Retrospective Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Feb 15, 2018; 9(2): 53-58
Published online Feb 15, 2018. doi: 10.4239/wjd.v9.i2.53
Blood glucose changes surrounding initiation of tumor-necrosis factor inhibitors and conventional disease-modifying anti-rheumatic drugs in veterans with rheumatoid arthritis
Patrick R Wood, Evan Manning, Joshua F Baker, Bryant England, Lisa Davis, Grant W Cannon, Ted R Mikuls, Liron Caplan
Patrick R Wood, Evan Manning, Liron Caplan, Denver Veterans Affairs Medical Center, Division of Rheumatology, University of Colorado, Aurora, CO 80045, United States
Joshua F Baker, Philadelphia Veterans Affairs Medical Center, Division of Rheumatology, University of Pennsylvania, Philadelphia, PA 19104, United States
Bryant England, Ted R Mikuls, Omaha Veterans Affairs Medical Center, Division of Rheumatology, University of Nebraska, Omaha, NE 68198, United States
Lisa Davis, Denver Health and Hospital, Division of Rheumatology, University of Colorado, Aurora, CO 80045, United States
Grant W Cannon, George Wahlen Veterans Affairs Medical Center, Division of Rheumatology, University of Utah, Salt Lake City, UT 84148, United States
Author contributions: All authors helped to perform the research and reviewed and edited the final manuscript; Wood PR and Caplan L contributed to writing the manuscript, conception and design; Wood PR, Manning E and Caplan L contributed to data analysis.
Supported by VA HSR&D MERIT Award IIR, No. 14-048-3 for Dr Caplan; and Dr. Wood is supported by a VA GME Enhancement Award.
Institutional review board statement: This study was approved by local IRBs (Colorado Multiple Institutional Review Board #06-0956) and the Scientific and Ethical Advisory Board of the VARA registry for analysis of VARA and VA administrative data.
Informed consent statement: All patients provided written consent prior to enrollment in the VARA registry.
Conflict-of-interest statement: All authors declare no conflicts-of-interest related to this article.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Liron Caplan, MD, PhD, Associate Professor, Denver Veterans Affairs Medical Center, Division of Rheumatology, University of Colorado, POB 6511, B115, Aurora, CO 80045, United States.
Telephone: +1-720-8575103 Fax: +1-720-8575992
Received: January 8, 2018
Peer-review started: January 8, 2018
First decision: February 9, 2018
Revised: February 13, 2018
Accepted: February 14, 2018
Article in press: February 14, 2018
Published online: February 15, 2018
Research background

Several case reports and series have described dramatic acute hypoglycemic effects for the immunosuppressive agents collectively called tumor necrosis factor inhibitors (TNFi’s). In addition, studies have shown various cardioprotective and metabolic effects for conventional anti-rheumatic therapies; however, few studies have examined acute blood glucose effects for these agents in large population studies.

Research motivation

A better estimate of frequency and scale hypoglycemia associated with the initiation of medicines for users of TNFi and other anti-inflammatory medications may give insight into the role of cytokines and the inflammatory cascade in glucose tolerance as well as better estimate risks and benefits for these medications to the clinician.

Research objectives

We wished to determine whether initiation of tumor necrosis factor inhibitors in rheumatoid arthritis patients leads to reductions in blood glucose as measured by random blood glucose or glycosylated hemoglobin A1c. Simultaneously, we wished to investigate for similar effects in conventional antirheumatic drugs, given the established lipid homeostasis and cardioprotective effects for these agents.

Research methods

An observational registry linking pharmacy, clinical laboratory, and other data was utilized to retrospectively identify the time of prescription of the agents in question. This registry and linked data was used to retrospectively identify glucose measures proximate to these medication start events, so that changes in blood glucose surrounding the medication start could be inferred.

Research results

Cohort-level glucose effects were not identified in this registry surrounding the start of tumor-necrosis factor inhibitors, although glucose-lowering changes were identified surrounding the initiation of the conventional antirheumatic treatments sulfasalazine and hydroxychloroquine. Hyperglycemic changes surrounding prednisone were identified, lending further internal validity to these results.

Research conclusions

This study adds to the literature supporting the potentially beneficial metabolic effects of conventional anti-rheumatic therapies sulfasalazine and hydroxychloroquine beyond their general anti-inflammatory effects. These data also lend reassurance against large-scale prevalence for previously reported adverse hypoglycemic effects for tumor-necrosis factor inhibitors. The results point to the need for additional, similar studies in other populations, particularly those with spondyloarthritis syndromes such as psoriatic arthritis.

Research perspectives

This study, while a null result regarding tumor necrosis factor-inhibitor-associated hypoglycemic effects, points to the need for additional clarification on the physiology and causes for hypoglycemic events with these medications. We suggest the need for similar studies in psoriasis and psoriatic arthritis patients, as well as the potential utility of a case-control approach for the future study of dramatic hypoglycemic effects and events with immunosuppressive medications.