Effect of Metabolic Risk Factors, Gene Polymorphisms and Family History Among T2DM Population in Asian Indians

Abstract

Women with a family history of diabetes (FHD) are at significantly increased risk of developing gestational diabetes mellitus, which is itself an important risk factor of childhood obesity and type 2 diabetes mellitus (T2DM) in early age. Elevated C-reactive protein (CRP) is a marker of low-grade systemic inflammation and involved in the etiology of diabetes. Insulin receptor substrate (IRS) molecules are key mediators in insulin signaling and development of diabetes. The present study was conducted on 100 healthy (non-diabetic, normotensive) adult Asian Indian women, including 50 with and 50 without FHD, living in and around Kolkata, India. During the gestation period they were studied twice, and followed up till delivery. During delivery both mothers’ venous blood and cord blood were collected to estimate serum CRP, glucose, and lipid profiles of the respective mothers and their newborns. Genotyping of IRS-1, IRS-2 and CRP polymorphisms was done from these blood samples. A comparison of the metabolic variables among the subjects with and without FHD revealed significant differences among them. We also found close association of several polymorphisms in case of all three genes for both mothers and their newborn babies. More specifically, genotyping results for mothers with FHD and their newborn babies show susceptibility to T2DM: (i) for IRS-1 via diseased A allele (57%) which is carried over to the newborn babies (43%), (ii) for IRS-2 via diseased D allele (80%) which is carried over to the newborn babies (65%), and (iii) for CRP via diseased G allele (70%) which is also carried over to the newborn babies (72%). This study leads to the conclusion that Asian Indian population are ethnically and genetically predisposed to the risk factors of diabetes, which is reflected in their gestational phase and it has a significant implication on their birth outcomes.