Lender D, Arauz-Pacheco C, Adams-Huet B, Raskin P
Department of Internal Medicine, University of Texas Southwestern Medical Center at Dallas, USA.
Hypertension. 1997 Jan;29(1 Pt 1):111-4. doi: 10.1161/01.hyp.29.1.111.
Essential hypertension is associated with multiple metabolic abnormalities, among them, hyperinsulinemia. This hyperinsulinemia is attributed to the presence of decreased insulin sensitivity (insulin resistance) with consequent compensatory insulin secretion. We tested the hypothesis that decreased insulin clearance is present in hypertensive subjects and contributes to hyperinsulinemia independently of the degree of insulin resistance. Seventy-five subjects were studied (48 hypertensive and 27 normotensive). Both groups were comparable in terms of age, body fat content, waist-to-hip ratio, and sex distribution. A primed continuous insulin infusion at 40 mU/m2 per minute was performed. Glucose was maintained at baseline levels with the euglycemic clamp technique. Hypertensive subjects were characterized by decreased insulin sensitivity (insulin-mediated glucose uptake: 5.14 +/- 0.28 versus 7.26 +/- 0.61 mg glucose/kg fat-free mass per minute, hypertensive versus normotensive, P = .002), increased insulin levels during the insulin infusions (804 +/- 36 versus 510 +/- 38 pmol/L, hypertensive versus normotensive, P < .001), and decreased insulin metabolic clearance rate (328 +/- 15 versus 521 +/- 30 mL/min per meter squared, hypertensive versus normotensive, P < .001). In an ANCOVA (including sex, degree of obesity, waist-to-hip ratio, and insulin sensitivity as covariates) the differences in insulin metabolic clearance rate between normotensive and hypertensive subjects remained highly significant (P < .001). Insulin metabolic clearance rate was significantly associated with fasting insulin levels. We conclude that essential hypertension is independently associated with decreased insulin metabolic clearance rate in addition to insulin resistance. A low insulin metabolic clearance rate may be a contributory factor to the hyperinsulinemia observed in essential hypertension.
原发性高血压与多种代谢异常相关，其中包括高胰岛素血症。这种高胰岛素血症归因于胰岛素敏感性降低（胰岛素抵抗），随之出现代偿性胰岛素分泌。我们检验了这样一个假设，即高血压患者存在胰岛素清除率降低，且与胰岛素抵抗程度无关，它是导致高胰岛素血症的原因。我们研究了75名受试者（48名高血压患者和27名血压正常者）。两组在年龄、体脂含量、腰臀比和性别分布方面具有可比性。以每分钟40 mU/m²的剂量进行静脉持续注射胰岛素并进行初始推注。采用正常血糖钳夹技术将血糖维持在基线水平。高血压患者的特点是胰岛素敏感性降低（胰岛素介导的葡萄糖摄取：高血压组为5.14±0.28，正常血压组为7.26±0.61 mg葡萄糖/千克去脂体重每分钟，P = 0.002），胰岛素输注期间胰岛素水平升高（高血压组为804±36，正常血压组为510±38 pmol/L，P < 0.001），胰岛素代谢清除率降低（高血压组为328±15，正常血压组为521±30 mL/分钟每平方米，P < 0.001）。在协方差分析（将性别、肥胖程度、腰臀比和胰岛素敏感性作为协变量）中，正常血压组和高血压组之间胰岛素代谢清除率的差异仍然非常显著（P < 0.001）。胰岛素代谢清除率与空腹胰岛素水平显著相关。我们得出结论，除胰岛素抵抗外，原发性高血压还与胰岛素代谢清除率降低独立相关。低胰岛素代谢清除率可能是原发性高血压中观察到的高胰岛素血症的一个促成因素。
