Insulin Resistance and Fibrosis Progression/Regression: Two way street?

[elias]

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4716529/

I'm fascinated by this topic, because I haven't seen much in the way of how we can proactively improve our chances for fibrosis/cirrhosis regression- other than the clearing of HCV.

If in fact insulin resistance is a strong co-factor in fibrosis progression, it may likewise be an equally strong co-factor in its regression

The prevalence of insulin resistance is ~25% of American adults.  And increases with age and body weight. This is likely an underestimate. Most who have IR are not diagnosed, and its definition keeps undergoing changes.

Furthermore, HCV itself is a risk factor for developing IR (Insulin Resistance).  So we can expect prevalence of IR to be much higher among those with chronic HCV. In such cases it's believed to resolve in large part after virological cure.

There's quite a body of reliable information on how to manage IR via specific lifestyle factors. Such as weight loss, exercise, dietary change, etc.

Furthermore, there's an array of pharmaceuticals with strong track records at controlling Insulin  Resistance. One of the most well known of these is metformin.
However, metformin is usually not given early on, but is reserved for when IR had progressed to Type 2 diabetes. Prior to that, lifestyle changes are very frequently quite successful in preventing progression.

Metformin is being looked into in a clinical trial to see its effect on fibrosis regression among those with insulin resistance:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4955144/

and:

https://clinicaltrials.gov/ct2/show/NCT02306070

The study enrolls both co-infected HC/HIV and HCV "mono-infected"

The above is also looking into the role IR plays in SVR success. This is more prominent in the interferon-based regimens, where IR was shown to have a negative effect on the odds for SVR. But it has been little studied in the newer DAA treatments.

Thoughts on this?

[Lynn K]

How would one know if they had insulin resistance?

My fasting glucose on my last test was 86

[elias]

Hi Lynn:

Fasting glucose of 86 is in normal range. But you might still be having  postprandial spikes into a too high range. Say after a carbohydrate-rich meal or concentrated sweets

This is still a bit new to me. But off top of my head, there's a test which registers the average glucose level for the past 2-3 months prior to your taking the test. It's called the Hemoglobin A1C test, or HbA1c. I think its now widely used in clinical practice:

http://www.webmd.com/diabetes/guide/glycated-hemoglobin-test-hba1c

There's also the older Oral Glucose Tolerance test: OGTT which involves drinking a highly concentrated glucose drink, after an 12 hour fast and taking serial postprandial measurements of blood glucose over a three hour period. Starting with the pre-drink fasting level. And then post-drink half hour followed by every hour. It's a bit uncomfortable and cumbersome.

There's also something called: "Metabolic Syndrome" which is really a cluster of irregularities. I forgot the details on it, but it does involve insulin incompetence of some sort among other things.

Not all these disorders will show as elevated glucose on the simpler tests. It may first show as the opposite. Too low blood sugar. Or hypoglycemia. So its a broad spectrum frought with some controversies. And risk of both over-diagnoses and under-diagnoses

Odd thing in my own case was I noticed a  much higher fasting blood glucose than usual. Almost in the pre-diabetic range. The doctor wasn't worried about that at all. He said if I just cut out concentrated sugars and exercised more, that would resolve. He was however concerned about spikes in ALT/AST. Which prompted the HCV testing. Over the years there'd be occasional slight elevations in those , but they self-corrected when repeating the test a few months later. So I was told to ignore those.  At this workup however, it continued rising from test to test. At same time, there was this higher fasting blood glucose. I'm now thinking this was  HCV-related, as both become manifest at about the same time.

[Lynn K]

Ok thanks

From a quick google search I don't think for me with low glucose testing results I am in danger at the moment. Actually some of my tests were as low as 60 and if anything I was worried about low blood sugar. My dad had problems with hypoglycemia  so maybe I am shielded

[elias]

I used to have hypoglycemia. Was told by some it doesn't matter at all. Others felt it was precursor to later diabetes, or can be. I'm skeptical of this, and it might be one of those over-diagnosed "syndromes". But..

[elias]

Hi:

I just got results of my four week vl and metabolic panel tests after beginning Epclusa.

Something very interesting here pertaining to this topic.
(aside from viral load being :UNDETECTED)

My glucose reading on the metabolic panel he ran was 78 (reference range:65-99mg/dl)

Prior to this, it was~100 and higher. Into low prediabetic range.

This recent result was not even a fasting glucose reading. since I had high glucose intake before that test.

If this type of glucose reading keeps up, it might suggest that those rising glucose levels from last summer and early Fall were due to the HCV acting up. It'll take a few such tests before I can conclude that. But this looks hopeful so far.

Definitely a subject I'd love to know more about

[Lynn K]

I also noticed my non fasting results being on the low side and personally found that tone concerning to me I was concerned about developing hypoglycemia like my dad. It seemed I could not raise my blood sugar. Finally I ate a banana before the test and was amle to get my score above 100 so for me that alleviated some of my concerns. I am just thinking with cirrhosis our sugar metabolism isn't working exactly right.

https://www.ncbi.nlm.nih.gov/m/pubmed/24332992/

Hypoglycemia is associated with increased mortality in patients with acute decompensated liver cirrhosis.

I was told the Glucose test doesn't mean much unless it is a fasting test. Maybe next time you have one try it fasting test that will provide more information. I was afraid to do a fasting test for awhile I was concerned I would get a below normal result but when I tested last time I did a fasting test and it was in normal range thank goodness for that

[elias]

Hypoglycemia is often a problem if one is diabetic and taking glucose-lowering medication.  Can at times cause glucose to fall to dangerous levels. Maybe check that full article to see if thats the kind of hypoglycemia theyre talking about there. Also how they define it. Some kinds of hypoglycemia are after a glucose spike  followed by a "crash' downward. Some r purely idiosyncratic, and just have lower- but even-levels.

I was told the Glucose test doesn't mean much unless it is a fasting test. Maybe next time you have one try it fasting test that will provide more information.

Non-fasting glucose will if anything be higher than fasting glucose. So in my recent results, the 78 reading would mean the fasting level is likely lower. Which is good, since those hit over 100 a few months ago. I'll of course have it repeated when i reach SVR ~5 months from now. Preferably, even sooner. In way of viral clearance, all I have now is undetected at 4 weeks. It's purely speculative on my part if this normalization of glucose is causally connected to lowered HCV level and normalization of liver enzymes. We shall see

[Lynn K]

 I had not read about hepatitis C affecting glucose test results only advanced liver disease having  that kind of effect of course I am more interested in the effect of cirrhosis on glucose test results.

 In my situation I was having trouble getting an above normal reading even after testing while non-fasting so I was worried about that I may be developing hypoglycemia due to my liver cirrhosis

 I agree non-fasting test results should be higher than fasting test results which was my concern as I could not raise my non-fasting test results to above 100 but on the test form it says that there is no normal result range for non-fasting testing so basically if it is a non-fasting test the result is essentially meaningless

[lporterrn]

Great labs Elias. Now the big thing is to watch the LDLs - it is quite common to end up with higher cholesterol after you are cured since having hep C is associated with low or normal LDLs, and then we clear hep C and find out what our real LDLs are...
Sigh, it seems like it's one thing after another, but still, I am glad to be free of hep C.

[elias]

Thanks for the head's up, Lucinda!!

All my lipid/cholesterol readings were perfect range. Hope that wasn't due to to HCV covering up irregularities.

But just in case it was, I'll work on the regimen used for insulin resistance which is even more rigorous in some ways than the heart-smart diet. My weight is fine. So at least no need to contend with that.

I'll continue posting  bout those metabolic tests  and results. Because it may be one among several paths to helping with fibrosis regression. Which seems even trickier than ridding the HCV.  Given where the science is at now

Thanks for posting about that Liver Conference report on insulin resistance. It might be an important clue to healing after HCV is cleared

[Sergey]

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4716529/

I'm fascinated by this topic, because I haven't seen much in the way of how we can proactively improve our chances for fibrosis/cirrhosis regression- other than the clearing of HCV.

Yes, one study shows fibrosis regression in substantional percent of HCV-infected people after 3-months of diet/exercise weight reduction program - www.ncbi.nlm.nih.gov/pmc/articles/PMC1773265/




According to results, in some cases it may be possible to reduce fibrosis from F3 to F1 just in 3 months without HCV treatment. My own experience was not so great - after several kilograms of weight loss using dietary restriction of carbohydrates, fibroscan values were improved from 17 to 16. Not great, but not bad too.

[lporterrn]

Thanks Sergey. Nice to see improvement!
Liver specialists are paying more attention to the effects of exercise, diet, and weight loss on the liver. The data are compelling enough to motivate me, and to lace up those athletic shoes on a regular basis - daily when at all possible.

[Sergey]

Lucinda, thank you. Yes, it is good to do exercises, I prefer to be active too. I feel that it is important to maintain normal body weight for liver health, especially for people with HCV. In average, difference in fibrosis progression speed seems significant for obese people vs. with normal weight. One study (http://onlinelibrary.wiley.com/doi/10.1002/hep.26644/full) show 3.8% of cirrhosis per 35 years with normal weight and 21.8% for obese people. More than 5 fold difference! Really, some people in the study were treated, it may distort these percentages, but, in anyway, looks like significant difference.

[lporterrn]

It looks like exercise is as important as a healthy weight. In a retrospective analysis of obese middle-aged men (Hepatology, April 2015), researcher Sechang Oh and colleagues reported that moderate to vigorous physical activity had a dramatic effect. Those who engaged in ≥ 250 minutes a week of moderate to vigorous physical activity had the most improvement of NAFLD.

That is more than four hours of exercise weekly. This amount of regular physical activity seemed to improve liver health, regardless of weight loss. Other research shows similar benefits. When it came to liver health, aerobic activity resulted in greater improvement than resistance training.

We are fortunate to not have to be convinced of the life-enhancing (and saving) value of a healthy lifestyle. These changes are very hard to make - even harder to keep. I post this here as much as a reminder to myself than to others. I had a ton of excuses for not exercising last week. Threads like this help me to get back on track.

[elias]

Thanks Lucinda:

I'm one of those who doesn't need to lose weight, but do need to exercise more.

Diet is  much more unclear. I see quite a number here advocating for low carbohydrate high protein diet. And avoiding grains. I know this isnt fully accepted in terms of insulin resistance. Not sure of liver health though. For IR, I've read it's the type of carbohydrate (simple versus complex) and if high fiber or not..Also, much depends on what else is on that plate..There remains much confusion on this..

In terms of more specific foods/supplements, this site offers some guides:

http://hepatitiscnewdrugs.blogspot.com/p/is-there-natural-way-to-improve-liver.html

I was hoping:

1) You might consider writing a book on this issue of liver health, especially after HCV is cleared. So that we get reliable information. Or updating your earlier works and writings?

2) Creating a separate section on liver health and/or fibrosis regression on this forum. Some useful posts on this here, but they're too scattered in different sections. I'd expect increasing demand for that once the HCV is cleared.

Thanks much, Lucinda for all your work on our behalf

-elias

[lporterrn]

Elias,
You made me laugh. I have so many unfinished manuscripts, that the thought of another liver book caught me in a momentary fantasy. Be that as it may.

In my opinion, we just plain don't have the evidence regarding the how part of diet. Lots of opinions, no data. I believe that we have genetic differences, and there are people that need the more paleo approach, while others may do better with the vegan or vegetarian approach. Then there is the Mediterranean diet. I tend to subscribe to Michael Pollan's simple model: Eat food, not much, mostly plants. I am ultra strict about keeping sodium to a minimum (harder than it seems - I observe 1000 mgs because I have Meniere's disease). Sleep is the #1 thing I do for health - it enables me to do everything else.
This is pretty much what I do: https://www.hepmag.com/basics/hepatitis-c-basics/nutrition-exercise

As for the new section - I love it! Will see if I can generate interest.

FYI, Hep blogger Karen Hoyt is coming out with a diet-related liver-loving book  - looks good so far.