Normal hepatic insulin sensitivity in lean, mild noninsulin-dependent diabetic patients

We studied hepatic and extrahepatic insulin sensitivity and insulin release in seven nonobese patients with mild noninsulin-dependent diabetes mellitus (NIDDM) and 10 control subjects, matched for age, body mass index, and physical fitness. Glucose turnover was studied during sequential hyperinsulinemic euglycemic clamps (insulin infusion, 0.25 and 1.0 mU/kg BW.min), applying the hot-GINF (tracer-enriched glucose infusion) technique and using [6-3H]glucose. Hepatic glucose production was lower in hyperglycemic NIDDM patients during the basal period (P < 0.01), but was equivalent at similar glucose and insulin levels attained during both clamps. In contrast, during the low and high insulin clamps, glucose utilization was lower in NIDDM [14.90 +/- 1.00 vs. 17.24 +/- 0.83 (P < 0.01) and 41.37 +/- 3.05 vs. 50.54 +/- 3.61 mumol/kg BW.min (P < 0.01)]. Accordingly, the glucose infusion rate necessary to maintain euglycemia was lower in NIDDM [7.72 +/- 2.00 vs. 10.68 +/- 1.17 (P < 0.05) and 42.14 +/- 4.50 vs. 51.60 +/- 4.28 mumol/kg BW.min (P < 0.01)]. There was, however, a considerable overlap between patients and controls in the parameters describing insulin sensitivity. The insulin response to orally administered glucose as well as that to a standardized glucose infusion test (GIT) were diminished in NIDDM [average incremental insulin secretion during an oral glucose tolerance test, 88 +/- 28 vs. 251 +/- 50 pmol/L.min (P < 0.05); during first 10 min of GIT, 7 +/- 16 vs. 234 +/- 29 pmol/L.min (P < 0.001)]. There was no overlap in acute phase insulin secretion during the GIT between the groups. In conclusion, nonobese, mild NIDDM patients showed no impairment in hepatic, but a slight reduction in extrahepatic insulin sensitivity, with extensive overlap between diabetic and control subjects. In contrast, impairment of insulin release was very pronounced and without overlap.