Cross-sectional study of the pathophysiologic and clinical features in the first-degree relatives of type 2 diabetic patients

To explore the pathophysiologic and clinical features and investigate the roles of insulin resistance and insulin secretion in the pathogenesis of type 2 diabetes mellitus.A total of 888 first-degree relatives without glucose intolerance history underwent an oral glucose test (OGTT) and their level of HbA1c, insulin concentration and lipid levels were determined. The homeostasis model assessment was used to estimate insulin resistance (HOMA(IR)) and beta-cell function (HOMA-beta). The ratio of incremental glucose (DeltaG30) and insulin (DeltaI30) response was used to evaluate the early insulin secretion. DeltaI30/DeltaG30/HOMAIR was used to evaluate the glucose disposition index (DI).In the subjects, 167 were diagnosed with diabetes, 180 with impaired glucose tolerance or/and impaired fasting glucose (impared glucose regulation), 457 with normal glucose tolerance and normal HbA1c, and 84 with normal glucose tolerance and high HbA1c. From normal glucose tolerance through impared glucose regulation to diabetes mellitus, the HOMA(IR), body mass index (BMI), waist/hip ratio (WHR) and serum triglyceride (TG) progressively increased, HOMA-beta cell, DeltaI30/DeltaG30, DI and high density liproprotein (HDL) progressively decreased. Subjects with normal glucose tolerance were divided into three tertile subgroups (1/3, 2/3 and 3/3 groups) with different area under the curve of OGTT glucose, after being adjusted by sex, age, BMI, the 3/3 group was found having higher HOMA(IR), and lower HOMA-beta, DeltaI30/DeltaG30/, and DI than the 1/3 group.Both insulin resistance and impaired beta cell function are important pathophysiologic changes contributing to the onset and development of type 2 diabetes. These changes and lipid profile have occurred before a patient is diagnosed with abnormal glucose tolerance.PubMed02159-623