Sulfasalazine Improves Insulin Resistance and Endothelial Dysfunction in Metabolic Syndrome Patients
Kanchan Vohra
Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, India
Pawan Krishan *
Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, India
Sudhir Varma
Department of Cardiology, Sadbhavna Medical and Heart Institute, Patiala, India
Harpreet Singh Kalra
Department of Medicine, Sadbhavna Medical and Heart Institute, Patiala, India
*Author to whom correspondence should be addressed.
Abstract
Aim: Metabolic syndrome (MetS) and all its components are independently characterized by the presence of low-grade chronic inflammation. The study aimed at controlling inflammation using sulfasalazine 500mg, once a day treatment in comparison to placebo in MetS patients.
Study Design: Double blind, randomized, placebo controlled study.
Place and Duration of Study: Sadbhavna Medical and Heart Institute, Patiala; and, Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, Punjab, between January-November 2014.
Methodology: 50 eligible subjects (Male / Female = 45/5, n=25/group), fulfilling the National Cholesterol education Program-Adult Treatment Panel (NCEP-ATP III) diagnostic criteria of MetS, were randomly assigned to once daily drug or placebo tablets for 20 weeks. Blood pressure, serum high sensitivity C-reactive protein (hsCRP), tumor necrosis factor–alpha (TNF-α), lipid profile, fasting plasma glucose and insulin levels, homeostatic model assessment-insulin resistance (HOMA-IR), endothelial-dependent flow-mediated dilation (FMD) of brachial artery, right common carotid artery’s intima-media thickness (IMT) and artery stiffness indices [(Young elastic modulus (YEM), stiffness index (SI) and carotid arterial compliance (CAC)] by Doppler Ultrasound were assessed at baseline and after 20 weeks treatment. Tolerability of drug was also measured using hematological and biochemical analysis. Statistical significance was accepted at p ≤.05.
Results: FMD improved as 25.66±6.47% versus 12.41±3.22%, p<0.01; and insulin resistance (HOMA-IR) decreased as 7.05±3.48 versus 11.32±6.08, p<0.01, from baseline in drug group as compared to placebo group, whereas endothelium-independent vasodilatation (p=0.23) and baseline brachial artery diameter (p=0.95) remained unchanged in both the groups. Serum triglycerides (p=0.04), hsCRP (p<0.01) and TNF-α (p<0.01) levels were considerably altered, but there was no effect on carotid IMT, YEM, CAC and SI (all p≥0.05). Biochemical and hematological safety variables were significantly altered, but were still found with-in the normal limits.
Conclusion: Thus, sulfasalazine may prevent cardiovascular disease risk in MetS patients by reducing insulin resistance and endothelial dysfunction via halting inflammatory process. Moreover, it was found tolerable.
Keywords: Metabolic syndrome, inflammation, insulin resistance, flow mediated dilatation, endothelial dysfunction