Helderman J H, Elahi D, Andersen D K, Raizes G S, Tobin J D, Shocken D, Andres R
Diabetes. 1983 Feb;32(2):106-11. doi: 10.2337/diab.32.2.106.
The effect of thiazide diuretics on the glucose tolerance of seven normal men in whom potassium loss was prevented with supplementation was studied using the glucose clamp technique. An initial control 2-h hyperglycemic clamp was performed to create a square wave of hyperglycemia 125 mg/dl above basal. At 1 h, 40 g glucose/m2 body surface area was ingested. Serial insulin (IRI) and gastric inhibitory polypeptide (GIP) levels were measured as well as the level of glucose infusion necessary to maintain the stable hyperglycemic level. After the initial study, subjects were placed on a 10-day course of 100 mg hydrochlorothiazide and 80 meq potassium per day. Subjects were monitored for dietary potassium intake, urinary potassium, and sodium losses, and the replacement of potassium adjusted accordingly. A repeat glucose clamp was done on day 10. When potassium losses were prevented, thiazides induced no alterations in glucose tolerance, beta-cell sensitivity to glucose, GIP-cell sensitivity to glucose, beta-cell sensitivity to GIP, or tissue sensitivity to insulin. Two control studies in which hypokalemia was allowed to ensue after hydrochlorothiazide ingestion revealed a diminution in glucose tolerance, a consequence of diminished pancreatic beta-cell response to glucose. We conclude that the thiazide effect on glucose tolerance is a consequence of the resultant hypokalemia that the diuretic may create.
采用葡萄糖钳夹技术研究了噻嗪类利尿剂对7名通过补充钾来预防钾流失的正常男性葡萄糖耐量的影响。首先进行2小时的高血糖钳夹对照实验，以产生高于基础水平125mg/dl的高血糖方波。在1小时时，摄入40g葡萄糖/m²体表面积。测量了胰岛素（IRI）和胃抑制多肽（GIP）的系列水平以及维持稳定高血糖水平所需的葡萄糖输注水平。在初始研究后，受试者接受为期10天的疗程，每天服用100mg氢氯噻嗪和80meq钾。监测受试者的膳食钾摄入量、尿钾和钠流失情况，并相应调整钾的补充量。在第10天进行重复葡萄糖钳夹实验。当钾流失得到预防时，噻嗪类药物不会引起葡萄糖耐量、β细胞对葡萄糖的敏感性、GIP细胞对葡萄糖的敏感性、β细胞对GIP的敏感性或组织对胰岛素的敏感性发生改变。两项对照研究显示，在摄入氢氯噻嗪后任由低钾血症发展，会导致葡萄糖耐量降低，这是胰腺β细胞对葡萄糖反应减弱的结果。我们得出结论，噻嗪类药物对葡萄糖耐量的影响是利尿剂可能导致的低钾血症的结果。
