Aa
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
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
Great thread, I think this helped me get to SVR and now cured.
Of course the Incivek, Peg and Riba were responsible :) I think watching my sugar very closely helped quite a bit.
Of course the Incivek, Peg and Riba were responsible :) I think watching my sugar very closely helped quite a bit.
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.
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.
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 :)
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 :)
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
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
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 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
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 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
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, and some never adjest to the gastro issues. If one has any colitis or diverticulitis gas and diarrea 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
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, and some never adjest to the gastro issues. If one has any colitis or diverticulitis gas and diarrea 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
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 forum, you'll find some folks on 2,3 even 4 meds for their diebetes. 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
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 forum, you'll find some folks on 2,3 even 4 meds for their diebetes. 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
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 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 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
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 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
.
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
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 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
.
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
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
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
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
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
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
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
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
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 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 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
(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
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 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 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
(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
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
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
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, and as Cowriter pointed out, that curve, untreated takes about 7 years.
Going from type 2 to type 1 diebetes 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
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, and as Cowriter pointed out, that curve, untreated takes about 7 years.
Going from type 2 to type 1 diebetes 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
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
jasper
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.
Have a great weekend.
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
-------------
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
"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.
_________________________________________________________________________
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.
"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
One more thing, he is thin for his height. 155 lbs. 6'1" but the A1c hangs around 6.2
which is very good.
which is very good.
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
Trinity
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