Quantitation of Insulin-stimulated Glucose Disposal in Patients with Non-insulin-dependent Diabetes Mellitus

Glucose disposal rates (Rd) during an insulin clamp study reflect both basal and insulin-stimulated Rd. To quantify the amount of glucose taken up in response to a known increase ininsulin concentration, two consecutive studies were performed on 10 patients with mild to moderate NIDDM (mean fasting glucose = 146 mg/ dl) and 10 normal subjects. Endogenous insulin secretion was inhibited by somatostatin and plasma glucose level maintained at 180 mg/dl for 5 h. Rd (mg/m2/min) was determined isotopically for 2.5 h at insulin concentrations ∼6 μU/ml and during 2.5 h of physiologic hyperinsulinemia at ∼60 μU/ml (total glucose disposal), with the increase in Rd resulting from the approximate 10-fold elevation of plasma insulin concentration defined as insulin-stimulated glucose disposal. Results showed that the increment in Rd resulting from the elevation of plasma insulin concentration was relatively minor in NIDDM (38 ± 6), increasing from a mean (±SEM) value of 83 ± 8 to 121 ±12. Similar values in normal subjects were 90 ± 7 and 274 ± 26 with an increment of 183 ± 21. Thus, insulin-stimulated glucose uptake in patients with NIDDM was only one-fifth of that in normals, and accounted for only 31% (38 ÷ 121) of total glucose disposal during the clamp study. These data indicate that the majority of previous insulin clamp studies of in vivo insulin action in patients with NIDDM, in which total glucose disposal and insulinstimulated glucose disposal have been equated, have underestimated the magnitude of insulin resistance present in NIDDM. This conclusion is highlighted by the fact that the current study was carried out in patients with relatively mild NIDDM, and the possibility exists that physiologic increments of plasma insulin have essentially no effect on peripheral glucose disposal in patients with moresevere NIDDM.