Insulin resistance emerges prior to β-cell function deficiency in non-diabetic first-degree relatives of patients with type 2 diabetes mellitus

Objective To investigate the insulin resistance and β-cell function in non-diabetic first-degree relatives (FDR) of patients with type 2 diabetes.Methods Of the first-degree relatives of type 2 diabetic patients,10 subjects with normal glucose tolerance(NGT) and 13 with impaired glucose tolerance(IGT) were included.The other 9 healthy subjects without family history of diabetes served as the controls.Insulin resistance was measured by hyperinsulin-euglycemic clamp,and islet β-cell function by intravenous glucose tolerance test (IVGTY).Results NC group(7.04±0.62 and 6.16±0.73 vs 10.22±0.93,both P＜0.05).There was no difference in GIR between the former two groups.The first phase insulin secretion (natural logarithm transformed data) of the NGT group was higher than that of IGT group(3.87±0.24 vs 3.03±0.28,P＜0.05),but not significant with that of NC group (3.37±0.30).The results of the disposition index (DI,natural logarithm transformed data)in NGT group (1.43 ±0.22) and NC group(1.18±0.41) were greater than that in IGT group (0.32±0.20,P＜0.01 or P＜0.05).No difference existed between IGT and NC groups.Conclusions Insulin resistance emerges in non-diabetic firstdegree relatives of patients with type 2 diabetes while glucose tolerance remains normal.Blood glucose rises only when β-cell function fails to compensate. Key words: Diabetes mellitus，type 2; First-degree relatives; Insulin resistance; Islet β-cell function; Glucose clamp technique