AIMS/HYPOTHESIS The aim of this study was to determine the mechanism(s) for hypoglycaemia occurring late following oral glucose loading in patients with cystic fibrosis (CF). METHODS A 3 h 75 g OGTT was performed in 27 non-diabetic adults with CF who were classified based on this test as experiencing hypoglycaemia (glucose <3.3 mmol/l with or without symptoms or glucose <3.9 mmol/l with symptoms, n = 14) or not (n = 13). Beta cell function, incretin (glucagon-like peptide-1 [GLP-1] and glucose-dependent insulinotropic peptide [GIP]) and counterregulatory hormone responses (glucagon, catecholamines, growth hormone and cortisol) were assessed. RESULTS The two groups did not differ in age, weight or BMI. There were more male participants and individuals with pancreatic exocrine insufficiency in the hypoglycaemia group. Fasting plasma glucose did not differ between the two groups (5.3 ± 0.16 vs 5.3 ± 0.10 mmol/l). Both fasting insulin (20.7 ± 2.9 vs 36.5 ± 4.8 pmol/l; p = 0.009) and C-peptide (0.38 ± 0.03 vs 0.56 ± 0.05 nmol/l; p = 0.002) were lower in those who experienced hypoglycaemia. Following glucose ingestion, glucose concentrations were significantly lower in the hypoglycaemia group from 135 min onwards, with a nadir of 3.2 ± 0.2 vs 4.8 ± 0.3 mmol/l at 180 min (p < 0.001). The test was terminated early in three participants because of a glucose level <2.5 mmol/l. Insulin and C-peptide concentrations were also lower in the hypoglycaemia group, while incretin hormone responses were not different. Modelling demonstrated that those experiencing hypoglycaemia were more insulin sensitive (439 ± 17.3 vs 398 ± 13.1 ml min-1 m-2, p = 0.074 based on values until 120 min [n = 14]; 512 ± 18.9 vs 438 ± 15.5 ml min-1 m-2, p = 0.006 based on values until 180 min [n = 11]). In line with their better insulin sensitivity, those experiencing hypoglycaemia had lower insulin secretion rates (ISRfasting: 50.8 ± 3.2 vs 74.0 ± 5.9 pmol min-1 m-2, p = 0.002; ISROGTT: 44.9 ± 5.0 vs 63.4 ± 5.2 nmol/m2, p = 0.018) and beta cell glucose sensitivity (47.4 ± 4.5 vs 79.2 ± 7.5 pmol min-1 m-2 [mmol/l]-1, p = 0.001). Despite the difference in glucose concentrations, there were no significant increases in glucagon, noradrenaline, cortisol or growth hormone levels. Adrenaline increased by only 66% and 61% above baseline at 165 and 180 min when glucose concentrations were 3.8 ± 0.2 and 3.2 ± 0.2 mmol/l, respectively. CONCLUSIONS/INTERPRETATION Hypoglycaemia occurring late during an OGTT in people with CF was not associated with the expected counterregulatory hormone response, which may be a consequence of more advanced pancreatic dysfunction/destruction.

中文翻译：

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成年性囊性纤维化患者口服葡萄糖后对低血糖的反调节反应受损。

目的/假设这项研究的目的是确定在患有囊性纤维化（CF）的患者口服葡萄糖负荷后晚期发生低血糖的机制。方法对27例非糖尿病成人CF进行3 h 75 g OGTT，根据该测试将其归类为发生低血糖（葡萄糖<3.3 mmol / l有症状或无症状，或葡萄糖<3.9 mmol / l有症状，n = 14）或否（n = 13）。评估了β细胞功能，肠降血糖素（胰高血糖素样肽1 [GLP-1]和葡萄糖依赖性促胰岛素肽[GIP]）和反调节激素反应（胰高血糖素，儿茶酚胺，生长激素和皮质醇）。结果两组的年龄，体重或BMI均无差异。低血糖组中有更多的男性参与者和胰腺外分泌功能不全的个体。两组之间的空腹血糖无差异（5.3±0.16 vs 5.3±0.10 mmol / l）。在发生低血糖的患者中，空腹胰岛素（20.7±2.9 vs 36.5±4.8 pmol / l； p = 0.009）和C肽（0.38±0.03 vs 0.56±0.05 nmol / l； p = 0.002）均较低。摄入葡萄糖后，低血糖组的葡萄糖浓度从135分钟起显着降低，最低点为180分钟时的最低点为3.2±0.2 vs 4.8±0.3 mmol / l（p <0.001）。由于葡萄糖水平<2.5 mmol / l，该测试在三名参与者中提前终止。低血糖组的胰岛素和C肽浓度也较低，而肠降血糖素激素反应无差异。模型表明，那些发生低血糖症的人对胰岛素的敏感性更高（439±17.3 vs 398±13.1 ml min-1 m-2，p = 0。074基于直到120分钟[n = 14]的值；512±18.9 vs 438±15.5 ml min-1 m-2，基于直到180 min的值，p = 0.006 [n = 11]）。与他们具有更好的胰岛素敏感性一样，患有低血糖症的患者的胰岛素分泌率更低（ISRfasting：50.8±3.2 vs 74.0±5.9 pmol min-1 m-2，p = 0.002; ISROGTT：44.9±5.0 vs 63.4±5.2 nmol / m2 ，p = 0.018）和β细胞葡萄糖敏感性（47.4±4.5 vs 79.2±7.5 pmol min-1 m-2 [mmol / l] -1，p = 0.001）。尽管葡萄糖浓度存在差异，但胰高血糖素，去甲肾上腺素，皮质醇或生长激素水平没有明显增加。当葡萄糖浓度分别为3.8±0.2和3.2±0.2 mmol / l时，肾上腺素在165和180分钟时仅比基线增加66％和61％。