Improved Glycemic Control Enhances the Incretin Effect in Patients With Type 2 Diabetes

• Published in: The journal of clinical endocrinology and metabolism Vol. 98; no. 12; pp. 4702 - 4708
• Main Authors: An, Zhibo, Prigeon, Ronald L, D'Alessio, David A
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Endocrine Society 01.12.2013; Copyright by The Endocrine Society
• Subjects: Biological and medical sciences; Body Mass Index; C-Peptide - blood; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - metabolism; Diabetes. Impaired glucose tolerance; Drug Monitoring; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Feeding. Feeding behavior; Female; Fundamental and applied biological sciences. Psychology; Glucose Clamp Technique; Humans; Hyperglycemia - prevention & control; Hypoglycemic Agents - administration & dosage; Hypoglycemic Agents - therapeutic use; Incretins - blood; Incretins - metabolism; Insulin - blood; Insulin - metabolism; Insulin Glargine; Insulin Resistance; Insulin Secretion; Insulin, Long-Acting - administration & dosage; Insulin, Long-Acting - therapeutic use; Insulin-Secreting Cells - drug effects; Insulin-Secreting Cells - metabolism; Male; Medical sciences; Middle Aged; Overweight - complications; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Vertebrates: endocrinology; Endocrinopathy; Type 2 diabetes; Human; Glycemic control; Obesity; Incretin; Nutrition; Nutrition disorder; Patient; Metabolic diseases; Target tissue resistance; Insulin resistance; Endocrinology; Nutritional status; Glycemia
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2013-1199

Background and Aims: 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. 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 iv glucose, and iv 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 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). Conclusion: 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.