Department of Clinical Sciences, Lund University, Clinical Research Center, Entrance 72, Bldg 91, Floor 12, Malmö University Hospital, SE 20502 Malmö, Sweden.
Circulation. 2010 May 18;121(19):2102-8. doi: 10.1161/CIRCULATIONAHA.109.909663. Epub 2010 May 3.
Animal studies suggest that the arginine vasopressin system may play a role in glucose metabolism, but data from humans are limited.
We analyzed plasma copeptin (copeptin), a stable C-terminal fragment of the arginine vasopressin prohormone. Using baseline and longitudinal data from a Swedish population-based sample (n=4742; mean age, 58 years; 60% women) and multivariable logistic regression, we examined the association of increasing quartiles of copeptin (lowest quartile as reference) with prevalent diabetes mellitus at baseline, insulin resistance (top quartile of fasting plasma insulin among nondiabetic subjects), and incident diabetes mellitus on long-term follow-up. New-onset diabetes mellitus 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 mellitus (P=0.04) and insulin resistance (P<0.001). During 12.6 years of follow-up, 174 subjects (4%) developed new-onset diabetes mellitus. The odds of developing diabetes mellitus 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 mellitus 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 mellitus independently of established clinical risk factors, including fasting glucose and insulin. These findings could have implications for risk assessment, novel antidiabetic treatments, and metabolic side effects from arginine vasopressin system modulation.
动物研究表明，精氨酸加压素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），即精氨酸加压素原的稳定 C 端片段。我们使用来自瑞典人群基础样本（n=4742；平均年龄 58 岁；60%为女性）的基线和纵向数据，以及多变量逻辑回归，检查了 copeptin 四分位递增（最低四分位作为参考）与基线时现患糖尿病、胰岛素抵抗（非糖尿病受试者中空腹血浆胰岛素的最高四分位）以及长期随访中新发糖尿病的相关性。新发糖尿病通过 3 个国家和地区登记处确定。所有模型均调整了临床和人体测量危险因素、胱抑素 C 和 C 反应蛋白。在横断面分析中，cpeptin 升高与现患糖尿病（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%）发生新发糖尿病。即使在进一步调整基线空腹血糖和胰岛素后，copeptin 四分位递增与糖尿病发病风险增加相关（调整后的优势比，1.0、1.37、1.79 和 2.09；趋势 P 值=0.004）。在基线空腹全血葡萄糖<5.4 mmol/L 的受试者中进行分析时，与新发糖尿病的相关性仍然显著（调整后的优势比，1.0、1.80、1.92 和 3.48；P=0.001）。
升高的 copeptin 独立于包括空腹血糖和胰岛素在内的既定临床危险因素预测糖尿病发病风险增加。这些发现可能对风险评估、新型抗糖尿病治疗和精氨酸加压素系统调节的代谢副作用具有重要意义。
