Plasma copeptin and the risk of diabetes mellitus.
Plasma copeptin and the risk of diabetes mellitus.
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血浆copeptin和糖尿病的风险。
DOI：
10.1161/circulationaha.109.909663
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发表时间：
2010-05-18
期刊：
影响因子：
37.8
通讯作者：
Melander O
中科院分区：
文献类型：
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作者：
Enhörning S;Wang TJ;Nilsson PM;Almgren P;Hedblad B;Berglund G;Struck J;Morgenthaler NG;Bergmann A;Lindholm E;Groop L;Lyssenko V;Orho-Melander M;Newton-Cheh C;Melander O
动物研究表明精氨酸抗利尿激素（AVP）系统可能在葡萄糖代谢中发挥作用，但来自人类的数据有限。我们分析了血浆copeptin (copeptin)，这是AVP前激素的一个稳定的c端片段。使用瑞典人群样本（n=4742，平均年龄58岁，60%为女性）的基线和纵向数据，我们使用多变量logistic回归检查了copeptin增加四分位数（最低四分位数作为参考）与基线流行糖尿病、胰岛素抵抗（非糖尿病受试者空腹血浆胰岛素的最高四分位数）和长期随访中糖尿病发生率的关系。通过3个国家和地区登记来确定新发糖尿病。所有模型均根据临床和人体测量危险因素、胱抑素C和C反应蛋白进行调整。在横断面分析中，copeptin升高与糖尿病患病率（P=0.04）和胰岛素抵抗（P<0.001）相关。在12.6年的随访中，174名受试者（4%）发展为新发糖尿病。即使在对基线空腹血糖和胰岛素进行额外调整后，随着copeptin的增加，发生糖尿病的几率也会增加（调整后的优势比分别为1.0、1.37、1.79和2.09；趋势P =0.004）。在仅限于基线空腹全血糖<5.4 mmol/L受试者的分析中，与糖尿病事件的关联仍然显著（校正优势比为1.0、1.80、1.92和3.48；P=0.001）。copeptin升高预示糖尿病风险增加，独立于已建立的临床风险因素，包括空腹血糖和胰岛素。这些发现可能对风险评估、新型抗糖尿病治疗和AVP系统调节的代谢副作用具有启示意义。
Animal studies suggest that the arginine vasopressin (AVP) system may play a role in glucose metabolism, but data from humans are limited. We analysed plasma copeptin (copeptin), a stable C-terminal fragment of the AVP pro-hormone. Using baseline and longitudinal data from a Swedish population-based sample (n=4742, mean age 58 years, 60% women), we examined the association of increasing quartiles of copeptin (lowest quartile as reference) with prevalent diabetes at baseline, insulin resistance (top quartile of fasting plasma insulin among non-diabetic subjects), and incident diabetes on long-term follow up using multivariable logistic regression. New-onset diabetes was ascertained through 3 national and regional registers. All models were adjusted for clinical and anthropometric risk factors, cystatin C, and C-reactive protein. In cross-sectional analyses, increasing copeptin was associated with prevalent diabetes (P=0.04) and insulin resistance (P<0.001). During 12.6 years of follow up 174 subjects (4%) developed new-onset diabetes. The odds of developing diabetes increased across increasing quartiles of copeptin, even after additional adjustment for baseline fasting glucose and insulin (adjusted odds ratios 1.0, 1.37, 1.79, and 2.09; P for trend =0.004). The association with incident diabetes remained significant in analyses restricted to subjects with fasting whole blood glucose <5.4 mmol/L at baseline (adjusted odds ratios 1.0, 1.80, 1.92, and 3.48; P=0.001). Elevated copeptin predicts increased risk for diabetes, independent of established clinical risk factors, including fasting glucose and insulin. These findings could have implications for risk assessment, novel anti-diabetic treatments, and metabolic side effects from AVP system modulation.