Jing Yan1, Danfeng Peng1, Feng Jiang1, Rong Zhang1, Miao Chen1, Tao Wang1, Dandan Yan1, Shiyun Wang1, Xuhong Hou1, Yuqian Bao1, Cheng Hu2,3, Weiping Jia4. 1. Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Key Clinical Center for Diabetes, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, People's Republic of China. 2. Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Key Clinical Center for Diabetes, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, People's Republic of China. alfredhc@sjtu.edu.cn. 3. Institute for Metabolic Diseases, Shanghai Jiao Tong University Affiliated Sixth People's Hospital South Campus, Shanghai, People's Republic of China. alfredhc@sjtu.edu.cn. 4. Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Key Clinical Center for Diabetes, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, People's Republic of China. wpjia@sjtu.edu.cn.
Abstract
AIMS/HYPOTHESIS: We aimed to evaluate the combined effects of type 2 diabetes risk variants on predicting deterioration of blood glucose and progression of beta cell function and insulin sensitivity in a 9 year prospective cohort from the Chinese population. METHODS: We constructed a weighted genetic risk score (GRS) model based on 40 variants associated with type 2 diabetes validated in an established cross-sectional Chinese population (n = 6,822). The weighted scores were categorised into tertiles to assess the predictive capacity for incidence of type 2 diabetes and impaired glucose regulation (IGR), as well as for changes in Stumvoll first- and second-phase insulin secretion indices and Gutt's insulin sensitivity index (ISI) in a community-based 9 year prospective cohort (n = 2,495), including 2,192 individuals with normal glucose tolerance and 303 with IGR at baseline, through logistic, Cox and multiple linear regression tests. RESULTS: Weighted GRS predicted the incidence of type 2 diabetes and IGR in logistic regression (OR 1.236, 95% CI 1.100, 1.389, p = 0.0004) as well as in the Cox model (HR 1.129, 95% CI 1.026, 1.242, p = 0.0128) after adjusting for age, sex, BMI, smoking and alcohol status at baseline. Moreover, we observed that weighted GRS was able to predict deterioration in beta cell function (β = -0.0480, p = 9.66 × 10(-5) and β = -0.0303, p = 3.32 × 10(-5) for first- and second-phase insulin secretion, respectively), but not insulin sensitivity (p = 0.3815), during the 9 year follow-up period. CONCLUSIONS/ INTERPRETATION: The weighted GRS predicted blood glucose deterioration arising from change in beta cell function in the Chinese population. Individuals in the intermediate- or high-weighted GRS group exhibited progressive deterioration of beta cell function.
AIMS/HYPOTHESIS: We aimed to evaluate the combined effects of type 2 diabetes risk variants on predicting deterioration of blood glucose and progression of beta cell function and insulin sensitivity in a 9 year prospective cohort from the Chinese population. METHODS: We constructed a weighted genetic risk score (GRS) model based on 40 variants associated with type 2 diabetes validated in an established cross-sectional Chinese population (n = 6,822). The weighted scores were categorised into tertiles to assess the predictive capacity for incidence of type 2 diabetes and impaired glucose regulation (IGR), as well as for changes in Stumvoll first- and second-phase insulin secretion indices and Gutt's insulin sensitivity index (ISI) in a community-based 9 year prospective cohort (n = 2,495), including 2,192 individuals with normal glucose tolerance and 303 with IGR at baseline, through logistic, Cox and multiple linear regression tests. RESULTS: Weighted GRS predicted the incidence of type 2 diabetes and IGR in logistic regression (OR 1.236, 95% CI 1.100, 1.389, p = 0.0004) as well as in the Cox model (HR 1.129, 95% CI 1.026, 1.242, p = 0.0128) after adjusting for age, sex, BMI, smoking and alcohol status at baseline. Moreover, we observed that weighted GRS was able to predict deterioration in beta cell function (β = -0.0480, p = 9.66 × 10(-5) and β = -0.0303, p = 3.32 × 10(-5) for first- and second-phase insulin secretion, respectively), but not insulin sensitivity (p = 0.3815), during the 9 year follow-up period. CONCLUSIONS/ INTERPRETATION: The weighted GRS predicted blood glucose deterioration arising from change in beta cell function in the Chinese population. Individuals in the intermediate- or high-weighted GRS group exhibited progressive deterioration of beta cell function.
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