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      A favorable effect of hydroxychloroquine on glucose and lipid metabolism beyond its anti-inflammatory role

      Author(s): 1 , 1 , 2
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      Journal: Therapeutic Advances in Endocrinology and Metabolism
      Publisher: SAGE Publications

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          Abstract

          Hydroxychloroquine (HCQ), a commonly used antimalarial drug in rheumatic diseases, has shown favorable metabolic effects on both glucose control and lipid profiles. We describe a case of a young woman with type 1 diabetes whose glycemic control was optimized with the introduction of HCQ as a treatment for her Sjogren syndrome in addition to a subtle yet measurable improvement in her lipid profile. An increasing body of evidence supports the beneficial impacts of HCQ in various ancillary conditions, including diabetes mellitus and dyslipidemia. However, mechanisms of action responsible for these effects remain ill-defined and may include alterations in insulin metabolism and signaling through cellular receptors. These favorable metabolic effects of HCQ and further understanding of underlying mechanisms may provide an additional rational for its use in rheumatic diseases, conditions associated with an elevated cardiovascular risk.

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          Hydroxychloroquine: From Malaria to Autoimmunity

          Ilan Ben-Zvi, Shaye Kivity, Pnina Langevitz … (2011)
          Quinine was first recognized as a potent antimalarial agent hundreds of years ago. Since then, the beneficial effects of quinine and its more advanced synthetic forms, chloroquine and hydroxychloroquine, have been increasingly recognized in a myriad of other diseases in addition to malaria. In recent years, antimalarials were shown to have various immunomodulatory effects, and currently have an established role in the management of rheumatic diseases, such as systemic lupus erythematosus and rheumatoid arthritis, skin diseases, and in the treatment of chronic Q fever. Lately, additional metabolic, cardiovascular, antithrombotic, and antineoplastic effects of antimalarials were shown. In this review, we discuss the known various immunomodulatory mechanisms of antimalarials and the current evidence for their beneficial effects in various diseases and in potential novel applications.
          Article 0 comments Cited 115 times – based on 0 reviews     Review now
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            Salicylate (salsalate) in patients with type 2 diabetes: a randomized trial.

            Allison B. Goldfine, Vivian Fonseca, Kathleen A Jablonski … (2013)
            Short-duration studies show that salsalate improves glycemia in type 2 diabetes mellitus (T2DM). To assess 1-year efficacy and safety of salsalate in T2DM. Placebo-controlled, parallel trial; computerized randomization and centralized allocation, with patients, providers, and researchers blinded to assignment. (ClinicalTrials.gov: NCT00799643). 3 private practices and 18 academic centers in the United States. Persons aged 18 to 75 years with fasting glucose levels of 12.5 mmol/L or less (≤225 mg/dL) and hemoglobin A1c (HbA1c) levels of 7.0% to 9.5% who were treated for diabetes. 286 participants were randomly assigned (between January 2009 and July 2011) to 48 weeks of placebo (n = 140) or salsalate, 3.5 g/d (n = 146), in addition to current therapies, and 283 participants were analyzed (placebo, n = 137; salsalate, n = 146). Change in hemoglobin A1c level (primary outcome) and safety and efficacy measures. The mean HbA1c level over 48 weeks was 0.37% lower in the salsalate group than in the placebo group (95% CI, -0.53% to -0.21%; P < 0.001). Glycemia improved despite more reductions in concomitant diabetes medications in salsalate recipients than in placebo recipients. Lower circulating leukocyte, neutrophil, and lymphocyte counts show the anti-inflammatory effects of salsalate. Adiponectin and hematocrit levels increased more and fasting glucose, uric acid, and triglyceride levels decreased with salsalate, but weight and low-density lipoprotein cholesterol levels also increased. Urinary albumin levels increased but reversed on discontinuation; estimated glomerular filtration rates were unchanged. Trial duration and number of patients studied were insufficient to determine long-term risk-benefit of salsalate in T2DM. Salsalate improves glycemia in patients with T2DM and decreases inflammatory mediators. Continued evaluation of mixed cardiorenal signals is warranted.
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              Hydroxychloroquine and risk of diabetes in patients with rheumatoid arthritis.

              Timothy R. Elliott, Vijaya Bharathi Lingala, Lawrence Ward … (2007)
              Hydroxychloroquine, a commonly used antirheumatic medication, has hypoglycemic effects and may reduce the risk of diabetes mellitus. To determine the association between hydroxychloroquine use and the incidence of self-reported diabetes in a cohort of patients with rheumatoid arthritis. A prospective, multicenter observational study of 4905 adults with rheumatoid arthritis (1808 had taken hydroxychloroquine and 3097 had never taken hydroxychloroquine) and no diagnosis or treatment for diabetes in outpatient university-based and community-based rheumatology practices with 21.5 years of follow-up (January 1983 through July 2004). Diabetes by self-report of diagnosis or hypoglycemic medication use. During the observation period, incident diabetes was reported by 54 patients who had taken hydroxychloroquine and by 171 patients who had never taken hydroxychloroquine, with incidence rates of 5.2 per 1000 patient-years of observation compared with 8.9 per 1000 patient-years of observation, respectively (P < .001). In time-varying multivariable analysis with adjustments for possible confounding factors, the hazard ratio for incident diabetes among patients who had taken hydroxychloroquine was 0.62 (95% confidence interval, 0.42-0.92) compared with those who had not taken hydroxychloroquine. In Poisson regression, the risk of incident diabetes was significantly reduced with increased duration of hydroxychloroquine use (P < .001 for trend); among those taking hydroxychloroquine for more than 4 years (n = 384), the adjusted relative risk of developing diabetes was 0.23 (95% confidence interval, 0.11-0.50; P < .001), compared with those who had not taken hydroxychloroquine. Among patients with rheumatoid arthritis, use of hydroxychloroquine is associated with a reduced risk of diabetes.
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                Author and article information

                Journal
                Title: Therapeutic Advances in Endocrinology and Metabolism
                Abbreviated Title: Therapeutic Advances in Endocrinology
                Publisher: SAGE Publications
                ISSN (Print): 2042-0188
                ISSN (Electronic): 2042-0196
                Publication date Created: September 05 2014
                Publication date Created: August 2014
                Publication date (Electronic): August 18 2014
                Publication date (Print): August 2014
                Volume: 5
                Issue: 4
                Pages: 77-85
                Affiliations
                [1 ]Department of Internal Medicine, Division of Endocrinology and Metabolism, American University of Beirut-Medical Center, New York, USA
                [2 ]Department of Internal Medicine, Division of Endocrinology and Metabolism, American University of Beirut-Medical Center, 3 Dag Hammarskjold Plaza, 8th floor, New York, NY 10017, USA
                Article
                DOI: 10.1177/2042018814547204
                PMC ID: 4206615
                PubMed ID: 25343023
                SO-VID: aab53f65-e7dd-409d-b35a-d73fc1243558
                Copyright © © 2014
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                http://journals.sagepub.com/page/policies/text-and-data-mining-license

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