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).

RESEARCH DESIGN AND 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: Allison B Goldfine, J Stewart Buck, Cyrus Desouza, Vivian Fonseca, Yii-Der Ida Chen, Steven E Shoelson, Kathleen A Jablonski, Mark A Creager, TINSAL-FMD (Targeting Inflammation Using Salsalate in Type 2 Diabetes–Flow-Mediated Dilation) Ancillary Study Team
• Journal: Diabetes care (Diabetes Care) Vol. 36 Issue 12 Pg. 4132-9 (Dec 2013) ISSN: 1935-5548 [Electronic] United States
• PMID: 24130358 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Blood Glucose
• Hypoglycemic Agents
• Salicylates
• salicylsalicylic acid

Topics

• Administration, Oral
• Adult
• Anti-Inflammatory Agents, Non-Steroidal (administration & dosage)
• Blood Glucose (metabolism)
• Brachial Artery (diagnostic imaging, drug effects, physiopathology)
• Diabetes Mellitus, Type 2 (blood, complications, drug therapy)
• Dose-Response Relationship, Drug
• Double-Blind Method
• Drug Therapy, Combination
• Endothelium, Vascular (diagnostic imaging, drug effects, physiopathology)
• Female
• Follow-Up Studies
• Humans
• Hypoglycemic Agents (therapeutic use)
• Inflammation (drug therapy, etiology, metabolism)
• Male
• Middle Aged
• Regional Blood Flow
• Salicylates (administration & dosage)
• Single-Blind Method
• Time Factors
• Treatment Outcome
• Ultrasonography
• Vasodilation (drug effects, physiology)