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.

[mikesimon]

I am a type 2 diabetic and I too achieved SVR after 2 failed tries. My glucose control was the same during all three treatments. What changed was dose and duration. The 3rd time I increased my ribavirin and treated with Pegasys whereas the first 2 was  regular interferon/ribavirin and the second was Peg-Intron/ribavirin. I don't think the choice of Peg made a difference. I think the increased ribavirin was the determinative factor and the extended treatment probably didn't hurt either.
My genotype was 1b and VL from 2.5 million to 6.5 million - highest at the start of my third and successful treatment.
Mike

[Marc1955]

I think there is something that is (perhaps) being overlooked in this discussion on IR. According to the article originally cited in the Journal of Hepatology, there is evidence that HCV can create IR. So the IR among HCV patients may not simply be related to lifestyle issue, but perhaps to the HCV itself.

I don't disagree with what has been said above – lifestyle changes need to be the first line of defense. But if the HCV is somehow implicated in the presence of the IR, then there are going to need to be different approaches.

(Sorry for extending this overly long thread -;))

[bajawoman]

HR thought I was stage 2 approaching stage 3  but he also thought I could wait for the newer drugs believe he mentioned Vertex but if I decided I did not want to wait and wanted to treat now not to do it without alinia and metaformin  so I am waiting but in the meantime trying to get a handle on my IR but like others have mentioned too this is not an overnight or fast process   thanks for all your input and suggestions
baja

Bill I would personally like to see what you post to Co I find it very interesting and in my opinion this type of information will be beneficial to some here on the forum with diabetes problems   thanks  baja

[Bill1954]

Bill1954 previously) "I am a type 2 diabetic that SVRrd. Although I had a slow response during the first treatment, the second time I cleared relatively early, and went on to achieve sustained viral response."
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CO previouly) I am going to take a wild guess and say that perhaps your blood sugar control was better the second time?
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Bill1954) I believe my BG control was adequate both times; although it wasn’t as tight as I recall during the latter part of the second treatment.

Bill1954 previously) "Type 1 diabetes typically involves underproduction of insulin from the beta cells in the pancreas."
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CO previously) Actually Bill, Type 1 means that you don't produce ANY insulin at all.  
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Bill1954) You got me there. I was responding to another poster that had used the term “underproduction”. I should have been more precise.

Bill1954 previously) " A type 1diabetic typically requires very little exogenous insulin; they can get by with injecting small amounts."
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CO previously) Think about it.  They don't produce any insulin at all.

Bill1954) I hold my position on this; a type 1 diabetic typically requires far less insulin than a type 2 DM patient due to IR. I required up to 100+ units of insulin during treatment to maintain BG control, presumably due to existing insulin resistance. A type 1 diabetic would have become ill with that much insulin, I’d imagine.

Bill1954 previously) "but it doesn’t *preclude* SVR"
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CO) I disagree with that, however, I do agree that IR is only one of many hurdles.
So you assert that insulin resistance precludes SVR? That’s a pretty strong statement, in light of the fact that diabetics with IR continue to achieve sustained viral response. I assume that type 2 DM patients continue to  have some level of insulin resistance.


Bill1954) "some members on this board have become obsessed by insulin resistance"
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CO previously) You can't be talking about me.  I didn't just become.  I've been obssessed with it for years...LOL

Bill1954) LOLOL! Your words, not mine!!
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CO previously) I find your case incredibly interesting and wish I could see what the difference was between the two times you treated (same with FlGuy) since high levels of insulin make interferon ineffective and that includes injected insulin...and you were on quite a bit of Lantus insulin.

It's fascinating.  I would love it if you share more details.

Co

Bill1954) I’d be delighted to share any info you find relevant. Co. You can ask questions here, or feel free to ask me in private message (PM might be better; we won't take up bandwith on this thread). .

I’m not sure how much help I can be; while I kept good BG diaries throughout HCV treatment, they were forwarded to my doctor for the most part; I don’t generally keep copies for myself. I do have copies of A1c test results, but as we’ve discussed previously, they probably don’t accurately reflect control *or* insulin resistance.

Thanks again for your participation in the forum; you continue to provide thought-provoking, valuable  information here.

Best to you—

Bill

[jmjm530]

Fibro Scan showed   JAN 09

8.7  k Pa
1QR  6.9
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So what does that kpa translate to -- stage 1-2 leaning toward 2? If so, and if your other scores are also around stage 1-2, then what's the rush to treat? What is the justification to treat now as opposed to waiting for the newer drugs?

If you're really f1-2, and are 60 something, and have had this disease for many years -- then you're obviously showing very slow progression. In this scenario, personally I'd go into watch and wait mode (liver healthy lifestyle, etc) with periodic (every 6-12 months) fibroscans as well as periodic visits to a hepatologist. I'd still do the biopsy, but that's been already discussed.

As long as you're running things by HR, you might want to ask him why he suggests treating at F1-F2 as opposed to waiting two years until the PIs come out of trial.

-- Jim

[bajawoman]

Hey I like your comments don't be sorry you are dead on   I was going to the gym love weights and excercise I really do it is the only times with excercise that my weight was good except for fad diets that definatley don't work  but all that said  What happened to me is I had an accident I was in great health (didn't know about the HCV ) but in 2001 I fell off my second story and a piece of rebar when though my forearm trying to stop the fall I flipped and landed on my back  breaking ribs etc and almost lost my arm I still am missing a part of my forearm  super lucky there  but needless to say the excercise stopped and then when I was almost ready to go again I took a vacation and tripped on a step and broke my leg just above my ankle  Geez ruined the vacation
and I wasn't even drunk
so now it is 2009 and I have been carrying around this weight for about 8 years  post menopausal didn't help either or the stress of work  
So I am going to try  It is just now the HCV really makes me tired  the supps help  since the fall I suffer from Vertigo so have to really watch my step  fast walking for me is not possible yet but could be in my future with starting with baby steps
I do need a trainer and I do some stretching but get incredibly wiped out with any attempts at excercise  and I do not overdue just feel wiped out like the flu the next day

but I have discussed this with my GI he wants me to begin with 5 min a day on my treadmill I invested in a few months back  something in my brain just won't click on I guess I have to be dragged to the thing  boy am I pitiful   baja