Impaired pancreatic beta cell compensatory function is the main cause of type 2 diabetes in individuals with high genetic risk: a 9 year prospective cohort study in the Chinese population
Impaired pancreatic beta cell compensatory function is the main cause of type 2 diabetes in individuals with high genetic risk: a 9 year prospective cohort study in the Chinese population
复制标题
DOI：
10.1007/s00125-016-3939-y
复制
发表时间：
2016-07-01
期刊：
影响因子：
8.2
通讯作者：
Jia, Weiping
中科院分区：
文献类型：
--
作者：
Yan, Jing;Peng, Danfeng;Jia, Weiping
目的/假设我们的目的是评估2型糖尿病风险变异体在预测中国人群9年前瞻性队列中血糖恶化、β细胞功能进展和胰岛素敏感性的联合作用。方法我们构建了一个基于40个与2型糖尿病相关的变异体的加权遗传风险评分（GRS）模型，该模型在一个已建立的中国人群横断面中得到验证（n = 6 822）。将加权评分分为三分位数，以评估对2型糖尿病和糖调节受损（IGR）发生率的预测能力，以及对基于社区的9年前瞻性队列中Stumvoll第一时相和第二时相胰岛素分泌指数和Gutt胰岛素敏感性指数（ISI）变化的预测能力结果Logistic回归分析显示，加权GRS能预测2型糖尿病和IGR的发生（OR 1.236，95% CI 1.100，1.389，p = 0.0004）以及校正基线时年龄、性别、BMI、吸烟和饮酒状态后的考克斯模型（HR 1.129，95% CI 1.026，1.242，p = 0.0128）。此外，我们观察到加权GRS能够预测β细胞功能的恶化，（第一时相和第二时相胰岛素分泌分别为β =-0.0480，p = 9.66 x 10（-5）和β =-0.0303，p = 3.32 x 10（-5）），但不包括胰岛素敏感性（p = 0.3815），在9年的随访期。结论/解释加权GRS预测血糖恶化所产生的β细胞功能的变化，在中国人口。中等或高体重GRS组的个体表现出β细胞功能的进行性恶化。
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 (beta = -0.0480, p = 9.66 x 10(-5) and beta = -0.0303, p = 3.32 x 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.