title: Metformin, but not rosiglitazone, attenuates the increasing plasma levels of a new cardiovascular marker, fibulin-1, in patients with type 2 diabetes.
abstract: OBJECTIVE The extracellular matrix protein fibulin-1 is upregulated in the arterial wall in type 2 diabetes (T2D) and circulates in increased concentrations in diabetes. Metformin is an antidiabetic drug with beneficial cardiovascular disease effects in diabetes. We hypothesized that metformin would influence the increased level of plasma fibulin-1 in diabetes. RESEARCH DESIGN AND METHODS After a 4-week run-in period, 371 eligible patients with T2D were randomized to treatment groups in a factorial design including insulin alone (control), +metformin, +rosiglitazone, or +both metformin and rosiglitazone. Plasma fibulin-1 was analyzed at the beginning of the study and after 18 and 24 months. RESULTS Plasma fibulin-1 increased in all groups throughout the 2-year period; however, the increase was strongly attenuated among patients treated with metformin. A highly significant difference was observed when the mean change in plasma fibulin-1 was compared between metformin- and non-metformin-treated individuals both at 18 and 24 months of treatment, but rosiglitazone had no effect. Metformin and rosiglitazone alone reduced the HbA1c levels to comparable levels and in combination even further. CONCLUSIONS Metformin attenuates the increase in plasma fibulin-1 concentrations in T2D, independently of glycemic effects. Changes in fibulin-1 may reflect an important element in diabetic arteriopathy that can be influenced by metformin.
authors.affiliation: Corresponding author: Lars M. Rasmussen, lars.melholt.rasmussen@rsyd.dk.
authors.forename: Vibe
authors.initials: V
authors.lastname: Skov
authors.forename: Claudia
authors.initials: C
authors.lastname: Cangemi
authors.forename: Jeppe
authors.initials: J
authors.lastname: Gram
authors.forename: Mette M
authors.initials: MM
authors.lastname: Christensen
authors.forename: Ellen
authors.initials: E
authors.lastname: Grodum
authors.forename: Ditte
authors.initials: D
authors.lastname: Sørensen
authors.forename: W Scott
authors.initials: WS
authors.lastname: Argraves
authors.forename: Jan E
authors.initials: JE
authors.lastname: Henriksen
authors.forename: Lars M
authors.initials: LM
authors.lastname: Rasmussen
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000097:blood* / Q000187:drug effects*; D002319:Cardiovascular System / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D003925:Diabetic Angiopathies / Q000097:blood / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D007328:Insulin / Q000627:therapeutic use; D008297:Male; D008687:Metformin / Q000008:administration & dosage*; D008875:Middle Aged; D011446:Prospective Studies; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000008:administration & dosage*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D002135:Calcium-Binding Proteins; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D008687:Metformin; D000077154:Rosiglitazone; D045162:Thiazolidinediones; C060820:fibulin