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Fibromyalgia and Insulin Resistance: Correlational or Causal Relationship?

A preliminary study explores the potential link between fibromyalgia and impaired glucose metabolism.

With Miguel Pappolla, MD, PhD, and Leonard Goldstein, PhD, DDS

Characterized by chronic and widespread pain and fatigue, fibromyalgia remains poorly understood. The condition is also hard to diagnose, difficult to manage, and diminishes the quality of life for those struggling with it.1 A report estimated a global prevalence of 2.7%, with females outnumbering males nearly three to one.2 In addition, a couple of studies have noted that fibromyalgia seems to be more prevalent among individuals with Type 2 diabetes (T2d)3,4—suggesting a link between the two conditions that is worthy of further study. While experts agree that genetics and environmental factors are at play with fibromyalgia, little is known regarding how and why the syndrome develops.

Diagnostic criteria for fibromyalgia come from the American College of Rheumatology (ACR); whose guidelines use a rating scale from 0 to 31 by combining the Widespread Pain Index (patient reports of pain or tenderness within the last week for 19 different body regions) and the Severity Scale (patient ratings, from 0 to 3, of the severity of symptoms like fatigue and brain fog). According to the ACR, a score of 13 or higher corresponds to a diagnosis of fibromyalgia.5

Is insulin resistance the cause of fibromyalgia? (Source: 123RF)

Similarities Between Fibromyalgia and Insulin Resistance

Although more recent reviews1,6 of fibromyalgia research do not make mention of the purported link between the syndrome and insulin resistance or diabetes, the two conditions affect brain vasculature in strikingly similar ways.

According to Miguel Pappolla, MD, PhD, a professor of neurology at the University of Texas Medical Branch and medical director of St. Michael’s Pain and Spine Clinics in Houston, insulin resistance is known to impair brain microcirculation, leading to hypoperfusion in certain brain regions. “What is very interesting,” he said, “is that patients with fibromyalgia also have hypoperfusion in several brain areas.” The question remains, however, whether insulin resistance may be behind these similar decreases in blood flow experienced by those with fibromyalgia.

To investigate this question, Dr. Pappolla led a retrospective, cross-sectional study, reviewing medical records from 23 patients (21 females, 2 males; 11 White, 8 Hispanic, 4 African American; ages 35 to 60) at St. Michael’s Pain and Spine Clinics.7 All 23 patients met the ACR criteria for diagnosis with fibromyalgia.

As a measure of insulin resistance, the team selected the hemoglobin A1C, in which values between 5.7 and 6.4 define prediabetes, and values of 6.5 or more constitute diabetes. They compared the A1Cs on record for the 23 patients with fibromyalgia to those of two separate control groups: the non-diabetic subset (1,350 people) from the Framingham Offspring Study characterized by normal glucose tolerance (FOS NGT) and the non-diabetic subset (1,592 people) from the National Health and Nutrition Examination Survey (NHANES).

“When we looked at patients who would fall within the diagnosis of fibromyalgia, their hemoglobin A1Cs were significantly higher than the values presented in two control populations,” said Dr. Pappolla. On average, A1Cs from the fibromyalgia sample exceeded those from the FOS NGT sample by 0.59 (P < 0.0001) and those from the NHANES sample by 0.39 (P = 0.0002).

Importantly, Dr. Pappolla’s team sorted the A1Cs from all three samples by age. “That was the key element,” he said. “If you look at the data, a lot of the patients with fibromyalgia have A1Cs below 5.7, which is currently considered to be within the normal range. But, when you compare them with controls of the same age, they’re not quite normal. They’re statistically higher than the controls, and that’s telling us there is something going on with glucose metabolism.”

Leonard Goldstein, PhD, DDS, assistant vice president for clinical education development at A.T. Still University and a member of PPM’s Editorial Advisory Board, concedes that these preliminary findings make sense—even if they demand rigorous follow-up studies. “Insulin resistance may not be the cause, but I think it’s certainly involved in fibromyalgia.”

The study also retrospectively explored whether treatment of insulin resistance reduced the degree of pain experienced by the fibromyalgia patients. To treat the insulin resistance, a subgroup of 16 of the 23 patients with fibromyalgia had received metformin in addition to standard treatment (pregabalin, gabapentin, and/or SNRIs)and, per protocol at St. Michael’s, pain scores (Numeric Pain Rating Scale [NPRS] 0 to 10) were recorded at each patient encounter. A review of NPRS scores at three time points—initial visit, after standard treatment, and after treatment with metformin—revealed significant drop-offs in pain between each period. The median pain score decreased from eight (initial) to four (after standard treatment) to 0.25 (after metformin). A total of 8 of the 16 patients ultimately reported no pain at all.

Study Limitations and Future Outlook

Dr. Pappolla emphasized that his team’s findings came with several caveats. First, due to the study’s retrospective, cross-sectional design, the study did not reveal any potentially causative timeline between the development of insulin resistance and fibromyalgia. This relationship may be further complicated as individuals with fibromyalgia are often overweight or obese, and such excess body weight may predispose patients to insulin resistance. Lastly, interpreting the results related to metformin treatment was a challenge for two reasons: the study lacked a placebo-control group for comparison, and metformin’s ability to reduce pain may come through other pathways unrelated to insulin resistance.

A larger, randomized control trial investigating metformin’s therapeutic effects for patients with fibromyalgia would be beneficial, noted Dr. Goldstein. “If they could get the same results,” he said, “this would eliminate [the] many people who have been given opioids to deal with pain.”

Dr. Pappolla acknowledged the small sample and that more evidence is needed to impact the care of patients with fibromyalgia. However, he believes that these preliminary findings open an intriguing avenue of research with potentially radical consequences for fibromyalgia management.

Last updated on: July 19, 2019
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