Preserved GLP-1 and exaggerated GIP secretion in type 2 diabetes and relationships with triglycerides and ALT

Objective: To (1) compare incretin responses to oral glucose and mixed meal of diabetic patients with the normoglycaemic population and (2) to investigate whether incretin responses are associated with hypertriglyceridemia and alanine aminotransferase (ALT) as liver fat marker. Design: A population-based study. Methods: A number of 163 persons with normal glucose metabolism, 20 with intermediate hyperglycaemia and 20 persons with type 2 diabetes, aged 40-65 years participated. Participants received a mixed meal and oral glucose load on separate occasions. GLP-1, GIP and glucagon profiles were analysed as total and incremental area under the curve (tAUC and iAUC). Results: In diabetic patients compared with persons with normal glucose metabolism, we found increased GLP-1 secretion (tAUC hour-1) following oral glucose (23.2 pmol/l (95% CI 17.7-28.7) versus 18.0 (16.9-19.1), p<0.05), but not after mixed meal. GIP secretion among diabetic patients was increased on both occasions (82.9 pmol/l (55.9-109.8) versus 47.1 (43.8-50.4) for oral glucose and 130.6 (92.5-168.7) versus 83.2 (77.5-88.9) for mixed meal, both p<0.05). After oral glucose, GLP-1 (tAUC hour-1) was inversely related to fasting triglycerides. GIP (tAUC hour-1) was positively related to fasting and postprandial triglycerides. Higher fasting GIP levels were related to higher fasting and postprandial triglyceride levels and ALT. Conclusion: The present 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.