Does insulin resistance cause fibromyalgia?

Summary: Study finds a pathogenic relationship between insulin resistance and fibromyalgia. Treating fibromyalgia with metformin, a drug that combats insulin resistance, resulted in a dramatic reduction of pain levels for patients.

Source: UT Medical Branch Galveston

Researchers led by a team from The University of Texas Medical Branch at Galveston were able to dramatically reduce the pain of fibromyalgia patients with medication that targeted insulin resistance.

This discovery could dramatically alter the way that chronic pain can be identified and managed. Dr. Miguel Pappolla, UTMB professor of neurology, said that although the discovery is very preliminary, it may lead to a revolutionary shift on how fibromyalgia and related forms of chronic pain are treated. The new approach has the potential to save billions of dollars to the health care system and decrease many peoples’ dependence on opiates for pain management.

The UTMB team of researchers, along with collaborators from across the U.S., including the National Institutes of Health, were able for the first time, to separate patients with fibromyalgia from normal individuals using a common blood test for insulin resistance, or pre-diabetes. They then treated the fibromyalgia patients with a medication targeting insulin resistance, which dramatically reduced their pain levels. The study was recently published in PLOS ONE.

Fibromyalgia is one of the most common conditions causing chronic pain and disability. The global economic impact of fibromyalgia is enormous – in the U.S. alone and related health care costs are about $100 billion each year. Despite extensive research, the cause of fibromyalgia is unknown, so there’s no specific diagnostics or therapies for this condition other than pain-reducing drugs.

“Earlier studies discovered that insulin resistance causes dysfunction within the brain’s small blood vessels. Since this issue is also present in fibromyalgia, we investigated whether insulin resistance is the missing link in this disorder,” Pappolla said. “We showed that most – if not all – patients with fibromyalgia can be identified by their A1c levels, which reflects average blood sugar levels over the past two to three months.”

Pre-diabetics with slightly elevated A1c values carry a higher risk of developing central (brain) pain, a hallmark of fibromyalgia and other chronic pain disorders.”

The researchers identified patients who were referred to a subspecialty pain medicine clinic to be treated for widespread muscular/connective tissue pain. All patients who met the criteria for fibromyalgia were separated into smaller groups by age. When compared with age-matched controls, the A1c levels of the fibromyalgia patients were significantly higher.

“Considering the extensive research on fibromyalgia, we were puzzled that prior studies had overlooked this simple connection,” said Pappolla. “The main reason for this oversight is that about half of fibromyalgia patients have A1c values currently considered within the normal range. However, this is the first study to analyze these levels normalized for the person’s age, as optimal A1c levels do vary throughout life. Adjustment for the patients’ age was critical in highlighting the differences between patients and control subjects.”

This shows an outline of a person with a red brain
Pre-diabetics with slightly elevated A1c values carry a higher risk of developing central (brain) pain, a hallmark of fibromyalgia and other chronic pain disorders. The image is adapted from the UT Medical Branch Galveston news release.

For the fibromyalgia patients, metformin, a drug developed to combat insulin resistance was added to their current medications. They showed dramatic reductions in their pain levels.

Other authors include UTMB’s Clark Andersen and Xiang Fang as well as Laxmaiah Manchikanti from Louisiana State University School of Medicine Health Sciences Center; Nigel Greig from the National Institutes of Health; Fawad Ahmed from St. Michael’s Pain & Spine Clinics; Michael Seffinger from the College of Osteopathic Medicine of the Pacific and Andrea Trescot from the Pain and Headache Center in Eagle River, Alaska.

About this neuroscience research article

Source:
UT Medical Branch Galveston
Media Contacts:
Donna Ramirez – UT Medical Branch Galveston
Image Source:
The image is adapted from the UT Medical Branch Galveston news release.

Original Research: Open access
“Is insulin resistance the cause of fibromyalgia? A preliminary report”. Miguel A. Pappolla, Laxmaiah Manchikanti, Clark R. Andersen, Nigel H. Greig, Fawad Ahmed, Xiang Fang, Michael A. Seffinger, Andrea M. Trescot.
PLOS ONE doi:10.1371/journal.pone.0216079

Abstract

Is insulin resistance the cause of fibromyalgia? A preliminary report

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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