Department of Endocrinology, Hvidovre University Hospital, Copenhagen, Denmark.
Diabetes. 2011 May;60(5):1599-607. doi: 10.2337/db10-1790. Epub 2011 Mar 25.
To investigate the effect of exogenous as well as endogenous glucagon-like peptide 1 (GLP-1) on postprandial glucose excursions and to characterize the secretion of incretin hormones in type 1 diabetic patients with and without residual β-cell function.
Eight type 1 diabetic patients with (T1D+), eight without (T1D-) residual β-cell function, and eight healthy matched control subjects were studied during a mixed meal with concomitant infusion of GLP-1 (1.2 pmol/kg/min), saline, or exendin 9-39 (300 pmol/kg/min). Before the meal, half dose of usual fast-acting insulin was injected. Plasma glucose (PG), glucagon, C-peptide, total GLP-1, intact glucose-dependent insulinotropic polypeptide (GIP), free fatty acids, triglycerides, and gastric emptying rate (GE) by plasma acetaminophen were measured.
Incretin responses did not differ between patients and control subjects. Infusion of GLP-1 decreased peak PG by 45% in both groups of type 1 diabetic patients. In T1D+ patients, postprandial PG decreased below fasting levels and was indistinguishable from control subjects infused with saline. In T1D- patients, postprandial PG remained at fasting levels. GLP-1 infusion reduced GE and glucagon levels in all groups and increased fasting C-peptide in T1D+ patients and control subjects. Blocking endogenous GLP-1 receptor action increased endogenous GLP-1 secretion in all groups and increased postprandial glucose, glucagon, and GE in T1D+ and T1D- patients. The insulinogenic index (the ratio of insulin to glucose) decreased in T1D+ patients during blockade of endogenous GLP-1 receptor action.
Type 1 diabetic patients have normal incretin responses to meals. In type 1 diabetic patients, exogenous GLP-1 decreases peak postprandial glucose by 45% regardless of residual β-cell function. Endogenous GLP-1 regulates postprandial glucose excursions by modulating glucagon levels, GE, and β-cell responsiveness to glucose. Long-term effects of GLP-1 in type 1 diabetic patients should be investigated in future clinical trials.
研究外源性和内源性胰高血糖素样肽 1（GLP-1）对餐后血糖波动的影响，并分析具有和不具有残留β细胞功能的 1 型糖尿病患者的肠促胰岛素激素分泌情况。
8 例具有（T1D+）和不具有（T1D-）残留β细胞功能的 1 型糖尿病患者以及 8 例健康匹配的对照者，在进餐后同时输注 GLP-1（1.2 pmol/kg/min）、生理盐水或 exendin 9-39（300 pmol/kg/min）。进餐前，半量速效胰岛素常规注射。测量血糖（PG）、胰高血糖素、C 肽、总 GLP-1、完整葡萄糖依赖性胰岛素释放肽（GIP）、游离脂肪酸、甘油三酯和胃排空率（GE）。
1 型糖尿病患者与对照组之间的肠促胰岛素反应没有差异。GLP-1 输注可使两组 1 型糖尿病患者的餐后 PG 峰值降低 45%。在 T1D+患者中，餐后 PG 降低至空腹水平以下，与生理盐水输注的对照组患者无差异。在 T1D-患者中，餐后 PG 仍维持在空腹水平。GLP-1 输注可降低所有组的 GE 和胰高血糖素水平，并增加 T1D+患者和对照组的空腹 C 肽。阻断内源性 GLP-1 受体作用可增加所有组的内源性 GLP-1 分泌，并增加 T1D+和 T1D-患者的餐后 PG、胰高血糖素和 GE。在阻断内源性 GLP-1 受体作用时，T1D+患者的胰岛素原指数（胰岛素与血糖的比值）降低。
1 型糖尿病患者对进餐具有正常的肠促胰岛素反应。在 1 型糖尿病患者中，外源性 GLP-1 可使餐后血糖峰值降低 45%，而与残留β细胞功能无关。内源性 GLP-1 通过调节胰高血糖素水平、GE 和β细胞对葡萄糖的反应来调节餐后血糖波动。在未来的临床试验中应研究 GLP-1 在 1 型糖尿病患者中的长期作用。
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