Neuroendocrine perturbations as a cause of insulin resistance

The fetal origins hypothesis states that fetal undernutrition in middle to late gestation, which leads to disproportionate fetal growth, programmes later coronary heart disease. Animal studies have shown that undernutrition before birth programmes persisting changes in a range of metabolic, physiological, and structural parameters. Studies in humans have shown that men and women whose birth weights were at the lower end of the normal range, who were thin or short at birth, or who were small in relation to placental size have increased rates of coronary heart disease. We are beginning to understand something of the mechanisms underlying these associations. The programming of blood pressure, insulin responses to glucose, cholesterol metabolism, blood coagulation, and hormonal settings are all areas of active research.

Salivary cortisol concentration was found to be directly proportional to the serum unbound cortisol concentration both in normal men and women and in women with elevated cortisol-binding globulin (CBG). The correlation was excellent in dynamic tests of adrenal function (dexamethasone suppression, ACTH stimulation), in normals and patients with adrenal insufficiency, in tests of circadian variation and randomly collected samples. Women in the third trimester of normal pregnancy exhibited elevated salivary cortisol throughout the day. The relationship between salivary and serum total cortisol concentration was markedly non-linear with a more rapid increase in salivary concentration once the serum CBG was saturated. The rate of equilibrium of cortisol between blood and saliva was very fast, being much less than 5 minutes. These data, combined with a simple, stress-free, non-invasive collection procedure, lead us to suggest that salivary cortisol is a more appropriate measure for the clinical assessment of adrenocortical function than is serum cortisol.