Four weeks of near-normalisation of blood glucose improves the insulin response to glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide in patients with type 2 diabetes

• Published in: Diabetologia 2009-02, Vol.52 (2), p.199-207
• Main Authors: Højberg, P. V, Vilsbøll, T, Rabøl, R, Knop, F. K, Bache, M, Krarup, T, Holst, J. J, Madsbad, S
• Format: Article
• Language: English
• Subjects: Adult; Beta-cell responsiveness; Biological and medical sciences; Blood Glucose - drug effects; Blood Glucose - metabolism; C-Peptide - blood; Diabetes; Diabetes Mellitus, Type 2 - blood; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Fasting; Fructosamine - blood; Gastric Inhibitory Polypeptide - administration & dosage; Gastric Inhibitory Polypeptide - pharmacology; Glucagon; Glucagon-Like Peptide 1 - administration & dosage; Glucagon-Like Peptide 1 - pharmacology; Glucose; Glucose-dependent insulinotropic polypeptide; Glugagon like peptide-1; Glycated Hemoglobin A - drug effects; Glycated Hemoglobin A - metabolism; Hormones; Human Physiology; Humans; Incretin hormones; Infusions, Intravenous; Insulin; Insulin - blood; Insulin treatment; Internal Medicine; Investigations; Male; Medical sciences; Medicine; Medicine & Public Health; Metabolic Diseases; Middle Aged; Physiology; Polypeptides; Reference Values; Type 2 diabetes mellitus
• ISSN: 0012-186X; 1432-0428
• DOI: 10.1007/s00125-008-1195-5

Objective The incretin effect is attenuated in patients with type 2 diabetes mellitus, partly as a result of impaired beta cell responsiveness to glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1). The aim of the present study was to investigate whether 4 weeks of near-normalisation of the blood glucose level could improve insulin responses to GIP and GLP-1 in patients with type 2 diabetes. Methods Eight obese patients with type 2 diabetes with poor glycaemic control (HbA₁c 8.6 ± 1.3%), were investigated before and after 4 weeks of near-normalisation of blood glucose (mean blood glucose 7.4 ± 1.2 mmol/l) using insulin treatment. Before and after insulin treatment the participants underwent three hyperglycaemic clamps (15 mmol/l) with infusion of GLP-1, GIP or saline. Insulin responses were evaluated as the incremental area under the plasma C-peptide curve. Results Before and after near-normalisation of blood glucose, the C-peptide responses did not differ during the early phase of insulin secretion (0-10 min). The late phase C-peptide response (10-120 min) increased during GIP infusion from 33.0 ± 8.5 to 103.9 ± 24.2 (nmol/l) x (110 min)⁻¹ (p < 0.05) and during GLP-1 infusion from 48.7 ± 11.8 to 126.6 ± 32.5 (nmol/l) x (110 min)⁻¹ (p < 0.05), whereas during saline infusion the late-phase response did not differ before vs after near-normalisation of blood glucose (40.2 ± 11.2 vs 46.5 ± 12.7 [nmol/l] x [110 min]⁻¹). Conclusions Near-normalisation of blood glucose for 4 weeks improves beta cell responsiveness to both GLP-1 and GIP by a factor of three to four. No effect was found on beta cell responsiveness to glucose alone. ClinicalTrials.gov ID no.: NCT 00612950 Funding: This study was supported by The Novo Nordisk Foundation, The Medical Science Research Foundation for Copenhagen.