Objective    To investigate the dysfunction of islet β-cell and insalin-resistence in newly diagnosed  type 2 diabetic patients (T2D) with family history

and explore the role of β-cell dysfunction in the worsening of glucose tolerance.     Methods    An oral glucose tolerance test(OGTT) and insulin release test were given to 158 newly diagnosed patients (T2D) with family history and their 62 spouses with normal glucose tolerance (NC group)who had no diabetic family history.  The subjects were divided into 3 groups based on the level of fasting plsama glucose(FPG): DM1(FPG6.1 mmol/L)

DM2(6.1 mmol/L≤FPG7.8 mmol/L)

DM3(FPG≥7.8 mmol/L).  Insulin sensitivity was estimated by Homeostasis model assessment for insulin resistence(Homa-IR) and insulin action index (IAI).  The islet β-cell function was evaluated by 3 insulin release indices[Homa-β

ΔI30/ΔG30: the ratio of incremental glucose and insulin 30 min after glucose intake

modified beta-cell function index(MBCI) and their corresponding disposition indices (DI1=Homa-β/Homa-IR

DI2=ΔI30/ΔG30/Homa-IR

DI3=MBCI×IAI)].     Results    (1)Progressive increase was observed in the Homa-IR from DMI through DM2 to DM3 as FPG augmented while progressive decrease in IAI (all P0.01 or 0.05) in newly diagnosed T2D. Compared with  insulin sensitivity

islet β-cell function declined more obviously. (2)In  NC group

the level of FPG was mainly determined by Homa-IR

however

Homa-β which could explain the FPG growing up to 90% in DM3 group was a more important contributor than Homa-IR for FPG in subgroups of newly diagnosed diabetes.     Conclusion    Both decreased insulin sensitivity and impaired β-cell function are associated with increased glucose level in newly diagnosed diabetes.  Future more

β-cell function declines more obvious than insulin sensitivity. It indicates that β-cell function defect may play more important role in the development and progression of T2D.