Bottlenecks in Evolution, Bottlenecks in Type 2 Diabetes

We are in the midst of an unprecedented epidemic of obesity, which is accompanied by a type 2 diabetes epidemic. Whereas >80% of people with type 2 diabetes are obese, ~80% of obese people do not develop diabetes. My laboratory studies this dichotomy by searching for genes that confer susceptibility to type 2 diabetes. This involves genetic screens in obese mice segregating for diabetes susceptibility alleles as well as genomic studies to identify coordinately regulated genes responsible for the pathogenesis of diabetes.

Throughout most of human history, famine, injury, and infection were the major causes of death. Some populations experienced exceptionally harsh conditions and thus might have been under strong selection for allelic variants conferring resistance to famine. The thrifty gene hypothesis states that these variants, in the context of overnutrition, may conspire to increase the susceptibility to type 2 diabetes.

In type 2 diabetes, there is an increased demand for insulin — usually due to obesity-induced insulin resistance — that confronts a limited ability of beta-cells to secrete insulin. Many potential pathways can play a role in setting this limit. These pathways have an evolutionary history that goes back to single-celled organisms.