Twins in metabolic and diabetes research: what do they tell us?

The purpose of this review is to provide a critical update of the impact of the 'thrifty phenotype hypothesis' on metabolism, and its implications for heritability estimates as obtained in so-called classical twin studies.

Our recent studies demonstrated a complex age or time-dependent relationship between different and independent markers of an adverse intrauterine environment, including birth weight, twin and zygosity status on one side, and distinct defects of insulin secretion and glucose metabolism on the other side.

These novel findings may, to some unknown extent, influence and perhaps bias the heritability estimates of type 2 diabetes-related traits obtained using classical twin analyses. The studies add to the increasing evidence of the intrauterine environment as a - or the - key player in the cause and pathophysiology of type 2 diabetes and the metabolic syndrome. We and others have shown that monozygotic twins represent a powerful tool to demonstrate nongenetic associations between low birth weight and different phenotypes of the metabolic syndrome, including type 2 diabetes, insulin resistance and, recently, hypertension. Future studies of discordant monozygotic twins may provide novel and crucial mechanistic explanations of the link between low birth weight and the metabolic syndrome.