The thrifty phenotype hypothesis revisited

Abstract

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.

Prevalence and risk factors of gestational diabetes in Punjab, North India: results from a population screening program

“…Indeed, low adult height was identified as an independent risk factor of GDM, even above and beyond the effect of illiteracy, using both the WHO 1999 as well as the WHO 2013 criteria (Table 4). Besides social class, adult height may be a marker of early pre-and post-natal nutrition and growth, and may to some extent support the role of the early environment and developmental programming on risk of developing GDM in India (29).…”

The prenatal environment and type 1 diabetes

“…'Perinatal' factors such as birth order and maternal age at delivery have long been investigated in studies of the aetiology of various postnatal traits such as intelligence [1], but the idea that chronic diseases that typically present in adult life, such as cancer and diabetes, might originate in utero is only slowly gaining acceptance [2,3]. Although the mechanisms remain poorly defined, an association between low birthweight and increased risk of type 2 diabetes is now fairly well established [2].…”

Maternal Protein Restriction Leads to Pancreatic Failure in Offspring: Role of Misexpressed MicroRNA-375

“…Indeed, several epidemiological studies of human populations highlighted a direct correlation between intrauterine growth retardation (IUGR) and the appearance of insulin resistance and T2D in adult life (1,2). Such observations have led to the concept of developmental origins of adult disease, which proposes that crucial programming of human disorders originates in early life (3,4).…”