Changes in serum potassium mediate thiazide-induced diabetes.
Changes in serum potassium mediate thiazide-induced diabetes.
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DOI：
10.1161/hypertensionaha.108.119438
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发表时间：
2008-12
期刊：
影响因子：
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通讯作者：
Parekh RS
中科院分区：
文献类型：
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作者：
Shafi T;Appel LJ;Miller ER 3rd;Klag MJ;Parekh RS
被推荐为一线抗高血压药物的噻嗪类药物与糖尿病风险增加有关。噻嗪类药物还能降低血钾。为了确定噻嗪诱发的糖尿病是否是由钾的变化引起的，我们分析了3,790名非糖尿病参与者的数据，这些参与者参加了老年收缩期高血压计划(SHEP)，这是一项随机临床试验，研究对象是60岁以上的≥患者，接受氯替利酮或安慰剂治疗的单独的收缩期高血压。根据自我报告、抗糖尿病药物使用、空腹血糖≥126 mg/dL或随机血糖≥200 mg/dL来定义事件糖尿病。在随访期间的459例糖尿病患者中，42%的患者发生在第一年。在第一年，氯苯吡酮组和安慰剂组的糖尿病未调整发病率分别为6.1和3.0。在第一年，服用氯苯磺隆的调整后的糖尿病风险(危险比[HR])为2.07(95%可信区间[CI]，1.5-2.83；p<；0.001)。校正血钾变化后，危险显著降低(HR，1.54，95%CI，1.09-2.17；p=0.01)，风险降低程度(41%；95%CI，34-49%)与中介效应一致。血钾每降低0.5mEq/L，调整后的糖尿病风险增加45%(95%可信区间，24%-70%；p<；0.001)。第一年后，氯苯吡酮的使用与糖尿病风险的增加无关。综上所述，噻嗪诱导的糖尿病在开始治疗后早期发生，并且似乎是通过血清钾的变化来调节的。补钾可预防噻嗪诱导的糖尿病。这一假设可以也应该在随机试验中进行检验。
Thiazides, recommended as first-line anti-hypertensive therapy, are associated with an increased risk of diabetes. Thiazides also lower serum potassium. To determine if thiazide-induced diabetes is mediated by changes in potassium, we analyzed data from 3,790 non-diabetic participants in the Systolic Hypertension in Elderly Program (SHEP), a randomized clinical trial of isolated systolic hypertension in individuals aged ≥60 years treated with chlorthalidone or placebo. Incident diabetes was defined by self-report, antidiabetic medication use, fasting glucose ≥126 mg/dL, or random glucose ≥200 mg/dL. Mediating variable was change in serum potassium during year 1. Of the 459 incident cases of diabetes during follow-up, 42% occurred during year 1. In year 1, the unadjusted incidence rates of diabetes per 100 person-years were 6.1 and 3.0 in the chlorthalidone and placebo groups, respectively. In year 1, the adjusted diabetes risk (hazard ratio [HR]) with chlorthalidone was 2.07 (95% Confidence Interval [CI], 1.51–2.83; p<0.001). After adjustment for change in serum potassium, the risk was significantly reduced (HR, 1.54, 95% CI, 1.09–2.17; p=0.01); the extent of risk attenuation (41%; 95% CI, 34–49%) is consistent with a mediating effect. Each 0.5 mEq/L decrease in serum potassium was independently associated with a 45% higher adjusted diabetes risk (95% CI, 24%–70%; p<0.001). After year 1, chlorthalidone use was not associated with increased diabetes risk. In conclusion, thiazide-induced diabetes occurs early after initiating treatment and appears to be mediated by changes in serum potassium. Potassium supplementation might prevent thiazide-induced diabetes. This hypothesis can and should be tested in a randomized trial.