The Role of Insulin Secretion and Insulin Resistance in the Development of Korean Type 2 Diabetes Mellitus

Abstract

Background: Impaired insulin secretion, peripheral insulin resistance, a disproportionately elevatedrate of hepatic glucose production and influence of inherited or enviromental factors contribute to the pathogenesis of type 2 diabetes mellitus(DM). But, which defect is primary is still controversial To detennine whether insulin resistance or insulin deficiency is primary in the pathogenesis of type 2 DM, we studied normal glucose tolerant offsprings of type 2 diabetic patients. Methods: 22 offsprings of type 2 diabetic patients with normal glucose tolerance, ranging in age from 20 to 40 years, and 17 control subjects in same age range who had no family history of diabetes, and 21 diabetic subjects were included. We performed 75 g oral glucose: tolerance test, euglycemic hyperinsulinemic clamp test and hyperglycemic clamp test. Results: With euglycemic clamp test, the values of peripheral insulin sensitivity, M, were 8.590.94 mg/kg/min in control group, 6.980.65 mg/kg/min in offspring group, and 5.190.89 mg/kg/min in diabetes group (P<0.05). Considering that lower limit of the nonnal range were 3.78 mg/kg/min in M and 3.10 mg/kg/min in M/I, the frequency of insulin resistance was 14.3% in the offspring group and 33.3% in diabetes group. First and second phase insulin secretion during hyperglycemic clamp test were blunted in diabetes group. In the offspring group, first and second phase insulin secretion during hyperglycemic clamp test were increased greater than control group, though statistically insignificant. The mean first phase insulin secretion were 38.556.81 pU/mL in control group, 55.099.40pU/mL in the offspring group and 6.020.98 ,uU/mL in diabetes group (P<0.05). The mean second phase insulin secretion were 65.1115.5 pU/mL in control group, 90.25 11.911U/mL in the offspring group and 17.6 2.71 pUmL in diabetes group (P<0.05). Considering that lower limit of the normal range were 19.5 pU/mL in the first phase insulin secretion and 26.1 lrU/mL in the second phase insulin secretion, thefrequency of impaired insulin secretion was 14.3 % in the offspring group and 100 % in diabetes group. There was an inverse relation between insulin resistance and insulin secretion in control subjects. But in the offspring group, this relation was absent. Conclusion: Our results show that both insulin resistance and impaired insulin secretion contribute to the development of type 2 DM in Koreans. In addition, diabetic subjects had more severe impairment in insulin secretory capacity than insulin resistance.