metformin, it can reverse liver disease and IR

I'm having a real dilemna here, and I would really like to see more discussion of this topic.

here is a great synopsis I just found:


http://www.nature.com/nm/journal/v6/n9/full/nm0900_998.html

WOW, that was a mouthful!!

in light of the findings from all those studies listed I would think this needs much closer examination.

In light of the fact that I am currently UND and have no virus, the reversal of fatty liver and less necrosis and less HCC all sounds very appealing, not to mention any reduction in IR would mean ones own Interferon response would be better post tx. and this alone may increase ones chances of an SVR even if begun at the end of an SOC regime.
Perhaps now, more than any other time it could help insure one will recognize any lingering HCV and seek and destroy as designed.
As long as one kept the dose low, monitored the liver, and watched for lactic acidosis, what would be the harm in trying?

arguments in favor or opposed please weigh in, if obese women went from 20% to 60% SVR that should tell us something??

mb

[bajawoman]

Well I may not be the brightest kid on the block but was raised to use logic and finding out I had IR made all the difference in my approach to treatment for HCV


I listened to CoWriter CS and HR all three said the same thing need to treat  the IR  First

Once you are diabetic it is a steady downhill road no cure for Diabetes but there is a definate program to treat Type 2 diabetes with out having to take injections the rest of your life

So finding out IR sooner rather than too late, was a blessing and I am going to be forever thankful and greatful  to coming on this forum which I was lucky enough to Meet Meet Cowriter who spotted my IR  right away and had me order blood work for a HOMA test which I immediately did

Then Meeting CockSparrow who steared me to HR  with their help and with CoWriter

I was able to make up my own mind after discussing my situation with them and
My GI who I am treating under sharing all the knowlege and studies with him

I saved myself from going on treatment ill prepared and enlightened my GI who now can help others he reads all the info I send him and shares it with his associates in the mainland Mexico

I am IN FAVOR and one does not have to be OBESE to have IR  OBESE can happen from being IR or genetic tendencies that needs to be recognized in Children Obese tendencies and  with IR/Diabetic parents or grandparents needs to be handled and under control from an early age  ComeAgain is right  Not a good thing to have whether you have HCV or not

I am stage 2 fatty liver stage 3 fibrosis I am working on the IR with the sups HR recommended  and the sups  recommended by HR to keep my fibrosis stable I am going to work on the HVC  
my viral load last June was 47,300,000  

I will get another viral load test before treatment
and continue to monitor my liver with  visits to my GI and Lab work

Thanks MB for posting
Saludos
baja

[merryBe]

thanks, say didn't you say you were taking some HR recommended things for IR.

which ones are you taking for that?

I'm looking at all alternatives now.  My doc recommended I go on Byetta if the BS goes back up, but it's expensive, and shots and monitoring...yuk.

So that wouldn;t be my first choice, although he seems to think it's safer for the liver.

I'm going to take some studies to my endocrinologist next week in the hope of doing all to avoid another pony ride (after 22 months who can blame me).....

So everybody throw me whatever YOU"VE GOT !!!!!

mb

[merryBe]

speaking of all this, here's a cool HOMA calculator I found:

http://www.dtu.ox.ac.uk/index.php?maindoc=/homa/index.php

mb

[bajawoman]

Basically the same ones CS is taking that HR recommended to him  Gauf also has posted on his profile
I get all my sups on line and they send them to me here in Mexico HR recommended where to buy them and I did on line The Resveritrol is the only one I get direct from Resveritrol.com
I am taking Resveritrol 1000 working up to 2000mg per day
I am also taking from LifeExtentions.com
Mega Silymarin 900mg twice a day(milk thistle
Taurine one cap a day 500mg bought this in good health food store in LA
Green Tea Extract 725 mg one cap a day
curcumin Tumeric 250mg 3 a day bought this in good health food store in LA
NAC 600mg twice a day  bought this in good health food store in LA
Super R-Lioic Acid 300 mg twice a day
fish oil omega  4 caps a day bought this in Costco
TMG powder twice a day
folic acid vitamin B12 caps twice a day with the TMG ad R-Lipoc acid
CoQ10 50mg twice a day
Mary I also bought from Life Extentions the Human Growth Hormone after reading your posts it is in Liquid form 30 drops under the tongue in the morning as suggested on the bottle
hope I am not leaving anything out  I became a member of LEF.com or lifeextentions and I get a discount the sups come within about 10 days to Mexico after ordering they ship all over the world  good company I will order all my sups from them when I run out of the ones I bought from other places
baja

[merryBe]

so how much of a reduction did you get on you IR/HOMA etc.

I thank you for reading my long winded post, but I'm afraid to tell you the evidence that the oral forms of HGH work is very sketchy at best.
I did quite a bit of reading hoping some oral argine or something would work, but the thing that consistantly raises the IGF is the actual human enginneered hormonal protein
chain. Which is still injectable only.

However, IF you are monitoring you IGF and getting a rise in your level than please let me know so I can add that to my thread. I know Merck was working on a oral version, however it was raising peoples IGF  AND their BLOOD SUGARS, which is NOT a good thing.  The injectable human growth hormone does not do this.

Best to you in upcoming tx. you are doing lots of things right, please preload with an antidepressant to save grief, and please don't wait too much longer,  47 mil is a great concern and one would think you would be anxious to treat at that number.

Have you considered preloading Alinia? It may be far less expensive in Mexico, being it is an antiparacytical it is in wider use in warmer climes.

mb

[bajawoman]

I am not actually taking the IGF drops did do for a few days but did not mix well with the sups the sups by themselves do take some getting used to

I know I need to do something soon which is what I am trying to get the IR down and if I have to treat sooner than later;
sooner being with better drugs as  HR recommended
but he said to definatley not TX without Alinia if I cannot wait  and use Metaformin if I need it
I have been on Lexapro for some time but just 10mg a day

I am happy with the sups I feel I am doing something positive
getting a CAT scan this friday and lab work to check my HOMA  and a HEP B panel

I want to tx sooner may not wait for the new drugs but really want to know more about who I am physically going in  so worried that it may cause more congnitive damage
and RA pain or whatever it is pain which is pretty bad now

also doing research on Occult Hepatitis B which I may or may not have will find out soon seems from some older articles by Dr D it could be a negative for SVR too

[merryBe]

hmm..I'd actually be more suspicious of the curcurmin causing gastro issue, I couldn't tolerate it AT all.

as to the drops, the liklihood is they'll do nothing...there are always plenty of companies counting on people NOT doing their homework, and here absorption and conversition are key with HGH.
I don't know how familiar you are with the term bioidentical hormones, but I was on them before any of my docs other patients, long before susan summers or oprah discovered them medical research had proved the differences in all the identicals vs. synthrtic subs.

there is a letter writing campaign for compassionate use of teleprevir now in here, you may want to join in that.  Eventually Inovio seems to have the greatest promise I think, right now anyway their vaccine kills 99% of virons,,,,then SOC is a mop up..and much easier to get to SVR...however they are only just now starting phase 3 so it'll be a while.

I'm sure opinions will vary in here, but 47 million means from what I understand that your liver damage will be occuring more quickly, your immune system is already worn out.
The labs don't always tell the whole story either....sometimes while in the latter stages (3/4) they can go back to almost normal...as most of the liver is shot they are deceptively low as they are only reflecting what the little liver tissue left is doing.

I think jmjm elaborated on this once, but my memory is not always accurate.

In any event, at that viral load your stage could go up at one stage per year or more, so from what I understand the higher the VL the more imperative to treat EVEN if it only means you knock down the virus while treating for a year, it would give your liver a rest, and a better chance at still being intact enough to treat with better drugs when they do come out.
You are right to be concerned about the RA, but remember the better drugs, all of the and antivirals and new PI's also have the SOC included, so either way you'll be getting the same chance at exascerbating that. However, yout immune system is in overdrive is you have RA, having enough INF on board to deal with the virus MAy improve it.

Look at it this way you have 47 million virions in each tiny ml of blood. just a few drops contains that many...a ml is only 1/4 of a teaspoon...makes you wonder how the blood still fits into the same space!!
So you are fighting all that virus with no help...and now your immune system has gone beseerk fight it...and is attacking other things too....so maybe the boost that bringing INF on board will give you, might give your spleen enough of a rest to settle down...and actually slow your autoimmune stuff....not saying it will work that way, just saying it can.
It can go either way. They don't tell you that. Heck they use INF on MS, and it slows that down, so I'm just saying....you gotta do your own homework, there are always down sides and upsides... Yet the bottom line is if you don't try then your liver will eventually suffer too much injury to keep up...and you've gotta have a liver to live.

I'm not trying to scare you here, just trying to make sure you understand what's at stake.
My liver was at stage 3/4...and the doc still said well you could live another 5-15 years...
easy for him to say...he didn't have the enlarged liver and spleen, he wasn't in pain going beyond all distraction, or exausted to the point of not knowing if he's wake up....
that ain't livin'....if you catch my drift.

Have you got any recent labs? Are you treating state side or in baja??

I wish I could give you something more hopeful than SOC, I did write to the MD heading up the Inovio research a while back, to try and get  the ph 3 locations...so far no response there.

mb

[Trinity4]

All I can say to that is if you are not IR or have type 2 diabetes you don't want to be on metformin.  My husband is diabetic and needs it but why would you want to take it if you don't need it?  

Too much IR resistance information going around these days.  Either your IR or your not.  Tx life doesn't revolve around IR resistance, diabetes, obesity etc, etc.  I think it's good to be aware, but all the information lately has been a bit much. Prior to tx fasting glucose was normal.  My fasting has been at 100 - 103  for the last several months. 52 wks into tx.  Can't change anything now and I believe it's do the tx meds and the addition of Neup.  If it doesn't go away after tx, then I'll check into it. Otherwise, I'm not going to worry about.

Merrybe I'm not trying to hijack your thread.  I hope people chime in and give you input.  I'm getting weary of all the IR stuff that's all.  There are many many other concerns while on tx besides IR and it can become overwhelming if you let it effect you.  By the way, I've stopped checking my fasting glucose.  It was becoming obsessive.

Trin

[JennyPenny]

I really like your post. It is important to have a balanced view of these things. Like you, I believe IR is important but it isn't the be all end all to treatment success. We have on our message board, plenty of obese, type 2 diabetics with geno 1, who have successfully completed treatment. It is just one more thing to look at.

[desrt]

JennyPenny
Agree. Miles has been exploring the link between IR and IR for 6 years that I know of (and taking Metfomin) and has never cleared. I went into tx  IR, came out IR, and am SVR 6 years (many thanks to you, Linda B, and many others.)

CockSparrow may or may not SVR this time. I pray he does.

Bajawoman:
Who's your daddy?
http://www.medhelp.org/posts/show/678572
Oh well, you're getting it taken care of and in your case it may mak a difference. Good Luck.

[nelson958]

What is IR please?

Nelson

[bajawoman]

The formula to see whether you're insulin resistant (is called HOMA) .....you multiply the insulin x fasting blood sugar and divide them by 405.
IR is Insulin Resistant or pre diabetic can be useful to know prior or during tx

[desrt]

IR is insulin resistance also sometimes used to mean interferon resistance. IR and IR are connected.

[CoWriter]

desrt said....
"Bajawoman:
Who's your daddy?"

Tell him who your daddy is....ROFL

Co

[CoWriter]

It reverses fatty liver in people too.  There's an abstract from AASLD about it.  That being said, I would never recommend going on Metformin after you SVR'd if you don't really need it.

Bayetta doesn't work like Metformin does BTW.

Co

[CoWriter]

" I'm getting weary of all the IR stuff that's all. '
-----------------

I totally understand.  Probably just as weary as I get when I hear people recommending fat with riba.

Co

[mikesimon]

I found it interesting nonetheless.

http://www.medscape.com/viewarticle/589647

Metformin May Up Alzheimer's Protein if Used Alone
Metformin Beta-Amyloid Effect Raises Alzheimer's Concerns

Janis Kelly

March 16, 2009 — Diabetes mellitus is associated with increased risk for Alzheimer's disease (AD), but a new study of metformin suggests that diabetes treatments might bear some of the blame.

Yaomin Chen, PhD, from the Burnham Institute for Medical Research, in La Jolla, California, and colleagues report in the March 10 issue of the Proceedings of the National Academy of Sciences that metformin increased insulin's reduction of intracellular and extracellular beta-amyloid accumulation, but metformin by itself actually increased levels of the Alzheimer's-linked peptides.

This finding, which was observed in vitro and in animal models of AD, raises the specter of a wave of new Alzheimer's cases in diabetic patients who have been taking metformin for years. It is the most popular antidiabetic drug in the United States and 1 of only 2 oral antidiabetics on the World Health Organization List of Essential Medicines (along with glibenclamide). In 2006, there were 35 million prescriptions for generic metformin filled in the United States.

Senior author Francesca-Fang Liao, PhD, told Medscape Psychiatry that although this was an animal study, the findings are worrisome enough that physicians should promptly follow up any complaints of cognitive decline in patients taking metformin.

"Our data suggest that metformin used alone might potentially facilitate development of AD pathology," Dr. Liao said. "This raised the question of whether the increased AD risk in diabetes mellitus patients might be due to the medication itself.

"Extensive animal studies as well as epidemiological data from clinical patients should be collected and carefully analyzed to address this question." Dr. Liao was at the Burnham Institute for Medical Research when this study was done but is now at the University of Tennessee Health Science Center, in Memphis.

Safer to Use Metformin in Combination Therapy?

The upregulation of beta-amyloid generation by metformin in animal models of AD occurred at steady-state plasma levels at and even below those reported in diabetic patients.

Metformin is an insulin-sensitizing drug, and the researchers found that giving it together with insulin added to insulin's known ability to reduce beta-amyloid generation.

"Our data suggest that the potentially deleterious effects of metformin to AD patients may be avoided by using it in combination with insulin; the combination may result in a beneficial effect in treating both type 2 [diabetes mellitus] and in mitigating AD progression," the researchers write.

AD expert Michal S. Beeri, MD, from the Mount Sinai School of Medicine, in New York, told Medscape Psychiatry, "The report by Chen is very interesting and consistent with a study from our group showing that brains of diabetics who, when alive, received combination therapy (ie, insulin plus an insulin sensitizer) had 80% less neuritic plaques (1 of the hallmark lesions of AD).

"This paper is also consistent with another study published in the Proceedings of the National Academy of Sciences [De Felice FG et al. Proc Natl Acad Sci. 2009;106:1971-1976] showing that soluble beta-amyloid oligomers (precursors of neuritic plaques) promote loss of surface of insulin receptor, that this loss can be prevented by insulin, and, most interesting, that adding the insulin sensitizer rosiglitazone [Avandia, GlaxoSmithKline] to insulin potentiates this protection.

"These studies suggest that there might be some protective mechanism that is triggered when the brain is exposed to insulin and insulin sensitizers at the same time, and this in turn has therapeutic potential," she said.

Randomized Control Trials Needed

With regard to the apparent deleterious effects of metformin, Dr. Beeri is more cautious, noting that large, placebo-controlled, double-blind trials will be required to establish that this happens in human patients as well as in animal models and in vitro.

"I think Chen's study is very important and strengthens the concept of diabetes medication effects on Alzheimer's neuropathology, but at this point I do not think that there is clinical evidence for clinicians to be concerned when treating their diabetic patients with metformin," she said.

The study was supported by National Institutes of Health grants, the Alzheimer's Association, and a Zenith Award. The authors report no conflicts of interest.

[portann]

I read that yesterday but was literally afraid to post it. Too much zealotry going on.

My cousin is a researcher and endocrinologist, head hunted by the Mayo Clinic, and director of a Metabolic Syndrome clinic.  He doesn't see the world through the one lens of Insulin Religion.

In fact, he's not very happy with Metformin. He'd roll his eyes to hear our Metformin converts. Perhaps his gold medal at medical school was a sham or at least some of our members might say so.

Never think that you completely understand things and, as a corollary, never trust anyone who tries to convince you that he does.

[mikesimon]

I did find it interesting but if there is any connection between Metformin and Alzheimer's disease I doubt very much that it applies to short term use. I would guess that if there is a connection it would be with long term usage. I am diabetic so I probably have more interest in this subject than most. I don't use Metformin however.
Mike

[FlGuy]

'Diabetes mellitus is associated with increased risk for Alzheimer's disease (AD), but a new study of metformin suggests that diabetes treatments might bear some of the blame. '

Thanks for the good news.  My doc just upped my dose.  I'll have to ask him about this next time I see him.  If I can rememebr, that is.

[CoWriter]

Thanks Mike.  I hadn't seen that one. Seems as if it's one of those "damned if you do and damned if you don't"

Diabetes increases the risk of Alzheimer's even without the Metformin.  

The question is....would Metformin do that is you had to take it for let's say....48 weeks?  And if you're only IR, not diabetic.  

I know you don't know....I don't either.  I'm just thinking out loud.

Co

[FlGuy]

What is the line of demarcation between IR and diabetic?  Is there a numeric value?

[CoWriter]

You're diabetic if your fasting blood sugar is above 126 on two consecutive occasions.  But sometimes you start to beccome insulin resistant years before you become diabetic.

A fasting blood sugar above 100, an abnormal HOMA or an abnormal 2 hour glucose tolerance test would tell you whether you're IR and not yet diabetic.

Co

[JennyPenny]

Let me know what you find out from your doc FlGuy. I just started metformin last week.

Desrt, ok so can I have another clue as to who you are? Desrt does not ring a bell. And I just got off the phone with Miles. I'd love to tell him hi from you.

[portann]

Miles? Is that the very esteemed MK?

[merryBe]

thanks guys for all your replies, not trying to be a zealot here, just saying...when one sees that fatty liver decreases SVR and suvival rates, and when correcting IR gives a 20 to 30% increase in SVR, one has to start weighing the benefits versus the right.

Mike,
thanks for that study, and I know there's a up and a down side to all of this....I was against metformin for the whole of last year. Yet in light of these recent numbers, I think one has to at least give pause. Even yesterday when Willing on Cocksparrows 3x thread, whose opinions I pay great attention to sited some objetions, I had to give pause because it seemed too knee jerk to me...no regard for the stats was even acknowledged.
Then too someone objected to the studies being only on fat women, as if IR knows the difference. High BS is high BS not matter where the genitals reside....so who better to test that 120 willing fat ladies....the fact that it was only women doesn't negate the results at all. After all we are not talking about gonadatropin here...we are referencing insulin and how it's regulated which is the same in both sexes.

My plan was to try to reduce IR especially for the time of my tapering (beginning in 3 weeks) and the duration of the critical 6 months so that while my spleen is coming back on line I might have the advance of keeping the highest levels in natural INF in circulation in order to deal with what few virons may be left around, as per HR's discussion regarding the splenic lag time is just seems a reasonable strategy to consider.

In light of your study, I would aquiese, and say let's think short term only.. I would not consider it a long term solution, but to be honest I was thinking for myself of a short stint on it as a preventative to relapse.
Short term, to correct Nash and/or IR until you could reeducate people might be a good alternative. Why because they don't have to start injections and (and my doc and I have discussed this) they should make classes mandatory for prediebetics. Why, is because some folks have no clue and very bad eating habits. Preventative medicine to stop the onslaught of diebeties and heart disease is paramount if we are to have any heath dollars left.  The rise in diebetes (diabetes) fro soda pop alone is staggering, and we have to reteach a whole generation of adults and children why drinking sugar is cutting 20 years off their lives.

Certainly for those with NASH the revarsal stats are suffcient to take a closer look, and again once that reversal has occured one should withdraw the drug. My question to Dr. Been is, how long and at what doses did these plaques occur at that rate.
Many drugs short term are god sends, like the ativan I have to take for the riba mania I experienced. Certainly I will be weaning off this very soon, to avoid long term sides...but in this interim it has been essential and I could never had endured this treatment without it as my body was shaking uncontrollably...I was waking up with whole body quivers.
See my point?  Why couldn't metformin help borderline IR with their SVR....

and further, one person who was not helped by it does not disprove the concept. On that logic no one should try SOC since it's only 50-90 percent...the people not helped does not negate the efficacy of something however. It lowers it, but does not negate it.

I think also we might want to consider what too much sugar does to the brain.
My mother in law suffered some issues towards her end but I'm not sure it was the metformins fault. I blame more the fact that my ex kept refusing to beleive she was diebetic (diabetic), and taking her sugar laden treats which she continued to gobble up. So my question would be, how much is the metformin vs. the drug not being sufficient considering the caloric intake or lack of dietary adherances.

Port ann did you read the study I posted? do you know how hard it is for those with NASH to clear this disease and understand the implications are their chances would go from 5% to normal is the NASH could be addressed???

and trinity...well bless you both gals....we all get cranky....ame?


sigh......I'm not sure what you all are rerferencing,as far as being tied of a subject....or of "converts".  I stopped eating many things that were bad for me to improve my health 40 years ago.  Even if everything refarding IR were dead wrong, which I doubt, you'd still have the benefit of a lot more health if dietary changes were made.

In case you did not notice I was not here for the last 2 months, due to illnesses, so it's new to me, I'm not tired of the discussion. If you are, or you don't like the subject...move on for goodness sakes.

If anyone is tired of it, it's their priveledge to change the channel, to not join the thread....whatever.....however, I think it is rude to just tell people to shut up because you either don't agree, or are tired of something.

There;s research on both sides now and that makes for a healthy discussion.
Only in medhelp does one witness these type of discourses with accompanying research to educate..... If one doesn't like these type discourses, there's always the social side.

When I was weary of reading stiff, I just went away for a while, and rested and recharged my jets....which is a lot healthier for all of us that had I just started gripping or trying to censor others.

peace out

mb

[merryBe]

almost forgot, was reading up on the higher risks of heart disease with avandia just yesterday....couple that with the HCV adding to the risk, and that one is out...jusy my opinion.

as far as >>>>>>>>>>>>With regard to the apparent deleterious effects of metformin, Dr. Beeri is more cautious, noting that large, placebo-controlled, double-blind trials will be required to establish that this happens in human patients as well as in animal models and in vitro

I could save these guys a couple mil here, the answer is there will be more, much more..
reason being it's people...not rats whose calories you control.
the biggest problem with people is denial. I worked with stroke victims for years...many as a result of their diebetes (diabetes).
The issue is, patient takes a pill to keep BS down...patient now thinks they can eat that bowl of icecream. They negate the medications benefit enough, and they are right back to IR, and that causes more craving for sugars and carbs...comfort food...because the cells are starving in the midst of plenty.

If you could every get folks to give up their macaroni and creamy noodles...and eat a balanced diet. Unfortunately older folks grew up in the deprssion think meat is a luxury and rarely eat enough protein and younger folks have no clue what all the pop and coffee drinks are doing to them.
So the real culprit is psychological...it's like the heart patient taking a cholesterol lowering drug and figuring that 12 ounces tenderloin won't hurt him cause he's on meds and had the bypass......and he'll go the way of the Dodo bird....

mb

[merryBe]

I know, that was my point, that was primarily what the link was about that I gave. I think the IR research has already been posted enough for folks to have seen that, but the more overlooked aspect has been the NASH and that link was very comprehensive.

When first diagnosed I was told the NASH could lower my chances from 50% to 5% depending on it's severity.
At the same time my doc told me not to try to lose weight. I thought he must have said that due to oxidative stress or my difficulty sleeping on the Riba already...but he now says he doesn't recall having told me not to....yeah...and I went home scratching my head wondering what he knew that no one on this board knew....
now he says "oh I just figured you would lose naturally"...but that didn't happen, in fact once I went to 10 HGB I couldn't walk anywhere without being breatless.....and then when they put me on remeron I became ravenous at night. So now I weigh 10 lbs MORE than a year and a half ago. sheesh.

anyway, that nash article was one I wanted people to see...and I'm still weighing whether a teeny bit of metformin to keep INF from being canceled out might be a short term plus...say for 6 months.  wonder what my endo will say to this.

mb

[geterdone]

When I was younger I never thought of the implications of eating habits and health issues that I would have later in life and here it is, late and after a serious grounding of treatment I am always learning something new. I am not as young as yesterday but not as old as I will be tomorrow. Damn merrbe, I felt an excitable rage build up after that post to the point a shower was needed. The discussions of IR gives one pause as to the intake of fats and sugar before and during treatment but if I could only roll back the hands of time. Kind of like thaat taper to ;)

jasper

[merryBe]

hey jas...oh what the heck, you did outstanding for the time you were in!!
You get 20 pats for being ahead of the whole pack....

ok, let me throw this out there and see what sticks to the wall....
and anybody's who get's p'od' can  just throw their noodles at me..


Don't you wonder why so many are so resistant to the idea??  Could it be we all love our hershey's or alfredo's a wee bit too much...and having given up beer we are not about to sacrifice our noodles as well??

I just don't see any other explaination except that folk don't like the idea of major life style changes, they feel they've been through enough.
Just a hair brain guessing, but hey, I've got a healthy appetite, and it isn't always directed at my health......
but what else really would make several years now of confirming research still seem irrelavant. There is a connection. Maybe because lean people have no IR results with them aren't reflective, only logical..they are already at low BS.
Maybe women do a little better due to fat stores, or estrogen who knows, but we aren't tatalking about gonadatropin etc, we are talking about insulin, and why they left fat men out of the study I do not know...but insulin metabolism is not substantially different between the sexes, so men should also benefit. Maybe the researcher was tired of drop outs, and women stick with studies better, who knows...but our pancreases and livers work the same regardless of sex.

For my money it's all tied together, the thyroid pancreas and pituitary are all part of the endocrine system, they all go downhill with this disease, producing a complex variety of dysfunctions, IR being definitely among them. And lets not even get into the heart and brain changes or we will really depress everybody.

yet facts remain facts:

It's time we recognized this disease is taking a toll on not just many but most of our major glands and organs. Ergo let's help our selves with as much knowledge and as many meds as will do the trick.

It's really not as hard as people think, I don't miss alcohol at all since I only  drank 4 times a year....and the hard one...sugar, wasn't as hard as I thought. Once I got used to fruit instead for desert it actually became preferable, and now I can't even eat store bought baked goods, they choke me they are so sweet.
It's all what you are used to. I quit pop 30 years ago so I'm ahead of the curve there.

What was wrong with your taper? I read it and it look fine to me. Not sure about why you kept on the riba, what was the reasoning there???  but other than that it looked right on.

have you heard from st. george?

mb.

[Trinity4]

and trinity...well bless you both gals....we all get cranky....ame?


"sigh......I'm not sure what you all are rerferencing,as far as being tied of a subject....
In case you did not notice I was not here for the last 2 months, due to illnesses, so it's new to me, I'm not tired of the discussion. If you are, or you don't like the subject...move on for goodness sakes.

If anyone is tired of it, it's their priveledge to change the channel, to not join the thread....whatever.....however, I think it is rude to just tell people to shut up because you either don't agree, or are tired of something.:
_________________________________________________________________________

Exactly Merrybe, you haven't been here for the last 2 months so you haven't seen all the discussion regarding IR.  Nobody said "shutup" or was rude.  We only stated our difference of opinion.  If anyone is an active member of the forum, you see the same topics posted over and over.  The thing is we all get it about IR plain and simple.  
What people choose to do with that information is stricktly up to them but the awarness level of IR has certainly been brought to the forefront.
I'm not obese or overweight and my diet is very healthy. I'm active and work all day but I may have some problems with IR someday and I think it will be due in part to the treatment drugs and degree of liver damage.  I will deal with it when the time comes.
Also, to suggest and low dose regiment of metformin after tx is ludicrous to me.  I don't view that drug as something on could take beneficially in low doses unless they are diabetic.  I've seen what it can do to someone first hand, low dose or not.  Common sense says if it ain't broke don't fix it.  
That is my opposing view point, with no crankiness attached.

Trinity

[merryBe]

points well taken, I'm sorry I missed all the fun!! I was having too much fun getting rid of nasty infections and thinking I was losing my hearing....but hey, no body has to agree...
but getting it is important.

What I said won't apply to everyone, but I witnessed it in my mother in law and many of my patients. Even having suffered strokes due to their diet most were reluctant to make changes even when given good instruction many would revert to their former diets and suffer the consequences.
Our eating is pattern very early in life and is one of the hardest things to change.

We aren't talking about a huge change in BS, only a 10 to 20 pt drop would be normal, especially at a low dose.

My logic is based on knowing as INF goes low keeping it in circulation become critical as virons try to reemerge, and insulin cancels out INF so keeping you insulin and IR under control and BS a little on the low side would give you the same results as the lean people all get which are 30%-40% less relaspes.

If you have some clinical experience with metformin patients and not just one anecdotal case or experience, than I would appreciate you sharing that. Other than the study mike mentioned, which is for long term use a concern, and the slight increase in leg cramps and skin changes I'm not aware of too many complications with metformin. Of course I only had a few of my PT patients on it, they eventually ended up on insulin anyway. Metformin is seldom more than a steping stone unless scrict adherance to diet is followed, which as I said, I never saw happening, especially not with the elder patients.

mb

[JennyPenny]

Yikes! I am so confused. I just started metformin last Wednesday. It has nothing to do with treatment as I can never treat again because my neuts go to 0 and I land in the hospital where it takes weeks of neupogen to get me back. I've been dealing with IR for at least two years and I guess I went into a bit of denial about having another chronic illness. Lately I've had a couple of fasting glucose readings of between 150-175 so my PCP started me on 500 mg of metformin at dinner time. In just one week I've noticed 2 things....my craving for carbs is down by at least 50% and my fasting glucose is around 110.

Are you guys saying that metformin is NOT a good drug whether you have liver disease or not? This concerns me as I have been cirrhotic at least since 1992 and hate the thought of doing more damage to my already poor liver. But I guess sometimes we have to weigh the risks against the benefits.

Portann, can you explain why your cousin rolls his eyes at Metformin? I'd love to know what a "real" doc thinks, especially one who works in that field. I am as guilty as the next one of playing doctor on the internet, so any time I can listen to someone with credentials, I like to do that. It upsets me when people quote studies and believe them as gospel especially when they are talking about rats. I've been around a long time and I still tend to ask my doc if a particular study is valid. It has sure shown me what I don't know.

Yes, I talk to the "real and esteemed" MKA almost everyday. He is a very close friend and works with us in my organization. BTW, he is the skinniest thing...I mean skinny like he cannot keep weight on and he is a type 2 diabetic. I know that obesity is one of the causes of diabetes but plenty of us are not obese and never have been. I believe there are many factors with liver disease being one.

[JennyPenny]

Thanks for the message. Good to see you!

[Trinity4]

Jenny,

Here is my little bit of input.  My husband takes metformin.  Has for many years  Type II. I've seen him go hypoglycemic many times.  It's a balancing act when you take anti diabetics.  You have to keep a certain amount of food in your system to work with the medication.  We've had to adjust dosages and diet now and then and he does well for the most part but when his blood sugar spirals down he exhibits symptoms of hunger, headache, confusion, irritability, drowsiness, weakness, dizziness, tremors, sweating, fast heartbeat which can also lead to seizure (convulsions), fainting, or coma (severe hypoglycemia can be fatal).
As long as you monitor your blood sugar you should be fine.  That is why I say if you need metformin take it, if there is no medical reason I don't advise it.

Trinity

[JennyPenny]

Trinity, thanks so much for that information. My PCP warned me about hypoglycemia and that is why she is starting me with a low dose of metformin. I totally agree with you, taking it without having diabetes is going a bit overboard IMHO. Hope your hubby stays well.

[Bill1954]

I not sure metformin encourages hypoglycemia; at least it’s never been a problem for me, when used by itself as a stand-alone therepy. It’s an insulin sensitizer, and makes one’s endogenous interferon more effective. It might be a problem if it’s combined with other medications including insulin as this is well know to be a factor in low blood glucose.

I’ve been taking metformin for about 7 years now; and recently achieved SVR. I’m fairly sure I was insulin resistant throughout HCV treatment; I additionally required as much as 110 units/day Lantus insulin along with Actos and Glipizide to effectively manage my DM II. I realize this doesn’t apply to you, but wanted to mention it on this thread to show that IR doesn’t preclude SVR.

My understanding is that extended metformin can lead to weight gain; be sure to check with your doctor about this if it’s an issue for you.

Take care—

Bill

[Willy50]

I'm glad that you posted this information.  I knew that you were type 2 and had SVR'ed but was unaware that you had been of metformin or other like drugs.   This made me wonder if such drugs were needed for IR folks or diabetics in order to clear and SVR.

Thank you; it cleared up a source of confusion for me.  No doubt it may have been mentioned elsewhere but I hadn't been aware of it.  So now, instead of the *exception to the rule* it would seem that your experience helps support the idea of controlling IR in order to better respond to TX.

Thanks for helping un-confound me.....

Willy

[Bill1954]

Hi Willy;

You wrote “So now, instead of the *exception to the rule* it would seem that your experience helps support the idea of controlling IR in order to better respond to TX.”

To the contrary; I spoke up because I was insulin resistant throughout HCV treatment; and I achieved SVR *despite* this condition; not to demonstrate that metformin was necessarily instrumental in this instance.

Although my A1c test results were low, I tend to believe this was due to hemolosys from ribavirin, not excellent blood sugar control. I required 110 units/day Lantus insulin *despite* the insulin sensitizer metformin; without insulin resistance, that large amount of insulin would have made me quite sick, I’d think.

That’s a lot of insulin. For instance, a type 1 diabetic typically doesn’t have IR; they just fail to produce endogenous insulin, or very little. If an average type 1 diabetic injected 100+ units Lantus insulin, they would most likely become hypoglycemic; while I tolerated it quite well. I believe this demonstrates I was insulin resistant throughout my HCV treatment.

The concept of taking metformin if not absolutely necessary for BG/IR control is one of the most preposterous proposals I’ve encountered in here; there’s no medical substantiation for this to my knowledge.

Perhaps Cowriter will lend us her thoughts on this.

Take care—

Bill

[Willy50]

Thanks again; now I'm back where I started.  I guess that I assumed that the Metformin corrected those scores, or aided in response somehow.

LOL; as you might see......I'm out of my depth here and trying to round out what I (I use this word cautiously) *know* about the subject.  ; )

I'll continue to read from the sidelines.  At least your results were interesting to me in light of the discussion.  So far as interpreting what it all means, I'll gladly leave it to someone else.

It seems to me that this is an area that I'm going to have to get up to speed on.  Thanks for contributing your experience and information.  Thanks also for correcting my assumption.

best,
willy (re-un-confounded)

[Bill1954]

LOL, “re-un-confounded”!

Of course you’re always welcome to dig in and learn with the diabetics, Willy; I’m still a babe in the woods with this cr@p myself; your input is always welcome, guy.

As I mentioned above, I believe I was dealing with insulin resistance through most of the three years I was in treatment for HCV.

The A1c test results I mentioned above are ‘glycosylated hemoglobin” results. This blood test measures the amount of glucose that has joined hemoglobin over the course of the average (120 day) life span of a red blood cell, and normally provides a good snapshot or history of average blood glucose results over that period. The A1c test is considered the ‘gold standard’ for DM management.

http://en.wikipedia.org/wiki/HbA1c

It’s theorized that this test is inefficient for those of us that are undergoing HCV treatment. The ribavirin obviously causes increased hemolosys, retiring RBC’s ahead of their 120 day schedule. This is thought to render the A1c test ineffective; people/diabetics that are undergoing HCV treatment with ribavirin should consult with their doctors remind them that this might be an issue to compensate for.

When I first completed treatment, my insulin needs dropped enough to eliminate it. Now, three months later, I may need to start it up again; my blood sugar is getting out of control again, independent of diet. I need to exercise, something that I still haven’t been compliant with lately.

Maybe some of this will help fill the gaps in knowledge. Have a great day, and take care—

Bill

[portann]

Thanks, Bill. You write so clearly and I appreciate it.  :)

I've also noticed you are very thoughtful and patient in your replies to newbies. They're lucky to hear from you.

Port

[FlGuy]

As we've previoulsy written, we've both witnessed the riba effects on a1c.  For a time I  thought that I was a blood-sugar superstar.  The 'thank you' to riba, the concept incredible in itself, was short lived.  One of the matters that continues to confuse me is the part that a damaged liver plays in all this or if IR/DM is independent of a fibrotic/cirrhosed liver.  So, the liverheads (at least some) say a liver can recover with SVR.  The question I have is if the progress through IR and DM is slowed with a better liver. Or does the liver have anything/nothing to do with it at all.
My challenge is different from yours, I can handle the exercise side of things it's the religious diet that trips me.

[jmjm530]

Now, three months later, I may need to start it up again; my blood sugar is getting out of control again, independent of diet.
--------------
I don't know how much effort you want to put into diet, but if you haven't already tried something as carb restrictive as "Phase I" of the South Beach diet, you might want to -- but be warned, it's pretty carb restrictive meaning for example, no bread, rice,  or alcohol and limited fruit. If you google "South Beach Diet" you will get to the site and then check the Phase 1 food list.

I say this because of my own experience with Phase 1, but with the caveat we're not very good match-ups since I'm not IR. Still, I do have a number of metabolic syndrome factors such as high tri's, low HDL and high bp, and was literally astounded at the changes when I *strictly* adhered to stage 1. The lipid scores almost paralleled what I got on Lipitor (I was not on Lipitor when on Phase1) with my LDL approaching 70 I believe from over 140 pre Phase 1. To top it off my bp normalized. I did exercise 30-60 minutes twice a day during that time and can't remember if I watched my sodium intake except that probably following Phase 1 naturally lowers sodium intake since a lot of fresh vegetables and really nothing processed.

Unfortunately, when I switched to the less carb restrictive  Phase II (or maybe I jumped to Phase III LOL) I lost pretty much all of the benefits and am now back on Lipitor but just might give Phase I another crack one day very soon.

I have no idea how a diet like this might translate to your blood sugar issues, but thought I'd throw this out in case you haven't tried some a regimen and might be interested.

All the best,

-- Jim

[Bill1954]

Hey, FlGuy—

I wanted to bring the phenomena of riba/A1c up again, for anyone just tuning in so they might benefit.

I really have no idea how these (DM and liver disease) are intertwined. As I mentioned above, I seemed to have a respite from high blood sugar immediately post treatment; however, this doesn’t seem to be a lasting deal. I despise DM management; whether it involves diet, exercise, meds, testing, etc. It much more demanding of patient interaction than HCV management, and may be nearly as devastating to our health in the long run as viral hepatitis. My father and maternal uncle both have it; my uncle is blind and missing toes and parts of his feet from the disease. This leaves me motivated, but apparently not enough; grrrr!!!

I’ve gained a lot of weight due to inactivity post treatment; this is probably a big part of my IR dilemma… I believe adipose tissue/fat = IR in those that are predisposed to it. One of the problems is that many of the drugs we use to manage DM also tend to promote weight gain.

I tried to ask my treatment doc about the interaction of DMII and liver disease; they shied away from specifics, saying that they really don’t know enough about yet to discuss it.

I hope you are doing well, and enjoying the first day of spring. Take care—

Bill

[JennyPenny]

Thank you so much for your reply. My doc told me that metformin was one of the drugs that causes a small weight loss in some people while the other oral drugs often cause weight gain. I guess I will have to wait and see what happens with that.

Good for you on your SVR. I'm always happy to hear when someone clears.

[Bill1954]

JennyPenny; interesting that your doc said metformin promoted weight loss, rather than gain. It’s quite possible tht I have misunderstood this; I have been taking other oral anti diabetes meds along side metformin for years; I may have gotten this confused. I hope it helps you manage your IR… diabetes is an unpleasant disease to deal with. Good luck, and take care—

Bill

Mr. Jim; thanks for sharing. I do try to monitor carbs, but only in the setting of ~300g/day. I’ve never tried to really cut back; nor has it been suggested by either my doc or the diabetes educator/dietician at the clinic.

I might look into this; I do need to take corrective action soon. Thanks again for your thoughts—

Bill

[jmjm530]

Definitely run it by your docs, because as I said, our stats are different and I'm unfamiliar with diet protocols for someone like yourself who is diabetic. I believe it was Dr.  D. ,  or perhaps another doc who also recommends South Beach, along with "SugarBusters"  but if memory serves me it was more mentioned in the context of dealing with fatty liver and not diabetes.

-- Jim

[CoWriter]

"I not sure metformin encourages hypoglycemia; at least it’s never been a problem for me, when used by itself as a stand-alone therepy. It’s an insulin sensitizer, and makes one’s endogenous interferon more effective. It might be a problem if it’s combined with other medications including insulin as this is well know to be a factor in low blood glucose. "
------------------------

You're right.  Metformin does not promote hypoglycemia.  Only medications that increase insulin production can do that.


"Although my A1c test results were low, I tend to believe this was due to hemolosys from ribavirin, not excellent blood sugar control."
--------------------

You're right.  The test is done on hemoglobin, so being anemic will cause a low reading.


"The concept of taking metformin if not absolutely necessary for BG/IR control is one of the most preposterous proposals I’ve encountered in here; there’s no medical substantiation for this to my knowledge.

Perhaps Cowriter will lend us her thoughts on this. "
-------------------------

Even though I believe that maintaining insulin sensitivity throughtout Tx will decrease the chance of relapse to some degree, there is absolutely no data that says that adding Metformin at the EOT after obtaining SVR will prevent relapse.  If somebody is not IR, it will probably do nothing.

Co

[JennyPenny]

My doctor sent me to a diabetes educator and she told me that counting carbs is the best way to control my diabetes. She has me on 10 grams of carbs a day which sounds like what you are doing (300 mg) if I understand you correctly. Thank goodness for low carb ice cream!

[JennyPenny]

Why don't they have an edit button here? I meant 150 mg daily.

[merryBe]

well I learned 2 things, my anemia may be what is keeping my BS low not just my diet, and 2 that my proposal is preposterous, kindly chosen words.....

the truth Bill is prior to tx I was predietbetic according my GP and totally diebetic (diabetic) according to my endocrinologist. It too him 2 4 hr tests to get my blood sugar down to 40...which I guess is very unusual....

For some reason my BS improved during tx, and I'm not sure why.

If it happens to be just the tx pushing it down artificially, then that gives me one more reason to be concerned coming off tx.  

co writer,
I've been wondering continually what gave the sudden improvements, was it the frowth hormone (which some literature say raise BS and some says no....was it the diet alone in spite of the INF being known to also often raise Bs's.
This concept that the bllod being low throws thE a1c off....thanks for that.
I had stopped monitoring my BS because of the good AC1....maybe I should start again.
I'll ask my doc if the AC1 could be off and to do the HOMA too...thanks, I've learned a lot.

mb

[CoWriter]

"interesting that your doc said metformin promoted weight loss"
--------------

It does.

Co

[CoWriter]

"She has me on 10 grams of carbs a day"
------------

That can't be.  A slice of bread is 15 grams of carbs.

Co

[CoWriter]

"my anemia may be what is keeping my BS low "
------------------------

During Tx, you can't trust the results of a HgA1C because the test is done on hemoglobin.  If your hemoglobin is low, it will give you false low results.


"I've been wondering continually what gave the sudden improvements, was it the frowth hormone (which some literature say raise BS and some says no....was it the diet alone in spite of the INF being known to also often raise Bs's. "
-----------------------

Interferon can also lower blood sugar.  Though I don't usually see that happen, it can.  Or perhaps it was a combination of the growth hormone and diet.  


"that my proposal is preposterous"
-----------------------

I've been accussed of doing the same once or twice....LOL So what?  It makes us unforgetable...LOL

Co

[merryBe]

there are some interesting articles on the Cocksparrow 3x thread regarding all this.
Co-writer gave some pros, and Willing gave some cons. Mike also found the altztmers article above in this thread.
My early readings, and my doctors also felt that my best chance to regulate IR would be metformin if NOT for the liver disease, but that the research was showing metformin is hard of the liver and therefore not the first choice. That said, one has to weigh where the patient is at. If elderly and confused it's hard to get them to remember their shots, and so even though insulin, or a combo of metformin and insulin might be safer (as the research suggests) the question will be can you get adherance.
I used to do home visits for therapies, and I remember one advanced diebetic (diabetic) who couldn't remember how to use his pen, and one morning remembered not once but twice...luckily I was coming over that morning and found in comatose in time....but a few weeks later he was not so lucky, and this time his daughter found him, and he passed 3 weeks later.

I think one must weigh the risks vs benfit. Certainly at high dosing hypoglcemia becomes a real threat and can be life threatening....Personally, if I knew I couldn't control my IR or diebetes (diabetes) any more with diet, I would consider an insulin pump and only use human insulin. That's only because the sides are only avoidable if you really do keep on top of things, and that involves so much testing and injecting it gets old fast. Plus it doesn't give a steady state the way the pump does.
Especially if you have any memory problems due to ammonia/brain/fog/ or other memory/retention problems this can make your life go a lot smoother.
Sorry to hear you have to contend with all of this, but as Bill pointed out and proved, you can still be successful in treatment if you are determined as he was.

mb

[bandman54]

I thought if you are IR (I am) your body produces plenty of insulin.. it just doesn't open the cells properly, that being said, what good would an insulin pump do??
But I really know very little about this, so feel free to correct me if I am wrong on this.

I have also never heard that metformin is hard on the liver... please tell me this is not so.
oy!

bandman

[Bill1954]

Thanks for your input, CoWriter. There seems to be much more data about metformin promoting weight lose rather than weight gain; it looks like I may have gotten it confused with one of the other drugs. It’s always good to hear your perspective on things—

Bill

[desrt]

Strict diet and exercise: unable to lose more than 5# (230-225).
Add Metformin: lost 40# in six months (230-190).
(6'2")

[Trinity4]

Just of claify the hypoglycemia my husband experiences.  He takes glipizide/metformin 5/500  4 x day plus metoprolol, warfarin and digoxin which will lower blood sugar too so I was incorrect in saying the metformin soley causes the drop in blood sugar.  He probably shouldn't be taking the glipizide/metormin with all those other drugs from what I've read so may have to look into this.

Trinity

[Trinity4]

One more thing, he is thin for his height.  155 lbs. 6'1" but the A1c hangs around 6.2
which is very good.

[CoWriter]

"Update - in response to questions, it appears that metformin may well cross into the brain, presumably at least partly by some sort of active transport. There's some evidence both ways, but it's certainly possible that relevant levels make it in. With any luck, this will be found not to translate to humans, or not with any real clinical effect"

http://pipeline.corante.com/archives/2009/02/26/does_glucophage_make_alzheimers_worse.php


So far none of the studies were done on humans.

Co

[JennyPenny]

"Sorry to hear you have to contend with all of this, but as Bill pointed out and proved, you can still be successful in treatment if you are determined as he was."
_________________________________________________________________________


I'm not sure what you mean by the above statement as you don't know how much treatment I have done. I am running neck in neck with Miles and Susan 400. Very few have been more determined than I. So I kinda sorta resent your statement. It's like blaming the victim.

Co....I realize bread is 15 grams. I am so new at this counting carbs bit I am getting my measurements all mixed up. I am allowed between 135 - 150 grams of carbs a day. In other words 9-10 servings at 15 grams per serving.

Sorry for the confusion.

[jmjm530]

JP: . I am as guilty as the next one of playing doctor on the internet, so any time I can listen to someone with credentials, I like to do that.... I've been around a long time and I still tend to ask my doc if a particular study is valid. It has sure shown me what I don't know.
-------------
We tend to think alike. While this place is an excellent resource, I personally used it as a  starting place for my treatment decisions and not as an ending place.

After seeing something here of interest, I would then do my best to further my knowledge through other studies and websites. Then, armed with a tentative plan, I would run it by my treatment doctor -- or at two very important junctures of treatment, I ran my hypothesis by three or more liver specialists.

In doing so, sometimes my plan was confirmed, sometimes it was criticized and sometimes I was left about as clear (or confused) as when I started :)

But what I did learn is that there is nothing like running something by a good liver specialist with a large clinical practice who has your entire chart in front of you. That's not to say that  I always agreed, but I always weighted their opinion very heavily and would have felt very insecure with some of my treatment decisions had I not done this very important step.

-- Jim

[JennyPenny]

Hi there, Jim. We do think a lot a like. I certainly appreciate your always balanced approach. I, too, have learned a ton of stuff on some message boards, but it is always prudent to check it out with your favorite hep doc.

Have a great weekend.

[geterdone]

Thanks MerryBe, I’ll take those twenty pats on the back. Yes, I thought the taper was right on mark also, but few have followed through with it thus far. I can only see the benefits of the taper because I don’t know what the risks would have been if not. The Riba taper… humm… well when colonel sander divulges the recipe then you’ll know. The interesting thing is I have not found ANY research of the negatives on the lasting effects of our beloved meds with any credence and evidence to substantiate why there is no long last effects, why is that? Because there is none? I am a believer in that if you have any unseen or hidden predisposed illness it will surface during the course of treatment.

jasper

[merryBe]

as I understand it, and correct me if I'm wrong anyone, the way the oral drugs in metforims class work it to help the cell overcome it's resistance to the insulin present.
The insulin is present BUT the cell is shut down, and not recognizing that the insulin is knock on the door...first insulin must open the door, then it and the food (blood sugars) can get in and feed the cell. So if there is a key to the door it's insulin, but if there is a grease to make the key turn in the lock, it's metformin and the like.

That said, there comes a time, even when on oral meds for a while, that the IR is no longer the only problem, the other problem becomes that the pancreas is kaput and simply stops making enough insulin to go round. You see because it was made to overproduce insulin for years, by not treating the IR with diet, excersise and meds as need be, now you have a gland unable to produce enough, so even if you are correcting for the IR with the metformin, you may still have to add some insulin.

Willing discussed this above as potentially a better outcome for some...again this would be dependant on what was going on with the gland.

Sometimes just correcting the IR can last a lifetime, but if diet isn't corrected, weight is not reduced, the odds are the person will progress from IR to full blown diebetes (diabetes), and as Cowriter pointed out, that curve, untreated takes about 7 years.

Going from type 2 to type 1 diebetes (diabetes) is not unheard of, nor is having both at the same time. The shut down of the pancreas is caused by overwork and/or autoimmune conditions. What happens there is the insulin producing cells begin to disappear. They are called the isles of langerhans...they are protected by things like enough vitamin D (which may be part of Cocksparrows reason for including that.)
One can also develop pancreatitis...the pancreas makes several digestive aides besides insulin. Calcium is amongst them, but when these juices back up in the gland the gland can digest itself or be destroyed that way.....which is why passing a gall stone can be dangerous...if it gets stuck it the common bile duct...it will chew up your pancreas.

that's about all I know...oh except for I've asked 3 doctors....before this latest ASSLD came out, if I should be on metformin  and they all said no...not best for liver patients.
However, I have a theory now that it may have a lot to do with what dose you need.
It has to do with how things work in the liver...how hard the liver works to detox them.
It has to do with the P450....I'll post something cowriter wrote aabout that.
If you weren't overtaxing with too many other drugs..it might be OK..the kicker is....while on tx there's hardly such a thing as being on too little drugs.
Quite a dilemna if I do say so.

However, think this one through...we just saw a post on African doing 30% worse on tx.
Now if research came out they could improve that by 20-30% and docs ignored it, they holler genocide! (well Rev. Wright would anyway)...Same with HIV...if suddenly they found a way to improve or cure 10% more HIV patients do you not think they would holler from the rafters that it was discrimination to suppress those findings....even if it was ONLY in a subgroup...like fatties...who happen to have the highest rates of IR...HELLO...which is why they are fat, because of IR, in most case....how the heck can we not pay attention and try to do all we can.
It's not as if everyone in here has a 90% cure rate....many are at 50 at the high end, and 20% if they are IR........so OF COURSE we are looking for answers here!

mb

[merryBe]

here is the long and short of it courtest of COWriter, to whom all the credit goes.

I was having trouble getting my mind around P450 metabolism and she took the time to  explain it better than any place I had looked, so she get's real kudos here.

Only one thing isn't mentioned here and I'll have to ask her now that I thought of it...
but I think I'll start a new thread for it.



Cytochrome P450  is a group of enzymes. "Cyto", means cell.  "Chrome" means color.   Cytochromes are colored with iron.  Cytochrome P450  is located on the inner membrane of the mitochondria of liver cells (the mitochondria is the powerplant of the cell...it stores oxygen to power the cell).  CYP450, is a target of the hepatitis C virus.  The virus gets help from CYP450.

Why does HCV target the mitochondria?  Because the mitochondria is the location of the interferon response mechanism. By damaging the mitochondria, the Hep C virus stops the interferon response.

So the CYP450 group of enzymes are implicated with liver destruction by Hepatitis C.   So it is possible that inhibiting CYP450, might give you more time to wait for a cure, might help slow down or reverse liver damage, and it may help other drugs clear the virus.  

CYP450 has other family members called isoforms.......

CYP2E1  - Causes mitochondrial damage and oxidative stress on the liver cell.  This is liver enzymes worst enemy.  Alcohol is a CYP2E1 substrate. Even in people who don't drink, CYP2E1 is implicated in non-alcoholic steatohepatitis (NASH)...fatty liver.  What inhibits CYP2E1?  Antabuse....the drug that helps you stop drinking alcohol by making you violently ill if you do drink.  The way it makes you sick is by inhibiting alcohol's metabolizer.  Whenever you inhibit a metabolizer, you raise the level of that drug in your bloodstream and liver....and it makes you sick.

CYP3A4   - Allows HCV to move from cell to cell.  Cell migration is one of the ways in which HCV keeps itself alive and multiplying.  It has to keep moving to new cells.  So inhibiting CYP3A4 will lower your viral load.

A recent study showed that grapefruit juice lowered viral load, because there's a bioflavanoid in grapefruit juice that inhibits CYP3A4.  

HOWEVER, the problem with inhibiting CYP450 enzymes is that many prescription drugs are metabolized by these enzymes..... and by inhibiting them, that can raise the level of the drug in your blood and it can cause an overdose.  (taking Tylenol and alcohol together can cause the level of Tylenol to be toxic.  That's why we always tell people that Tylenol by itself is not really a problem but never to take it with alcohol).

So for example, if you take a blood pressure medication that is metabolized by CYP3A4, inhibiting this enzyme with grapefruit juice may  raise the levels of the blood pressure med in your blood and IN YOUR LIVER....and it can cause an overdose (and your blood pressure to go down too low).

So if you want to lower your viral load by drinking grapefruit juice, you'll need to make sure that you're not taking any meds that are metabolized by CYP450.

(WARNING: Do not drink grapefruit juice during HCV treatment since it can cause oxidative stress and impact treatment success.  Also, be aware that the effect from a small amount of grapefruit juice can last all day).


Another enzyme, CYP1A2, is also implicated in liver damage (and tobacco related cancer)....and SMOKING INCREASES THE ACTIVITY OF THIS ENZYME THREEFOLD!!!!!  You know what else induces this enzyme?  Caffeine.....and Marijuana.....and exposure to polycyclic aromatic hydrocarbons, such as those found in charbroiled foods.:

It's all very complicated.....and some people are more sensitive than others ......and this info is very new.

You also have to be careful using supplements.....St. John's Wort, an over-the-counter anti-depressant, targets CytochromeP450....and interferon (and PI's) inhibits CYP450.  So basically, St John's Wort interferes with the interferon.


Something else that's important.....

HYPERINSULINEMIA  INCREASES CYP1A and CYP2E1  (fasting also induces CYP2E1).

Interferon is a CYP450 1A2 INHIBITOR....a WEAK inhibitor.  And insulin is a CYP450 1A2 INDUCER.  That's how I found out that it was the insulin that made interferon ineffective.  I had been looking for the causal connection between insulin resistance and interferon resistance......and it turned out to be insulin.  Hyperinsulinemia caused by insulin resistance.

(Hey....did you notice how well I stuck insulin resistance in the conversation?  I'm a master at it.....LOL)

Co
P.S,  Sorry.....I wrote you a book....LOL


And just in case you post this somewhere and they ask you for sources....

"CYP1A2 can be induced by exposure to polycyclic aromatic hydrocarbons, such as those found in charbroiled foods and cigarette smoke. This is the only CYP450 isoform affected by tobacco. Cigarette smoking can result in an increase of as much as threefold in CYP1A2 activity."

http://www.aafp.org/afp/980101ap/cupp.html


Hyperinsulinemia causes a preferential increase in hepatic P450 1A2 activity.
"administration of insulin ........also enhances P450 1A2 activity, presumably as a result of hyperinsulinemia."

http://www.ncbi.nlm.nih.gov/pubmed/1562279?dopt=Abstract


Star fruit is a better inhibitor of CYP3A than grapefruit juice.... POTENT INHIBITION BY STAR FRUIT OF HUMAN CYTOCHROME P450 3A (CYP3A) ACTIVITY

http://dmd.aspetjournals.org/cgi/content/abstract/32/6/581?ijkey=3142833449ed0472aa65ca659aaecdd53316e051&keytype2=tf_ipsecsha


Inhibitory effect of fruit juices on CYP3A activity.
"The inhibitory potential of human CYP3A was in the order: grapefruit > black mulberry > wild grape >pomegranate > black raspberry."

http://dmd.aspetjournals.org/cgi/content/abstract/34/4/521?ijkey=8fc3bc688dccea368d29077e08e6a92230856feb&keytype2=tf_ipsecsha


Effects of different spices (ginger) on CYP3A4

http://dmd.aspetjournals.org/cgi/content/abstract/36/7/1283

[merryBe]

update on my situation.

My AC1 has risen to 5.5 my fasting glucose to 144. This in spite of all the dietary changes AND in even with the lower HGB of 10, which could be making my reading inordinately LOWER than they really are (thanks for telling me Co).

Ergo my endocrinologist confirmed what Cowriter has been saying.
He also looked over the studies I brought him on TZD's pioglozone and metforming as well as the Nash studies at the top of this thread.

Then too we considered this study

http://qjmed.oxfordjournals.org/cgi/content/full/96/4/315-b

Bottom line, one watches for hypoglycemia, obviously, one monitors liver, obviously,
lactidacidosis is a 1 in 300,000 occurance that should not dissuade the majority, people with NO virus may benefit from lowering their IR in that their interferon will work better, and their Nash can reverse. People with virus in early stage grade may also benefit.

Ergo, In light of the fact that I do not currently have the virsu, and my ALT/AST and other liver numbers have all returned to normal, it has been decided that a short course
of metformin CX (Time released)  500 mg. should be tried for the several benefits it may solicit.

If any of my liver numbers or BS's indicate problems we will discontinue, but presently this tx seems a reasonable solution to at least try. My diebetes (diabetes) may resolve itself in a few months once the INF is permanently lower, he said, since INF may be sriving part of the high BS, but we'll have to wait and see if improvement occurs there before deciding whether to cut back the HGH as well, or just resign ourselves to some sort of IR intervention permanently.

So that's it for now.
I know Bill thinks it's preposterous, but was unaware of my medical history or how long this struggle had been ongoing, or how borderline diebetic (diabetic) I have been for years.

I was actually not surprised by the higher numbers, In fact, I fasted 12 hrs. before my last draw.......but somehow knew my numbers wouldn't be as good as they had been.......
as I started having changes in my feet a few months back....
numbness on the top of all toes...
so I knew something was changing,
even though my monthly fasting glucoses weren't showing it...
again, COwriter you were right there too.
I wish I had known sooner about all this, and that the anemia I've had all year was hiding my true higher numbers...but at least now I do know.

FYI, part of the bad rap metformin has gotten was based on things like the lactic acidosis scare.....but since we can see by the study that the occurence is 1 in 300,000...I think that is something doctors need to review and get past. That is a very low risk considering the potential benefits rate and it should not carry the weight it currently still does.
MY endo was also one who did not think metformin was good for liver patients, but has reevaluated that in light of the most recent findings, and especially for those whose livers are now UND he thinks it does make sense to keep the IR down and try to reverse any fatty liver.  SO he has changed his mind.  
We had an hour appt. so he was able to sit and read the studies...
I don't think he would go along with this if he did not think it could improve my diebetes (diabetes)
(which he says I do have) and improve my NASH, and improve my chances of permanent SVR just because I say so. He's been an endocrinologist for 30 years and did not think the proposal preposterous at all.....

One more thing, I spoke to him about my intent to begin walking again as soon as the HGB got up a couple pts.
He said yes, to walk......BUT TO NOT eat any carbs after my walk. Carbs will cancel out any of the lower IR resistance that walking would achieve. And that lasts about 12 hrs.  So after a walk, high protein snacks only for best control of IR.

mb

[bajawoman]

HOLA  I have been really learning a lot from Co she has taught me so much ; my computers being super taxed with all the info I am collecting and passing on to my GI

"OK remember in the Rodriguez-Torres study where it talks about the rations of mitochondrial dna dropping from 200-1 down to 30-1 with certains antivirals and PI therapies?? "

A decrease in the ratio of mitochondrial to nuclear DNA from its normal 100-to-1 (NOT 200-1) to approximately 30-to-1 leads to clinical mitochondrial toxicity.
(oxidative stress also causes mitochondrial DNA depletion).


"Wouldn't this then mean that since the mitochondrial is "the powerplant that drives the cell" that this would creat a marked drop in ability to metabolize any and all drugs?"

But the mitochondria is not only in the liver....and drugs are absorbed differently in different tissue and organs.

Mitochondrial toxicity in the liver may promote lactic acidosis. Mitochondrial toxicity in adipose tissue might promote body composition change....lipodystrophy (which of course is associated with IR). Mitochondrial dysfunction in peripheral nerves is suspected to cause neuropathy.

Mitochondrial dysfunction caused by Ribavirin, can also be related to development of pancreatitis....which can raise your blood sugar >>>IR : )


"So your explaination of CYP2E1 means that tx componds the whole issue as one is having a tremendous drain of RNA/DNA brought on chiefly by the riba, or telprevir.."

Some drugs can cause more mitochondrial toxicity than others. For example, some of the PI's used by HIV patients (or co-infected) can cause mitochondrial damage in the liver, which can cause lactic acidosis....so for them it is riskier to take Metformin which can also cause lactic acidosis.

But for an HCV patient, the risk of lactic acidosis is rare and usually happen as a secondary event caused by things like trauma. So for them, the risk of lactic acidosis is not the same as for co-infected patients.


I just wonder what you think of the metformin in light of this. Would preloading be safest, and continuing as long as stage/grade and enxymes indicated tolerance was good?

Tx should be started when you're sensitive to insulin to give you the best chance for SVR. It shouldn't be, let's predose for a month or three months, but when you're sensitive to insulin.


"7 very small meals is better than 3 large ones in terms of how overtaxed the liver gets, especially when disease has reduced its size and function.
So how much of a role would you say this plays in say, for instance whether one should be on any drug therapy in addition to SOC. "

Depends what you're eating. Are you eating charbroiled foods 7 times a day? Because that will induce CYP1A2. Do you skip breakfast? Because fasting induces CYP2E1. Are you drinking grape juice or pomegranate juice? Because they'll inhibit CYP3A.


"I know you know but for those who do not...the study I'm referencing"

The entire link didn't post. You're missing the end of it. Here you go....I clicked it with my magic IR wand and got you the part that's missing ; )

/SIDE_EFFECTS.pdf

[bandman54]

I am aware of all that concerning cp450.

What I was wondering is how will an insulin pump help someone with IR.  Doesn't make sense.

Now, if you progress to the point where your pancreas is not producing insulin, you are a diabetic and an insulin pump might be in order.  

Also, A1C is of little importance in trying to figure out your IR.  I am extremely IR, and have a great A1C.    So I am not diabetic, but I am IR.  (homa 3.4 and it was higher!) but I could progress to diabetes (as my father did).

bandman

[apache1]

Insulin pump for IR...good question BM, I must have missed that.
Guess they think if your not sensitive enough to insulin, just pump in more, and more, till it gets it done...lmao

dang...where's CO when ya need her

[bandman54]

Insulin pump won't help for IR.
If you are IR you are producing plenty of insulin (my fasting insulin is high) but it can not "unlock" your cells very well to let the glucose in.  Your cells are "insulin resistant".

At least that is my understanding.

bandman

[merryBe]

I am SO sorry if you misunderstood and took personally my remark to be determined.

I'm in no way suggesting you are not. This was a general statement intended to encourage everyone to be pro-active, and I did not assume you weren't.

Just giving general advice to a general question.

Perhaps it might help you to understand why I made a statement concerning determination. Like you I have tried mightily, not only in tx but in weight loss.
It is frustrating when all our efforts do not always pay off. (for instance before I knew my pituitary wasn't working I tried weight loss for a year at 800-1200 calories a day...counting every drop of oil and calorie...yet only lost 4 lbs due to my metabolic issues.  Such things are very frustrating to say the least....and plenty in here have been real warriors.
However, that said, do you recall that lately there have been several TV commercials about people with diebetes (diabetes) saying "I shouldn't have waited so long".
Well there's a reason for those commercials. One person said, I was afraid of the word, afraid to even try the medicine because I didn't want it to be true.
There are folks like this too Penny. Sometime they lose sight and more before they get treated for their diebetes (diabetes)
.
When I was doing physical therapy the saddest cases were the amputations.
Trying to get people to walk again, missing toes or even a calf is not easy.

Unfortunately 2 factors played into such losses one was docotor driven, docs didn't used to tell folks they were prediebetic, or even call it that. They didn't get treatment for IR because they didn't know, and the docs didn't recognoze the signs either...

But now that has changed, yet still there is a subgroup that is terrified of the diagnosis, and does not realize that their life will be happier and healthier if they do make the diet and/or medications adjustments.

sometimes I am saying things for everyones benefit, and I forget that someone may think such statements are aimed at them when they are not.
Again sorry for that.

mb

[merryBe]

sorry if I didn't explain the whole thing well....CoW could undoubtedly do it better.

again sometime a person can have both insulin resistance AND lack of insulin being produced.  This is known as having type 1 and type 2 diebetes (diabetes) simultaneously.

At the time this occurs treating for the IR may mean adding 2 oral meds rather than one, to make cells more receptive, but if the pancreas is giving out, or under auto-immune attack it can stop producing enough insulin, couple that with the fact that the cells are now resisting, and a low level, and you have a real connundrum.

The solve for this is a combo therapy,
Abstract
Purpose
To compare the efficacy of adding pioglitazone or bedtime isophane (NPH) insulin to maximal doses of metformin and an insulin secretagogue in patients with poor glucose control.

Methods
We conducted a nonblinded, open-label, randomized controlled trial involving 62 patients with type 2 diabetes and glycosylated hemoglobin (HbA1C) levels >8.0%. Patients received either pioglitazone or bedtime NPH insulin in addition to their usual diabetes medication for 16 weeks. Outcome measurements of glycemic control, hypoglycemia, blood pressure, lipid levels, microalbuminuria, and quality of life were assessed at baseline and at 16 weeks.

Results
HbA1C levels were lowered to a similar degree in each treatment arm (pioglitazone: –1.9% ± 1.5%; insulin: –2.3% ± 1.5%; P = 0.32), but hypoglycemia was less common among patients who received pioglitazone than those who received insulin (37% [11/30] vs. 68% [19/28], P = 0.02). Pioglitazone, but not insulin, resulted in an increase in high-density lipoprotein (HDL) cholesterol levels. Both treatments had similar effects on weight, other lipid values, blood pressure, and urine microalbumin levels.

Conclusion
Adding pioglitazone or bedtime insulin for 16 weeks improved glycemic control in type 2 diabetic patients with secondary oral agent failure. Pioglitazone was associated with less hypoglycemia and improved HDL cholesterol levels.

This is what happens after years of IR....the dynamic changes as the pancreas can't keep up...Co writer did talk about this also I recall.
Eventually any type 2 diebetic (diabetic) can become a type 1 as well.
Type 1 is usually seen in young people and type 2 in older folks. Type 2 is related to diet and excercise whereas type 1 has to do with the pancreatic cells that make insulin dying and not being replaced, usually due to genetics or auto-immune things.
In the older and obese, it is believed the the long time of untreated IR which forces the pancreas to overproduce for years trying to cope with the insulin resistance is what finally just wear the poor thing out. Then you have 2 problems at once to treat.

mb

[merryBe]

yes, if one becomes both type 1 and 2, then a pump might be option if like I said you had issues with shots, or remembering.

remember the longer one has IR and leaves it untreated or not controlled by some means, be that meds diet or some combo of both (it should be both because not changing diet means IR dosages have to be higher and that leads to more dangerous side effects).  but the longer IR goes untreated, the more risk the pancreas will give up  finally, leading to type 1...and this is where blindness and the loss of limbs, being found comatose etc become very real and present dangers.

the pumps have issues also, they are not problem free and require some adjestment. One should read up on them and have realistic expectaions.

One can also use pumps now for Byetta...if  one has not progressed to a true type 1 then this is also a good option.

Of course, for those who are used to shots after tx...it may be easy for them, but there is definitely more work in testing...and less micro control than with a pump.

Example: children with type 1 have wild fluctuations and are often fitted with pumps allowing for a much more even BS throughout the day, and for microinjections to kick in when needed. A pump cannot stop all fluctuations but it gives an opportunity to control mini amounts, and bring up the levels a few ml at a time without repeated injections. It is safer for the patient than to overshoot..or overcorrect...and for the aged and children it is easier for another adult to help you monitor what the pump is doing.

I'd suggest folks check out the diebetic (diabetic) forum, you'll find some folks on 2,3 even 4 meds for their diebetes (diabetes).  Many try to stay on orals too long when their disease has really progressed to where more is needed.

Ps. just because we haven't heard of things, doesn't mean they aren't real. There are millions of things none of us have heard of...that are true none the less.

mb

[merryBe]

I noticed you are on metformin and insulin....maybe folks will see your post and know it's possible.

Regarding the extended time released form of metformin:

My doc said for 3 reasons it would be a better fit for me.

1. it works over a 12 hour period, causing far less chance of hypoglycemia.
2. it will put less into the LIVER at any given moment, making it less likely to overtax the liver. 500 mg all at once is far more taxing than 500 mg over 12 hrs.
3. it has far less gastro intestinal issues. The non time release has a 2 or 3 day diarrea (diarrhea), and some never adjest to the gastro issues. If one has any colitis or diverticulitis gas and diarrea (diarrhea) can be a really painful issue, not just annoying but painful.
The only downside to the TR metformin is sometimes some will come out in your stool, unused, still in pill form. But the benefits seem a much better fit for a liver patient to me.
The food usually takes 12 hr's to get through the digestive tract at least, and that's why the pill is designed to take that long to fully break down and absorb.

mb

[merryBe]

Bill, I see you are on metformin and insulin.....hopefully people will see that.

3 reasons my doc gave why time release is better

1. The liver has 500mg over 12 hours not all at once, better for liver patients to not overtax with too much of any drug at once.

2. the chance of overshooting into hypoglecemia is almost nil...much safer that way.

3. the gut tolerates it better. For those on reg metformin, diarrea (diarrhea) is an issue, some for just a few days, but some few regularly. If one has colitis, gastritis or diverticulitis there can be pain not just gas or the runs...and again the time release dissolves and absorbs slowly and greatly lessens the gastic sides.

You may not agree, but these conditions 1 and 3 I have, and 2 I have seen people go hypo....a very scary and unpleasant thing...

So to me my doctor made a lot of sense here.

mb

[merryBe]

Hey there sun lover, just wanted to mention you may want to think twice about the green tea extract as you start your treatment.

Not that green tea doesn't have benefits, it does, but the caffiene contant can be quite high, and that with the riba can really mess with people.

So check the caffiene level, and try to get a decaffed version when you start tx OK.
Trust me on this, the Riba is like eating some of those nasty no-doz tablets....it's like a bad speed trip....all of the sides, none of the fun....adding caffienated drinks to that may be too much....at least, it can be.

mb

[jmjm530]

MB,

It's an interesting topic, but I believe the system crashes if you post ten consecutive posts in a thread without a response. Also, the rules state only one "call a friend" allowed per thread when answering questions :)

[merryBe]

Update: some of you may have read my Ativan thread and know of the Mr. Toads wild ride I've been on but for those who don't

I began metformin and to try to withdraw from Ativan at about the same time.

Unfortunately I was not aware that cutting my ativan in half could produce severe symptoms, so I suspected metformin might be causing lactic acidosis as my muscle became extremely sore.

It turns out it was NOT the metformin, it was the ativan, but we did not discover this until after my doc had switched me to Byetta.

Thanks to Cowriter, and NONE of my doctors, we discovered that my HOMA was 7 which is not good AT ALL.

Ergo, I would go back to Metformin without hesitation if need be, but for now the Byetta is working wonderfully, my fasting sugars are in the75-95 range, for first time in my life!
Whereas before they were in the 110-150 range.

I'm grateful that Cowriter picked up on the fact that my fasting sugars were not matching my A1C numbers. The anemia being the culprit there.
All my fasting glucoses were well above the 105 average the A1c was claiming, yet not one of my docs picked up on that.

I'm certainly not suggesting that one drug is better than the other, I've not researched that at all yet, I'm just grateful that something is working , and that we have had the priveledge of having someone teach us who knows more than the average bear.

Hoping we all continue to do well.