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We postulate a critical role for the quantity and quality of dietary carbohydrate in the pathogenesis of non-insulin-dependent diabetes mellitus (NIDDM). Our primate ancestors ate a high-carbohydrate diet and the brain and reproductive tissues evolved a specific requirement for glucose as a source of fuel. But the Ice Ages which dominated the last two million years of human evolution brought a low-carbohydrate, high-protein diet. Certain metabolic adaptations were therefore necessary to accommodate the low glucose intake. Studies in both humans and experimental animals indicate that the adaptive (phenotypic) response to low-carbohydrate intake is insulin resistance. This provides the clue that insulin resistance is the mechanism for coping with a shortage of dietary glucose. We propose that the low-carbohydrate carnivorous diet would have disadvantaged reproduction in insulin-sensitive individuals and positively selected for individuals with insulin resistance. Natural selection would therefore result in a high proportion of people with genetically-determined insulin resistance. Other factors, such as geographic isolation, have contributed to further increases in the prevalence of the genotype in some population groups. Europeans may have a low incidence of diabetes because they were among the first to adopt agriculture and their diet has been high in carbohydrate for 10,000 years. The selection pressure for insulin resistance (i.e., a low-carbohydrate diet) was therefore relaxed much sooner in Caucasians than in other populations. Hence the prevalence of genes producing insulin resistance should be lower in the European population and any other group exposed to high-carbohydrate intake for a sufficiently long period of time.

The carnivore connection: dietary carbohydrate in the evolution of NIDDM