Aims:
The relative contribution of β-cell function and insulin sensitivity in the pathogenesis of type 2 diabetes (T2D) are not fully understood. We investigated the role of genetic variants of β-cell function in deterioration of glucose tolerance, from a 9-year prospective cohort in the Chinese population.
Methods:
 We first genotyped 89 SNPs associated T2D in a cross-sectional population in China and found that 40 SNPs had a significant association with diabetes risk (P<0.05). Then, multiple linear regression showed that the 12 of 40 SNPs were significantly associated with β-cell function indicated by HOMA-β, Stumvoll1st and 2nd index. Then, a β-genetic risk score model (β-GRS） was constructed to assess its predicting effects on incidence rate of T2D and impaired glucose regulation (IGR) in a community-based 9-year prospective cohort (N=2495), including 2192 normal glucose tolerance and 303 IGR patients at baseline through Logistic, Cox and multiple linear regression tests. 
Results:
During 9-year follow up, 260 develop  T2D and 326 developed IGR. 12 SNPs of 40 were associated with β-cell function indicated as HOMA-β, Stumvoll 1st and 2nd phase insulin secretion indices (Table 1). β-GRS was constructed by summing up the alleles negatively associated with β-cell function. β-GRS could predict  incidence of T2D and IGR in the logistic regression (OR 1.236, 95% CI 1.094, 1.395, P=0.0006) as well as in the Cox model (HR 1.038, 95% CI 1.002, 1.078, P=0.041) after adjusting for age, sex, body mass index (BMI) at baseline (Figure 1). In addition, β-GRS also predict change in β-cell function (Stumvoll 1st : P=0.0259, , Stumvoll 2nd : P=0.0083, respectively) during the 9-year follow-up period (Figure 2). As β-GRS increase, β-cell compensatory function decrease. 
Conclusions:
β-GRS could predict deterioration of glucose tolerance in the Chinese population. Chinese population are susceptible to type 2 diabetes due to their poor β-cell function.

Effects of beta cell function related genetic variants on predicting type 2 diabetes in a 9 year prospective cohort