Targeting inflammation using salsalate in patientswith type 2 diabetes: Effects on flow-mediated dilation (TINSAL-FMD)

Allison B. Goldfine, J. Stewart Buck, Cyrus V Desouza, Vivian Fonseca, Yii Der Ida Chen, Steven E. Shoelson, Kathleen A. Jablonski, Mark A. Creager

Research output: Contribution to journalArticle

28 Citations (Scopus)

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, placebocontrolled 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/m2), 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.

Original languageEnglish (US)
Pages (from-to)4132-4139
Number of pages8
JournalDiabetes Care
Volume36
Issue number12
DOIs
StatePublished - Dec 1 2013

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Type 2 Diabetes Mellitus
Dilatation
Inflammation
Placebos
Nitroglycerin
Random Allocation
Endothelium
salicylsalicylic acid
Brachial Artery
National Institutes of Health (U.S.)
Leukocyte Count
LDL Cholesterol
Blood Vessels
Albumins
Fasting
Creatinine
Research Design
Arteries
Safety
Glucose

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Advanced and Specialized Nursing

Cite this

Goldfine, A. B., Stewart Buck, J., Desouza, C. V., Fonseca, V., Chen, Y. D. I., Shoelson, S. E., ... Creager, M. A. (2013). Targeting inflammation using salsalate in patientswith type 2 diabetes: Effects on flow-mediated dilation (TINSAL-FMD). Diabetes Care, 36(12), 4132-4139. https://doi.org/10.2337/dc13-0859

Targeting inflammation using salsalate in patientswith type 2 diabetes : Effects on flow-mediated dilation (TINSAL-FMD). / Goldfine, Allison B.; Stewart Buck, J.; Desouza, Cyrus V; Fonseca, Vivian; Chen, Yii Der Ida; Shoelson, Steven E.; Jablonski, Kathleen A.; Creager, Mark A.

In: Diabetes Care, Vol. 36, No. 12, 01.12.2013, p. 4132-4139.

Research output: Contribution to journalArticle

Goldfine, AB, Stewart Buck, J, Desouza, CV, Fonseca, V, Chen, YDI, Shoelson, SE, Jablonski, KA & Creager, MA 2013, 'Targeting inflammation using salsalate in patientswith type 2 diabetes: Effects on flow-mediated dilation (TINSAL-FMD)', Diabetes Care, vol. 36, no. 12, pp. 4132-4139. https://doi.org/10.2337/dc13-0859
Goldfine, Allison B. ; Stewart Buck, J. ; Desouza, Cyrus V ; Fonseca, Vivian ; Chen, Yii Der Ida ; Shoelson, Steven E. ; Jablonski, Kathleen A. ; Creager, Mark A. / Targeting inflammation using salsalate in patientswith type 2 diabetes : Effects on flow-mediated dilation (TINSAL-FMD). In: Diabetes Care. 2013 ; Vol. 36, No. 12. pp. 4132-4139.
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AU - Desouza, Cyrus V

AU - Fonseca, Vivian

AU - Chen, Yii Der Ida

AU - Shoelson, Steven E.

AU - Jablonski, Kathleen A.

AU - Creager, Mark A.

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N2 - 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, placebocontrolled 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/m2), 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.

AB - 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, placebocontrolled 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/m2), 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.

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