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OBJECTIVE: South Asians are diagnosed with type 2 diabetes (T2D) more than a decade earlier in life than seen in European populations. We hypothesized that studying the genomics of age of diagnosis in these populations may give insight into the earlier age diagnosis of T2D among individuals of South Asian descent. RESEARCH DESIGN AND METHODS: We conducted a meta-analysis of genome-wide association studies (GWAS) of age at diagnosis of T2D in 34,001 individuals from four independent cohorts of European and South Asian Indians. RESULTS: We identified two signals near the TCF7L2 and CDKAL1 genes associated with age at the onset of T2D. The strongest genome-wide significant variants at chromosome 10q25.3 in TCF7L2 (rs7903146; P = 2.4 × 10−12, β = −0.436; SE 0.02) and chromosome 6p22.3 in CDKAL1 (rs9368219; P = 2.29 × 10−8; β = −0.053; SE 0.01) were directionally consistent across ethnic groups and present at similar frequencies; however, both loci harbored additional independent signals that were only present in the South Indian cohorts. A genome-wide signal was also obtained at chromosome 10q26.12 in WDR11 (rs3011366; P = 3.255 × 10−8; β = 1.44; SE 0.25), specifically in the South Indian cohorts. Heritability estimates for the age at diagnosis were much stronger in South Indians than Europeans, and a polygenic risk score constructed based on South Indian GWAS explained ∼2% trait variance. CONCLUSIONS: Our findings provide a better understanding of ethnic differences in the age at diagnosis and indicate the potential importance of ethnic differences in the genetic architecture underpinning T2D. [ABSTRACT FROM AUTHOR]

Objective: Diabetes increases the risk of premature mortality and considerably impacts on work productivity. We sought to examine the impact of diabetes in India, in terms of excess premature mortality, years of life lost (YLL), productivity-adjusted life years (PALYs) lost, and its associated economic impact.Research Design and Methods: A life table model was constructed to examine the productivity of the Indian working-age population currently aged 20-59 years with diabetes, followed until death or retirement age (60 years). The same cohort was resimulated, hypothetically assuming that they did not have diabetes. The total difference between the two cohorts, in terms of excess deaths, YLL and PALYs lost reflected the impact of diabetes. Data regarding the prevalence of diabetes, mortality, labor force dropouts, and productivity loss attributable to diabetes were derived from published sources.Results: In 2017, an estimated 54.4 million (7.6%) people of working-age in India had diabetes. With simulated follow-up until death or retirement age, diabetes was predicted to cause 8.5 million excess deaths (62.7% of all deaths), 42.7 million YLL (7.4% of total estimated years of life lived), and 89.0 million PALYs lost (23.3% of total estimated PALYs), equating to an estimated Indian rupee 176.6 trillion (U.S. dollars 2.6 trillion; purchasing power parity 9.8 trillion) in lost gross domestic product.Conclusions: Our study demonstrates the impact of diabetes on productivity loss and highlights the importance of health strategies aimed at the prevention of diabetes. [ABSTRACT FROM AUTHOR]

OBJECTIVE There are few data on the incidence rates of diabetes and prediabetes (dysglycemia) in Asian Indians. This article presents the incidence of diabetes and prediabetes and the predictors of progression in a population-based Asian Indian cohort. RESEARCH DESIGN AND METHODS Data on progression to diabetes and prediabetes from 1,376 individuals, a subset of 2,207 of the Chennai Urban Rural Epidemiology Study (CURES) cohort (phase 3) with normal glucose tolerance (NGT) or prediabetes at baseline, who were followed for a median of 9.1 years (11,629 person-years), are presented. During follow-up, 534 died and 1,077 with NGT and 299 with prediabetes at baseline were reinvestigated in a 10-year follow-up study. Diabetes and prediabetes were diagnosed based on the American Diabetes Association criteria. Incidence rates were calculated and predictors of progression to prediabetes and/or diabetes were estimated using the Cox proportional hazards model. RESULTS The incidence rates of diabetes, prediabetes, and "any dysglycemia" were 22.2, 29.5, and 51.7 per 1,000 person-years, respectively. Among those with NGT, 19.4% converted to diabetes and 25.7% to prediabetes, giving an overall conversion rate to dysglycemia of 45.1%. Among those with prediabetes, 58.9% converted to diabetes. Predictors of progression to dysglycemia were advancing age, family history of diabetes, 2-h plasma glucose, glycated hemoglobin (HbA1c), low HDL cholesterol, and physical inactivity. CONCLUSIONS Asian Indians have one of the highest incidence rates of diabetes, with rapid conversion from normoglycemia to dysglycemia. Public health interventions should target modifiable risk factors to slow down the diabetes epidemic in this population. [ABSTRACT FROM AUTHOR]

OBJECTIVE Objectives of this ancillary analysis of a prospective, prevention study among Asian Indians with impaired glucose tolerance (IGT) were a) to quantify the reduction in incident diabetes at 24 months in participants who achieved normal glucose tolerance (NGT) at 6 months (NGT-6 m) compared with the other participants, b) the factors influencing the reversal to NGT at the end of the study at 24months (NGT-24 m), and c) to assess changes in cardiometabolic risk factors in different categories of dysglycemia at 24 months. RESEARCH DESIGN AND METHODS Data from a 2-year primary prevention trial were used. Effect of reversion to NGT-6 m on incidence of type 2 diabetes mellitus (T2DM) was analyzed using the Cox proportional hazards model. Predictive variables for reversal to NGT were identified using multiple logistic regression analysis. Changes in cardiometabolic risk factors were estimated according to the final glycemic status using fixed-effect, mixed-linear regression modeling. RESULTS The risk of T2DMin 2 years was lower by 75% in NGT-6 m group (hazard ratio 0.25 [95% CI 0.12-0.52]). Predictive variables for reversal to NGT-24 m were good baseline β-cell function (odds ratio [OR] 2.79 [95% CI 2.30-3.40]) and its further improvement (OR 5.70 [95% CI 4.58-7.08]), and NGT-6 m (OR 2.10 [95% CI 1.14-3.83]). BMI decreased in those who reverted to NGT. Deterioration to T2DM was associated with an increase in the levels of cardiometabolic risk factors. CONCLUSIONS Early reversion to NGT by lifestyle intervention in prediabetic men was associated with a significant reduction in subsequent incidence of diabetes. Good baseline β-cell function and its further improvement and NGT-6 m were associated with reversion to NGT-24 months. Reversion to NGT was associated with modest improvements, whereas conversion to T2DM was associated with significant worsening of the cardiometabolic risk profile. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to a study by R. M. Anjana and colleagues regarding predictors of diabetes and prediabetes progression among Asian Indians, which appeared within the issue.

A letter to the editor is presented in response to the article "Comment on Anjana et al. Incidence of diabetes and prediabetes and predictors of progression among Asian Indians:10-year follow-up of the Chennai Urban Rural Epidemiology Study (CURES)" by D. Dutta and S. Mukhopadhyay in a 2015 issue.

A letter to the editor is presented in response to the article "Incidence of diabetes and prediabetes and predictors of progression among Asian Indians: 10-year follow-up of the Chennai Urban Rural Epidemiology Study (CURES)" by Anjana R.M. and colleagues in a 2015 issue.