Objective: To investigate the roles of insulin resistance and beta-cell function in the pathogenesis of type 2 diabetes mellitus.
Methods: 614 first-degree relatives without glucose intolerance history underwent an oral glucose test (OGTT) and their levels of HbA1c were determined. According to the single OGTT results and WHO criteria, 118 (19.2%) of the 614 subjects were newly diagnosed with diabetes, 121 (19.7%) with impaired glucose tolerance (IGT) or/and impaired fasting glucose (IFG), 375 with normal glucose tolerance (NGT), of which 316 (51.5%) subjects were with HbA1c in normal level range (4% approximately 6%) and the others with high HbA1c level (9.6%). Homeostasis model assessment of insulin resistance (Homa(IR)) was used to estimate insulin resistance, Homa-beta cell was used to evaluate basal insulin secretion, incremental glucose (DeltaG30) and insulin (DeltaI30) response was calculated as the difference between the values 30 min after glucose intake to evaluate the early insulin secretion, DeltaI30/DeltaG30/HOMA(IR) was used to evaluate the disposition index (DI).
Results: Decreasing glucose tolerance was associated with insulin resistance, beta cell function and DI. From normal glucose tolerance condition through IFG /IGT to diabetic, the Homa IR progressively increased (NGT 0.76 +/- 0.6, IFG/IGT 1.0 +/- 0.6, DM 1.5 +/- 0.6, P < 0.001), Homa-beta cell (NGT 5.3 +/- 0.7, IFG/IGT 5.1 +/- 0.7, DM 4.1 +/- 0.9), I30/DeltaG30 (NGT 2.8 +/- 0.9, IFG/IGT 2.2 +/- 1.0, DM 1.3 +/- 1.0) and DI (NGT 2.0 +/- 0.9, IFG/IGT 1.1 +/- 0.9, DM -0.2 +/- 1.2), progressively decreased (P < 0.001). Normal subjects were divided into three tertile groups with different area under the curve of OGTT glucose. After adjusted by sex, age, BMI and WHR, the upper terile group was found having high Homa IR and lower Homa-beta, DeltaI30/DeltaG30/, I than lower tertile group.
Conclusion: Abnormal glucose tolerance is common in first-degree relatives of non-insulin-dependent Diabetes Mellitus patients, both insulin resistance and impaired beta cell function are associated with impaired glucose metabolism, which have existed before diagnosis of IFG, IGT and diabetes.