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

Jul 19, 2013European journal of endocrinology

Normal GLP-1 but increased GIP hormone levels in type 2 diabetes linked to blood fat and liver enzyme levels

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Abstract

Diabetic patients exhibited increased GLP-1 secretion after oral glucose with a tAUC of 23.2 pmol/l compared to 18.0 pmol/l in those with normal glucose metabolism.

GLP-1 secretion was significantly higher in diabetic patients after oral glucose than after a mixed meal.
GIP secretion was elevated in diabetic patients during both oral glucose and mixed meal tests.
After oral glucose, higher GLP-1 levels were associated with lower fasting triglyceride levels.
In contrast, GIP levels were positively related to both fasting and postprandial triglyceride levels.
Increased fasting GIP levels correlated with higher fasting and postprandial triglyceride and ALT levels.

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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.

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

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