Burden of Type 2 Diabetes and Associated Cardiometabolic Traits and Their Heritability Estimates in Endogamous Ethnic Groups of India: Findings From the INDIGENIUS Consortium.

To assess the burden of type 2 diabetes (T2D) and its genetic profile in endogamous populations of India given the paucity of data, we aimed to determine the prevalence of T2D and estimate its heritability using family-based cohorts from three distinct Endogamous Ethnic Groups (EEGs) representing Northern (Rajasthan [Agarwals: AG]) and Southern (Tamil Nadu [Chettiars: CH] and Andhra Pradesh [Reddys: RE]) states of India. For comparison, family-based data collected previously from another North Indian Punjabi Sikh (SI) EEG was used. In addition, we examined various T2D-related cardiometabolic traits and determined their heritabilities. These studies were conducted as part of the Indian Diabetes Genetic Studies in collaboration with US (INDIGENIUS) Consortium. The pedigree, demographic, phenotypic, covariate data and samples were collected from the CH, AG, and RE EEGs. The status of T2D was defined by ADA guidelines (fasting glucose ≥ 126 mg/dl or HbA1c ≥ 6.5% and/or use of diabetes medication/history). The prevalence of T2D in CH (N = 517, families = 21, mean age = 47y, mean BMI = 27), AG (N = 530, Families = 25, mean age = 43y, mean BMI = 27), and RE (N = 500, Families = 22, mean age = 46y, mean BMI = 27) was found to be 33%, 37%, and 36%, respectively, Also, the study participants from these EEGs were found to be at increased cardiometabolic risk (e.g., obesity and prediabetes). Similar characteristics for the SI EEG (N = 1,260, Families = 324, Age = 51y, BMI = 27, T2D = 75%) were obtained previously. We used the variance components approach to carry out genetic analyses after adjusting for covariate effects. The heritability (h2) estimates of T2D in the CH, RE, SI, and AG were found to be 30%, 46%, 54%, and 82% respectively, and statistically significant (P ≤ 0.05). Other T2D related traits (e.g., BMI, lipids, blood pressure) in AG, CH, and RE EEGs exhibited strong additive genetic influences (h2 range: 17% [triglycerides/AG and hs-CRP/RE] - 86% [glucose/non-T2D/AG]). Our findings highlight the high burden of T2D in Indian EEGs with significant and differential additive genetic influences on T2D and related traits.

Autoimmune hypothyroidism presenting as pituitary hyperplasia.

Pituitary hyperplasia with hyperprolactinemia has been described as a rare presentation of primary hypothyroidism. A 12-y-old child presented with intermittent headache, easy fatigability, coarseness of facial features, and hoarseness of voice for 6 mo duration. Brain imaging findings showed pituitary hyperplasia; hormonal assessment revealed primary hypothyroidism and hyperprolactinemia. Pituitary hyperplasia regressed with thyroid hormone replacement therapy. This report describes an unusual case of pituitary hyperplasia with hyperprolactinemia secondary to primary hypothyroidism.

A study on metabolic variables and its association with high sensitive C-reactive protein in obese children and adolescents.

Obesity in children and adolescents predispose to the development of obesity in adulthood and subsequent cardiovascular disease. High-sensitivity C-reactive protein (hsCRP) is a marker of low grade inflammatory state, which characterizes an atherosclerotic process. The aim of this study was to assess the metabolic abnormalities and its association with hsCRP in obese children and adolescents. A total of 62 obese children and adolescents and 24 healthy children and adolescents with a normal weight were recruited. In all subjects, anthropometric and biochemical parameters were measured. Body mass index (BMI) and blood pressure were significantly higher in the obese children and adolescents than the control. Obese children had significantly higher hsCRP levels (P < 0.001), total cholesterol, triglyceride, low-density lipoprotein-cholesterol (LDL-C) and lower high-density lipoprotein-cholesterol than the control group. Furthermore, homeostatic model assessment-insulin resistance (HOMA-IR) was significantly higher in obese children compared with the normal weight children. Furthermore, hsCRP showed a positive correlation with BMI (r = 0.357; P = 0.028), total cholesterol (r = 0.367; P = 0.008) and LDL-C (r = 0.356; P = 0.01), insulin (r = 0.311; P = 0.026) and not with HOMA-IR (r = 0.244; P = 0.084)). In conclusion, obese children and adolescents have significantly increased hsCRP compared with a normal weight group. Early intervention and prevention of obesity in children and adolescents decreases cardiovascular disease in later life.