Zillich Alan J, Garg Jay, Basu Sanjib, Bakris George L, Carter Barry L
Purdue University College of Pharmacy, Department of Pharmacy Practice, West Lafayette, Indiana, USA.
Hypertension. 2006 Aug;48(2):219-24. doi: 10.1161/01.HYP.0000231552.10054.aa. Epub 2006 Jun 26.
National guidelines and a recent clinical trial have supported the use of thiazide diuretics as the preferred initial pharmacological treatment for hypertension. However, evidence from this and other clinical trials have also found an increased incidence of new onset diabetes among those patients receiving thiazide diuretics. The mechanisms responsible for the increased incidence of diabetes with thiazide diuretics have not been fully elucidated. This article provides a review of intervention studies that included data on the relation between thiazide-induced hypokalemia and glucose intolerance. We conducted a literature search from 1966 to June 2004 to identify clinical trials using thiazide diuretics where the metabolic effects on potassium and glucose are reported. A total of 59 clinical trials constituting 83 thiazide diuretic study arms were identified. Trial size, length, type of thiazide diuretic, and dose varied substantially among the studies. The association between average changes in potassium and glucose in the study arms is considered jointly in a weighted statistical model. The Pearson's correlation coefficient, weighted by study sample size, for the relationship between glucose and potassium was -0.54 (95% CI, -0.67 to -0.36; P < 0.01). A sensitivity analysis, which considered subset analyses and effect of covariates, as well as inverse-variance weighting, supported this finding. These data suggest that thiazide-induced hypokalemia is associated with increased blood glucose. Treatment of thiazide-induced hypokalemia may reverse glucose intolerance and possibly prevent the future development of diabetes.
国家指南和最近的一项临床试验支持使用噻嗪类利尿剂作为高血压首选的初始药物治疗。然而，来自该试验及其他临床试验的证据也发现，接受噻嗪类利尿剂治疗的患者中新发糖尿病的发病率有所增加。噻嗪类利尿剂导致糖尿病发病率增加的机制尚未完全阐明。本文综述了干预性研究，这些研究纳入了噻嗪类药物引起的低钾血症与葡萄糖不耐受之间关系的数据。我们检索了1966年至2004年6月的文献，以确定使用噻嗪类利尿剂且报告了对钾和葡萄糖代谢影响的临床试验。共识别出59项临床试验，构成83个噻嗪类利尿剂研究组。各研究在试验规模、时长、噻嗪类利尿剂类型和剂量方面差异很大。在加权统计模型中综合考虑研究组中钾和葡萄糖平均变化之间的关联。葡萄糖与钾之间关系的Pearson相关系数经研究样本量加权后为-0.54（95%CI，-0.67至-0.36；P<0.01）。一项敏感性分析，考虑了亚组分析、协变量的影响以及逆方差加权，支持了这一发现。这些数据表明，噻嗪类药物引起的低钾血症与血糖升高有关。治疗噻嗪类药物引起的低钾血症可能会逆转葡萄糖不耐受，并有可能预防未来糖尿病 的发生。
