Austin A, Kalhan S C, Orenstein D, Nixon P, Arslanian S
Division of Endocrinology, Children's National Medical Center, Washington, D.C. 20010.
J Clin Endocrinol Metab. 1994 Jul;79(1):80-5. doi: 10.1210/jcem.79.1.8027259.
The roles of insulin deficiency and insulin resistance in the pathogenesis of glucose intolerance in cystic fibrosis (CF) were evaluated in eight patients (aged 16.5 +/- 1.9 yr), four with normal glucose tolerance (NGT) and four with impaired glucose tolerance (IGT), and in seven healthy control (CN) subjects. First and second phase insulin secretions were evaluated during a hyperglycemic clamp. Hepatic glucose production (HGP) and insulin-stimulated glucose disposal were measured using [6,6-2H2]glucose and a stepwise hyperinsulinemic-euglycemic clamp. First and second phase insulin levels were significantly lower in both groups of CF patients compared with control values. There was an inverse relationship between glycohemoglobin level and first phase insulin (r = -0.81; P = 0.015) and second phase insulin (r = -0.97; P < 0.001). During the hyperglycemic clamp, the insulin sensitivity index was lower in CF-IGT, but not CF-NGT, compared with control values (6.66 +/- 1.79, 12.82 +/- 1.61, and 13.02 +/- 1.78 mumol/kg.min/pmol.L, respectively; P < 0.05). Basal HGP and fasting plasma glucose were higher in CF vs. CN [24.8 +/- 2.9 vs. 16.9 +/- 1.4 mumol/kg.min (P = 0.036) and 5.8 +/- 0.2 vs. 5.4 +/- 0.1 mmol/L (P = 0.035), respectively]. During the hyperinsulinemic euglycemic clamp, insulin-stimulated glucose disposal was significantly lower in CF-IGT (45.68 +/- 4.87 mumol/kg.min) vs. CF-NGT (78.99 +/- 1.34 mumol/kg.min) and CN (71.74 +/- 6.88 mumol/kg.min). Insulin sensitivity was lower in CF-IGT vs. CF-NGT (7.04 +/- 0.86 and 14.38 +/- 0.84 mumol/kg.min/pmol.L; P < 0.05). We conclude that 1) glycohemoglobin is a strong correlate of insulin deficiency in CF; and 2) glucose intolerance in this group of CF patients occurred as a consequence of concomitant insulin deficiency and insulin resistance.
在8例患者（年龄16.5±1.9岁）、4例糖耐量正常（NGT）和4例糖耐量受损（IGT）患者以及7例健康对照（CN）受试者中，评估了胰岛素缺乏和胰岛素抵抗在囊性纤维化（CF）糖耐量异常发病机制中的作用。在高血糖钳夹期间评估了第一相和第二相胰岛素分泌。使用[6,6-2H2]葡萄糖和逐步高胰岛素-正常血糖钳夹测量肝葡萄糖生成（HGP）和胰岛素刺激的葡萄糖处置。与对照值相比，两组CF患者的第一相和第二相胰岛素水平均显著降低。糖化血红蛋白水平与第一相胰岛素（r = -0.81；P = 0.015）和第二相胰岛素（r = -0.97；P < 0.001）之间呈负相关。在高血糖钳夹期间，与对照值相比，CF-IGT组的胰岛素敏感性指数较低，但CF-NGT组未降低（分别为6.66±1.79、12.82±1.61和13.02±1.78μmol/kg·min/pmol·L；P < 0.05）。与CN组相比，CF组的基础HGP和空腹血糖更高[分别为24.8±2.9与16.9±1.4μmol/kg·min（P = 0.036）和5.8±0.2与5.4±0.1mmol/L（P = 0.035）]。在高胰岛素-正常血糖钳夹期间，CF-IGT组胰岛素刺激的葡萄糖处置显著低于CF-NGT组（45.68±4.87μmol/kg·min）和CN组（71.74±6.88μmol/kg·min）。CF-IGT组的胰岛素敏感性低于CF-NGT组（7.04±0.86和14.38±0.84μmol/kg·min/pmol·L；P < 0.05）。我们得出结论：1）糖化血红蛋白与CF中的胰岛素缺乏密切相关；2）这组CF患者的糖耐量异常是胰岛素缺乏和胰岛素抵抗共同作用的结果。
