Can Insulin Resistance Exist as a Primary Defect in Noninsulin-Dependent Diabetes Mellitus?*

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Abstract
In this study we have attempted to quantify the plasma insulin response to glucose and insulin action in 22 nonobese subjects: 11 with normal glucose tolerance and 11 with mild [mean fasting plasma glucose concentration, 128 ± (±sem) 5 mg/dL] noninsulin-dependent diabetes mellitus (NIDDM). Estimates of the plasma insulin response were made by determining the plasma insulin concentration at hourly intervals from 0800–1600 h, before and after mixed meals consumed at 0800 h (breakfast) and 1200 h (lunch). Insulin action was assessed by measuring glucose uptake during insulin clamp studies performed at steady state plasma insulin levels of approximately 10 and 60 μU/mL, with the difference between the 2 values defined as insulin-stimulated glucose uptake. Plasma glucose (P < 0.001) and insulin (P < 0.001) concentrations were significantly higher in patients with NIDDM throughout the 8-h period (by two-way analysis of variance). However, mean (± sem) insulin-stimulated glucose uptake was markedly reduced (P < 0.001) in patients with type 2 diabetes mellitus (112 ± 72 vs. 336 ± 44 mg/m2 min−1). Thus, patients with NIDDM and mild fasting hyperglycemia were both insulin resistant and hy-perinsulinemic compared to normal individuals. These data indicate that a defect in insulin-stimulated glucose uptake can occur in NIDDM in the absence of significant hyperglycemia and/or hypoinsulinemia.