Interesting Study on Insulin Resistance

[MYS]

J Hepatol. 2009 Apr;50(4):712-718.

Insulin resistance predicts response to peginterferon-alpha/ribavirin combination therapy in chronic hepatitis C patients.

Dai CY, Huang JF, Hsieh MY, Hou NJ, Lin ZY, Chen SC, Hsieh MY, Wang LY, Chang WY, Chuang WL, Yu ML.
Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, No. 100, Tzyou 1st Rd, Kaohsiung 807, Taiwan; Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Occupational and Environmental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.

BACKGROUND/AIMS: Insulin resistance (IR) might be associated with hepatitis C virus (HCV) infection. This study aimed to elucidate impact of IR and beta-cell function on the response to peginterferon-alpha (PEG-IFN)/ribavirin combination therapy in chronic hepatitis C (CHC) patients.

METHODS: Three hundred and thirty patients without overt diabetes were treated with combination therapy with (PEG-IFN)/ribavirin for 24 weeks. The IR and beta-cell function were evaluated by homeostasis model assessment of IR (HOMA-IR) and homeostasis model assessment of beta-cell function (HOMA-beta) before treatment.

RESULTS: HCV genotype, pretreatment HCV RNA level and pretreatment HOMA-IR, but not HOMA-beta, were independent factors associated with sustained virologic response (SVR). In 150 patients with genotype 1b infection, pretreatment HCV RNA level, HOMA-IR and age were independent predictors for SVR. The significantly lower SVR rate in high HOMA-IR patients was observed in 76 patients with high HCV RNA levels (400,000IU/mL) who were defined as 'difficult-to-treat' patients. The mean HOMA-IR of 'difficult-to-treat' patients was significantly lower in 42 sustained responders than in 34 non-responders.

CONCLUSIONS: IR was associated with SVR to (PEG-IFN)/ribavirin therapy for CHC, especially among 'difficult-to-treat' patients. These findings suggested clinical application of pretreatment HOMA-IR could enable treatment outcome to be predicted and treatment regimens to be determined.

[jmjm530]

Just want to add that I agree with HRs "points" theory and personally expand it to include doctors, even hepatolgists, i.e. the more pointed expert opinions you get, the more apt you are to go in the right direction. During the course of my treatment I had at least four such points (hepatolgists) giving input at critical junctures. This may be excessive, but I don't think second opinions are.

-- Jim

[portann]

I'm also really glad you didn't jump into treatment. You and I  joined the forum at about the same time and I wish I'd been lucky enough to pause and consider my options. Instead, I plunged in.

I'm almost finished now, so I did it.

Would I have done it, if I knew then what I know now? No, definitely not, in my situation. Based on a liver biopsy that showed mild progression, I would have waited for the PI's for one reason only. Do you think for better odds? Actually, no. Only for shorter treatment time. It's like your diet. Would you take the one that could show results in 24 weeks or 48 weeks? Dieting is so hard but tx can bring you to your knees.

Go for your biopsy if you can, and maybe that will give you the option of waiting for the PI's. The more time on tx, possibly the more opportunity for underlying autoimmune disorders to rise to the surface and give you a run for your money the rest of your days.

You've learned so much in a few months. Good luck.

[jmjm530]

PA: . Do you think for better odds? Actually, no. Only for shorter treatment time. It's like your diet.
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Interesting and on-the-mark comment.

When I was at my doc's office while treating one day, I was asked if a Vertex rep could interview me for a few minutes, as they were in the office that day doing some sort of survey.

The one thing that stuck in my mind -- and this was very early on -- before it was called Telaprevir and maybe even before they started human trials -- the one thing that stuck out was they were focusing in even then on the number 24 (as in weeks) because apparently their research/interviews had shown that after 24 weeks is when a lot of people start to go downhill in terms of side effects. It's not that you necessarily have more sides in the last 24 but it seems you just keep getting more and more and more worn down and never get to recover. I'm sure that if I had stopped at 24, my post tx recovery would have been a lot easier and I might have been spared some of the lingering issues.

-- Jim

[Willy50]

I agree with Portann, but of course, the benefits don't stop with shorter TX time and all the other alluded issues that can come from extended chemotherapy.

I think the most recent TVR SVR results in EU were over 80%- nearly double that one could expect in the USA for SOC.

Reigning in the discussion back to the topic...... folks in Europe often do better than their North American counterparts.  Why??????  It could be they they get more exercise, have better diet and (no question about this I think) have less IR issues than the United States.  (but then who has more?)

best,
Willy

[jmjm530]

It could be they they get more exercise, have better diet and (no question about this I think) have less IR issues than the United States.  (but then who has more?)
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That has been the theory for some years now and in fact one reason why some of the early european trial results may have over-estimated SVR results in terms of the U.S. population. Hopefully this does not get me into too much trouble - getting ready to duck -- but when in Europe I could always spot a European woman (from an American) at 100 yards, they just didn't have that "healthy" farm-fed look :) And European men also appear much leaner. It's a different aesthetic. Whenever I drop down to my ideal BMI through diet I always get comments like "you look thin" or "did you lose weight" but the sub-text isn't necessarily complimentary because I think what Americans think looks "healthy" is about 10-15 pounds overweight.

-- Jim

[apache1]

Baja, I see exercise is the 1 element missing in your routine.

By the end of tx, I gained 18lbs.
I did stop most all exercise on tx. First time I consistently did not work out in 25 years.

I could not lose weight on tx, even for weeks after tx, even going on a strict diet.
THEN,
started brisk walking for an hour a day, then progressed to running and lifting again ...slowly.
The first week I started my exercise routine, I droped 4 lbs (mostly brisk walking)
After 8 weeks lost 12 lbs. No dieting. Just good healthy meals with realistic portions size

My point being, diets did nothing for me, maybe I was eating good enough already. I am not on a diet now, but eat good. Even have a piece of cake or ice cream once in a while, and my weight/bmi stays the same...as long as I don't miss my EXERCISE. I recently got a cold/flu (first time in 20 years) and stopped exercise for a week, gained 4lbs, quick.

I repeat, exercise made a drastic and immediate difference for me. I have exercised regularly for decades without ever stopping, until TX. Never realized how much it effected my metabolism and spirit, till I stopped for months, than started back up.
EXERCISE, also helped elevate my mood.

See a Dr and get the ok to slowly start an exercise program.
I hope you can get the Dr's ok.
Its not easy to start exercise, but it grows on you till it becomes part of your life. It is work, and you do sweat.
Sweat is good. You need to sweat, and get the fluids/blood pumping thru you.

Even a continuous semi brisk walk for 1hour per day, every day, will probably see immediate results. Thats what I did for my first couple weeks before I started running again. For me, exercise and weight control go hand in hand.

Please don't take this as criticism or me judging you. I am not.
I am only trying to motivate you into the world of exercise. IMO it is the key to good health.
For you, exercise is at least worth a try, especially since diets don't seem to work for us.


jmo
apache