NORMAL HEPATIC INSULIN SENSITIVITY IN LEAN, MILD NONINSULIN-DEPENDENTDIABETIC-PATIENTS

We studied hepatic and extrahepatic insulin sensitivity and insulin re lease in seven nonobese patients with mild noninsulin-dependent diabet es mellitus (NIDDM) and 10 control subjects, matched for age, body mas s index, and physical fitness. Glucose turnover was studied during seq uential hyperinsulinemic euglycemic clamps (insulin infusion, 0.25 and 1.0 mU/kg BW . min), applying the hot-GINF (tracer-enriched glucose i nfusion) technique and using [6-H-3] glucose. Hepatic glucose producti on was lower in hyperglycemic NIDDM patients during the basal period ( P < 0.01), but was equivalent at similar glucose and insulin levels at tained during both clamps. In contrast, during the low and high insuli n clamps, glucose utilization was lower in NIDDM [14.90 +/- 1.00 vs. 1 7.24 +/- 0.83 (P < 0.01) and 41.37 +/- 3.05 vs. 50.54 +/- 3.61 mu mol/ kg BW . min (P < 0.01)]. Accordingly, the glucose infusion rate necess ary 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 mu mol/kg B W . min (P < 0.01)]. There was, however, a considerable overlap betwee n patients and controls in the parameters describing insulin sensitivi ty. The insulin response to orally administered glucose as well as tha t to a standardized glucose infusion test (GIT) were diminished in NID DM [average incremental insulin secretion during an oral glucose toler ance test, 88 +/- 28 vs. 251 +/- 50 pmol/L . min (P < 0.05); during fi rst 10 min of GIT, 7 +/- 16 vs. 234 +/- 29 pmol/L . min (P < 0.001)]. There mas no overlap in acute phase insulin secretion during the GIT b etween the groups. In conclusion, nonobese, mild NIDDM patients showed no impairment in hepatic, but a slight reduction in extrahepatic insu lin sensitivity, with extensive overlap between diabetic and control s ubjects. In contrast, impairment of insulin release was very pronounce d and without overlap.