Higher HCC risk with increased insulin resistance

[nygirl7]

Just FYI - if you have IR you might want to also keep on top of this one too.

Better safe than sorry....I don't want to be the harbinger of doom but I know IR is a problem for some folks around here. I hate HCC if you can't tell.....no more of my friends should die of this.

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Higher HCC risk with increased insulin resistance in hepatitis C patients
May 12, 2010

Recent studies have demonstrated that type 2 diabetes mellitus (DM) is associated with high risk of hepatocellular carcinoma (HCC) development in patients with chronic hepatitis C. Insulin resistance (IR), which correlates inversely with circulating adiponectin concentration, is a consistent finding in patients with type 2 DM. Chronic hepatitis C virus (HCV) infection has been reported to be associated with increased IR. Recent studies suggest that IR plays a crucial role in fibrosis progression, and has been demonstrated to have a negative impact on treatment responses to antiviral therapy in patients with chronic hepatitis C.


A research article to be published on May 14, 2010 in the World Journal of Gastroenterology addresses this question. The research team led by Dr. Hung from Kaohsiung Chang Gung Memorial Hospital prospectively investigated the IR assessed by the homeostasis model (HOMA-IR) and serum adiponectin level in two independent cohorts of consecutive newly diagnosed HCC patients and those with different clinical stages of chronic HCV infection.

Among 165 HCC patients, type 2 DM was more prevalent in HCV subjects compared to hepatitis B virus (HBV) or non-HBV, non-HCV cases. HOMA-IR was higher in HCC patients with HCV than in those with HBV infection. In 188 patients with chronic hepatitis C, HCC subjects had higher blood sugar, insulin level and HOMA-IR than those with chronic hepatitis and advanced fibrosis.

Based on stepwise logistic regression analysis, HOMA-IR was one of the independent factors associated with HCC development. This result was similar even if the diabetic subjects were excluded for analysis. The research team concluded that increased IR, regardless of the presence of diabetes, is significantly associated with HCC development in patients with chronic HCV infection.

These findings may have important prognostic and therapeutic implications in the management of chronic HCV-infected patients. Since IR is a potentially modifiable factor, therapeutic intervention aimed at decreasing IR may be warranted in these patients.

More information: Hung CH, Wang JH, Hu TH, Chen CH, Chang KC, Yen YH, Kuo YH, Tsai MC, Lu SN, Lee CM. Insulin resistance is associated with hepatocellular carcinoma in chronic hepatitis C infection. World J Gastroenterol 2010; 16(18): 2265-2271 http://www.wjgnet.com/1007-9327/full/v16/i18/2265.htm

Provided by World Journal of Gastroenterology (news : web)

http://www.physorg.com/news192880615.html

[Cory255]

You stated--, "Ranges for HOMA1, HOMA2, scores generally seem to consider lt 2 OK."

HOMA1 & HOMA2 are two completely different calculations.  Any score GREATER than 2 means your IR (with HOMA1).  My HOMA1 score is 2.04.  I'm IR!  

As of right now it is unknown when IR starts with the HOMA2, (2 definitely wouldn't be OK),  IR probably starts somewhere in the range of 1 maybe 1.1.  

[willing]

the discrepancy between Homa1 and Homa2 is an interesting aspect of the IR world. I'll post what some reading on the subject dug up when I have  a bit more time but here's what seems to be the gist of it:

- Wallace and coworkers introduced HOMA1 in '85 as a measure of IR that was easier to obtain than the gold-standard assay (euglycemic clamp)

- in '96 they modified the index to apply a non-linear (and more accurate) fit to the underlying data - HOMA2.

- you can get a rough idea of the difference between the two indices from Fig. 2 of a (free access) summary of HOMA usage published in '04
http://care.diabetesjournals.org/content/27/6/1487.full

- as the authors note, there's a much less accurate fit to the data with HOMA1 and the index tends to  underestimate your insulin sensitivity (%S) "the equations were based on the 1985 HOMA1 model, which was calibrated to an insulin assay used in the 1970s, and systematically underestimate %S and consequently overestimate %B when compared with newer assays" (that is,  HOMA1 makes you look more IR than you are)

- nevertheless, essentially *all* the studies that have found correlation between high HOMA and bad things (failure to SVR, increased fibrosis, increased HCC risk)  have used the HOMA1 index. The reason, as best I can make out, is that Matthews et al never got around to publishing the non-linear fit equations which remain buried in the calculator they implemented and make available for download. This doesn't mean the correlation is invalid, just inaccurate.

Overall, the high HOMA/bad-things correlation seems valid (lots of support) but based on  studies that used a HOMA measure *known* to be inaccurate. Bottom line is that if  you suspect IR is an issue calculate your %S with the updated HOMA2 index and/or check with your Dr. about a euglycemic pump test before deciding it's a problem -it may not be.

[nygirl7]

I think this is the most I ever understood IR.

http://www.huffingtonpost.com/susan-b-dopart-ms-rd/weight-loss-tips-are-your_b_598250.html?ir=Daily%20Brief

[Cory255]

Very interesting how my HOMA1 score is 2.04 and my HOMA2's 1.2.

That sounds a lot better with the HOMA2 score.  Thanks.    

[IAmTheWalrus]

Great information. I was concerned about this during TX as my blood glucose was often a little elevated. Post TP I had to take insulin but glucose returned to normal whan I got off the steroids.

After TX, and subsequent relapse, I got an insulin test and computed HOMA score as 2.8. The problem is that I could not find any references to what this meant. What is too high, what is too low, etc.

I hope the info here will shed a little more light for me. I really think I am IR and suspect it could have been a factor in my relapse.

[willing]

the HOMA2 score for 88 mg/dL and 9.4 uU/ml is 1.2. (you can get the calculator for Matthew's revised index at the Oxford university link above to check).  Ranges for HOMA1, HOMA2, scores generally seem to consider lt 2 OK. Here's a Stanford paper that reports insulin/glucose/HOMA values for 490, healthy, non-diabetics. (free-access)
http://www.ncbi.nlm.nih.gov/pubmed/10868826

From Table 1, avg fasting insulin was 12 and average HOMA-IR 2.7 .

Overall,  doesn't look like IR is an issue for you.