To investigate changes in the sensitivity of early insulin repsonse to glucose, a pulse stimulation of 1.0, 2.5, and 5.0 g glucose was carried out at intervals of 30 min in 73 nonobese subjects suspected of having an impaired carbohydrate tolerance (CHT) and 24 body-weight and sex-matched healthy controls without a family history of diabetes. CHT was characterized by means of a 2-h glucose infusion test (GIT; 12 mg/kg-min), primed by an initial injection of 0.33 g/kg. Subjects suspected of having an impaired CHT (glucosuria in all subjects, 49 of whom exibited a borderline or pathologic 50-g standard oral glucose tolerance test and 27 of whom had a family history of diabetes) were classified as having a normal, borderline, and pathologic CHT according to the result of GIT. Compared with controls the early insulin response (∆IRI area, 0–5 min) during GIT was significantly reduced in subjects with normal, borderline, and pathologic CHT. During staircase glucose stimulation, a dose-dependent significant increase of the ∆max IRI response was observed in controls, whereas this strong relationship was lacking in all other groups studied. In subjects with normal, borderline, and pathologic CHT, ∆max IRI responses revealed by pulse stimulation of 1.0, 2.5, and 5.0 g glucose were significantly reduced compared with controls. Besides quantitative differences in early insulin response among all groups studied, a shift of the glucoseinsulin dose-response curve to the right was found in subjects with normal, borderline, and pathologic CHT. Our results provide further evidence of a reduced sensitivity of the pancreatic beta-cells to glucose during development of carbohydrate intolerance. The staircase glucose stimulation enables both a quantitative evaluation of the early insulin response to glucose and a characterization of the glucose-insulin dose-response relationship. For this reason the test seems to be a useful tool in studying the sensitivity of the pancreatic beta-cells to glucose.

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