Changes of early insulin responses to glucose in obese subjects with normal and impaired carbohydrate tolerance.

We have studied changes in the sensitivity of the early insulin response to glucose by means of an intravenous pulse-stimulation of 1.0 g, 2.5 g and 5.0 glucose at intervals of 30 min in 24 non-obese healthy controls without a family history of diabetes and in obese subjects with normal (n = 7) and pathological carbohydrate tolerance (n = 23). All subjects were characterized regarding carbohydrate tolerance (CHT) by using a 2 h-glucose infusion test (GIT; 12 mg/kg/min), primed by an initial injection of 0.33 g/kg glucose. Compared with controls the early insulin response (delta IRI-area 0-5 min) during GIT was slightly increased in obesity with normal CHT and it was significantly reduced in obesity with pathological CHT. With regard to the late insulin response phase (delta IRI-area 30-120 min) both obese groups were characterized by a significant hyperinsulinemia. During staircase glucose stimulation a dose-dependent significant increase of the maximal IRI-response was observed in controls whereas this strong relationship was lacking in the two obese groups. The dose-response curve in obesity with normal CHT was displaced toward the left of the control curve whereas a right shift was found in obesity with pathological CHT. There was a significant correlation between early insulin response during GIT and maximal insulin response revealed by staircase glucose stimulation in obese subjects with pathological CHT. No close relationship of this type could be detected in the other groups so far studied. Our findings suggest an increased sensitivity of the beta-cells to glucose in the hyperinsulinemia stages of obesity with normal CHT. In contrast to this, a reduced sensitivity of the early insulin response to glucose is suggested in obesity with pathological CHT. A staircase glucose stimulation seems to be a useful tool in studying the early insulin response to glucose.