NOTE: THE STUDY MENTIONED IN THE FIRST PARAGRAPH OF THIS BLOG WAS BASED ON HAS BEEN RETRACTED BY PLOS ONE DUE TO ETHICS VIOLATIONS. HOWEVER, SINCE OTHER SOURCES ARE CORRECT WRT MECHANISM, I WILL LEAVE THE BLOG UP WITH THIS WARNING.
I shared a study last week on Facebook indicating that insulin resistance may play a role in a majority of cases of Fibromyalgia. The study looked at the relationship between hemoglobin A1c(HgA1c) and a diagnosis of Fibromyalgia, but to find an effect they needed to stratify by age. This makes sense because an HgA1c of 5.7% is rather common for a 65 year old, but quite high for a 25 or even 35 year old.
HgA1c functions as an estimate of your average blood glucose over the last 3 months. An HgA1c of 5.7% effectively puts a person on the low end of pre-diabetes, indicating that they are insulin resistant to some degree. It’s important to realize that this study was small and simply a snapshot. But in the grander scheme of things and coupled with a lot of other data we have in Fibromyalgia and insulin resistance, this relationship certainly makes a lot of sense.
To further strengthen the claim that insulin resistance plays a role in Fibromyalgia, the researchers treated patients with Metformin, one of the primary medications used to treat Type 2 diabetes. What they found was that prior to any treatment, patients rated their pain as an average of 6 out of 10. When they were given standard treatment with pain meds, the pain dropped to an average of 4 out of 10.
When they were treated with standard treatment and Metformin, their pain all but disappeared. The average pain rating was less than 0.5 and half of the patients had a 0 out of 10. Interestingly, 2 of the patients didn’t respond to pain therapy alone, but when given Metformin their pain disappeared.
Circadian Disruption in Fibromylagia
Whether or not insulin resistance or hyperglycemia are directly causal to Fibromyalgia, there is a ton of evidence linking other factors associated with Fibromyalgia and insulin resistance. Insulin was recently discovered as the chief signal regulating how the feeding/fasting cycle synchronizes circadian clocks throughout the body. Insulin resistance causes system-wide circadian disruption.
We’ve known for decades that people with Fibromyalgia have disturbed circadian rhythms. I hesitate to say that Circadian disruption causes Fibromylagia because it appears more likely that behaviors induced by a Fibromyalgia diagnosis cause circadian disruption and make the disease path and symptomology much worse.
While it has been shown that the circadian rhythm of melatonin and cortisol are disturbed in people with Fibromyalgia, this may be partially behavioral. A study following the activity patterns of people with Fibromyalgia found that patterns more closely aligned to healthy circadian rhythms led to a decrease in symptom severity including pain, fatigue, mood and physical disability. It’s important to point out that both cortisol and melatonin play a role in regulating insulin sensitivity,
This may be where we get a little closer to the relationship between fibromyalgia and insulin resistance. Even in healthy individuals, 5 days of bed rest led to a 67% increased insulin response to glucose. Of course, sleep, eating patterns, and stress also play roles in regulating insulin sensitivity, physical activity isn’t the only important factor here. But I don’t think I’m alone in believing that being sedentary is sufficient to cause Fibromyalgia.
Insulin resistance and leaky gut in Fibromylagia
Gastrointestinal symptoms are also common in people with Fibromyalgia. In one study, researchers found that 98% of people with Fibromyalgia had a functional gastrointestinal disorder including abdominal pain, bloating, constipation, feeling of a lump in the throat, and post-meal fullness.
Another study found that 100% of participants with Fibromyalgia tested positive for small intestinal bacterial overgrowth(SIBO). Not surprisingly, in one study, 70% of people with Fibromyalgia tested positive for intestinal permeability(leaky gut), compared to less than 2% of healthy controls.
Recently, evidence for a relationship between insulin resistance and leaky gut has emerged. A study in 2018 found that hyperglycemia induces leaky gut in mice, and in humans, the metric that most closely correlates to the amount of bacterial components in the blood is HgA1c. A pretty cool adjunct to this information is that in addition to improving insulin resistance, Metformin also reduces leaky gut.
So, it’s entirely possible that rather than insulin resistance directly causing Fibromylagia, the triumvirate of insulin resistance, circadian disruption, and leaky gut may cause metabolic abnormalities that lead to an accumulation of damage that presents as the symptoms behind fibromyalgia.
While insulin resistance may truly be a causative factor in fibromyalgia, there are other factors associated with both that may be equally if not more important. Both circadian disruption and leaky gut play roles in both, and it may actually be the combination of the 3 that ultimately needs to be addressed.
As mentioned above, being sedentary for 5 days can cause insulin resistance in healthy people, but physical activity will quickly reverse this temporary condition. Insulin resistance, leaky gut, and circadian disruption feed in to one another: circadian disruption increases leaky gut, leaky gut increases systemic inflammation which increases insulin resistance, and hyperglycemia due to insulin resistance increases leaky gut.
This is a much more difficult nut to crack, and given that we see all 3 in people with Fibromyalgia, they may function to reinforce one another. Thus, circadian disruption, leaky gut, and insulin resistance may be a vicious cycle that needs to be broken in order to provide symptomatic relief for people with Fibromyalgia.