Is Type 2 Diabetes the Result of a “Thrifty Genotype” or a “Thrifty Phenotype”?

Robert S. Lindsay

Robert S. Lindsay

MedStar Research Institute, Washington, DC, USA

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First published: 01 July 2003

Abstract

While a number of important risk factors for development of type 2 diabetes have been described—most notably overweight and obesity—much of the detail of the etiology of the disease remains unknown. Both genetic and environmental factors will be important and disease risk is likely to reflect a complex interaction of both. Certain aspects of the epidemiology of type 2 diabetes, the widespread predisposition to the disease, increased predisposition in certain ethnic groups, and more recently, well-described associations of diabetes risk and lower birth weight have prompted a number of hypotheses. These hypotheses attempt to explain these important epidemiological features of type 2 diabetes but also place our understanding of the etiology of type 2 diabetes in a wider context. A unifying theme of the thrifty genotype and thrifty phenotype hypotheses is the concept that predisposition to type 2 diabetes may reflect previous nutritional conditions. In the case of the thrifty genotype the nutritional history of populations favors genetic polymorphisms, which also render individuals diabetes prone. By contrast the thrifty phenotype proposes that adverse nutritional conditions in the early environment predispose to later disease in individuals. Both hypotheses are connected by a further underlying aim—to aid our understanding of the causes of type 2 diabetes and thus find ways to prevent, treat, and ultimately cure the disease.

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