title: Improved glycemic control induced by both metformin and repaglinide is associated with a reduction in blood levels of 3-deoxyglucosone in nonobese patients with type 2 diabetes.
abstract: OBJECTIVE
  Metformin has been reported to reduce α-dicarbonyls, which are known to contribute to diabetic complications. It is unclear whether this is due to direct quenching of α-dicarbonyls or to an improvement in glycemic control. We therefore compared the effects of metformin versus repaglinide, an antihyperglycemic agent with an insulin-secreting mechanism, on the levels of the α-dicarbonyl 3-deoxyglucosone (3DG).
  
  
  METHODS
  We conducted a single-center, double-masked, double-dummy, crossover study involving 96 nonobese patients with type 2 diabetes. After a 1-month run-in on diet-only treatment, patients were randomized to either repaglinide (6 mg daily) followed by metformin (2 g daily) or vice versa each during 4 months with a 1-month washout between interventions.
  
  
  RESULTS
  3DG levels decreased after both metformin (-19.3% (95% confidence interval (CI): -23.5, -14.8)) and repaglinide (-20.8% (95% CI: -24.9, -16.3)) treatments, but no difference was found between treatments (1.8% (95% CI: -3.8, 7.8)). Regardless of the treatment, changes in glycemic variables were associated with changes in 3DG. Specifically, 3DG decreased by 22.7% (95% CI: 19.0, 26.5) per s.d. decrease in fasting plasma glucose (PG), by 20.0% (95% CI: 16.2, 23.9) per s.d. decrease in seven-point mean plasma glucose, by 22.5% (95% CI: 18.6, 26.6) per s.d. decrease in area under the curve for PG, by 17.2% (95% CI: 13.8, 20.6) per s.d. decrease in HbAlc, and by 10.9% (95% CI: 6.4, 15.5) per s.d. decrease in Amadori albumin. In addition, decreases in 3DG were associated with decreases in advanced glycation endproducts and endothelial markers.
  
  
  CONCLUSIONS
  Improved glycemic control induced by both metformin and repaglinide is associated with a reduction in 3DG levels in nonobese individuals with type 2 diabetes. This may constitute a shared metabolic pathway through which both treatments have a beneficial impact on the cardiovascular risk.
authors.affiliation: Cardiovascular Research Institute Maastricht (CARIM), Department of Internal Medicine, Maastricht University Medical Centre, Debeyelaan 25, PO Box 5800, 6202AZ Maastricht, The Netherlands.
authors.forename: Lian
authors.initials: L
authors.lastname: Engelen
authors.forename: Søren S
authors.initials: SS
authors.lastname: Lund
authors.forename: Isabel
authors.initials: I
authors.lastname: Ferreira
authors.forename: Lise
authors.initials: L
authors.lastname: Tarnow
authors.forename: Hans-Henrik
authors.initials: HH
authors.lastname: Parving
authors.forename: Jørgen
authors.initials: J
authors.lastname: Gram
authors.forename: Kaj
authors.initials: K
authors.lastname: Winther
authors.forename: Oluf
authors.initials: O
authors.lastname: Pedersen
authors.forename: Tom
authors.initials: T
authors.lastname: Teerlink
authors.forename: Rob
authors.initials: R
authors.lastname: Barto
authors.forename: Coen D A
authors.initials: CD
authors.lastname: Stehouwer
authors.forename: Allan A
authors.initials: AA
authors.lastname: Vaag
authors.forename: Casper G
authors.initials: CG
authors.lastname: Schalkwijk
mesh_terms: D002219:Carbamates / Q000627:therapeutic use*; D016001:Confidence Intervals; D003847:Deoxyglucose / Q000031:analogs & derivatives* / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008687:Metformin / Q000627:therapeutic use*; D010880:Piperidines / Q000627:therapeutic use*
chemical_list: D002219:Carbamates; D007004:Hypoglycemic Agents; D010880:Piperidines; C072379:repaglinide; D008687:Metformin; D003847:Deoxyglucose; C016350:3-deoxyglucosone