Is insulin resistance the cause of fibromyalgia? (Prelim report) (2019) Pappolla et al - Retracted Dec. 2019

This is of interest because it is reporting amazing results (it is however a rather preliminary study).

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0216079

 

I've skimmed it. I can't see if it was blinded?

 

My fibro pain basically disappears when avoiding MCAS/MCS triggers.

 

What are your triggers? I'm now starting to figure out mcas and I know I'm suffering.. I avoid gluten and sugar so far...

 

@adambeyoncelowe,

It certainily was not blinded. it was a "retrospective cross-sectional study". i’m interested to see the responses to this study, because insulin resistance is such a different approach to the problem.

here is their statement about limitations of the study....

 

Am I right in reading this correctly. Was Metformin not offered alone but only in connection with what they call ST?

ST being something like an anti-depressant or Lyria type drug and no on was on Metformin alone?

 

Maybe,as it’s FOXO1 related and then there’s the idea of brain insulin resistance

 

Missed that completely! So foggy at the moment. Thank you.

 

ST is the acronym for "standard treatment". here is their description:

 

My critique of this study:

• Nowhere does it mention how long each participant has had fibro. The longer one has it, the less likely one is to be physically fit one the more likely one is to be overweight (higher BMI). This is a major risk factor in developing prediabetes (IR, elevated HgA1c). This is basic and should have been explored. BMI isn't even mentioned.

• Nowhere in the study does the investigator say how many of his sample had small fiber neuropathy. He mentions that they were tested for it or some were. Were they selected on the basis of having small fiber neuropathy and therefore would likely respond to metformin? He doesn't say. I registered on PLOS ONE to make that comment.

Interesting (Pappollo is a neurologist at U-TX-Galveston and a spine clinic). He has applied for preliminary patent entitled: Formulations and Methoda for Treatment of Fibromyaliga and Related Myofascial Disorders.

I don't know what to make of the miraculous pain reduction.

I need to be on metformin sooner or later. I guess I will give it a try, if my doc is willing, next month. Will keep you informed.

What Pappollo seems to be hypothesizing is that fibro develops because of insulin resistance. Even when the HgA1c is normal, it is 0.54 units higher per age adjusted controls than it should be. And this is enough to initiate the illness.

• From the introduction, quoted material: (IR = insulin resistance or abnormal HgA1c).

"Prior observations indicate that IR causes dysfunctions in the brain microvasculature leading to focal cerebral hypoperfusion [11]. Since similar brain perfusion abnormalities are present in patients with FM [12], we hypothesized that IR may be the missing link in this disorder. In order to search for initial evidence in support of this hypothesis, we conducted a retrospective chart review of patients with FM focusing on potential laboratory abnormalities. In contrast with prior studies, when we applied an age correction to the data available for analysis, specifically to the HbA1c values, unexpected findings came to light. Here, we report that a series of patients with FM belong to a distinct population that can be segregated from a control group by their HbA1c values, a biomarker for impaired glucose metabolism, characterized by insulin resistance [13, 14].

In order to supplement this finding, we also reviewed the evolution of the pain scores of patients with FM who had had their IR treated pharmacologically. This subgroup of patients reported dramatic improvements of their myofascial pain after treatment with metformin.

This evidence, although preliminary, suggests a pathogenetic relationship between FM and IR, which may lead to a paradigm shift in the management of this disorder."

Wouldn't it just be easier to do survey metformin's effective on pain in fibro patients?

 

Parsing it down: Pappollo proposes that insulin resistance causes fibromyalgia.
That metformin is highly effective in reducing fibromyalgia pain.
He also applied for a provisional patent for a novel treatment program for fibromyalgia and myofascial disorders (could be based on metformin?).

I don't know if his comparator population is representative or not for assessing HgA1c's by age.
I'm sure you can disprove the hypothesis that insulin resistance initiates fibromyalgia.

Have to rule out the placebo response versus ? did he chose patients already showing positive small fiber neuropathy on lab who might respond in pain reduction via metformin?

 

Haven't seen anyone on Twitter getting excited or having a response from Metformin with Fibro. Hmmm.

 

There was someone with CFS on one of the old internet groups years ago. Just the one that I remember.

 

I hate spending two hours trying to decipher why bogus science is bogus.

 

I have ME but also have the type of pain that I was unreliably informed a week or 2 ago is only associated with FMS.

I don't think I have FMS but I do have FMS type pain.

Apparently ME is pain free and if you have pain then that means you also have FMS.

I was on metformin for several years until I became completely intolerant of it.

I do not remember being in any less pain in those years, in fact I remember being in more pain,

That may be unrelated, as at the time I was on metformin I was not on co-codamol.

So I'm fairly sure that at least in my case metformin does not act as a painkiller for that type of pain.

Good luck to those it does tho, for as long as they can tolerate the common side effects, which are painful and quite disabling in themselves.

 

It was a member on here, with a pet theory.

I may have been being a little sarcastic in my post above.

I was definitely being a little something

 

I struggled with this paper....it seems overly complicated and a lot of stats for just 23 patients with dubious controls.

Surely it just says that some people with FM have insulin resistance?. They don’t seem to have a control using people with insulin resistance without FM?

So a few general facts as I understand them:
Approximately one third of all people in the USA are classed as obese
If you are obese up to 30% of these can be insulin resistant
Obesity is more likely when you are older and female


I found it difficult to ascertain from the paper how they had adequately avoided sampling bias from regular obesity driven insulin resistance ..they seem to be comparing apples with oranges in the type 2 diabetes bit ...not all people with insulin resistance go on to get type 2 diabetes?
There is no effort to demonstrate how they avoided cherry picking the sample they used...I guess they assume we trust them? (That shows a level of sloppiness and arrogance I’ve seen somewhere else? Now where was it

They also used self reported pain scores but haven’t blinded the treatment as far as I can see?

Am I reading this wrong ?

This just seems a very casual observation comparing a very small sample using unblinded self reported measures of pain, and poor non matched controls (whatever they could find listed somewhere else in broader non-fm studies).

It’s written in a confused and misleading way rather than a proper scientific study imo. The method section is just atrocious...looks like it’s written as a blog rather than a proper description of what they did. Extremely amateurish and all over the place. I would be surprised if the author has any understanding of the scientific method.

 

@arewenearlythereyet,

I was confused also. from my reading, it is a "retrospective study".... so they just went and looked through their records and selected out these patients and they are saying, "look at these miraculous results (painwise and in being able to ID FM by a blood test). They don't say how they cherry picked their patients. So from what I read, there could have been 1000 other pre-diabetic patients with FM of theirs that they did not use in their report...

It does remind me of the story of the Haukeland group rituximab begininngs... seemingly significant symtom reduction amoung a select group of their patients...and eventually that led to proper clinical trials.

That said, the reduction in pain stated by the patients is quite stunning for a drug administration, but their story should be considered antedotal.

 

TBH it sounds a bit like a card trick, one of those where you keep slicing and picking a pile until it contains the card you want.