Predictive importance of dyslipidemia in diabetic retinopathy
Nutan Bedi, Dhaval N Doshi
Depatment of Opthalmology, Geetanjali Medical College, Udaipur Rajasthan,India
ABI Health Technologies, United Arab Emirates
Diabetes is one of the commonly emerging global health problems with considerable morbidity and complications. [1] More than 400 million people worldwide have diabetes, results in loss of 1.6 million lives per year. [2,3] Diabetic vascular complication such as retinopathy is frequent and contribute to the total disease burden. Early retinopatic changes include micro-aneurysms and retinal micro-hemorrhages resulting in early symptoms of diabetic complications.
The pathogenesis of diabetic retinopathy is not fully understood and controversies exist about why it occurs in some patients and not in others. [7] Dyslipidemia in diabetes is associated with the increased risk of complications. Reduced levels of nitric oxide and high lipid levels are known to cause endothelial dysfunction and were suggested to play a key role in retinal exudate formation in DR.
Various risk factors act synergistically for the development of retinopathic complications and the contributions of risk factors other than blood glucose level have yet to be clearly identified and quantified. Diabetic dyslipidemia has specific importance, and thus the present study was planned to see the effects of dyslipidemia on retinopathic complications of diabetes.
MATERIAL AND METHODS
Study population and design: In the present cross-sectional prospective study, a total of 150 type 2 diabetic patients were included. Diabetes was diagnosed according to American Diabetes Association’s revised criteria. Approval from the Ethics Committee was taken prior to study. Written informed consent was taken from all the participants after explaining detailed methodology to them.
Study Procedure: Baseline information on socio-demographic variables, smoking habits, physical activity level, medication use, parental history of diseases, and alcohol consumption were gathered by a standardized face to face interview. Diabetic patient attending Diabetic clinic, Ophthalmology and medicine OPD were identified, patients were evaluated for presence of diabetic retinopathy by fundoscopy. Lipid profile was done by fully-auto analyzer (XL- 300). Blood glucose was estimated by glucose oxidase method and glycosylated hemoglobin by immune-turbidometric method. Estimated values of total cholesterol >240 mg/dl, serum triglycerides>160mg/dl, HDL<40mg/dl, LDL>130mg/dl and VLDL>40mg/dl were considered as abnormal.
Data Collection & Statistical Analysis: Retinopathy was considered as a dependent parameter and various others as age, sex, blood pressure, total cholesterol values, HDL level, LDL level, triglyceride level, blood sugar, HbA1c values, duration of diabetes, and regular smoking as independent variables. Means or proportions for baseline clinical and laboratory characteristics were computed for subjects with and without retinopathy. For comparison of proportions (qualitative parameters), chi square test was used. P-values less than 0.05 were stated as statistically significant. Multiple Logistic regression analysis was done to know the effect of individual variable in relation to the development of diabetic complication.
RESULTS
The details of demographic profile of the study population revealed that the mean age of the study group was 60.4 years with average duration of diabetes 9.7 years. Lipid profile showed that in 150 patients, hypertriglyceridemia was most common abnormality in diabetic patients, followed by high level of LDL and VLDL. (Table1) Serum TG levels were high (>160 mg/dl) in 65 (43.33 %) patients, while high LDL level (>130mg/dl) were found in 53(35.33%) patients.
Table 2 shows the severity of retinopathy and the presence of clinically significant macular edema (CSME) among the patients with diabetic retinopathy. Moderate non-proliferative diabetic retinopathy (NPDR) was found to be present in 44.0% eyes followed by mild NPDR (24% eyes). Proliferative diabetic retinopathy (PDR) was present only in 5.4%.out of total 8 patients of PDR 50% shows CSME.
The fasting blood sugar was 161.9±51.7 mg/dl. Glycosylated hemoglobin was found to be 8.2%. Serum cholesterol was 182.9±50 mg/dl, Serum HDL was 40.6±13.2 mg/dl, Serum LDL was 110.3±41.3 mg/dl, Serum VLDL was 35.8±23.8 mg/dl and Serum Triglyceride (TG) was 175.8±110 mg/dl. Univariate analysis revealed that association between diabetic retinopathy and duration of disease, plasma fasting blood sugar levels, and serum HDL values was statistically significant (p<0.05). (Table 3)
Significant association of diabetic retinopathy with high levels of HbA1c and smoking habit of patient was found. (Table 4) On application of multiple logistic regressions, only duration of diabetes, serum FBS levels and serum HDL levels were found to be significantly affecting the development of diabetic retinopathy. (Table 5)
DISCUSSION
The present study showed the prevalence of dyslipidemia in diabetic population mainly comprising rural population of Middle West India. The common lipid abnormalities found in diabetic patients were low serum HDL levels, raised serum triglycerides and raised LDL levels. However, there are limited studies on diabetic dyslipidemia in Middle West India that looked for diabetic complications. The prevalence of dyslipidemia in diabetic population depends on so many factors as type and duration of diabetes, control of diabetes, other systemic disorders, obesity, ethnic variations etc.
Diabetic retinopathy in the present study was found to have significant correlation with the duration of disease. This finding was in correlation with a study conducted in Community hospitals of Lampang by Jenchitr et al, which revealed that the prevalence of diabetic retinopathy is associated with the duration of diabetes in patients. It also revealed that in the patients, who had suffered diabetes for 15-20 years, the prevalence of diabetic retinopathy would increase
Table to 53.06% and it was likely to develop to PDR.
The duration of diabetes is probably the strongest predictor for development and progression of retinopathy. Among younger-onset patients with diabetes in the Wisconsin epidemiologic study of diabetic retinopathy (WESDR), the prevalence of any retinopathy was 8% at 3years, 25% at 5years, 60% at 10 years and 80% at 15 years. The prevalence of PDR was 0% at 3 years and increased to 25% at 15 years. [10] The incidence of retinopathy also increased with increasing duration. The 4-year incidenceof developing proliferative retinopathy in the WESDR younger onset group increased from 0% during the first 5years to 27.9% during years 13-14 of diabetes.
Retinopathy is significantly associated with blood sugar levels. The U.K. Prospective Diabetes Study (UKPDS) demonstrated that improved blood glucose control reduced the risk of developing diabetic retinopathy.
Favoring the result of present study, a case control study in Kuwait comparing type II diabetic with retinopathy and without retinopathy by Al-Shammari et al revealed that poor blood sugar control and longer duration of diabetes mellitus are the risk factors for diabetic retinopathy and it seems convincing that diabetics who had these risk factors are more prone to develop diabetic retinopathy.
Diabetic retinopathy development due to abnormal level of lipids, especially low HDL, was having significant association in present study, which was in tune with the findings of Knuiman et al.
CONCLUSION
Along with blood sugar level and duration of disease, low levels of HDLs are also significantly associated with retinopathic changes. Hence appropriate preventive (multiphasic screening in form of lipid profile testing) and treatment strategies (targeting at low HDL levels) should be considered timely in type II diabetes patients.
LIMITATIONS
There can be enrollment of more participants in the study to increase the power; beside that as it was hospital based study, it can results in to selection bias of patients, temporal association could not be established with this study which is common limitation of cross sectional studies.
Conflict of Interest \
None
Source of Funding
Nil
Ethical conduct of research
The authors declare that this review article does not require Institutional Review Board/Ethics review or approval.
REFERENCES
1. Ezhilvendhan K, Sathiyamoorthy A, Prakash BJ, Bhava BS, Shenoy A. Association of dyslipidemia with diabetic retinopathy in Type 2 diabetes mellitus patients: A hospital-based study. J Pharm Bio all Sci 2021;13:S1062-7.
2. World Health Organisation (WHO). Diabetes. Available from: https://www.who.int/health-topics/ diabetes#tab=tab_1. [Last accessed on 2021; December 26]
3. Zimmet P, Alberti KGMM, Shaw J. Global and societal implications of the diabetes epidemic. Nature 2001;414:782-7.
4. Engerman RL. Pathogenesis of diabetic retinopathy. Diabetes 1989;38:1203-6.
5. Hammes HP, Lin J, Renner O, Shani M, Lundqvist A, Betsholtz C, et al. Pericytes and the pathogenesis of diabetic retinopathy. Diabetes 2002;51:3107-12.
6. Fong DS, Aiello L, Gardner TW, King GL, Blankenship G, Cavallerano JD, et al. Diabetic retinopathy. Diabetes Care 2003;26:226-9.
7. Busik JV, Reid GE, Lydic TA. Global analysis of retina lipids by complementary precursor ion and neutral loss mode tandem mass spectrometry. Methods Mol Biol 2009;579:33-70.
8. Hegde SS, Vekategowda HT. Association of lipid profile with diabetic retinopathy – A comparative study. Int J Health Sci Res. 2016;6:74-81
9. Jenchitr W, Samaiporn S, Lertmeemongkolchai P, Chongwiriyanurak T, Anujaree P, Chayaboon D et al. Prevalence of diabetic retinopathy in relation to duration of diabetes mellitus in community hospitals of Lampang. J Med Assoc Thai 2004;87(11):1321-6.
10. Klein R, Knudtson MD, Lee KE, Gagnon R, Klein BEK. The Wisconsin epidemiologic study of diabetic retinopathy XXII: The Twenty-Five-Year Progression of Retinopathy in Persons with Type 1 Diabetes. Ophthalmology 2008;115(11):1859-68.
11. United Kingdom Prospective Diabetes Study (UKPDS) Group. Effect of intensive blood-glucose control with metformin on complications in over weight patients with type 2 diabetes mellitus (UKPDS 34). Lancet 1998;352:85465.
12. Al-Shammari FKH, Al-Meraghi O, Nasif A, Al-Otaibi S. The prevalence of diabetic retinopathy and associated risk factors in type 2 diabetes mellitus in Al-Naeemarea (Kuwait). Middle East J Family Med 2005;3(2).
13. Knuiman MW, Welborn TA, McCann VJ, Stanton KG, Constable J. Prevalence of diabetic complications in relation to risk factors. Diabetes 1986(35):13321339.