Exposure to Environmental Chemicals as a Risk Factor for Diabetes Development

Abstract

The increasing prevalence of type 2 diabetes mellitus has been linked primarily to obesity and lack of exercise, but certain environmental chemicals can induce both insulin resistance and disruption of insulin secretion in experimental models. Epidemiologic studies support a role for environmental chemical exposure in the development of type 2 diabetes. However, epidemiological studies cannot settle the question of causative substances, as environmental exposures include complex mixtures of persistent halogenated compounds, which are mutually correlated. In vitro studies suggest differences in toxic profiles: for example, dioxin is toxic to beta cells, but has only weak effects on insulin resistance. A conundrum in the pathogenesis is the direction of changes in fasting insulin concentrations at increased exposures. An increase in fasting insulin would suggest a physiological response to insulin resistance, whereas a decrease could be a consequence of beta cell toxicity. In populations of exposed adults, dioxin exposure has shown a positive correlation with fasting insulin. As diabetes is particularly common in the elderly, who may have accumulated large body burdens of persistent environmental chemicals, we examined this issue in elderly Faroese with high pollutant exposures from traditional diets of pilot whale blubber. In 713 subjects aged 70–74 years (64% of eligible population), we estimated lifetime exposure levels from the past frequencies of dinners with pilot whale and other traditional food and by analysis of serum for polychlorinated biphenyls (PCBs) and related substances. Septuagenarians with type 2 diabetes or impaired fasting glycaemia tended to have higher PCB concentrations and higher past intakes of traditional food, especially during childhood and adolescence. In non-diabetic subjects, the fasting insulin concentration decreased by 7% (95% CI: −12, −2.1) for each doubling of the PCB concentration after adjustment for sex and body mass index. Conversely, an increase of the same magnitude was seen in the fasting glucose concentration. Impaired insulin secretion may therefore constitute an important part of the type 2 diabetes pathogenesis associated with exposure to persistent lipophilic food contaminants. Intensified abatement of exposure to relevant endocrine disruptors should be considered an attractive means of complementing preventive efforts against type 2 diabetes.