Twenty years ago, Hales and Barker along with their co-workers published some of their pioneering papers proposing the ‘thrifty phenotype hypothesis’ in Diabetologia (4;35:595–601 and 3;36:62–67). Their postulate that fetal programming could represent an important player in the origin of type 2 diabetes, the metabolic syndrome and cardiovascular disease (CVD) was met with great scepticism.More recently, their observations have been confirmed and expanded in many epidemiological and animal experimental studies, and human integrative physiological studies have provided insights into some of the underlying molecular mechanisms. Type 2 diabetes is a multiple-organ disease, and developmental programming, with its idea of organ plasticity, is a plausible hypothesis for a common basis for the widespread organ dysfunctions in type 2 diabetes and the metabolic syndrome. Only two among the 45 known type 2 diabetes susceptibility genes are associated with low birthweight, indicating that the association between low birthweight and type 2 diabetes is mainly non-genetic. Prevention programmes targeting adult lifestyle factors seems unable to stop the global propagation of type 2 diabetes, and intensive glucose control is inadequate to reduce the excess CVD mortality in type 2 diabetic patients. Today, the thrifty phenotype hypothesis has been established as a promising conceptual framework for a more sustainable intergenerational prevention of type 2 diabetes.

Objective: The World Health Organization (WHO) has in 2013 changed the diagnostic criteria for gestational diabetes mellitus (GDM) to acknowledge the putative effect of mildly elevated fasting plasma glucose (FPG) levels on pregnancy outcomes. We aimed to determine the prevalence and risk factors of GDM comparing the previous WHO 1999 criteria to the WHO 2013 criteria in North India. Methods: In a population-based screening programme, 5100 randomly selected North Indian women were studied using a cross-sectional design with a questionnaire, venous FPG and 2-h capillary plasma glucose (PG) after a 75 g oral glucose tolerance test performed between 24 and 28 weeks of pregnancy. Results: The prevalence of GDM was 35% using WHO 2013 criteria vs 9% using WHO 1999 criteria. FPG measurements identified 94% of WHO 2013 GDM cases as opposed to 11% of WHO 1999 GDM cases. In contrast, 2-h PG measurements identified only 13% of WHO 2013 GDM cases compared with 96% of the WHO 1999 GDM cases. Using logistic regression with backward elimination, urban habitat, illiteracy, non-vegetarianism, increased BMI, Hindu religion and low adult height were all independent risk factors of GDM using the 1999 criteria, whereas only urban habitat, low adult height and increased age were independent risk factors of GDM using the 2013 criteria. Conclusions: Intervention studies are needed to justify the WHO 2013 GDM criteria increasing the prevalence four fold to include more than one third of North Indian pregnant women.

Low birthweight (LBW) individuals and offspring of women with gestational diabetes mellitus (GDM) exhibit increased risk of developing type 2 diabetes (T2D) and associated cardiometabolic traits in adulthood, which for both groups may be mediated by adverse events and developmental changes in fetal life. T2D is a multifactorial disease occurring as a result of complicated interplay between genetic and both prenatal and postnatal nongenetic factors, and it remains unknown to what extent the increased risk of T2D associated with LBW or GDM in the mother may be due to, or confounded by, genetic factors. Indeed, it has been shown that genetic changes influencing risk of diabetes may also be associated with reduced fetal growth as a result of reduced insulin secretion and/or action. Similarly, increased risk of T2D among offspring could be explained by T2D susceptibility genes shared between the mother and her offspring. Epigenetic mechanisms may explain the link between factors operating in fetal life and later risk of developing T2D, but so far convincing evidence is lacking for epigenetic changes as a prime and direct cause of T2D. This review addresses recent literature on the early origins of adult disease hypothesis, with a special emphasis on the role of genetic compared with nongenetic and epigenetic risk determinants and disease mechanisms.