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PLoS One. 2019 May 6;14(5):e0216079. doi: 10.1371/journal.pone.0216079. eCollection 2019.

Is insulin resistance the cause of fibromyalgia? A preliminary report.

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Department of Neurology, University of Texas Medical Branch, Galveston, Texas, United States of America.
St. Michael's Pain & Spine Clinics, Houston, Texas, United States of America.
Department of Anesthesiology, LSU School of Medicine Health Sciences Center, New Orleans, Louisiana, United States of America.
Office of Biostatistics, University of Texas Medical Branch, Galveston, Texas, United States of America.
Drug Design and Development Section, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, United States of America.
Department of Neuromusculoskeletal Medicine, College of Osteopathic Medicine of the Pacific, Pomona, California, United States of America.
Pain and Headache Center, Eagle River, Alaska, United States of America.


Fibromyalgia (FM) is one of the most frequent generalized pain disorders with poorly understood neurobiological mechanisms. This condition accounts for an enormous proportion of healthcare costs. Despite extensive research, the etiology of FM is unknown and thus, there is no disease modifying therapy available for this condition. We show that most (if not all) patients with FM belong to a distinct population that can be segregated from a control group by their glycated hemoglobin A1c (HbA1c) levels, a surrogate marker of insulin resistance (IR). This was demonstrated by analyzing the data after introducing an age stratification correction into a linear regression model. This strategy showed highly significant differences between FM patients and control subjects (p < 0.0001 and p = 0.0002, for two separate control populations, respectively). A subgroup of patients meeting criteria for pre-diabetes or diabetes (patients with HbA1c values of 5.7% or greater) who had undergone treatment with metformin showed dramatic improvements of their widespread myofascial pain, as shown by their scores using a pre and post-treatment numerical pain rating scale (NPRS) for evaluation. Although preliminary, these findings suggest a pathogenetic relationship between FM and IR, which may lead to a radical paradigm shift in the management of this disorder.

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Conflict of interest statement

M. A. Pappolla filed a provisional patent application with the USPTO (number 62798828). Title: “Formulations and Methods for Treatment of Fibromyalgia and Related Myofascial Pain Disorders”. This does not alter our adherence to PLOS ONE policies on sharing data and materials. Other authors have nothing to declare.

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