s Early Treatment Diabetic Retinopathy Study. [7] The subjects were divided into 50 in each group such as: Group 1: Type 2 Diabetes mellitus patients without retinopathy patients (n=50) (DM); Group 2: Non-proliferative Diabetic retinopathy patients of Type 2 Diabetes mellitus (n=50) (NPDR); Group 3: Proliferative Diabetic retinopathy patients of Type 2 Diabetes mellitus (n=50) (PDR). The procedures followed in the study were in accordance with the Helsniki Declaration, 2013.[8] Anthropometric Parameters: BMI (kg/m2) was calculated by dividing weight and height square. Recommend value of BMI between 18.5-24.9 kg/m2 as normal range. Blood Pressure: Blood pressure was measured using Sphygmometer device after 5min rest and the mean of two measurements was considered. Blood samples: Blood samples for laboratory analysis were collected after a 12-hour overnight fasting. Subjects included in the study after complete clinical and ophthalmic examination. Blood was collected in separate vacutainers EDTA vacutainers for HbA1c and clot enhancer vacutainers for serum glucose, serum lipid profile tests procured from Bio-X, Mumbai. Biochemical parameters: Glycated hemoglobin value (HbA1c) was determined in blood sample by automated immunoturbidimetric assay, using Excel kit. Serum lipid profile (TG, TC, HDL, LDL, VLDL (Excel kits)) was determined by the coloremertic tests, using semi auto analyser (CAREX)

Results Chart 1: Lipid Profile of all subjects Statistical Analysis: All the results were analysed using SPSS (version 17.0) software. Risk factor assessment was performed by binary logistic regression analysis, category wise comparative studies were performed using the Chi - square test, Pearson’s correlation co-efficient of correlation of parameters. Values with abnormal distribution we used the Mann-Whitney U test. One way ANOVA was performed for comparison of means. The accepted level of significance for all analysis was P<0.01 and P<0.05. In the present study, the mean age of Diabetic retinopathy patients was 58.8 ± 0.32 years; there are 113 (75%) males and 37 (33%) females of Type 2 Diabetic patients. Table 1: Shows the binary logistic regression of risk factors analysis for the presence of any DR. Table 2: shows the risk of BMI and diabetic retinopathy in Type 2 Diabetic patients. Table 2 shows increased BMI (p ≤0.01) in diabetic patients with retinopathy compared to those without retinopathy. Whereas high serum triglycerides, total cholesterol and LDL was observed in proliferative diabetic retinopathy patients compared to those diabetic patients without retinopathy. Decreased HDL levels were observed in NPDR, PDR. In the present study there was a significant change in the serum lipids of Type 2 diabetic patients with retinopathy. Increased triglycerides (p=0.001), total cholesterol (p=0.01), and LDL (p=0.001) levels were significantly high in proliferative diabetic retinopathy and non proliferative diabetic retinopathy compared to diabetic patients without retinopathy [Graph 2]. Graph 1: Comparison of TG, TC, HDL, LDL in Type 2 diabetic retinopathy patients (n=100).

Table 2: Effect of Body Mass Index (BMI (Kg/m2)) on Diabetic retinopathy in Type 2

Table 1: Effect of various risk factors on Diabetic retinopathy in Type 2 diabetic Patients: In this study, binary logistic regression (Wald) was primarily used to estimate the association of independent factors and DR.

Diabetic patients The results were shown in Table Total no of Type 2 diabetic

Discussion ➢ Obesity causing impaired insulin action might be responsible for the progression of Diabetic retinopathy in Type 2 Diabetic patients (Seema Abhijeet Kaveeshwar., et al., 2014, and Henricsson M., 2003). ➢ Several fatty acid metabolites such as acyl-CoAs and diacylglycerol, which are the signaling molecules and activates protein kinase C pathway, Jun kinase pathway. These kinases inhibit insulin receptor signalling leads to impaired insulin action (Petersen and Shulman 2006). ➢ Endothelial dysfunction due to hypercholesterolemia in Type 2 Diabetes mellitus patients leads to retinal exudates formation in Diabetic retinopathy disease (Ebru Nevin Cetin, et al., 2013). Diacylglycerol (DAG) a lipid molecule, is the key activator of protein kinase pathway (PKC) is closely related to the development of Diabetic retinopathy (Rema M, et al., in 2005, Yo-Chen Chang, et al., 2013). ➢ Hence, the present study showed similar results as previous studies stating that high lipid levels i,e., high triglycerides , total cholesterol and LDL, VLDL levels are high in Diabetic retinopathy patients compared to diabetic patients without retinopathy

patients are n=150.

BMI

Without DR (%)

With DR (%)

Conclusions <18.5

4 (2.6)

NPDR (%)

PDR (%)

4 (2.6)

2 (1.3)

18.5-24.9

20 (13.3)

16 (10.6)

12 (8.0)

25-29.99

18 (12)

22 (14.6)

22 (14.6)

≥30

9 (6)

8 (5.3)

13 (9.3)

➢ The present study results show that proliferative Diabetic retinopathy patients have higher BMI compared to non-proliferative Diabetic retinopathy patients. ➢ Obesity causing impaired insulin action might be responsible for the progression of Diabetic retinopathy in Type 2 Diabetic patients. ➢ The study results suggest that increased serum levels of biomarkers provide a potential tool for risk assessment of Diabetic retinopathy. ➢ Hence regular screening for Diabetic retinopathy increases the chances of preventing diabetes related blindness. Hence early identification of Diabetic retinopathy and screening for the stage of Diabetic retinopathy can reduce the incidence and progression of Diabetic retinopathy

Figure 1: Stages and progression of diabetic retinopathy

Contact

References

Name: Dr.M. Nalini Maharjha’s College of Pharmacy, Phoolbaugh, Vizianagram, Andhra Pradesh. Email: nalinimathal8@gmail.com Ph no: 9705869019

1. Timothy S Kern and Alistar J Barber, “Retinal ganglion cells in diabetes”, J Physiol; 2008; 586 (pt 18); 4401-4408.

2. Unnikrishnan RI, Rema M, Pradeepa R, Deepa M, Shanthirani CS, Deepa R, Mohan V, “Prevalence and risk factors of diabetic retinopathy in an urban 3. Seema Abhijeet Kaveeshwar and Jon Comwal, “The current state of diabetes mellitus in India”, Australas MED J. 2014; 7(1): 45-48. 4. Henricsson M, Nystorm L, Blohme G, Ostman J, Kullberg C, Svensson M, Schollin A, Amgvist HJ, Bjork E, Bolinder J, Eriksson JW, Sundkvist G,” The incidence of retinopathy 10 years after diagnosis in young adult people with diabetes: result from the nationwide population-based Daibetes mellitus incidence study in Sweden (DISS),” Diabetes Care; 2003: 26(2); 349-54. 5. Petersen KF, Shulman GI, “Etiology of insulin resistance”, Am J Med; 2006; 119: S 10-6. 6. Rema M, Sujatha P, Pradeepa R. Visual outcomes of panretinal photocoagulation in diabetic retinopathy at one-year follow-up and associated risk factors. Indian J Ophthalmol 2005;53: 93-9. 7. Yo-Chen Chang and Wen-Chuan Wu, “Dyslipidemia and Diabetic Retinopathy”, Rev Diabet Stud; 2013 ;10(2-3): 121–132


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