Klauser R, Prager R, Gaube S, Gisinger C, Schnack C, Küenburg E, Schernthaner G
Department of Medicine II, University of Vienna, Austria.
Hypertension. 1991 Jan;17(1):15-21. doi: 10.1161/01.hyp.17.1.15.
Most antihypertensive drugs have negative effects on metabolic control in diabetic patients. Calcium antagonists have been widely used in antihypertensive treatment of diabetics, although a possible influence on glucose tolerance, insulin secretion, and insulin action is unknown. Therefore, the effect of the calcium antagonist isradipine on glucose tolerance and insulin secretion (75 g oral glucose tolerance test) and on peripheral and hepatic insulin action (euglycemic clamp) was evaluated in 11 type II diabetic patients. All patients were treated with placebo or isradipine for 8 weeks (double-blind, crossover design). A second group of six diabetic patients received a thiazide diuretic, hydrochlorothiazide, according to the same protocol. Systolic blood pressure was significantly lowered after isradipine and hydrochlorothiazide compared with placebo (127 +/- 3 versus 139 +/- 6 mm Hg and 129 +/- 4 versus 142 +/- 4, respectively; p less than 0.05). Fasting blood glucose (190 +/- 21 versus 152 +/- 15 mg/dl; p less than 0.01), glucose levels, basal and glucose-stimulated insulin levels were significantly higher after hydrochlorothiazide compared with placebo but remained unchanged after calcium antagonist treatment. Basal hepatic glucose production and peripheral insulin resistance were significantly elevated after hydrochlorothiazide compared with placebo or calcium antagonist therapy. These data indicate that the calcium antagonist isradipine has no effect on glucose tolerance, insulin secretion, and insulin action in type II diabetic patients and might therefore be a useful drug for antihypertensive treatment in diabetes mellitus. However, diuretic treatment can lead to impairment of metabolic control and reduction of insulin action in type II diabetes mellitus.
大多数抗高血压药物对糖尿病患者的代谢控制有负面影响。钙拮抗剂已广泛应用于糖尿病患者的抗高血压治疗，尽管其对葡萄糖耐量、胰岛素分泌和胰岛素作用的潜在影响尚不清楚。因此，在11例II型糖尿病患者中评估了钙拮抗剂伊拉地平对葡萄糖耐量和胰岛素分泌（75g口服葡萄糖耐量试验）以及对周围和肝脏胰岛素作用（正常血糖钳夹）的影响。所有患者接受安慰剂或伊拉地平治疗8周（双盲，交叉设计）。第二组6例糖尿病患者按照相同方案接受噻嗪类利尿剂氢氯噻嗪治疗。与安慰剂相比，伊拉地平和氢氯噻嗪治疗后收缩压显著降低（分别为127±3对139±6mmHg和129±4对142±4；p<0.05）。与安慰剂相比，氢氯噻嗪治疗后空腹血糖（190±21对152±15mg/dl；p<0.01）、血糖水平、基础和葡萄糖刺激的胰岛素水平显著升高，但钙拮抗剂治疗后保持不变。与安慰剂或钙拮抗剂治疗相比，氢氯噻嗪治疗后基础肝脏葡萄糖生成和周围胰岛素抵抗显著升高。这些数据表明，钙拮抗剂伊拉地平对II型糖尿病患者的葡萄糖耐量、胰岛素分泌和胰岛素作用无影响，因此可能是糖尿病抗高血压治疗的有用药物。然而，利尿剂治疗可导致II型糖尿病患者代谢控制受损和胰岛素作用降低。
