Improved glycemic control enhances the incretin effect in patients with type 2 diabetes

Abstract

Background and Aims: Impairment of the incretin effect is one of the hallmarks of type 2 diabetes mellitus (T2DM). However, it isunknownwhether 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. Methods: 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 4 glucose, and 4 glucose plus glucose ingestion. Results: 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 4 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). Conclusion: Intensified insulin treatment to improve glycemic control led to a disproportionate improvement of insulin secretion in response to oral compared with 4 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. © 2013 by The Endocrine Society.