Swakshyar Saumya Pal

Risk factors for diabetic retinopathy in self- reported rural population with diabetes

BACKGROUND Diabetes and its related microvascular complications like diabetic retinopathy (DR) are showing increased prevalence in India. However, the magnitude of DR in rural population with diabetes needs exploration. AIM To estimate the prevalence and risk factors for the presence and severity of diabetic retinopathy in the self-reported rural population with diabetes. SETTINGS AND DESIGN In a cross-sectional study, a total of 26,519 participants (age >or= 30 years) attended 198 diabetic retinopathy screening camps conducted in three southern districts of Tamilnadu, India, between February 2004 and April 2006. MATERIALS AND METHODS All the participants underwent a dilated eye examination to detect DR by indirect ophthalmoscopy. Systemic and ocular risk factor estimation was done in a comprehensive examination. STATISTICAL ANALYSIS Univariate and stepwise regression analyses were done to identify the independent risk factors associated with the presence and severity of retinopathy. RESULTS The prevalence of diabetic retinopathy was 17.6% among the self-reported rural population with diabetes. The prevalence of referable (sight threatening) retinopathy was 5.3%. Risk factors associated with the development of any DR were male gender (OR= 1.37), longer duration of diabetes (per year, OR= 1.07), lean body mass index (OR= 1.30), higher systolic blood pressure (per 10 mm Hg, OR= 1.18), and insulin treatment (OR= 1.34; P P CONCLUSION: The study identified risk factors associated with DR in the rural population with diabetes. The results suggested that there was a need for formulating effective preventive strategies to minimize avoidable blindness due to diabetes, in rural areas.

Does Neuronal Damage Precede Vascular Damage in Subjects with Type 2 Diabetes Mellitus and Having No Clinical Diabetic Retinopathy

Aim: To investigate the occurrence of neuronal damage, as the earliest change occurring, before the clinical evidence of diabetic retinopathy. Methods: 70 eyes of subjects with type 2 diabetes mellitus and with no evidence of diabetic retinopathy (cases) and 40 eyes of subjects with no diabetes mellitus (controls) were studied using spectral-domain OCT and microperimetry. The influence of age and gender on the outcome measures was also analyzed. Results: Age- and gender-matched subjects showed a decreased mean retinal nerve fiber layer thickness in cases when compared to the controls (27 vs. 33 µm; p = 0.018). Among the cases, subjects between 40 and 45 years of age showed a reduced mean central foveal thickness (175.1 vs. 198.1 µm; p = 0.05), mean retinal thickness in the central 6-mm fundus (260.5 vs. 275.3 µm; p = 0.006) and mean retinal nerve fiber layer thickness (29 vs. 39 µm; p = 0.036) when compared to the controls. However, no differences were noted in the microperimetry outcomes in cases when compared to the controls. The duration of diabetes and the glycemic control did not show any significant changes on the outcome measures in cases, except for a significantly lower mean retinal sensitivity in diabetics with glycosylated hemoglobin values <7% as compared to those with glycosylated hemoglobin ≥7% (14.1 ± 2.9 vs. 15.4 ± 1.7 dB; p = 0.027). Conclusion: The results suggest that there is some evidence of early neuronal damage particularly on spectral-domain OCT, before the clinical evidence of diabetic retinopathy, in subjects with type 2 diabetes mellitus.

Prevalence and risk factors for diabetic retinopathy in rural India. Sankara Nethralaya Diabetic Retinopathy Epidemiology and Molecular Genetic Study III (SN-DREAMS III), report no 2.

Objective The study was aimed at estimating the prevalence of type 2 diabetes mellitus and diabetic retinopathy in a rural population of South India. Design A population-based cross-sectional study. Participants 13 079 participants were enumerated. Methods A multistage cluster sampling method was used. All eligible participants underwent comprehensive eye examination. The fundi of all patients were photographed using 45°, four-field stereoscopic digital photography, and an additional 30° seven-field stereo digital pairs were taken for participants with diabetic retinopathy. The diagnosis of diabetic retinopathy was based on Kleins classification. Main outcome measures Prevalence of diabetes mellitus and diabetic retinopathy and associated risk factors. Results The prevalence of diabetes in the rural Indian population was 10.4% (95% CI 10.39% to 10.42%); the prevalence of diabetic retinopathy, among patients with diabetes mellitus, was 10.3% (95% CI 8.53% to 11.97%). Statistically significant variables, on multivariate analysis, associated with increased risk of diabetic retinopathy were: gender (men at greater risk; OR 1.52; 95% CI 1.01 to 2.29), use of insulin (OR 3.59; 95% CI 1.41 to 9.14), longer duration of diabetes (15 years; OR 6.01; 95% CI 2.63 to 13.75), systolic hypertension (OR 2.14; 95% CI 1.20 to 3.82), and participants with poor glycemic control (OR 3.37; 95% CI 2.13 to 5.34). Conclusions Nearly 1 of 10 individuals in rural South India, above the age of 40 years, showed evidence of type 2 diabetes mellitus. Likewise, among participants with diabetes, the prevalence of diabetic retinopathy was around 10%; the strongest predictor being the duration of diabetes.

Prevalence and Risk Factors for Cataract in Diabetes: Sankara Nethralaya Diabetic Retinopathy Epidemiology and Molecular Genetics Study, Report No. 17

PURPOSE To report the prevalence of cataract and its subtypes in patients with type 2 diabetes mellitus and the risk factors associated with these cataracts. METHODS One thousand two hundred eighty-three eligible subjects with type 2 diabetes mellitus, enrolled from a cross-sectional study, underwent examination at the base hospital. Lens opacity was graded by a trained ophthalmologist according to the Lens Opacity Classification System (LOCS) III system. RESULTS The age- and sex-adjusted prevalence of cataract in the study was 65.7% (95% confidence interval [CI], 65.6-65.8). Mixed cataracts were more common than monotype ones (41.6% vs. 19.4%). The prevalence of cataract was higher in women, subjects with known diabetes and those with longer duration of diabetes (51.4%, 50.3%, and 64.5%, respectively). The risk factors for any type of cataract were increasing age (odds ratio [OR], 1.14; 95% CI, 1.11-1.16), macroalbuminuria (OR, 4.61; 95% CI, 1.56-13.59) and increasing glycosylated hemoglobin (OR, 1.92; 95% CI, 1.22-3.00); higher hemoglobin (OR, 0.38; 95% CI, 0.22-0.64) was the protective factor. The risk factors for nuclear cataract included increasing age (OR, 1.15) and high serum triglycerides (OR, 6.83). For cortical cataract, increasing age (OR, 1.14) and poor glycemic control (OR, 2.43) were the risk factors; increasing hemoglobin (OR, 0.41) was the protective factor. For posterior subcapsular cataract, the risk factors included increasing age (OR, 1.11), being of the female sex (OR, 9.12), employment (OR, 9.80), and duration of diabetes (OR, 21.37). CONCLUSIONS Nearly two thirds of the diabetic population showed evidence of cataract; mixed cataracts were more common than the monotypes ones.

Albuminuria and Diabetic Retinopathy in Type 2 Diabetes Mellitus Sankara Nethralaya Diabetic Retinopathy Epidemiology And Molecular Genetic Study (SN-DREAMS, report 12)

BackgroundThe concordance of microalbuminuria and diabetic retinopathy (DR) has been well reported in persons with type 1 diabetes; however, for type 2 diabetes, there is paucity of data especially from population-based studies. The aim of this study was to estimate the prevalence of albuminuria (micro - and macroalbuminuria) among persons with type 2 diabetes and determine its role as a risk factor for presence and severity of DR.MethodsA population-based cross sectional study was conducted in cohort of 1414 subjects with type 2 diabetes from Chennai metropolis. All the subjects underwent comprehensive eye examination including 45 degrees four-field stereoscopic digital photography. DR was clinically graded using Early Treatment Diabetic Retinopathy Study scales. A morning urine sample was tested for albuminuria. Subjects were considered to have microalbuminuria, if the urinary albumin excretion was between 30 and 300 mg/24 hours, and macroalbuminuria at more than 300 mg/24 hours. The statistical software used was SPSS for Windows, Chicago, IL. Student t-test for comparing continuous variables, and χ2 test, to compare proportions amongst groups were used.ResultsThe prevalence of microalbuminuria in the study subjects was 15.9% (226/1414), and that of macroalbuminuria, 2.7% (38/1414). Individuals with macroalbuminuria in comparison to micro- or normoalbuminuria showed a greater prevalence of DR (60.5% vs. 31.0% vs. 14.1%, p < 0.001), and also a greater severity of the disease (60.9% vs. 21.4 vs. 9.9, p < 0.001).ConclusionsEvery 6th individual in the population of type 2 diabetes is likely to have albuminuria. Subjects with microalbuminuria were around 2 times as likely to have DR as those without microalbuminuria, and this risk became almost 6 times in the presence of macroalbuminuria.

Prevalence of Metabolic Syndrome and its influence on microvascular complications in the Indian population with Type 2 Diabetes Mellitus. Sankara Nethralaya Diabetic Retinopathy Epidemiology And Molecular Genetic Study (SN-DREAMS, report 14).

BackgroundThe Metabolic syndrome (MS) consists of central obesity, glucose intolerance, hyperinsulinemia, low high density lipoproteins, high triglycerides and hypertension. Different studies have observed that MS causes microvascular complications in patients with type 2 diabetes. The aim of the study was to find out the prevalence of MS in the Indian population with type 2 diabetes mellitus in relation to gender, duration of diabetes, and to evaluate the influence of MS and its individual components on microvascular complications such as diabetic retinopathy, diabetic nephropathy and diabetic neuropathy.MethodsA population-based cross sectional survey was conducted with 1414 patients having type 2 diabetes mellitus. The International Diabetes Federation (IDF) criteria were used to identify the metabolic syndrome. Diabetic retinopathy was graded using the stereoscopic digital fundus photography. Neuropathy was assessed by measuring the vibration perception threshold through a sensitometer. Nephropathy was diagnosed by the presence of microalbuminuria in the first morning urine sample.ResultsThe age and gender adjusted prevalence of MS, using the IDF criteria, in the South Indian population was 73.3%. The prevalence was higher in women (83.3%), compared to men (65.3%). In subjects with diabetes mellitus, without and with MS, the prevalence of retinopathy was 21.3% and 16.9% (p = 0.057); prevalence of nephropathy was 20.5% and 18.0% (p = 0.296), and prevalence of neuropathy was17.2% and 19.4% (p = 0.353) respectively. Overall and in women, the clustering of MS components led to an increase in the prevalence of diabetic nephropathy. The prevalence of retinopathy and neuropathy in MS subjects, who had diabetes for < 10 years, was more in both men and women; it was more in women but not in men when the duration of diabetes varied from 11-20 years.ConclusionsThe association of MS with microangiopathies decreased with an increase in the duration of diabetes. MS behaved differently in men and women. It may need to be managed differently in the two groups.

ICAM-1 K469E polymorphism is a genetic determinant for the clinical risk factors of T2D subjects with retinopathy in Indians: a population-based case–control study

Objective Elevated levels of intercellular adhesion molecule-1 (ICAM-1) are demonstrated in diabetes complications. The current study aims to understand association of K469E (rs5498) in ICAM-1 gene, in type 2 diabetic (T2D) subjects with retinopathy. Design Case–control study. Setting Sankara Nethralaya Diabetic Retinopathy Epidemiology and Molecular Genetic Study, an epidemiology study (on prevalence of diabetic retinopathy in T2D subjects (T2DR) from south India) and outpatient department of Sankara Nethralaya, a tertiary care hospital, in Chennai, India. Participants A total of 356 T2D subjects of >15 years of diabetes duration, with (n=199) and without (n=157) retinopathy. Methods The rs5498 polymorphism was genotyped by direct sequencing. Multivariate analysis for various clinical covariates was done using SPSS V.14. Comparative assessment of structure stability, folding rate of the variants were assessed using bioinformatics tools like STRIDE, MuPro, ModellerV97, fold rate server, etc. Results The AA genotype of rs5498 was seen at a higher frequency in the retinopathy group (p=0.012). The risk for diabetic retinopathy (DR) increased in the presence of AA genotype (OR=1.89–4.82) after the sequential addition of various clinical covariates. Multivariate logistic regression analysis showed 8.26 times high risk for developing DR in the AG genotype (p=0.003). Structural superimposition of ICAM-1 wild type (K469) and variant (E469) showed 0.943 Å of backbone root mean square deviation as calculated by PYMOL software. A difference in the fold rate time was also observed between the wild type (5.4/s) and variant (3.3/s). Conclusions This study shows that allele A of rs5498 in ICAM-1 is a putative risk predisposing allele for T2D retinopathy and its clinical covariates in Indian population. The folding rate of the protein decreases for the A allele implicating a potential effect on the structure and function of ICAM-1.

Sankara Nethralaya Diabetic Retinopathy Epidemiology and Molecular Genetic Study (SN--DREAMS III): study design and research methodology.

BackgroundTo describe the methodology of the Sankara Nethralaya Diabetic Retinopathy Epidemiology and Molecular Genetic Study III, an ongoing epidemiological study to estimate the prevalence of Diabetes and Diabetic Retinopathy in rural population of Kanchipuram and Thiravallur districts of Tamil Nadu, India and to elucidate the clinical, anthropometric, biochemical and genetic risk factors associated with diabetic retinopathy in this rural population.MethodsSankara Nethralaya Diabetic Retinopathy Epidemiology and Molecular Genetic Study III will be a mobile van based epidemiological study; 11,760 participants aged ≥ 40 years will be recruited from the study areas. Eligible subjects will undergo blood sugar estimation to diagnose Diabetes. Oral Glucose Tolerance Test will be done to conform diabetes. All subjects with diabetes will undergo complete information of knowledge, aptitude and practice of diabetes and diabetic retinopathy, Diet questionnaire, demographic data, socioeconomic status, physical activity, anthropometric measurements, and risk of sleep apnoea. A detailed medical and ocular history, a comprehensive eye examination including refraction, slit lamp biomicroscopy examination, indirect ophthalmoscopy, slit lamp biomicroscopy, digital stereo fundus photography and ultrasound of eye will be done in the mobile van. Blood will be collected for biochemical investigations including blood hemoglobin, glycosylated hemoglobin, lipid profile, urea and creatinine, genetic study. Urine will be collected for microalbuminuria. All fundus photographs will be graded at base hospital. Participants who need treatment will be sent to the base hospital. A computerized database is created for the records.ConclusionThe study is expected to provide an estimate of the prevalence of Diabetes and Diabetic Retinopathy and also a better understanding of the genetic, anthropometric and socio-economic risk factors associated with Diabetic Retinopathy in a Rural South Indian population.

Prevalence and risk factors for severity of diabetic neuropathy in type 2 diabetes mellitus

PURPOSE To estimate the prevalence of diabetic neuropathy (severity wise) and associated risk factors in a population having type 2 diabetes mellitus. MATERIALS AND METHODS A population-based sample of 1401 persons with diabetes (identified as per the WHO criteria) underwent comprehensive eye examination including stereoscopic digital photography (45° four field) for diabetic retinopathy grading. Vibration perception threshold (VPT) measurements were done to assess neuropathy (cut off ≥ 20 V). Severity of neuropathy was graded into three groups based on VPT score as mild (20-24.99 V), moderate (25-38.99 V), and severe (≥39 V). Univariate and multivariate analyses were done to find out the independent risk factors for severity of diabetic neuropathy. RESULTS In the overall group, the prevalence of diabetic neuropathy was 18.84% (95% CI: 16.79-20.88). The prevalence of mild diabetic neuropathy was 5.9% (95% CI: 4.68-7.15), moderate diabetic neuropathy was 7.9% (95% CI: 6.50-9.33), and severe diabetic neuropathy was 5% (95% CI: 3.86-6.14). Increasing age per year (P < 0.0001) was a statistically significant risk factor for all - mild, moderate, and severe - types of diabetic neuropathy. For severe diabetic neuropathy, other significant risk factors were duration of diabetes mellitus (P = 0.027), macroalbuminuria (P = 0.001), and presence of diabetic retinopathy (P = 0.020). CONCLUSIONS The results suggested that every fifth individual in a population of type 2 diabetes is likely to have diabetic neuropathy. Nearly 13% had neuropathy of moderate and severe category, making this group vulnerable for complications such as foot ulceration or lower limb amputation.

Impairment of Colour Vision in Diabetes with No Retinopathy: Sankara Nethralaya Diabetic Retinopathy Epidemiology and Molecular Genetics Study (SNDREAMS- II, Report 3)

Purpose To assess impairment of colour vision in type 2 diabetics with no diabetic retinopathy and elucidate associated risk factors in a population-based cross-sectional study. Methods This is part of Sankara Nethralaya Diabetic Retinopathy Epidemiology and Molecular-genetics Study (SN-DREAMS II) which was conducted between 2007–2010. FM 100 hue-test was performed in 253 subjects with no clinical evidence of diabetic retinopathy. All subjects underwent detailed ophthalmic evaluation including cataract grading using LOCS III and 45° 4-field stereoscopic fundus photography. Various ocular and systemic risk factors for impairment of colour vision (ICV) were assessed in subjects with diabetes but no retinopathy. P value of < 0.05 was considered statistically significant. Results The mean age of the study sample was 57.08 ± 9.21 (range: 44–86 years). Gender adjusted prevalence of ICV among subjects with diabetes with no retinopathy was 39.5% (CI: 33.5–45.5). The mean total error score in the study sample was 197.77 ± 100 (range: 19–583). The risk factors for ICV in the study were women OR: 1.79 (1.00–3.18), increased resting heart rate OR: 1.04 (1.01–1.07) and increased intraocular pressure OR: 1.12 (1.00–1.24). Significant protective factor was serum high-density lipoprotein OR: 0.96 (0.93–0.99). Conclusions Acquired ICV is an early indicator of neurodegenerative changes in the retina. ICV found in diabetic subjects without retinopathy may be of non-vascular etiology.