title: The sweet thing about Type 1 diabetes: a cryoprotective evolutionary adaptation.
abstract: The reasons for the uneven worldwide distribution of Type 1 diabetes mellitus have yet to be fully explained. Epidemiological studies have shown a higher prevalence of Type 1 diabetes in northern Europe, particularly in Scandinavian countries, and Sardinia. Recent animal research has uncovered the importance of the generation of elevated levels of glucose, glycerol and other sugar derivatives as a physiological means for cold adaptation. High concentrations of these substances depress the freezing point of body fluids and prevent the formation of ice crystals in cells through supercooling, thus acting as a cryoprotectant or antifreeze for vital organs as well as in their muscle tissue. In this paper, we hypothesize that factors predisposing to elevated levels of glucose, glycerol and other sugar derivatives may have been selected for, in part, as adaptive measures in exceedingly cold climates. This cryoprotective adaptation would have protected ancestral northern Europeans from the effects of suddenly increasingly colder climates, such as those believed to have arisen around 14,000 years ago and culminating in the Younger Dryas. When life expectancy was short, factors predisposing to Type 1 diabetes provided a survival advantage. However, deleterious consequences of this condition have become significant only in more modern times, as life expectancy has increased, thus outweighing their protective value. Examples of evolutionary adaptations conferring selection advantages against human pathogens that result in deleterious effects have been previously reported as epidemic pathogenic selection (EPS). Such proposed examples include the cystic fibrosis mutations in the CFTR gene bestowing resistance to Salmonella typhi and hemochromatosis mutations conferring protection against iron-seeking intracellular pathogens. This paper is one of the first accounts of a metabolic disorder providing a selection advantage not against a pathogenic stressor alone, but rather against a climatic change. We thus believe that the concept of EPS should now include environmental factors that may be nonorganismal in nature. In so doing we propose that factors resulting in Type 1 diabetes be considered a result of environmental pathogenic selection (EnPS).
authors.affiliation: Department of Pathology, Mount Sinai School of Medicine, Box 1134, New York, NY 10029, USA. sharon.moalem@mssm.edu
authors.forename: S
authors.initials: S
authors.lastname: Moalem
authors.forename: K B
authors.initials: KB
authors.lastname: Storey
authors.forename: M E
authors.initials: ME
authors.lastname: Percy
authors.forename: M C
authors.initials: MC
authors.lastname: Peros
authors.forename: D P
authors.initials: DP
authors.lastname: Perl
mesh_terms: D000064:Acclimatization; D000818:Animals; D021301:Antifreeze Proteins / Q000378:metabolism*; D003081:Cold Climate; D003451:Cryoprotective Agents / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism*; D019143:Evolution, Molecular; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008954:Models, Biological; D015995:Prevalence; D012537:Scandinavian and Nordic Countries / Q000453:epidemiology; D012641:Selection, Genetic
chemical_list: D021301:Antifreeze Proteins; D003451:Cryoprotective Agents