179856 tn?1333547362

Higher HCC risk with increased insulin resistance

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.


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)

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Avatar universal
HOMA1-IR = (FPI (mU/L) x FPG (mmol/L))/22.5

HOMA1-%B = (20 x FPI (mU/L))/(FPG (mmol/L) – 3.5)

Where FPI is fasting plasma insulin and FBG is fasting plasma glucose; to convert mg/dL to mmol/L, simply divide by 18.

The original model did not account for differences between hepatic and peripheral insulin sensitivity, increases in insulin secretion or decreases in hepatic glucose production for plasma glucose concentrations above 180 mg/dL, renal glucose losses, or the contribution of circulating proinsulin.  An updated HOMA model (HOMA2) has since been created, however it is a computer model and has no simple equation but it adjusted to account for these variations.  It models insulin sensitivity (HOMA2-%S) where 100% is normal which is the reciprocal of insulin resistance (100/S%).  In addition, the original HOMA model uses equations that were calibrated to insulin assays used in the 1970’s which result in underestimation of %-S and overestimation of %-B.  With knowledge of these differences, it is therefore important when evaluating studies to determine whether the HOMA formula or the computer-based HOMA was used to quantify insulin resistance and beta-cell function.
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Avatar universal
did a Dr. diagnose IR? that seems surprising with the numbers you posted. Unlike say fibrosis there are reliable gold-standard tests for IR that measure changes in  actual insulin/glucose dose/response levels instead of approximating them as HOMA does, so that seems the way to go if you want a definite answer.

Re homa1 vs homa2 yes agreed that essentially all studies have applied homa1 regardless of the fact the index systematically gives artificially high IR scores. To keep from comparing apples with oranges it seems best to use  HOMA1 for comparison with published studies and HOMA2 for a more reliable, corrected,  'absolute' indication of whether IR is an issue. For example, in one of the main IR vs SVR studies:
"Insulin resistance impairs sustained response rate to peginterferon plus ribavirin in chronic hepatitis C patients."
the average HOMA1   was 2.36 among SVRs and 3.76 among non-SVRs.

They also found better SVR rates among those with lower-than-average HOMA1, so there seems to be some motivation for pushing down your HOMA1 regardless of whether you're IR - though given HCV's known  effect on glucose metabolism the low HOMA1 group could also have had something else going for them - eg low VL.

(also sorry about my mistake in post above,  not sure why I wrote median HOMA1  of  2.7 among healthy volunteers,  that should be average).
Helpful - 0
223152 tn?1346978371
Good thread

I read this with interest and have pulled prior blood work to see what it tells me.  My glucose is easy -- it is written as Glucose, Serum or GLU.  It is written in mg/dL so requires modification, per Willing.    I am having a problem finding any insulin resistance tests. I have a book -- "Mosby's Manual of Diagnostic and Laboratory Tests " which give what I thought were all the blood tests.  Under Insulin we have assay, autoantibody (IAA), blood glucose, C-peptide, and some growth factor tests.  So what, pray tell is an insulin resistance test,  and is it only run when there are high level glucose tests?  

I am always searching for reasons I relapsed.  Glucose is in range -- about 88 last time --  but  I would like to calculate this insulin resistance, .  If there is another test to ask for, I would like to ask my doctor for it.

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Avatar universal
not much to it : (1) in addition to the glucose you also need an insulin or c-peptide measurement. For purposes of IR checking the authors recommend insulin which should be in the range 2-17 uU/mL (micro-units per milliliter) (2) make sure both are fasting tests as the levels can vary significantly around meals (3) after converting glucose from mg/dL just multiply the two together and divide by 22.5 to get your HOMA1 index. For HOMA2 you have to download the calculator from oxford
either as an executable or an an excel control.

If it's an issue it seems more likely to show up as non-response than relapse but definitely a good thing to rule out. Glucose 88 looks pretty good. Mine tends to be at the high end of normal and broke past 100 last year triggering a slow down in my fig-bar rate which caused it to coast back to 92 - but insulin is way low.
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Avatar universal
It just makes good sense for non responders or relapers to check for IR prior to retreatment so there is time to do something about it.  Can't leave anything to chance after treatment has failed the first time.


Helpful - 0
179856 tn?1333547362
It certainly makes sense to me - anything that can help to cut down the potential for failure is a good thing, especially for a relapser because there had to be some reason that it didn't work in the first place really.
Every avenue should be pursued, agree 100% Trin!
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