title: Preserved GLP-1 and exaggerated GIP secretion in type 2 diabetes and relationships with triglycerides and ALT.
abstract: 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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Epidemiology and Biostatistics and the EMGO Institute for Health and Care Research, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Marjan
authors.initials: M
authors.lastname: Alssema
authors.forename: Josina M
authors.initials: JM
authors.lastname: Rijkelijkhuizen
authors.forename: Jens J
authors.initials: JJ
authors.lastname: Holst
authors.forename: Tom
authors.initials: T
authors.lastname: Teerlink
authors.forename: Peter G
authors.initials: PG
authors.lastname: Scheffer
authors.forename: Elisabeth M W
authors.initials: EM
authors.lastname: Eekhoff
authors.forename: Amalia
authors.initials: A
authors.lastname: Gastaldelli
authors.forename: Andrea
authors.initials: A
authors.lastname: Mari
authors.forename: Leen M't
authors.initials: LM
authors.lastname: Hart
authors.forename: Giel
authors.initials: G
authors.lastname: Nijpels
authors.forename: Jacqueline M
authors.initials: JM
authors.lastname: Dekker
mesh_terms: D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood*; D019540:Area Under Curve; D015415:Biomarkers / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D004435:Eating / Q000502:physiology; D005260:Female; D005749:Gastric Inhibitory Polypeptide / Q000097:blood* / Q000378:metabolism; D005934:Glucagon / Q000097:blood / Q000378:metabolism; D052216:Glucagon-Like Peptide 1 / Q000097:blood* / Q000378:metabolism; D005947:Glucose / Q000008:administration & dosage; D005951:Glucose Tolerance Test; D006801:Humans; D054795:Incretins / Q000097:blood; D050356:Lipid Metabolism / Q000502:physiology; D008297:Male; D008875:Middle Aged; D014280:Triglycerides / Q000097:blood*
chemical_list: D015415:Biomarkers; D054795:Incretins; D014280:Triglycerides; D005749:Gastric Inhibitory Polypeptide; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D000410:Alanine Transaminase; D005947:Glucose