Identification of molecular markers associated with development and clinical outcome of gestational diabetes mellitus in West Bengal India

Abstract

Gestational diabetes mellitus (GDM) is considered as health hazard with respect to short and long term adverse effect on maternal and neonatal health. On the background of fragmented knowledge, present study aimed to analyze prevalence, population specific risk factor, pathogenesis and adverse disease outcome of GDM on case control basis in a Kolkata based population of West Bengal, India. newline newlinePrevalence of GDM in Kolkata was 17.2%. Older maternal age, presence of acanthosis nigricans and diabetic family history was found as major risk factors. Association of oxidative stress and related inflammation with GDM indicated incidence of insulin resistance in disease pathogenesis. Genetic predisposition seemed to play major role in development of GDM of our studied population; this was evident from significant association of genetic variants of type-2 diabetes from insulin synthesis/ processing (rs7903146, rs4132670 and rs12255372 of TCF7L2 and rs2269023 of PCSK2) and secretion pathways (rs5219 of KCNJ11, rs757110 of ABCC8, rs10830963 of MTNR1B) with disease condition. As disease specific adverse neonatal outcome, macrosomia (newborn with excess birth weight) and neonatal hypoglycaemia (abnormally low blood glucose level of newborn) were highlighted in studied population. In GDM pregnancy, phenomenon of intrauterine hypoxia was evident from higher incidence of placental histological anomalies like villous edema, increased syncytial knots, chorangiosis, and thickening of basement membrane than normal one. Over-expression of GLUT1 and GLUT3 in GDM placenta was found than normal one, indicating enhanced glucose transport to fetus and was predicted as consequence of hypoxic condition. In logistic regression, villous edema, chorangiosis and placental GLUT1 were established as independent predictors for both macrosomia and neonatal hypoglycaemia and increased syncytial knots for neonatal hypoglycaemia; this indicated importance of intrauterine hypoxia and enhanced fetal glucose transport in pathogenesis of GDM associated neona