Acarbose Decreases the Rheumatoid Arthritis Risk of Diabetic Patients and Attenuates the Incidence and Severity of Collagen-induced Arthritis in Mice.

Hsin-Hua Chen,Ching-Heng Lin,Chi-Chen Lin,Chao-Liang Wu,Der-Yuan Chen,Yi-Ming Chen,Kuo-Lung Lai,Ya-Hsuan Chao

doi:10.1038/srep18288

Abstract

Acarbose has been found to decrease some inflammatory parameters in diabetic patients. This study aimed to examine the influence of acarbose on rheumatoid arthritis (RA) risk in diabetes mellitus (DM) patients and on the incidence and severity of collagen-induced arthritis (CIA) in mice. In a nationwide, matched case–control study, we identified 723 incident RA cases and selected 7,230 age-, sex- and RA diagnosis date–matched controls from all newly treated DM patients. We found that use of acarbose at > 16,950 mg per year was associated with a lower RA risk (odds ratio 0.60; 95% CI, 0.41–0.89). In the CIA mouse study, acarbose was orally administered from days -7 to 38 relative to type II collagen (CII) immunization. The results revealed that acarbose at the dose of 500 mg/kg/day attenuated the incidence and severity of arthritis and the expression of proinflammatory cytokines, including TNF-α, IL-6 and IL-17 in the paw tissues. Acarbose further decreased the productions of anti-CII-IgG, IL-17 and IFN-γ by collagen-reactive lymph node cells. This work suggests that the use of acarbose decreased RA risk in DM patients and the incidence of CIA in mice. Acarbose also attenuated the severity of CIA via anti-inflammatory and immunomodulatory effects.

Highlights

The alpha-glucosidase inhibitor acarbose is an inexpensive and well-tolerated drug that has been widely used to treat diabetes mellitus (DM) for more than 20 years[7]
We investigated the anti-inflammatory effect of acarbose by comparing joint histologies and the proinflammatory cytokine levels in arthritic paw extracts between the acarbose-treated groups and controls using enzyme-linked immunosorbent assay (ELISA) assays
We found that the oral administration of acarbose reduces the risk of rheumatoid arthritis (RA) development in DM patients and attenuates the incidence and severity of collagen-induced arthritis (CIA) in mice

Summary

Introduction

The alpha-glucosidase inhibitor acarbose is an inexpensive and well-tolerated drug that has been widely used to treat diabetes mellitus (DM) for more than 20 years[7]. Due to its anti-inflammatory effect, acarbose attenuates the risks of cardiovascular disease[15] For this reason, we hypothesized that acarbose may possess the potential to reduce the risk of RA development or treat RA. The anti-arthritis effect of acarbose was examined by comparing visual scores of the paws between the acarbose-treated groups and controls. We investigated the anti-inflammatory effect of acarbose by comparing joint histologies and the proinflammatory cytokine levels in arthritic paw extracts between the acarbose-treated groups and controls using enzyme-linked immunosorbent assay (ELISA) assays. The immunomodulatory effect of acarbose was investigated by comparing the CII–specific antibodies in the serum and the proliferative responses/cytokine production in the lymph node (LN) cells between the acarbose-treated groups and controls

Objectives

Methods

Results

Discussion

Conclusion