The modern epidemic of obesity and insulin resistance with cardiovascular risk factor clustering is related to the development of type 2 diabetes and cardiovascular disease. Over 40 years ago, Neel postulated that insulin resistance should confer survival benefit. Extrapolating Neel's hypothesis, we propose that the cluster of associated abnormalities also confers survival benefit and is related to metabolic responses seen in seasonally responsive animals. Weight gain in preparation for winter is accompanied by a range of acute metabolic changes virtually identical to the long-term changes seen in type 2 diabetes. In seasonal animals the responses are acute, physiological and protective. In man, similar responses that would once have conferred survival benefit have become chronic, pathological and harmful in modern life. We hypothesise that type 2 diabetes and cardiovascular disease in man are the result of chronic and inappropriate pineal-hypothalamic-adipocyte interactions biologically related to seasonal change.
