Insulin resistance and hyperinsulinemia are already present in patients with incipient renal disease
Insulin resistance and hyperinsulinemia are already present in patients with incipient renal disease
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DOI：
10.1046/j.1523-1755.1998.00898.x
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发表时间：
1998-05-01
影响因子：
19.6
通讯作者：
Ritz, E
中科院分区：
文献类型：
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作者：
Fliser, D;Pacini, G;Ritz, E
尿毒症患者对胰岛素作用的抵抗已被记录，但尚不清楚其出现在肾脏疾病的哪个阶段。因此，我们检查了 29 名 IgA 肾小球肾炎 (IgAGN) 患者和 21 名处于肾衰竭不同阶段的成人多囊肾病 (ADPKD) 患者，以及健康年龄匹配的健康受试者。使用频繁采样的静脉内葡萄糖耐量试验（最小模型技术）评估胰岛素敏感性和葡萄糖代谢的其他变量。使用菊粉清除技术评估肾病患者的肾小球滤过率（GFR）。所有患者的平均胰岛素敏感性指数（SI），即胰岛素敏感性，均显着低于匹配的健康受试者（P < 0.001）（N = 16；14 名男性，平均年龄 42 +/- 3 岁；平均 SI 8.6 +/- 0.8 min(-1) mu U/ml）。免疫性肾病 (IgAGN) 或非免疫性肾病 (ADPKD) 患者的平均 SI 没有显着差异，并且与 GFR (r = 0.01，P < 0.52)、完整 PTH (r = 0.23，P < 0.11) 或骨化三醇浓度 (r = -0.03，P < 0.82) 不相关。因此，GFR 在正常范围内的肾病患者（N = 19；17 名男性，平均年龄 41 +/- 2 岁：平均 GFR 119 +/- 5 ml/min/1.73 m(2)；平均 SI 5.1 +/- 0.7 min(-1) mu U/ml）与轻度至中度肾衰竭患者（N = 16，15 名男性，46 +/- 3）相似。年龄：67 +/- 4 毫升/分钟/1.73 米(2)； 5.1 +/- 0.7 min(-1) mu U/ml) 和晚期肾衰竭患者（N = 15；13 名男性。46 +/- 3 岁。25 +/- 2 ml/min/1.73 m(2)；4.7 +/- 0.6 min(-1) mu U/ml）。患者的平均空腹血浆胰岛素浓度、糖耐量试验期间血浆胰岛素浓度曲线下面积（AUC）和总胰岛素输送量（TID）均显着高于健康受试者，反映了肾病患者的高胰岛素血症。此外，患者的空腹血浆胰岛素浓度（r=-0.32，P<0.009）：AUC（r=-0.62，P<0.0001）和TID（r=-0.34，P<0.001）与胰岛素敏感性（SI）显着相关。目前的数据表明，胰岛素抵抗和伴随的高胰岛素血症在肾脏疾病的早期就存在：也就是说，即使在肾小球滤过率在正常范围内的患者中，无论肾脏疾病的类型如何。这一观察结果可能对肾病患者的高心血管发病率和死亡率具有潜在影响。
In uremic patients resistance to the action of insulin has been documented, but it is not known at what stage of renal disease it appears. We therefore examined 29 patients with IgA glomerulonephritis (IgAGN) and 21 patients with adult polycystic kidney disease (ADPKD) in different stages of renal failure, and ill addition, healthy age-matched subjects. Insulin sensitivity and other variables of glucose metabolism were assessed using a frequent sampling intravenous glucose tolerance test (minimal-model technique). Glomerular filtration rate (GFR) was assessed in renal patients using the inulin-clearance technique. Mean insulin sensitivity index (SI), that is, insulin sensitivity, was significantly lower (P < 0.001) in all patients combined than in matched healthy subjects (N = 16; 14 males, mean age 42 +/- 3 years; mean SI 8.6 +/- 0.8 min(-1) mu U/ml). The mean SI was not significantly different in patients with renal disease of immune (IgAGN) or non-immune (ADPKD) origin, and it was not correlated with GFR (r = 0.01, P < 0.52), intact PTH (r = 0.23, P < 0.11) or calcitriol concentration (r = -0.03, P < 0.82). Consequently, the mean SI was similar in renal patients with GFR within the normal range (N = 19; 17 males, mean age 41 +/- 2 years: mean GFR 119 +/- 5 ml/min/1.73 m(2); mean SI 5.1 +/- 0.7 min(-1) mu U/ml), in patients with mild to moderate renal failure (N = 16, 15 males, 46 +/- 3 years: 67 +/- 4 ml/min/1.73 m(2); 5.1 +/- 0.7 min(-1) mu U/ml) and in patients with advanced renal failure (N = 15; 13 males. 46 +/- 3 years. 25 +/- 2 ml/min/1.73 m(2); 4.7 +/- 0.6 min(-1) mu U/ml). Mean fasted plasma insulin concentration, the area under the curve for plasma insulin concentration (AUC) and total insulin delivery (TID) during the glucose tolerance test were significantly higher in patients than in healthy subjects, reflecting hyperinsulinemia in renal patients. Further, fasted plasma insulin concentration (r= -0.32, P < 0.009): AUC (r = -0.62. P < 0.0001) and TID (r = -0.34. P < 0.001) in patients were significantly correlated with insulin sensitivity (SI). Thr present data document that insulin resistance and concomitant hyperinsulinemia are present early in the course of renal disease: that is, even in patients with GFR within the normal range, irrespective of the type of renal disease. This observation may have potential implications with respect to the high cardiovascular morbidity and mortality in patients with renal disease.