期刊
DIABETES
卷 70, 期 3, 页码 809-816出版社
AMER DIABETES ASSOC
DOI: 10.2337/db20-0564
关键词
-
资金
- National Key Research and Development Program of China [2016YFC1304901]
- Beijing Science and Technology Committee Funding [Z141100007414002, D131100005313008]
- National High-Technology Research and Development Program of China (863 Program) [2012AA02A509]
The low-frequency variant of GCK gene, rs13306393, was found to be associated with type 2 diabetes and prediabetes in the Chinese population. This variant increased the risk of developing diabetes and prediabetes by reducing insulin sensitivity rather than affecting beta-cell function, which should be considered in future clinical use of GCK activators.
Glucokinase (GCK) regulates insulin secretion and hepatic glucose metabolism, and its inactivating variants could cause diabetes. We aimed to evaluate the association of a low-frequency variant of GCK (rs13306393) with type 2 diabetes (T2D), prediabetes, or both (impaired glucose regulation [IGR]) in a Chinese population. An association study was first conducted in a random cluster sampling population (sample 1: 537 T2D, 768 prediabetes, and 1,912 control), and then another independent population (sample 2: 3,896 T2D, 2,301 prediabetes, and 868 control) was used to confirm the findings in sample 1. The A allele of rs13306393 was associated with T2D (odds ratio 3.08 [95% CI 1.77-5.36], P = 0.00007) in sample 1; rs13306393 was also associated with prediabetes (1.67 [1.05-2.65], P = 0.03) in sample 2. In a pooled analysis of the two samples, the A allele increased the risk of T2D (1.57 [1.15-2.15], P = 0.005), prediabetes (1.83 [1.33-2.54], P = 0.0003) or IGR (1.68 [1.26-2.25], P = 0.0004), insulin resistance estimated by HOMA (beta = 0.043, P = 0.001), HbA(1c) (beta = 0.029, P = 0.029), and urinary albumin excretion (beta = 0.033, P = 0.025), irrespective of age, sex, and BMI. Thus, the Chinese-specific low-frequency variant increased the risk of T2D through reducing insulin sensitivity rather than islet beta-cell function, which should be considered in the clinical use of GCK activators in the future.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据