Gestational Diabetes Mellitus in Asian Indian Population: Pathophysiology and Mechanism

Gestational diabetes mellitus (GDM), defined as glucose intolerance that is first recognized during pregnancy beyond 20 weeks of gestation, is rising globally. The prevalence varies widely across populations (1-25%), depending on the population studied. The abnormal glucose homeostasis during pregnancy, GDM is associated with short and long-term metabolic risks, both for the mother and the offspring. The pathophysiological basis of GDM is classically thought to stem from abnormal up-regulation of insulin production relative to the degree of increased insulin resistance intrinsic to pregnancy. Glucose regulation is a complex process involving interactions among multiple endocrine and neurobiological pathways. Studies in non-pregnant humans demonstrate that gliosis (a cellular inflammatory response) in the mediobasal hypothalamus (MBH) is associated with insulin resistance, independent of the level of adiposity. Recent data also suggests that baseline existence of MBH gliosis precedes the onset of glucose dysregulation 1 year later, suggesting that the in addition to the pancreas, brain changes may be a key driver in glucose metabolism. These data provide mechanistic insights into brain pathways which may increase risk for metabolic dysfunction leading to GDM.