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.

[CoWriter]

Second person just got the results of his 2 Week viral load....89.  And we made sure he wasn't IR before startin g Tx.  AND he is also a previous non-responder.  (he used the same approach as CS).

Co

[Gee704]

As more information becomes available, I would be happy to share.

This study is independent from tx. Although I am hoping IF I decide to treat, I will have a chance with a study with a PI within the same research environment. What interest me about this study (and possibly of one with a PI) is a shorter duration of treatment. If in fact diet plays a role in replication, not only should the duration for treatment shorten but maybe the success rate for SVR may go up? I am doing the study not only to help in the cure but also to broaden my knowledge.

There are three groups in the study. Healthy without Hep C or fatty liver, those with fatty liver, and Geno 1's not yet treating. They believe fatty liver develops in those with Hep C because the virus negatively affects a particular gene in the liver that is responsible for exporting fat. The gene, stearoyl CoA desaturase-1 creates a fat called oleate from another fat called stearate. Oleate is more easily exported than stearate from the liver. They will compare the amounts of oleate to stearate in the blood of the control groups while on two different diets. The first three weeks is a diet high in poly unsaturated fats and the 2nd three weeks will be a high carb diet.

Blood will be saved to run genetic studies from the Hep C control if they do find that a certain diet changes the ability of the virus to grow. This just may be helpful in future treatments - hopefully mine! Stay tuned.

[Bill1954]

Thanks for the link, Willing; I’ll take a look in a bit. Regarding blood glucose control; I was able to delete all insulin from my regimen about 4 months post HCV treatment due to multiple low BG results. However, recently, I’ve been having difficulty again, and have had to increase two of the three oral ant diabetes meds. One of the problems with diabetes management is other factors… weight, exercise etc. are all critical to tight control. It’s hard to determine whether or how much IFN directly influences this. Still no insulin, but…

Take care—

Bill

[willing]

until recently I wasn't aware that three of the SVRs whose posts I find very helpful were/are diabetic. Among the  documented and overlapping associations in this area (hcv associated with  higher incidence of ir; hcv+ir associated with higher steatosis/fibrosis and lower  tx odds; pre-treatment with IS may/may-not improve svr odds) is data suggesting improvement in glucose abnormalities *after* svr, eg

http://www.ncbi.nlm.nih.gov/pubmed/17065685

Since all 3 of you, with repeated effort and in spite of the unfavorable odds described above, *did* svr, did you see any improvement in your glucose profiles after tx?

[jmjm530]

Could you tell us more about the diet study? Is it part of a trial where you will be taking drugs to kill the virus, or is the diet study separate and after that you will treat privately. Thanks for joining the conversation, it all sounds interesting and I'm sure a lot of us would like to hear more if you are able to share.

-- Jim

[Gee704]

I was dx'd with Geno 1 July 08'. I have not yet begun tx but am about to begin a diet study this week concerning HCV and IR. One of the aims of this study is to find out if by changing the diet, can they change the ability of the HCV virus to grow.

In the purpose of the study paragraph for consent to participate it states that Hepatitis C can lead to insulin resistance. It also states that insulin is a hormone that helps your body use the sugar in the food you eat as fuel. In some people, the liver, muscle and fat stops responding to insulin as well as it should  and results in a condition called insulin resistance.

Hope this helps in the conversation here. I can post updates if I receive the information after completion of the study.

Gee704