The relative effects of time versus ambient glucose concentration on insulin-stimulated glucose uptake was estimated by performing 5-h insulin clamp studies in patients with NIDDM. Each experimental subject was studied three times, at steady-state plasma insulin levels ∼2000 μU/ml, but at different steady-state, plasma glucose concentrations (studies A, B, and C). Study A consisted of a 5-h clamp, with plasma glucose level maintained at the basal level of fasting hyperglycemia; study B differed in that the basal level of fasting hyperglycemia was reduced during the first hour to ∼80 mg/dl, and maintained there for the next 4 h; and study B was carried out by clamping the patient at the basal glucose level for 2 h, lowering the glucose concentration to approximately 80 mg/dl during the third hour, and then clamping at this level for the last 2 h. The glucose metabolic clearance rate (MCR) was calculated from 60 to 120 min and from 240 to 300 min during each study, and the results indicated that values for glucose MCR were time dependent, being significantly greater (20–60%) in the fifth than in the second hour in two (studies A and B) of the three studies. In contrast, glucose MCR was independent of plasma glucose concentration, and relatively constant in each subject, as long as it was measured during the same time period. The time-dependent increase in glucose MCR was associated with an approximate 30% increase in steady-state plasma insulin concentrations when comparing the second and fifth hours. These data emphasize the time-dependent increase in insulin-stimulated glucose disposal that occurs in insulin clamp studies, and point out the potential difficulties in interpretation that can evolve from sequential estimates of insulin-stimulated glucose disposal. In addition, they provide additional evidence that measurement of glucose MCR can be used to compare insulin stimulated glucose disposal in patients with NIDDM under the conditions used in these studies.

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