TY - JOUR

T1 - Preserved GLP-1 and exaggerated GIP secretion in type 2 diabetes and relationships with triglycerides and ALT

AU - Alssema, Marjan

AU - Rijkelijkhuizen, Josina M

AU - Holst, Jens Juul

AU - Teerlink, Tom

AU - Scheffer, Peter G

AU - Eekhoff, Elisabeth M W

AU - Gastaldelli, Amalia

AU - Mari, Andrea

AU - Hart, Leen M't

AU - Nijpels, Giel

AU - Dekker, Jacqueline M

PY - 2013/10

Y1 - 2013/10

N2 - 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.

AB - 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.

KW - Adult

KW - Aged

KW - Alanine Transaminase

KW - Area Under Curve

KW - Biological Markers

KW - Diabetes Mellitus, Type 2

KW - Eating

KW - Female

KW - Gastric Inhibitory Polypeptide

KW - Glucagon

KW - Glucagon-Like Peptide 1

KW - Glucose

KW - Glucose Tolerance Test

KW - Humans

KW - Incretins

KW - Lipid Metabolism

KW - Male

KW - Middle Aged

KW - Triglycerides

U2 - 10.1530/EJE-13-0487

DO - 10.1530/EJE-13-0487

M3 - Journal article

C2 - 23864340

VL - 169

SP - 421

EP - 430

JO - European Journal of Endocrinology

JF - European Journal of Endocrinology

SN - 0804-4643

IS - 4

ER -