Does a common mitochondrial DNA polymorphism underlie susceptibility to diabetes and the thrifty genotype?

Abstract

One of the most puzzling features of the commonest form of diabetes (Type 2 or non-insulin dependent diabetes) is the large differences in the prevalence of the disease in different countries and even different parts of the same country. Rates tend to be lower in populations that have retained a traditional lifestyle, for example in rural Africa, where the disease occurs in 1–2% of adults. The prevalence in European and white North American adults is typically around 5% (Ref. [1]). However, in populations exposed to rapid Westernization, for example, Asian immigrants to the UK, the prevalence is much higher than in Europeans. This trend is most marked in New World and Pacific communities, where the disease has become epidemic. In the Micronesian island of Nauru, for example, Type 2 diabetes has increased to a level above 30% in adults aged 30–64 years[1], since the end of the Second World War. Although the high level of Type 2 diabetes in these people is linked to increased obesity, change in diet and adoption of a sedentary lifestyle (caused in Nauru by the sudden affluence brought about by exploitation of mining resources), these factors cannot explain the high disease incidence. To explain the dramatic increase in Type 2 diabetes in these populations, the geneticist James Neel advanced the `thrifty genotype' hypothesis. He suggested that the genotype conferring susceptibility to Type 2 diabetes arose in human evolutionary history as a selective advantage in periods of uncertain food supply. Thus, people with the thrifty genotype could store fat better than others under adverse food conditions and were more likely to survive prolonged episodes of caloric deprivation such as the long voyages involved in the settlement of the Pacific islands[2]. With the change in diet and lifestyle associated with Westernization and an increased standard of living, however, the gene or genes conferring an advantage to their owners during periods of starvation have become disadvantageous, leading to an increased risk of diabetes.