Insulin-sensitive and insulin-resistant variants in NIDDM.

To define the sequence of events that is involved in the pathogenesis of non-insulin-dependent diabetes mellitus (NIDDM), we studied 16 NIDDM individuals (15 of 16 Black patients) with a mean age of 44 yr who had been near normoglycemic for 2-91 mo while off of antidiabetic medicine. With the euglycemic insulin clamp at 100 microU/ml insulin, we defined two populations, one with normal peripheral insulin sensitivity (glucose disposal 7.51 +/- 0.97 mg.kg-1.min-1) and the other with insulin resistance (glucose disposal 3.35 +/- 0.58 mg.kg-1.min-1; P less than .001). The populations did not differ in age, degree of obesity, fasting plasma glucose, glycosylated hemoglobin, clinical presentation, or clinical course. Basal plasma insulin levels were normal in the sensitive group and significantly elevated in the resistant group. Islet cell cytoplasmic antibodies were absent in all patients. Insulin action on the liver was normal in both groups. Basal hepatic glucose production measured with D-[3-3H]glucose was lower in the insulin-resistant group (1.53 +/- 0.11 mg.kg-1.min-1) than in the insulin-sensitive group (1.88 +/- 0.06 mg.kg-1.min-1) or normal control subjects (1.93 +/- 0.05 mg.kg-1.min-1). The decreased basal hepatic glucose production appeared to be secondary to the twofold higher fasting plasma insulin level seen in the insulin-resistant group. The insulin concentration necessary to suppress basal hepatic glucose production by 50% was 29.6 microU/ml in the insulin-sensitive group and 30.5 microU/ml in the insulin-resistant group.(ABSTRACT TRUNCATED AT 250 WORDS)