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Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS)

Discussion in 'General ME/CFS Discussion' started by Valentijn, Jan 26, 2017.

  1. Valentijn

    Valentijn Senior Member

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    I need to vent on a related topic, so the first post isn't going to be too relevant to the subject matter.

    I was diagnosed with diabetes 2 weeks ago, after blood glucose testing at 400 (22.2) on my fiance's blood glucose meter. It's being presumed to be Type 2, but that's unverified because the Dutch medical system prefers gambling with patients' internal organs instead of testing. Severe hyperglycemia and symptoms of moderate diabetic ketoacidosis (DKA) were ignored, because the Type 2 guidelines for Dutch GPs don't say anything about it. So I was sent home with no information at all, a low dose of a drug which takes a few weeks to start working, and a followup appointment in 2 months' time.

    I did some research, and discovered my A1c and fasting glucose meant I should've been started on insulin immediately, at least in the short term. But again, that's not in the Type 2 guidelines in the Netherlands. In the mean time, I lowered my carb intake to 20-30 carbs per meal and ordered ketone testing strips to make sure I wasn't heading into DKA. Glucose lowered a little, but was still in the range where DKA is a risk. Urine strips showed ketones present most of the time over the next 3 days, frequently at moderate (++) levels and once at large (+++) levels.

    I kept feeling very sick, went back to the doctor. She tested my glucose and happened to get one helluva spike. She then tested my urine and traces of ketones were present. She called an endocrinologist while we waited in the waiting room, then ordered a GAD56 auto-antibody test (seen in Type 1) and added a new drug which stimulates insulin production. Followup appointment was then moved up to be 3 days later.

    The first drug I was starting on, which takes a while to work, is Metformin. I had pretty unpleasant GI symptoms, which is normal for that drug. But this coincided with my likely DKA episode, and I was having pretty intense diarrhea, which would have caused some dehydration and aggravated the DKA, despite all of the water I was drinking. It was at that point where the test showed my blood glucose spike of 335 (18.5) in her office. That evening and the next morning I had 14 straight hours of moderate (++) ketone readings, with my large (+++) ketone reading.

    The new drug seemed to be helping, though blood sugar kept rising at night, through the morning, until I take my daily dose with breakfast. At the next appointment, the GP insisted that ketones in the urine are normal, and it's not possible for them to cause problems in Type 2 diabetes. She also doesn't seem to think that hyperglycemia chronically in the KDA range (240+ or 13.3+) is a problem. Basically, she knows sweet fuck-all about diabetes, yet is tasked with diagnosing and treating it. Another dose of metformin was added, in the evenings.

    At that point, some mild and transient symptoms which started with the first dose of metformin got a lot worse and pretty much constant. Arms burning, weak shoulders, arms aching, leg muscles twitching, nasty headache, extreme exhaustion, and being very cold all day. These are the symptoms of lactic acidosis, which metformin is known to cause in those who are susceptible. Usually it's due to organ dysfunction, but the GP did test thoroughly for that to make sure it was safe to prescribe the drug, even if she wouldn't test to make sure I have the disease which the drug is used for :p

    I researched the side-effects last night, and stopped taking the Metformin this morning. This morning was still pretty hellish, with some nausea joining the other symptoms. I had a three hour nap when I was too friggin tired to stay awake at 10am, and felt a bit better afterward. I've been able to eat a bit more, and the headache is receding enough for me to read and write a bit. Still shaky as hell. Also drinking a lot of water to help flush out whatever.
     
    Last edited: Jan 26, 2017
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  2. Sidereal

    Sidereal Senior Member

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    Sorry to hear this Val. Metformin is a really dangerous drug for ME/CFS. Have met others who had similar episodes of lactic acidosis from it. It inhibits complex I of the electron transport chain. In fact there may be an earlier thread on PR about it.
     
  3. Cheesus

    Cheesus Senior Member

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    That sounds like quite a trial. I hope you can get a clear diagnosis and some effective treatment soon.

    Would it be difficult to switch to a different GP?
     
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  4. Mary

    Mary Senior Member

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    @Valentijn - wow - that is rough. I've read several places that B1 - thiamine - can be helpful for diabetics, it can help regulate blood sugar as well as help prevent symptoms of diabetes, including neuropathy and so on.

    This first article is from 1940 (!) but I'm not surprised, as lots of nutrition-related research from decades ago was ignored in favor of drugs etc.: http://jamanetwork.com/journals/jamainternalmedicine/article-abstract/546554

    And there's lots of current info on this as well: https://www.ncbi.nlm.nih.gov/pubmed/18220605

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3376872/

    I hope you get some help soon ---
     
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  5. Valentijn

    Valentijn Senior Member

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    The really weird thing is that the symptoms of lactic acidosis which I was getting from the metformin were extremely similar to my ME symptoms, though unprovoked and making their appearance in a different matter.

    The burn was the same immediate burn from over-using a muscle, except it was all along my upper arms when I wasn't over-using them, and it was persisting. The headache feels a lot like the chronic ME headache I started getting after diagnosis, but keep under control with fish oil. The muscle twitches are a symptom I get with ME, but again, only shortly after after over-using a muscle. Feeling really cold? Sure, usually just my feet, unless I've been outside in the cold recently. I also get nausea with a crash, and exhaustion.

    It felt like getting a 2nd case of ME that was just behaving a little differently. I know we often describe our symptoms like a bad case of the flu, but I can tell the difference between the flu and a crash. The symptoms are roughly similar, but they are not the same. The lactic acidosis symptoms, on the other hand, felt exactly the same.

    Which got me thinking about lactic acidosis in ME. Studies have shown lactate weirdness in muscle cells, being over-produced by gut-bacteria, etc. Are we at risk of or chronically over-producing lactate? (Seriously, if you know of studies, please link them here ... I'm not up for much research myself currently.) It can cause all the symptoms I listed above, plus exercise intolerance and hypotension.

    And then I remembered that I have a rare mitochondrial mutation which is labeled as being pathogenic, and is on a gene associated with MELAS. Initially I thought it couldn't be related to my ME symptoms (long before my lactic acidosis episode) due to my mother and presumably her siblings having the same mutation but not developing the same illness.

    But apparently mitochondrial diseases aren't quite as simple as getting the mutation or not. Eggs hold in the neighborhood of 200,000 mitochondria, and it's not a matter of 1 mitochondrion getting passed to the embryo, but rather a sampling from all of it. The cells in the developing fetus can then have different alleles for the same SNP, if the mother has different mitochondria with the different alleles.

    When the mutation isn't particularly viable, the cells containing it might die ... but other cells which got the good version thrive. This means that nonviable mutations can be largely suppressed, and you get a normally developing embryo which becomes a (mostly) normal human being. Eventually, however, the mutant cells might take over in certain tissues, and then the disease becomes evident. This is how mitochondrial diseases caused by the same mutation can have late (or effectively no) onset instead of neonatal onset. It's also how symptoms can vary, as different tissues are taken over by the mutant.

    So it is possible that my pathogenic mutation really is pathogenic, even though it also defines the entire H1b1 maternal haplogroup. It could be largely skipping generations due to random luck, good culling of cells, and/or lack of the right trigger.

    And in addition to causing symptoms identical to ME, MELAS is known to cause diabetes. So there could be one cause for both diagnoses, especially since inactivity and weight-gain attributable to ME would cause a more typical Type 2 diabetes, and should not feature the production of ketones.
     
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  6. Valentijn

    Valentijn Senior Member

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    She's not the entire problem ... the Dutch GP Guidelines are abysmal when it comes to diagnosing Type 2 diabetes. If the patient isn't young and normal weight, it's always diagnosed as Type 2. Testing for insulin production (c-peptide) or auto-antibodies is absolutely not routine.

    The guidelines say absolutely nothing about what to do if the diabetic has severe hyperglycemia at onset. Symptoms of ketoacidosis are not mentioned at all, nor ketones. I also seem to recall that having the followup appointment in a month is mentioned in there.

    Admittedly, the GP has a distinct lack of curiosity, and/or extreme deference to authoritative texts. My previous one would at least think for herself and try to solve problems!
     
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  7. Valentijn

    Valentijn Senior Member

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    Oh, and my eyes are doing the "coming down from hyperglycemia" thing, and the focus is changing quite a bit. Makes reading extra fun!
     
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  8. Sidereal

    Sidereal Senior Member

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    Well I can't say how it is in the Netherlands but my father was diagnosed with type II diabetes many years ago in Austria. His BG was around 400. He was hospitalised and put on insulin injections immediately.

    DKA is a medical emergency. I cannot believe that your GP is treating this in such an idiotic fashion.
     
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  9. AndyPR

    AndyPR Senior Member

    Well, the latest Fluge and Mella results point to unprocessed glucose being turned into lactic acid, so if your medication is causing more lactic acid as well then I can't imagine it's very helpful at all to someone with ME.
     
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  10. Jenny TipsforME

    Jenny TipsforME Senior Member

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    You're Occam Razoring it well! Don't forget Hickam's Dictum though

    You could have lots of completely unrelated issues...

    I think I've read MELAS can express quite differently in families. Not entirely on topic but I found this article speculating about Darwin's family mitochondria issues interesting (possibly not top reading priority right now @Valentijn if you can't focus) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3632469/

    Those sound like scary glucose readings. Hope you get it under control quickly.

    When you can read, check this thread http://forums.phoenixrising.me/inde...-study-to-measure-blood-lactate-levels.40152/
    It is possible to measure lactate with a home monitor. Not cheap but not super expensive.

    Do you normally only get pain in specific overused muscles? I can get that but I have days when my whole body aches with burning type of pain, including my eyes.
     
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  11. Sidereal

    Sidereal Senior Member

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    What was your A1c and fasting BG btw?
     
  12. Valentijn

    Valentijn Senior Member

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    The 2nd drug (Gliclazide) helps a lot. It just seems to wear off by bedtime, so I'm high every night. But mostly in the 180-215 (10-12) range, and safely out of the KDA range. During the day it does a lot better, around 110-145 (6-8) with postprandial peaks just 20-35 (1-2) points higher.
     
    Last edited: Jan 26, 2017
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  13. Valentijn

    Valentijn Senior Member

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    A1c was 10.3% (88), and blood glucose on the fasting lab test was 300 (16.8).

    A1c was tested again a week later along with the GAD autoantibody, apparently to put any GAD results into perspective, though I won't have those results for a few weeks.
     
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  14. Valentijn

    Valentijn Senior Member

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    I also get delayed full-body pain during crashes. I used to have a deep (vascular?) chronic pain, but high dose injections of HydroxoB12 keeps that at bay.
     
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  15. Paralee

    Paralee Senior Member

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    @Valentijn , I'm so sorry. I hope this works out in your favor! Don't you just love those generation skipping little pathogen a**...never mind...dirty word. I got most of my grandmother's variants, but Mother didn't seem to get the ones I got, but she did get ones I didn't get.

    I hope your doc understands you, maybe you should go in there and just ask for her coat and put it on during the appointment?
     
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  16. Mary

    Mary Senior Member

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    @Valentijn - Sorry, I can't follow the technical discussion above. But - I wanted to call your attention to thiamine as helping reverse lactic acidosis - I have no idea if this could help you, but FWIW here's some info:

    "Reversal of severe lactic acidosis with thiamine in a renal allograft patient" (lactic acidosis related to severe hyperglycemia) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4502498/

    http://acutecaretesting.org/en/journal-scans/a-rare-cause-of-metabolic-lactic-acidosis-highlighted
    (related to thiamine deficiency)

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3388689/ - severe lactic acidosis reversed by thiamine
     
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  17. rosie26

    rosie26 Senior Member

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    Yes, I have been thinking a lot on those lines too recently. I think some or all (?) of us have been reset at a high lactic acid state. The gut and other areas of microbiome have reset after infection at a higher level. It feels this way in my situation and I get a lot burning symptoms.
     
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  18. Chocolove

    Chocolove Tournament of the Phoenix - Rise Again

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    @Valentijn These articles may be of interest:
    http://www.webmd.com/diabetes/news/20090608/metformin-linked-to-b12-deficiency
    June 8, 2009 -- The popular diabetes drug metformin may contribute to vitamin B12 deficiency, according to a new study.

    Researchers found that 40% of type 2 diabetes patients using metformin had vitamin B12 deficiency or were in the low-normal range for the essential vitamin. And 77% of metformin users with vitamin B12 deficiency also had peripheral neuropathy, a common form of nerve damage associated with type 2 diabetes.

    http://www.drwhitaker.com/knock-out-a-top-cause-of-diabetic-complications/
     
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  19. Chocolove

    Chocolove Tournament of the Phoenix - Rise Again

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    @Valentijn Here are some more articles you may find of interest:

    https://www.deepdyve.com/lp/elsevie...d-thiamine-levels-in-patients-with-y7RMAmbNso

    Lactic acidosis: MedlinePlus Medical Encyclopedia
    https://medlineplus.gov/ency/article/000391.htm
    Lactic acid is produced when oxygen levels in the body drop. ... A common medicine used to treat diabetes called metformin can also cause lactic acidosis.

    Thiamine and magnesium deficiencies: Keys to disease
    www.sciencedirect.com/science/article/pii/S0306987714004393
    Thiamine and magnesium deficiencies: Keys to disease. D. Lonsdale, Associate Emeritus, Cleveland Clinic, ... Evidence for altered thiamine metabolism in diabetes: ...
    Published in: Medical Hypotheses ยท 2015 Authors: D Lonsdale

    Gut Inflammation in Chronic Fatigue Syndrome - Medscape
    www.medscape.com/viewarticle/732378_11
    ... and the immune system play a role in the pathogenesis of chronic fatigue syndrome? ... Chronic fatigue syndrome: lactic acid ... obesity and diabetes ...
     
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  20. Chocolove

    Chocolove Tournament of the Phoenix - Rise Again

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