Four weeks of near-normalization of blood glucose has no effect on postprandial GLP-1 and GIP secretion, but augments pancreatic B-cell responsiveness to a meal in patients with Type 2 diabetes

• Published in: Diabetic medicine Vol. 25; no. 11; pp. 1268 - 1275
• Main Authors: Højberg, P. V., Vilsbøll, T., Zander, M., Knop, F. K., Krarup, T., Vølund, A., Holst, J. J., Madsbad, S.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-11-2008; Blackwell
• Subjects: Area Under Curve; B-cell function; Biological and medical sciences; Blood Glucose - metabolism; Diabetes Mellitus, Type 2 - metabolism; Diabetes. Impaired glucose tolerance; Eating - physiology; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Fasting - metabolism; Feeding. Feeding behavior; Female; Fundamental and applied biological sciences. Psychology; Gastric Inhibitory Polypeptide - metabolism; Glucagon - metabolism; Glucagon-Like Peptide 1 - metabolism; glucagon-like peptide-1; glucose-dependent insulinotropic polypeptide; Humans; Hyperglycemia - metabolism; Insulin - metabolism; Insulin Secretion; Insulin-Secreting Cells - metabolism; Male; meal response; Medical sciences; Middle Aged; Postprandial Period - physiology; Type 2 diabetes mellitus; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Vertebrates: endocrinology; Endocrinopathy; Type 2 diabetes; Cell function; Meal; glucagon-like peptide-1; Type 2 diabetes mellitus; glucose-dependent insulinotropic polypeptide; Gastrointestinal hormone; β Cell; Pancreas; Nutritional status; Human; Obesity; Nutrition; Postprandial; Secretion; Nutrition disorder; Patient; Metabolic diseases; B-Lymphocyte; Glucagon like peptide 1; B-cell function; meal response; Gastric inhibitory peptide; Endocrinology; Glycemia
• ISSN: 0742-3071; 1464-5491
• DOI: 10.1111/j.1464-5491.2008.02579.x

Objective   The aim of the present study was to investigate whether 4 weeks of near‐normalization of blood glucose (BG) improves incretin hormone secretion and pancreatic B‐cell function during a mixed meal.
Research design and methods   Nine patients with Type 2 diabetes in poor glycaemic control [glycated haemoglobin (HbA1c) 8.0 ± 0.4%] were investigated before and after 4 weeks of near‐normalization of BG (mean BG 6.4 ± 0.3 mmol/l) using insulin treatment. HbA1c after insulin treatment was 6.6 ± 0.3%. For comparison, nine healthy control subjects were also studied. Postprandial glucagon‐like peptide 1 (GLP‐1) and glucose‐dependent insulinotropic polypeptide (GIP) incremental responses were assessed during a mixed meal test. Fasting and postprandial pancreatic B‐cell function was determined from calculations of insulin secretion rates in relation to plasma glucose.
Results   There was no difference in IAUCtotalGLP‐1 or in IAUCtotalGIP between the two experimental days. B‐cell sensitivity to glucose (insulinogenic index) did not differ before and after insulin treatment in the fasting state (0.21 ± 0.17 vs. 0.25 ± 0.10 pmol kg−1 min−1/mmol l−1), but improved significantly during the first 30 min after start of the meal (0.28 ± 0.07 vs. 0.46 ± 0.06 pmol kg−1 min−1/mmol l−1) and during the following 4 h (0.34 ± 0.09 vs. 0.56 ± 0.07 pmol kg−1 min−1/ mmol l−1). The B‐cell responsiveness to changes in plasma glucose, expressed as the slope of the linear relationship between the insulin secretion rate and the concomitant plasma glucose increased from 0.59 ± 0.16 to 0.94 ± 0.13 pmol kg−1 min−1/ mmol l−1 (P < 0.07).
Conclusions   Four weeks of near‐normalization of BG had no effect on postprandial secretion of incretin hormones. Nevertheless, several parameters of meal‐induced insulin secretion improved after insulin treatment.