Impaired β-cell function, incretin effect, and glucagon suppression in patients with type 1 diabetes who have normal fasting glucose
Impaired β-cell function, incretin effect, and glucagon suppression in patients with type 1 diabetes who have normal fasting glucose
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DOI：
10.2337/diabetes.51.4.951
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发表时间：
2002-04-01
期刊：
影响因子：
7.7
通讯作者：
D'Alessio, DA
中科院分区：
文献类型：
--
作者：
Greenbaum, CJ;Prigeon, RL;D'Alessio, DA
我们最近在一组 1 型糖尿病受试者中描述了一种新的表型，其表现为口服葡萄糖负荷后血糖 >11.1 mmol/1 120 分钟，但空腹血糖水平正常。我们现在通过将这些受试者的胰岛激素分泌和葡萄糖处理参数与年龄匹配的非糖尿病对照受试者进行比较来描述这些受试者的代谢特征。 1 型糖尿病患者的空腹血糖、胰岛素和胰高血糖素值与对照组相似。此外，在血糖正常的情况下，对照组和糖尿病组对静脉注射精氨酸的胰岛素分泌反应相似（264 +/- 33.5 和 193 +/- 61.3 pmol/1；P = 0.3）。然而，β细胞功能对高血糖的反应存在显着差异。具体而言，糖尿病受试者的第一阶段胰岛素反应较低（329.1 +/- 39.6 vs. 91.3 +/- 34.1 pmol/1；P < 0.001），胰岛素对精氨酸反应的葡萄糖增强斜率也较低（102 +/- 18.7 vs. 30.2 +/- 6.1 pmol/1 每mmol/1；P = 0.005）对精氨酸的最大胰岛素反应（2,524 +/- 413 vs. 629 +/- 159 pmol/1；P = 0.001）。尽管胰高血糖素样肽 (GLP)-1 和抑胃肽 (GIP) 的血浆水平在对照组和糖尿病受试者之间没有差异，但糖尿病患者中肠促胰岛素的作用较低（70.3 +/- 5.4 vs. 52.1 +/- 5.9%；P = 0.03）。最后，口服和静脉注射葡萄糖后，患者体内的胰高血糖素缺乏抑制，这可能是导致餐后高血糖的原因。尽管患者有胰岛素抵抗的倾向，但患者和对照受试者之间的血糖有效性没有差异，胰岛素敏感性也没有差异（9.18 +/- 1.59 vs. 5.22 +/- 1.17 pmol (.) 1(-1) min(-1)；P = 0.08）。这些数据描述了一组新的 1 型糖尿病受试者，仅表现为口服葡萄糖负荷后的高血糖，这些受试者在血糖正常时胰岛功能正常，但在高血糖时 α 和 β 细胞分泌均存在明显缺陷。这种异常模式可能是 1 型糖尿病发展早期胰岛功能障碍的特征。
We have recently described a novel phenotype in a group of subjects with type 1 diabetes that is manifested by glucose >11.1 mmol/1 120 min after an oral glucose load, but with normal fasting glucose levels. We now describe the metabolic characteristics of these subjects by comparing parameters of islet hormone secretion and glucose disposal in these subjects to age-matched nondiabetic control subjects. The patients with type 1 diabetes had fasting glucose, insulin, and glucagon values similar to those of control subjects. Additionally, the insulin secretory response to intravenous arginine at euglycemia was similar in the control and diabetic groups (264 +/- 33.5 and 193 +/- 61.3 pmol/1; P = 0.3). However, marked differences in beta-cell function were found in response to hyperglycemia. specifically, the first-phase insulin response was lower in diabetic subjects (329.1 +/- 39.6 vs. 91.3 +/- 34.1 pmol/1; P < 0.001), as was the slope of glucose potentiation of the insulin response to arginine (102 +/- 18.7 vs. 30.2 +/- 6.1 pmol/1 per mmol/1; P = 0.005) and the maximum insulin response to arginine (2,524 +/- 413 vs. 629 +/- 159 pmol/1; P = 0.001). Although plasma levels of glucagon-like peptide (GLP)-1 and gastric inhibitory peptide (GIP) did not differ between control and diabetic subjects, the incretin effect was lower in the diabetic patients (70.3 +/- 5.4 vs. 52.1 +/- 5.9%; P = 0.03). Finally, there was a lack of suppression of glucagon in the patients after both oral and intravenous glucose administration, which may have contributed to their postprandial hyperglycemia. Glucose effectiveness did not differ between patients and control subjects, nor did insulin sensitivity, although there was a tendency for the patients to be insulin resistant (9.18 +/- 1.59 vs. 5.22 +/- 1.17 pmol (.) 1(-1) min(-1); P = 0.08). These data characterize a novel group of subjects with type 1 diabetes manifested solely by hyperglycemia following an oral glucose load in whom islet function is normal at euglycemia, but who have marked defects in both alpha- and beta-cell secretion at hyperglycemia. This pattern of abnormalities may be characteristic of islet dysfunction early in the development of type 1 diabetes.