MD, 2170 East Galbraith Road, Room E-319, University of Cincinnati, Cincinnati, OH 45237.
J Clin Endocrinol Metab. 2013 Dec;98(12):4702-8. doi: 10.1210/jc.2013-1199. Epub 2013 Oct 3.
Impairment of the incretin effect is one of the hallmarks of type 2 diabetes mellitus (T2DM). However, it is unknown whether this abnormality is specific to incretin-stimulated insulin secretion or a manifestation of generalized β-cell dysfunction. The aim of this study was to determine whether improved glycemic control restores the incretin effect.
Fifteen T2DM subjects were studied before and after 8 weeks of intensified treatment with insulin. The incretin effect was determined by comparing plasma insulin and C-peptide levels at clamped hyperglycemia from iv glucose, and iv glucose plus glucose ingestion.
Long-acting insulin, titrated to reduce fasting glucose to 7 mM, lowered hemoglobin A1c from 8.6% ± 0.2% to 7.1% ± 0.2% over 8 weeks. The incremental C-peptide responses and insulin secretion rates to iv glucose did not differ before and after insulin treatment (5.6 ± 1.0 and 6.0 ± 0.9 nmol/L·min and 0.75 ± 0.10 and 0.76 ± 0.11 pmol/min), but the C-peptide response to glucose ingestion was greater after treatment than before (10.9 ± 2.2 and 7.1 ± 0.9 nmol/L·min; P = .03) as were the insulin secretion rates (1.11 ± 0.22 and 0.67 ± 0.07 pmol/min; P = .04). The incretin effect computed from plasma C-peptide was 21.8% ± 6.5% before insulin treatment and increased 40.9% ± 3.9% after insulin treatment (P < .02).
Intensified insulin treatment to improve glycemic control led to a disproportionate improvement of insulin secretion in response to oral compared with iv glucose stimulation in patients with type 2 diabetes. This suggests that in T2DM the impaired incretin effect is independent of abnormal glucose-stimulated insulin secretion.
肠促胰岛素效应受损是 2 型糖尿病（T2DM）的特征之一。然而，这种异常是否仅与肠促胰岛素刺激的胰岛素分泌有关，还是β细胞功能普遍受损的表现尚不清楚。本研究旨在确定血糖控制的改善是否能恢复肠促胰岛素效应。
15 例 T2DM 患者在强化胰岛素治疗 8 周前后进行了研究。通过比较静脉葡萄糖和静脉葡萄糖加葡萄糖摄入时钳夹高血糖时的血浆胰岛素和 C 肽水平来确定肠促胰岛素效应。
长效胰岛素滴定以将空腹血糖降低至 7 mM，使血红蛋白 A1c 从 8.6%±0.2%降至 7.1%±0.2%，历时 8 周。静脉葡萄糖刺激后，胰岛素分泌率和 C 肽的增量反应在胰岛素治疗前后无差异（5.6±1.0 和 6.0±0.9 nmol/L·min 和 0.75±0.10 和 0.76±0.11 pmol/min），但葡萄糖摄入后 C 肽的反应更大（10.9±2.2 和 7.1±0.9 nmol/L·min；P=0.03），胰岛素分泌率也更大（1.11±0.22 和 0.67±0.07 pmol/min；P=0.04）。在胰岛素治疗前，血浆 C 肽计算的肠促胰岛素效应为 21.8%±6.5%，治疗后增加 40.9%±3.9%（P<0.02）。
强化胰岛素治疗以改善血糖控制，导致患者对口服葡萄糖刺激的胰岛素分泌不成比例地改善，而对静脉葡萄糖刺激的胰岛素分泌改善较小。这表明在 T2DM 中，受损的肠促胰岛素效应与异常的葡萄糖刺激的胰岛素分泌无关。
