title: Effects of short-term therapy with glibenclamide and repaglinide on incretin hormones and oxidative damage associated with postprandial hyperglycaemia in people with type 2 diabetes mellitus.
abstract: OBJECTIVE
  To examine the effects of glibenclamide and repaglinide on glucose stimulated insulin release, incretins, oxidative stress and cell adhesion molecules in patients with type 2 diabetes suboptimally treated with metformin.
  
  
  METHODS
  A randomized clinical trial was performed recruiting 27 subjects (HbA(1c) between 7.5 and 10.5%) free from cardiovascular and renal disease. Glucose, insulin, C-peptide, glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), total antioxidant status, F(2)-isoprostane, interleukin-6 and cell adhesion molecules were measured during an oral glucose load at baseline and after eight weeks of treatment. The areas under the curve were analysed at 45, 60 and 120 min (AUC(45), AUC(60), AUC(120)).
  
  
  RESULTS
  Significant improvements in glucose were observed with repaglinide (HBA(1c): -1.5%, fasting glucose: -2.8 mmol/L, 2-h glucose: -3.7 mmol/L, AUC(120): -18.9%) and glibenclamide (-1.0%, -2.2 mmol/L, -2.5 mmol/L, -17.5%). Repaglinide was also associated with an increase in the AUC(60) and AUC(120) for insulin (+56%, +61%) and C-peptide (+41%, +36%). GLP-1, GIP, IL-6, ICAM-1 and E-selectin levels did not change in either group. No association was observed between GLP-1, GIP-1 and plasma markers of oxidative stress.
  
  
  CONCLUSIONS
  Repaglinide is associated with improved postprandial glycaemic control via insulin and C-peptide release. We observed no direct effects of glibenclamide or repaglinide on plasma levels of GLP-1 or GIP. We observed no associations of GLP-1 and GIP with plasma markers of oxidative stress.
authors.affiliation: Diabetes Research Group, Institute of Life Sciences, Swansea University, Swansea SA2 8PP, UK. J.W.Stephens@Swansea.ac.uk
authors.forename: J W
authors.initials: JW
authors.lastname: Stephens
authors.forename: T B
authors.initials: TB
authors.lastname: Bodvarsdottir
authors.forename: K
authors.initials: K
authors.lastname: Wareham
authors.forename: S L
authors.initials: SL
authors.lastname: Prior
authors.forename: R M
authors.initials: RM
authors.lastname: Bracken
authors.forename: G D
authors.initials: GD
authors.lastname: Lowe
authors.forename: A
authors.initials: A
authors.lastname: Rumley
authors.forename: G
authors.initials: G
authors.lastname: Dunseath
authors.forename: S
authors.initials: S
authors.lastname: Luzio
authors.forename: C F
authors.initials: CF
authors.lastname: Deacon
authors.forename: J J
authors.initials: JJ
authors.lastname: Holst
authors.forename: S C
authors.initials: SC
authors.lastname: Bain
mesh_terms: D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D002219:Carbamates / Q000008:administration & dosage*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D019040:E-Selectin / Q000097:blood; D028441:F2-Isoprostanes / Q000097:blood; D005260:Female; D005749:Gastric Inhibitory Polypeptide / Q000097:blood; D052216:Glucagon-Like Peptide 1 / Q000097:blood; D005905:Glyburide / Q000008:administration & dosage*; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D006943:Hyperglycemia / Q000097:blood / Q000188:drug therapy*; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D054795:Incretins / Q000097:blood*; D007328:Insulin / Q000097:blood; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008687:Metformin / Q000008:administration & dosage; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects*; D010880:Piperidines / Q000008:administration & dosage*; D019518:Postprandial Period; D013997:Time Factors; D016896:Treatment Outcome; D014852:Wales
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D002219:Carbamates; D019040:E-Selectin; D028441:F2-Isoprostanes; D005749:Gastric Inhibitory Polypeptide; D052216:Glucagon-Like Peptide 1; D005905:Glyburide; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D054795:Incretins; D007328:Insulin; D018799:Intercellular Adhesion Molecule-1; D015850:Interleukin-6; D008687:Metformin; D010880:Piperidines; C508600:IL6 protein, human; C546936:SELE protein, human; C517652:hemoglobin A1c protein, human; C072379:repaglinide