Sex Hormones, Insulin Sensitivity, and Diabetes Mellitus

Abstract

Sex differences and the role of gonadal hormones in modulating insulin sensitivity and glucose tolerance are of increasing interest and importance because of the increasing prevalence of type 2 diabetes mellitus and the metabolic abnormalities associated with aging. Body composition is closely associated with insulin sensitivity, and increased body fat, particularly in the visceral compartment, is a risk factor for developing type 2 diabetes mellitus. Sex differences in body composition and/or insulin sensitivity are evident in humans throughout the lifespan. Ovarian hormones influence insulin sensitivity across the menstrual cycle, during pregnancy, and in the menopausal transition. Similarly, estrogens and progestins used for contraception and hormone replacement therapy affect glucoregulation. Nonhuman primates and humans have similar life histories and reproductive characteristics. As a result, nonhuman primates provide a valuable model for investigating factors related to insulin sensitivity. Studies of nonhuman primates have contributed significantly to our understanding of sex differences and the influence of sex steroids in this context. This brief review surveys present knowledge of the sex differences in body composition, insulin sensitivity, and risk for development of type 2 diabetes mellitus derived from studies in humans and nonhuman primates. The influences of endogenous and exogenous gonadal steroids are emphasized.

Nonhuman Primates and other Animal Models in Diabetes Research

“…111 This is important when assessing insulin action, because women have decreased insulin sensitivity during the luteal phase and improved sensitivity during the follicular phase of the normal menstrual cycle, 112 and similar findings have been reported in rhesus monkeys. 106 Natural menopause has also been reported in cynomolgus and rhesus macaques, chimpanzees, and baboons, 78,[113][114][115][116] and as in nondiabetic women, 117 and ovariectomized NHPs. 118,119 In general, an increase in body weight and a redistribution of body fat occurs postmenopausally, 120 which may contribute to increased IR.…”

Can Lifestyle Factors of Diabetes Mellitus Patients Affect Their Fertility?

“…The increase in DM2 is closely associated with the epidemic of obesity in industrialized countries (Bruns and Kemnitz, 2004). Reduced physical activity is a contributing factor as sedentary lifestyles become more common.…”

“…Elucidation of such risk factors will lead to interventions that can delay the onset or protect against the development of DM2 (Bruns and Kemnitz, 2004). Diabetes mellitus, whether due to lack of insulin secretion or resistance to insulin action, has adverse effects on all organ systems.…”

Sex Differences in Obesity-Related Glucose Intolerance and Insulin Resistance

“…In addition, sex hormones are directly involved in the regulation of glucose tolerance (20,21). In a prospective study that included over 500 women and men who did not have diabetes upon study entry, development of diabetes was associated with low levels of total testosterone in men and high levels of bioavailable testosterone in women (22).…”