Young-onset diabetes in Asian Indians is associated with lower measured and genetically determined beta cell function.

AIMS/HYPOTHESIS: South Asians in general, and Asian Indians in particular, have higher risk of type 2 diabetes compared with white Europeans, and a younger age of onset. The reasons for the younger age of onset in relation to obesity, beta cell function and insulin sensitivity are under-explored. METHODS: Two cohorts of Asian Indians, the ICMR-INDIAB cohort (Indian Council of Medical Research-India Diabetes Study) and the DMDSC cohort (Dr Mohan's Diabetes Specialties Centre), and one of white Europeans, the ESDC (East Scotland Diabetes Cohort), were used. Using a cross-sectional design, we examined the comparative prevalence of healthy, overweight and obese participants with young-onset diabetes, classified according to their BMI. We explored the role of clinically measured beta cell function in diabetes onset in Asian Indians. Finally, the comparative distribution of a partitioned polygenic score (pPS) for risk of diabetes due to poor beta cell function was examined. Replication of the genetic findings was sought using data from the UK Biobank. RESULTS: The prevalence of young-onset diabetes with normal BMI was 9.3% amongst white Europeans and 24-39% amongst Asian Indians. In Asian Indians with young-onset diabetes, after adjustment for family history of type 2 diabetes, sex, insulin sensitivity and HDL-cholesterol, stimulated C-peptide was 492 pmol/ml (IQR 353-616, p<0.0001) lower in lean compared with obese individuals. Asian Indians in our study, and South Asians from the UK Biobank, had a higher number of risk alleles than white Europeans. After weighting the pPS for beta cell function, Asian Indians have lower genetically determined beta cell function than white Europeans (p<0.0001). The pPS was associated with age of diagnosis in Asian Indians but not in white Europeans. The pPS explained 2% of the variation in clinically measured beta cell function, and 1.2%, 0.97%, and 0.36% of variance in age of diabetes amongst Asian Indians with normal BMI, or classified as overweight and obese BMI, respectively. CONCLUSIONS/INTERPRETATION: The prevalence of lean BMI in young-onset diabetes is over two times higher in Asian Indians compared with white Europeans. This phenotype of lean, young-onset diabetes appears driven in part by lower beta cell function. We demonstrate that Asian Indians with diabetes also have lower genetically determined beta cell function.

Development and validation of resource-driven risk prediction models for incident chronic kidney disease in type 2 diabetes.

Prediction models for population-based screening need, for global usage, to be resource-driven, involving predictors that are affordably resourced. Here, we report the development and validation of three resource-driven risk models to identify people with type 2 diabetes (T2DM) at risk of stage 3 CKD defined by a decline in estimated glomerular filtration rate (eGFR) to below 60 mL/min/1.73m2. The observational study cohort used for model development consisted of data from a primary care dataset of 20,510 multi-ethnic individuals with T2DM from London, UK (2007-2018). Discrimination and calibration of the resulting prediction models developed using cox regression were assessed using the c-statistic and calibration slope, respectively. Models were internally validated using tenfold cross-validation and externally validated on 13,346 primary care individuals from Wales, UK. The simplest model was simplified into a risk score to enable implementation in community-based medicine. The derived full model included demographic, laboratory parameters, medication-use, cardiovascular disease history (CVD) and sight threatening retinopathy status (STDR). Two less resource-intense models were developed by excluding CVD and STDR in the second model and HbA1c and HDL in the third model. All three 5-year risk models had good internal discrimination and calibration (optimism adjusted C-statistics were each 0.85 and calibration slopes 0.999-1.002). In Wales, models achieved excellent discrimination(c-statistics ranged 0.82-0.83). Calibration slopes at 5-years suggested models over-predicted risks, however were successfully updated to accommodate reduced incidence of stage 3 CKD in Wales, which improved their alignment with the observed rates in Wales (E/O ratios near to 1). The risk score demonstrated similar model performance compared to direct evaluation of the cox model. These resource-driven risk prediction models may enable universal screening for Stage 3 CKD to enable targeted early optimisation of risk factors for CKD.

Clinical Profile of Elderly Patients (Over 90 Years) with Type 2 Diabetes Seen at a Diabetes Center in South India.

Background: The current life expectancy in India is <70 years. Type 2 diabetes mellitus (T2DM) is known to reduce life expectancy by 6-8 years. Hence elderly people with T2DM in India would be rare. We report on the clinical profile of Asian Indian patients with T2DM who lived beyond 90 years of age and compared them with T2DM patients aged 50 to 60 years. Methods: From the diabetes electronic medical records of >470,000 diabetes patients, we identified T2DM patients who had lived ≥90 years and compared them with those in the 50-60 years age group, matched for gender and duration of diabetes. Clinical data included age at last visit, age at diagnosis, duration of diabetes, family history, smoking and alcohol, details of medications, body mass index (BMI), and blood pressure. Biochemical data included fasting and postprandial plasma glucose, glycated hemoglobin, fasting and stimulated C-peptide levels, lipid profile, and renal function studies. Assessment of retinopathy, nephropathy, neuropathy, coronary artery disease (CAD), and peripheral vascular disease (PVD) was also done. Results: A total of 325 T2DM patients aged ≥90 years and 278 T2DM patients aged between 50 and 60 years were selected for the study. Patients aged ≥90 years had higher systolic blood pressure (P < 0.001) and lower BMI (P < 0.001) than those between 50 and 60 years. Prevalence of retinopathy (29.7% vs. 53.5%) and macroalbuminuria (3.7% vs. 16.0%) was lower in the ≥90 years T2DM patients than in the 50-60 years age group. However, prevalence of neuropathy (89.8% vs. 50.8%), PVD (13.5% vs. 2.0%), and CAD (60.3% vs. 32.0%) was higher among the ≥90 years patients. Eighty-five percent of the T2DM aged ≥90 years were on oral hypoglycemic agents (OHAs), (of whom 64.9% were on sulfonylurea), 12% were on insulin, and 3% on diet alone. Among the 50-60 years old, 87.8% were on OHAs and 12.2% on insulin. Conclusions: This is the first report on the clinical profile of Asian Indians with T2DM aged ≥90 years, and significant differences are seen in their clinical profile compared with younger T2DM patients.