Tele-Ophthalmology Versus Face-to-Face Retinal Consultation for Assessment of Diabetic Retinopathy in Diabetes Care Centers in India: A Multicenter Cross-Sectional Study.

Aim: To evaluate the effectiveness of tele-ophthalmology (TO) versus face-to-face screening for diabetic retinopathy (DR) in diabetes care centers (DCC) across India. Methods: This is an observational, multicenter, retrospective, cross-sectional study of DR screening in individuals with diabetes performed across 35 branches of a chain of DCC in 20 cities in India over 1 year. In 30 DCC, DR screening was performed by TO, where retinal images obtained using Fundus on Phone camera were uploaded through the telemedicine network for centralized DR grading by eight retina specialists. In five DCC, DR screening was performed by fundus examination (FE) by the same retina specialists. The rate of detection of sight-threatening DR (STDR) (defined as the presence of proliferative DR and/or diabetic macular edema) through the two modes was compared. Results: A total of 58,612 individuals were screened for DR from January 1, 2018 to December 31, 2018: 25,316 by TO and 33,296 by FE. The mean age and mean duration of diabetes of the individuals with diabetes screened by TO was 55.8 ± 11.2 years and 9.5 ± 7.3 years; and in individuals screened by FE, it was 57.5 ± 11.6 years and 11.5 ± 8.0 years respectively. The mean glycated hemoglobin was 8.8% ± 2.1% and 8.5% ± 1.9% in the two groups, respectively. Any DR was detected in 31.7% (95% confidence interval [CI]: 31.0-32.3) by tele-screening and in 38.5% (95% CI: 37.9-39.0) by FE, whereas STDR was detected in 7.3% (95% CI: 7.0-7.7) by TO and in 10.5% (95% CI: 10.2-10.9) by FE. Overall, 11.4% individuals with diabetes in the TO group, including 4.1% with ungradable images, were advised referral to retina specialists for further management. Conclusion: Screening for DR at DCC using TO is feasible and effective for STDR detection in India and may be adopted throughout India.

Prevalence and risk factors for diabetic retinopathy in prediabetes in Asian Indians.

AIM: To assess the prevalence of diabetic retinopathy (DR) and associated risk factors in Asian Indians with prediabetes. METHODS: In a cross-sectional study conducted at two tertiary care diabetes centres in Chennai, India, clinical and biochemical assessment and nonmydriatic ultra-wide field fundus photography was performed in individuals with prediabetes (impaired fasting glucose [IFG] and/or impaired glucose tolerance [IGT]) based on oral glucose tolerance test (OGTT) and/or glycated hemoglobin (HbA1c) between 5.7% and 6.4% in 2019. The retinal photographs were graded by certified ophthalmologists. Systemic risk factors associated with DR in prediabetes were assessed. RESULTS: The mean age of the 192 individuals with prediabetes was 48 ± 13 years (55.2% were males). DR was present in 12 (6.3%) individuals of which nine (4.7%) had mild non-proliferative DR (NPDR) and three (1.6%) had moderate NPDR. None had severe sight-threatening DR. The Poisson multiple regression analysis showed that after adjusting for other systemic covariates, HbA1c values ≥ 6% (6-6.4%) was associated with 2 times higher relative risk of DR (Risk ratio 1.95 (95% CI 1.07-3.545, p = 0.028) in comparison to HbA1c < 6%). CONCLUSION: DR was present in about 6% of the Asian Indians with prediabetes. Higher HbA1c values among individuals with prediabetes was associated with twice the relative risk for DR. Robust control of HbA1c should be encouraged even before the diagnosis of diabetes is established.

Altered circulatory levels of miR-128, BDNF, cortisol and shortened telomeres in patients with type 2 diabetes and depression.

AIMS: Several studies have reported the role of biomarkers either in diabetes or depression. The present study is aimed at profiling the circulating levels of miR-128, brain-derived neurotrophic factor (BDNF), cortisol and telomere length in patients with type 2 diabetes with and without depression compared to individuals with normal glucose tolerance. METHODS: Study subjects (n = 160) were recruited from an ongoing epidemiological study in southern India. Non-diabetic and diabetic individuals were diagnosed as per the World Health Organization criteria. Depression score was derived using PHQ-12 questionnaire. Real-time quantitative PCR and ELISA methodologies were used to quantify the biomarkers. RESULTS: Circulatory levels of miR-128 and cortisol were significantly (p < 0.05) increased with decreased BDNF levels and shortened telomeres in T2DM patients with or without depression compared to NGT individuals. T2DM patients with depression had the highest levels of miR-128 and cortisol and lowest levels of BDNF and telomere length compared to other groups. Pearson correlation analysis showed miR-128 levels were negatively associated with BDNF, telomere length and HDL cholesterol and positively correlated with cortisol, depression score, poor glycemic control and insulin resistance. Regression analysis confirmed that miR-128 was significantly associated with depression score even after adjusted for several confounding factors. However, this association was lost when adjusted for cortisol or telomere length. CONCLUSIONS: Patients with type 2 diabetes and depression exhibited increased circulatory levels of miR-128 and serum cortisol and decreased levels of BDNF and shortened telomeres. These neuroendocrine signatures were more markedly altered in those with combined diabetes and depression.

Circulating MiRNAs of 'Asian Indian Phenotype' Identified in Subjects with Impaired Glucose Tolerance and Patients with Type 2 Diabetes.

Several omics technologies are underway worldwide with an aim to unravel the pathophysiology of a complex phenotype such as type 2 diabetes mellitus (T2DM). While recent studies imply a clinically relevant and potential biomarker role of circulatory miRNAs in the etiology of T2DM, there is lack of data on this aspect in Indians--an ethnic population characterized to represent 'Asian Indian phenotype' known to be more prone to develop T2DM and cardiovascular disease than Europeans. We performed global serum miRNA profiling and the validation of candidate miRNAs by qRT-PCR in a cohort of subjects comprised of normal glucose tolerance (NGT), impaired glucose tolerance (IGT) and patients with T2DM. Our study revealed 4 differentially expressed miRNAs (miR-128, miR-130b-3p, miR-374a-5p, miR-423-5p) in subjects with IGT and T2DM patients compared to control subjects. They were positively or negatively correlated to cholesterol levels, HbA1C, HOMA-IR and fasting insulin. Interestingly, circulating level of miR-128 and miR-130b-3p were also altered in serum of diet-induced diabetic mice compared to control animals. Among the altered circulating miRNAs, miR-128 had never been described in previous studies/populations and appeared to be a 'New Lead' in Indians. It was positively correlated with cholesterol both in prediabetic subjects and in diet-induced diabetic mice, suggesting that its increased level might be associated with the development of dyslipedemia associated with T2DM. Our findings imply directionality towards biomarker potential of miRNAs in the prevention/diagnosis/treatment outcomes of diabetes.

Regularity of follow-up, glycemic burden, and risk of microvascular complications in patients with type 2 diabetes: a 9-year follow-up study.

AIMS: To assess the relationship between regularity of follow-up and risk of complications in patients with type 2 diabetes (T2DM) followed up for 9 years at a tertiary diabetes center in India. METHODS: We compared glycemic burden [cumulative time spent above a HbA1c of 53 mmol/mol (7 %)] and incidence of diabetes complications (retinopathy, neuropathy, nephropathy, peripheral arterial disease, coronary heart disease) between 1,783 T2DM patients with "regular follow-up" (minimum of three visits and two HbA1c tests every year from 2003 to 2012), and 1,798 patients with "irregular follow-up" (two visits or less and one HbA1c or less per year during the same time period), retrospectively identified from medical records. Cox proportional hazards models were used to estimate risk associated with diabetes complications. RESULTS: Compared to those with regular follow-up, the irregular follow-up group had significantly higher mean fasting and postprandial plasma glucose, HbA1c, glycemic burden, total and LDL cholesterol, and triglycerides at every time point during the 9 years of follow-up. Those with irregular follow-up had double the total and mean monthly glycemic burden and 1.98 times higher risk of retinopathy (95 % CI 1.62, 2.42) and 2.11 times higher risk of nephropathy (95 % CI 1.73, 2.58) compared to those with regular follow-up, even after adjusting for time-varying confounding variables. Complications tended to develop significantly earlier and were more severe in those with irregular follow-up. CONCLUSION: Among patients with type 2 diabetes, regular follow-up was associated with significantly lower glycemic burden and lower incidence of retinopathy and nephropathy over a 9-year period.

Association of neutrophil-lymphocyte ratio with glucose intolerance: an indicator of systemic inflammation in patients with type 2 diabetes.

BACKGROUND: The neutrophil-lymphocyte ratio (NLR) has been demonstrated to be a better risk factor than total white blood cell count in the prediction of adverse outcomes in various medical conditions. This study analyzed the association of NLR with different grades of glucose tolerance and insulin resistance in Asian Indians. SUBJECTS AND METHODS: Study subjects were recruited from Phase 3 of the Chennai Urban Rural Epidemiology Study (CURES). For this cross-sectional analysis, subjects with normal glucose tolerance (NGT) (n=237), impaired glucose tolerance (IGT) (n=63), and type 2 diabetes mellitus (DM) (n=286) were selected. The hemogram was done in all subjects using a five-part hematology analyzer (model SF-3000; Sysmex, Kobe, Japan). The NLR was calculated as the ratio between counts for neutrophils and total lymphocytes. Fasting insulin was measured by enzyme-linked immunosorbent assay, and insulin resistance was calculated using the homeostasis model assessment (HOMA-IR). RESULTS: Subjects with DM showed a significantly higher NLR (2.2 ± 1.12) compared with IGT subjects (1.82 ± 0.63), who in turn had a higher ratio than NGT subjects (1.5 ± 0.41) (P<0.01). Pearson correlation analysis showed a significant positive correlation of NLR with glycated hemoglobin (r=0.411), fasting plasma glucose (r=0.378), and HOMA-IR (r=0.233) (P<0.001). Regression analysis showed a linear increase in NLR with increasing severity of glucose intolerance even after adjusting for age, waist circumference, blood pressure, triglycerides, and smoking. CONCLUSIONS: This is the first report on the correlation of NLR with different grades of glucose intolerance and insulin resistance. NLR can be used as an adjuvant prognostic marker for macro- and microvascular complications in patients with glucose intolerance.