Gestational Diabetes Mellitus in North India. Prevalence, Diagnostic Criteria, Pathophysiological Aspects and Genetic and Non-Genetic Origin in the State of Punjab.

Gestational diabetes mellitus(GDM) defines an unhealthy state of hyperglycaemia that develops in response to an otherwise normal physiological adaptive insulin resistance state during pregnancy. However, the exact plasma glucose levels differentiating the unhealthy GDM state from a normal pregnancy is unknown, and relies upon arbitrary cut off criteria based on associations with adverse health outcomes in mother and child. The normal hormonal and physiological changes during pregnancy and difficulties in assessing long term health outcomes associated with GDM in mother and child is a further complicating factor. Ethnic differences plays a major role in defining GDM with Asian people developing diabetes including GDM at a lower degree of overweight comparedwith non-Asian people. Epidemiological data points towards Asia as the present and future hub of diabetes. The thesis is based upon results obtained from the first state-of-the art epidemiological screening of 5000 women forGDM in Punjab, North India, using former WHO1999 compared with adapted WHO2013 criteria.The work documents that the proposed WHO2013 criteria increases the prevalence of GDM in North India from 9% using former criteria to include no less than 35% of all pregnant women. It documents a key role of impaired insulin secretion as opposed to peripheral insulin resistance in the pathyphysiology of GDM, and it shows that a myriad of risk factors including family history of diabetes, age, BMI, diet, religion, illeteracy and urban versus rural habitat influences risk of GDM, as well as impaired insulin secretion and action, in a hitherto unrecognized complex manner.Importantly, genetic analyses of 79 SNPs previously associated with type 2 diabetes (including 12 GDM loci), in Indian and non-Indian populations suggests that genetic as well as non-genetic origin of GDM in North India differ from other ethnic populations. Only few of the previously reported diabetes risk genes were associated with risk of GDM, some showed nominal significance and some associations in opposite directions, being protective against GDM in North India. The results underscores the need for large prospective studies of GDM women and their offspring in different ethnic groups to understand the quantitative and qualitative adverse health outcomes,diagnostic criteria as well as the need, tools and targets for prevention and treatment in a life-cycle perspective