title: Targeting inflammation using salsalate in patients with type 2 diabetes: effects on flow-mediated dilation (TINSAL-FMD).
abstract: OBJECTIVE
  To test whether inhibiting inflammation with salsalate improves endothelial function in patients with type 2 diabetes (T2D).
  
  
  METHODS
  We conducted an ancillary study to the National Institutes of Health-sponsored, multicenter, randomized, double-masked, placebo-controlled trial evaluating the safety and efficacy of salsalate in targeting inflammation to improve glycemia in patients with T2D. Flow-mediated, endothelium-dependent dilation (FMD) and endothelium-independent, nitroglycerin-mediated dilation (NMD) of the brachial artery were assessed at baseline and 3 and 6 months following randomization to either salsalate 3.5 g/day or placebo. The primary end point was change in FMD at 6 months.
  
  
  RESULTS
  A total of 88 participants were enrolled in the study, and data after randomization were available for 75. Patients in the treatment and control groups had similar ages (56 years), BMI (33 kg/m(2)), sex (64% male), ethnicity, current treatment, and baseline HbA1c (7.7% [61 mmol/mol]). In patients treated with salsalate versus placebo, HbA1c was reduced by 0.46% (5.0 mmol/mol; P < 0.001), fasting glucose by 16.1 mg/dL (P < 0.001), and white blood cell count by 430 cells/µL (P < 0.02). There was no difference in the mean change in either FMD (0.70% [95% CI -0.86 to 2.25%]; P = 0.38) or NMD (-0.59% [95% CI -2.70 to 1.51%]; P = 0.57) between the groups treated with salsalate and placebo at 6 months. Total and LDL cholesterol were 11 and 16 mg/dL higher, respectively, and urinary albumin was 2.0 µg/mg creatinine higher in the patients treated with salsalate compared with those treated with placebo (all P < 0.009).
  
  
  CONCLUSIONS
  Salsalate does not change FMD in peripheral conduit arteries in patients with T2D despite lowering HbA1c. This finding suggests that salsalate does not have an effect on vascular inflammation, inflammation does not cause endothelial dysfunction in T2D, or confounding effects of salsalate mitigate favorable effects on endothelial function.
authors.affiliation: Corresponding author: Mark A. Creager, mcreager@partners.org.
authors.forename: Allison B
authors.initials: AB
authors.lastname: Goldfine
authors.forename: J Stewart
authors.initials: JS
authors.lastname: Buck
authors.forename: Cyrus
authors.initials: C
authors.lastname: Desouza
authors.forename: Vivian
authors.initials: V
authors.lastname: Fonseca
authors.forename: Yii-Der Ida
authors.initials: YD
authors.lastname: Chen
authors.forename: Steven E
authors.initials: SE
authors.lastname: Shoelson
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Jablonski
authors.forename: Mark A
authors.initials: MA
authors.lastname: Creager
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage; D001786:Blood Glucose / Q000378:metabolism*; D001916:Brachial Artery / Q000000981:diagnostic imaging / Q000187:drug effects / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000150:complications / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004730:Endothelium, Vascular / Q000000981:diagnostic imaging / Q000187:drug effects / Q000503:physiopathology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007249:Inflammation / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D012039:Regional Blood Flow; D012459:Salicylates / Q000008:administration & dosage*; D016037:Single-Blind Method; D013997:Time Factors; D016896:Treatment Outcome; D014463:Ultrasonography; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D012459:Salicylates; C014182:salicylsalicylic acid