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]

I certainly do speak Spanish.  Wasn't it funny how much time I spent translating your results and HR ended up speaking Spanish....LOL

Love ya!

Co

[CoWriter]

Bill....Lantus controls fasting blood sugar.  What was your fasting blood sugar like the first time you treated?  The second?  

Mike....how much Riba?  Same question as Bill....what was your fasting like?

Co

[bajawoman]

Can a person have both types of IR?

[CoWriter]

Fasting 84
1 hour 119 (that was after drinking that gawdawful stuff)
2 hour 83
3 hour 76
4 hour 53

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My guess is that at that time you're producing too much insulin.  Next time you have a 3 or 4 hr GTT, ask your doctor to see if he would check the insulin.

Co

[CoWriter]

"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."
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That's right Mark.  There are two different types of IR.  Hepatic IR caused by the Hep C virus and peripheral IR caused by obesity.


"(Sorry for extending this overly long thread -;)) "
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I, for one, like to hear what people have to say on this subject.  Thank you for jumping in!

Co

[CoWriter]

Remember what we were discussing the other day?  Take a look at this....
"The number of P-STAT1 observed correlated significantly with the body mass index  and homeostatic model assessment"

: )
Co


Intervirology. 2009 Mar 4;51(6):394-399.

Predictive Value of the Phosphorylation of Signal Transducers and Activators of Transcription in the Outcome of Interferon Therapy for Chronic Hepatitis C.

Miyaaki H, Ichikawa T, Nakao K, Takeshita S, Shibata H, Ozawa E, Akiyama M, Miuma S, Eguchi K.
First Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki, Japan.

Objective: Signal transducers and activators of transcription (STATs) play a critical role in antiviral defense. To better understand pegylated interferon (IFN)-alpha and ribavirin combination therapy resistance, we examined the STAT expression in the liver. Methods: We immunostained Phospho-STAT1 (P-STAT1) and Phospho-STAT3 (P-STAT3) in 59 hepatitis C virus (HCV)-infected liver tissues and compared the expression of these STATs proteins and the clinicopathological factors. Results: The number of P-STAT1 observed correlated significantly with the body mass index (BMI; p = 0.03) and homeostatic model assessment (p = 0.007). The number of P-STAT3 observed correlated significantly with the ALT level (p = 0.002) and platelet count (p = 0.002). The number of P-STAT1 nuclei in the sustained virological response (SVR) group was significantly larger than in the non-SVR group (p = 0.003). On multivariance analysis, the number of P-STAT1 nuclei (p = 0.004) and age (p = 0.016) were significant predictors of SVR. Conclusions: P-STAT1 in the liver tissue prior to IFN therapy correlated with an increased BMI and increased insulin resistance, and might be a useful predictor of HCV clearance by IFN therapy. On the other hand, P-STAT3 might play a critical role in the hepatocellular response against inflammatory damage.