Type 2 diabetes and Healthy Obesity: Ancestral and Derived Phenotypes? (#254)
AimsTo propose firstly that Type 2 Diabetes and metabolically normal obesity can from an evolutionary perspective best be viewed as the phenotypic extremes of the wide variability in insulin metabolism seen in human populations. The second aim is to argue cogently that Type 2 Diabetes is , as James Neel suggested over 50 years ago, a manifestation of ancestral metabolic phenotype better adapted to the diet, energetic circumstances and mortality and fertility schedules of our hunter gatherer forebears. The third aim is to present evidence that high prevalence in some populations of metabolically normal obesity is a manifestation an adaptation to improvements in food security and standards of living. And lastly I will propose a mechanism by which recent and rapid evolution for this more insulin sensitive phenotype has occurred through the powerful mechanism of fertility selection and can account for much of the inter-ethnic variability seen in insulin response observed in human populations.
MethodsA review of the physiology of insulin metabolism and its impact on fertility, particularly in the context of seasonal and often severe food shortage.
An examination of the dynamics of indices of fertility and viability selection in populations undergoing nutritional and demographic transition over the last 250 years.
Reviewing the magnitude and distribution of the variability in the prevalence of Type 2 Diabetes in the light of these hypotheses.
ResultsThese analyses suggest that strong fertility selection for a more insulin sensitive phenotype is likely to have been greatly accelerated by the tectonic changes in demography and nutrition which accompanied the Industrial Revolution.
ConclusionThis evolutionary analysis suggests a shift in average levels of insulin resistance in modernising populations, a shift which may happen within decades rather than centuries, and a shift which may significantly reduce the future risks of Type 2 Diabetes.