Research Article: Is insulin resistance the cause of fibromyalgia? A preliminary report

Date Published: May 6, 2019

Publisher: Public Library of Science

Author(s): Miguel A. Pappolla, Laxmaiah Manchikanti, Clark R. Andersen, Nigel H. Greig, Fawad Ahmed, Xiang Fang, Michael A. Seffinger, Andrea M. Trescot, Christian Holscher.


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.

Partial Text

Fibromyalgia (FM) is one of the most frequent generalized pain disorders with poorly understood neurobiological mechanisms. In the general population, the estimated global prevalence of FM is 2.7% with a 3 to 1 female to male ratio [1]. However, studies suggest an even higher prevalence in primary care settings [2].

The results showed a highly significant association between FM and HbA1c levels. Stratification of the values in an age continuum, showed a clear-cut difference between the patients and the control groups. As can be visually appreciated in the graph in Fig 1, almost all patients in the FM group fell at or above the mean of the FOS control values, with highly significant differences between the FM patients and both control groups (p < 0.0001 and p = 0.0002 for the FOS and NHANES control populations, respectively). In addition, patients with FM in whom IR had been pharmacologically treated showed dramatic and statistically significant reductions in pain scores (p < 0.0001 for all groups) as shown in Fig 2 and Tables 2 and 3.   Source:


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