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Is insulin resistance the cause of fibromyalgia? In a subset of fibromyalgia patients, metformin dramatically improved pain

Hip

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A new study published in May 2019 finds preliminary evidence that fibromyalgia might be due to insulin resistance:

Is insulin resistance the cause of fibromyalgia? A preliminary report

The study found highly significant association between fibromyalgia and glycosylated haemoglobin (HbA1c) levels, a marker of insulin resistance.

Some fibromyalgia patients meeting the criteria for pre-diabetes or diabetes who were given metformin (which reduces insulin resistance) showed dramatic improvements of their myofascial pain.
 
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percyval577

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AMPK has been twice identified by one group to be inactive in ME/CFS muscle in response to exercise, but also possibly in response to Metformin. It doesn’t seem to help those here who’ve tried it either, I’ve inquired before.
Pharmacological activation of AMPK and glucose uptake in cultured human muscle cells from patients with ME/CFS Brown et al 2018

I personally could get muscle pain if I had drunken alcohol and took in 4-24h later much calcium, say in cheese or chocolate. But I never thought to have any problems in my muscles, for me it was clear to be a brain issue.
Also, when my movements induced a worsening in my body feelings (in first place heavy legs), I never thought to have any problems with my muscles.

Maybe the blood would be more interesting?
 
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The results are very spectacular; in the majority of the patients the pain is completly gone or almost completly gone if metformin (500 mg, 2 a day) is combined with standard treatment (e.g gabapentine, amitryptiline,..)

However, this study quoted another study saying the incidence of FM is 18% in people with diabetes mellitus type 2 compared to 2% in the control group. If you keep in mind that basicly every patient with diabetes type 2 is on metformin (at least in my country) how come no one noticed or reported such a positive effect from the metformin on the pain before? This is very strange to me.

I only had a quick look at the study, but they don't seem to mention how fast the pain was improving after metformin intake. I'd like to know that. And i'd like to know if it improved other symptoms beside pain.
 

voner

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thanks @Hip for posting this. Spectacular results that they are claiming! here is brief write up of the study:

https://www.sciencedaily.com/releases/2019/05/190507145523.htm

they seem to be also claiming, without saying so, to have found a potential biomarker..?

"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."
pretty big claims for such a small and selective data set.....

so... at 60 years old my A1C level was 5.4%... does that put me in the fibromyalgia category? my symptoms certainly do, but the A1C level seems low on their chart...

It will be very interesting to watch the reponses from other researchers.
 

Mel9

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A new study published in May 2019 finds preliminary evidence that fibromyalgia might be due to insulin resistance:

Is insulin resistance the cause of fibromyalgia? A preliminary report

The study found highly significant association between fibromyalgia and glycosylated haemoglobin (HbA1c) levels, a marker of insulin resistance.

Some fibromyalgia patients meeting the criteria for pre-diabetes or diabetes who were given metformin (which reduces insulin resistance) showed dramatic improvements of their myofascial pain.

Interesting and encourages me to start taking Metformin as a trial because I have insulin resistance .

They seem to have left the x-axis unlabelled on Figure 1. Any ideas what it is?
 

percyval577

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The AMPK pathway also appears here:

Identification of Mayalgic Encephalomyelitis/Chronic Fatique Synsrome-associated DAN methylation patterns Trivedi et al 2018 (including Klimas)
p.10
... MAPK pathway ...
the IL-10, IL-17, Il-1 and iL-8 signalling pathways (all with important immuneregulatory roles) ...

the AMPK pathway (master regulator of cellular energy homeostasis that is activated in response to stresses that deplete cellular ATP supplies) ...

and metabolic pathways such as ...
They follow up mentioning B-cell immune response, T-cell generation and activation, PBMC´s in respect of targeting MAPK, NF-kB and TGF, furthermore miRNA generation and biometal regulation.

For significiance (eg) in respect of PBMC´s methylation p.9.
They say also that the global methylation level does not differ to HC´s


p.14
... still inconclusive ... wether ... compensatory homeostatic mechanism or result from an adaptive immuneresponse ...
 
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Hufsamor

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Im joining a diabetes 2 group at Facebook,
and I asked if anyone could confirm this study,
if anyone with fibromyalgia got less pain after starting up on metformin.

I have received 17 answers.

5 are worse.

1 are better, but she had turned her whole life upside down, starting to exercise, eating healthy, doing all the right things, so she didn't know if the lessening of pain had to do with the metformin.

The rest of the answers was a union NO. Not less pain at all.
 

pattismith

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Testosterone supplementation improves women fibromyalgia. I did a trial and it was quickly effective and beneficial in that area.
on the other hand, testosterone in women can cause insulin resistance...

If really insuline resistance is a cause for fibro, then testosterone therapy may not be beneficial very long and only a transient benefit….
 
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pattismith

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Some fibromyalgia patients meeting the criteria for pre-diabetes or diabetes who were given metformin (which reduces insulin resistance) showed dramatic improvements of their myofascial pain.
I wonder if this subset of fibro patients were actually Myotonic Dystrophic (DM) patients or if Fibro and DM may share common pathologic mechanisms.

In a study, they found 2 patients in 63 Fibro had DM2.

In this article: "Individuals with DM1 and DM2 have peripheral insulin resistance and increased proinsulin levels that can lead to glucose intolerance, hyperinsulinemia, and an increased risk of developing type 2 diabetes. ... Unlike most other muscular dystrophies, myotonic dystrophies affect a great variety of other organs than muscle."

In this study about promising molecules to treat DM1, some AMPK activators are reviewed, and Metformin among them:

"Metformin (Table 1) is an FDA-approved antidiabetic drug and was earlier reported to improve hyperglycemia through increased insulin-independent glucose uptake in peripheral muscles of DM1 patients (72).

Most recently, metformin was investigated in in vitro DM1 models of human embryonic stem cells and in primary myoblasts derived from patients (73).

The drug appeared to modify the alternative splicing of a subset of genes associated with DM1 in these cell models, as it partially rescued the aberrant splicing of INSR E11, CLCN1 E7a, TNNT2 E5, ATP2A1 E22, and DMD E78.
The effect on the modification of the alternative splicing has been linked to the inhibition of the complex I of the respiratory chain, which in turn raises the intracellular AMP/ATP ratio, which triggers the activation of AMPK."