Alterations in the Ultradian Oscillations of Insulin Secretion and Plasma Glucose in Aging

Normal insulin secretion includes oscillations with a period length of 80-150 min which are tightly coupled to glucose oscillations of similar period. To determine whether normal aging is associated with alterations in these ultradian oscillations, eight, modestly overweight, older men (65 +/- 5 years) and eight weight-matched young control subjects (25 +/- 4 years) were studied during 53 h of constant glucose infusion. Blood samples were collected every 20 min and insulin secretion rates were calculated by deconvolution. Ultradian oscillations of glucose and insulin secretion were evident in both groups. Pulse frequency was similar for glucose and insulin secretion, and was not affected by age. The absolute amplitude of the glucose oscillations was similar in both groups but their relative amplitude was slightly dampened in the older adults. Both the absolute and the relative amplitudes of insulin secretory oscillations were markedly reduced in the older subjects. The normal linear increase in the amplitude of insulin oscillations occurring with increasing amplitudes of glucose oscillations was still present in the older adults but analysis of covariance indicated that the slope was significantly lower than in the young control subjects (p < 0.0005), reflecting a decreased responsiveness of the beta cell to glucose changes. The temporal concordance between insulin and glucose oscillations, as estimated by pulse concomitancy and cross-correlation, was also lower in older subjects. The similarities between the alterations in the ultradian oscillations of insulin secretion and glucose in older healthy adults and those occurring in diabetic patients suggest that an impairment of beta-cell function may play a primary role in the deterioration of glucose tolerance in aging.