Alssema, Marjan2; Rijkelijkhuizen, Josina M3; Holst, Jens Juul5; Teerlink, Tom3; Scheffer, Peter G3; Eekhoff, Elisabeth M W3; Gastaldelli, Amalia3; Mari, Andrea3; Hart, Leen M't3; Nijpels, Giel3; Dekker, Jacqueline M3
1 Section of Endocrinology Research, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, Københavns Universitet2 VU University Medical Center, EMGO Institute for Health Care Research3 unknown4 Section for Translational Metabolic Physiology, The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, Københavns Universitet5 Section for Translational Metabolic Physiology, The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, Københavns Universitet
OBJECTIVE: To i) compare incretin responses to oral glucose and mixed meal of diabetic patients with the normoglycaemic population and ii) to investigate whether incretin responses are associated with hypertriglyceridaemia and alanine aminotransferase (ALT) as liver fat marker. DESIGN: A population-based study. METHODS: A total of 163 persons with normal glucose metabolism (NGM), 20 with intermediate hyperglycaemia and 20 with type 2 diabetes aged 40-65 years participated. Participants received a mixed meal and oral glucose load on separate occasions. Glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP) and glucagon profiles were analysed as total area under the curve (tAUC) and incremental area under the curve. RESULTS: In diabetic patients compared with persons with NGM, we found increased GLP-1 secretion (tAUC per hour) following oral glucose (23.2 pmol/l (95% CI 17.7-28.7) vs 18.0 (95% CI 16.9-19.1), P<0.05) but not after the mixed meal. GIP secretion among diabetic patients was increased on both occasions (82.9 pmol/l (55.9-109.8) vs 47.1 (43.8-50.4) for oral glucose and 130.6 (92.5-168.7) vs 83.2 (77.5-88.9) for mixed meal, both P<0.05). After oral glucose, GLP-1 (tAUC per hour) was inversely related to fasting triglycerides. GIP (tAUC per hour) was positively related to fasting and postprandial triglycerides. Higher fasting GIP levels were related to higher fasting and postprandial triglyceride levels and ALT. CONCLUSION: This study confirms that in type 2 diabetes, GLP-1 secretion is generally preserved and that GIP secretion is exaggerated. The mechanism underlying the divergent associations of GLP-1 and GIP metabolism with fat metabolism and liver fat accumulation warrants further study.
European Journal of Endocrinology, 2013, Vol 169, Issue 4, p. 421-30