THE RELATIONSHIP BETWEEN INSULIN-RESISTANCE AND INSULIN-SECRETION IN JAPANESE SUBJECTS WITH BORDERLINE GLUCOSE-INTOLERANCE

Insulin resistance and impaired insulin secretion can be involved in t he development of non-insulin-dependent diabetes mellitus (NIDDM), but their relative importance or temporal relationship are poorly underst ood. To elucidate this issue, we studied 51 subjects with borderline g lucose intolerance (BGI) and 18 normal glucose tolerant subjects (NGT) according to the Japan Diabetes Society criteria. The glucose infusio n rate (GIR, mg/kg/min), an index of whole body insulin resistance (IR ), was measured by the euglycemic (80mg/dl) hyperinsulinemic clamp tec hnique (insulin infusion rate 1.12mU/kg/min). Insulinogenic index (Del ta IRI/Delta BS at 30 min) and the insulin area under the curve during a 75-g oral glucose tolerance test (OGTT) were estimated. In the BGI subjects, the GIR values showed marked variation ranging from 2.24 to 10.44 mg/kg/min (5.54 +/- 0.31, mean +/- S.E.M.). The GIR values were lower in obese BGI subjects compared with non-obese BGI and NGT subjec ts, and the insulin area was markedly higher in BGI subjects with incr eased insulin resistance. There was a significant negative correlation between the GIR values and the insulin area or Delta IRI/Delta BS (30 ') ratio in the subjects with BGI either in the whole group or solely in the non-obese group. We conclude that the increased insulin secreti on compensates for the peripheral insulin resistance of subjects with slightly deteriorated glucose tolerance, implying that insulin resista nce plays an important role in the pathogenesis of NIDDM in some fract ion of Japanese population.