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.

[GreatBird]

My understanding is that diabetes type 1 involves underproducing insulin. Type 2 is with overproduction. Do you know whether the diabetics who cleared were type 1 or type 2?

[Bill1954]

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. I think part of the misunderstanding here is that some members on this board have become obsessed by insulin resistance, and look at it as if it were a panacea to HCV treatment; but it doesn’t *preclude* SVR; it’s only another hurdle to jump on the path. I’m not suggesting it be ignored either; but a balance needs to be found.

Type 1 diabetes typically involves underproduction of insulin from the beta cells in the pancreas. Type 2, on the other hand, can be a combination of factors; underproduction of insulin, coupled with insulin resistance that prevents cells from absorbing or utilizing the insulin that *is* produced. A type 1diabetic typically requires very little exogenous insulin; they can get by with injecting small amounts. I, on the other hand, at times require very large amounts of insulin because my body is unable to ‘accept’ either my own insulin (endogenous), or the insulin we inject (exogenous). It’s common for type 2 diabetics such as myself to require both oral insulin sensitizers (metformin) as well as insulin injections to maintain firm blood sugar control.

Take care—

Bill

[Max60]

My original post asked for clarification. . . which was not given.

What were the viral loads? What were the ages of the successful and unsuccessful participants?  Who do the terms 'difficult to treat' mean precisely in the context of this study?

Is there some reason you can not post the full text?

[jdwithhcv]

Google this and you will get the articles.  

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

[geterdone]

did you know the first time around that your IR would play a part in your not being successful in treatment? Just curious, thanks!
jasper

[Bill1954]

Actually, both treatments occurred prior to current studies showing any correlation between insulin resistance and SVR; any attempts at challenging IR were in the interest of blood glucose control only.


Bill