A life course approach to diabetes

Several factors that affect females across the life course are associated with risk for type 2 diabetes mellitus (T2DM), including genetics, parent-of-origin effects, the intrauterine environment, reproductive and pregnancy characteristics, and lifestyle and socioeconomic circumstances. Genome-wide association studies have identified many genetic variants involved in the pathogenesis of T2DM. The intrauterine environment, including maternal diabetes and adiposity, is an important risk factor for obesity and T2DM. Maternally expressed genes and matrilineal inheritance of mitochondrial DNA may play important roles in the excess maternal transmission of T2DM. Low birthweight, particularly when followed by accelerated postnatal growth, is associated with diabetes risk in adulthood. Puberty and pregnancy are other critical time points when increased insulin resistance may increase diabetes susceptibility. There appears to be a female predominance of youth-onset T2DM, which may reflect the role of sex steroids and/or socioenvironmental factors in the pathogenesis of T2DM. Gestational diabetes and/or multigravida increase T2DM risk, which may be due to gestational physiological changes and lifestyle behaviours. Reproductive factors, including age of menarche and menopause, as well as cycle length and regularity, are also implicated in T2DM risk. The relationship of socioeconomic status to diabetes risk varies between cultures, usually mirroring the prevailing socioeconomic patterns of obesity. A better understanding of the mechanisms involved in T2DM risk is needed to address the growing burden of T2DM, especially as T2DM is now increasingly affecting children. This chapter highlights important time points throughout a woman’s life course that may influence her risk of T2DM.