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Silvia Hinojosa-Price, RN, corresponds with Dr. Zobair Younossi, M.D., M.P.H. Director, Center for Liver Diseases, Medical Director, Liver Transplant Program, with questions related to insulin resistance in advanced liver disease, as well as lower response to antiviral therapy. 


Dr. Younossi, I have several questions related to the subject of insulin resistance.

Based on the information about insulin resistance lowering SVR, I would like to know how many of you test for insulin resistance and use insulin sensitizers even though the patient may not be diagnosed as a diabetic yet--just insulin resistant.  If so, what are you using, and have you seen any toxic effects from glitazones?

Since the HCV damages the mitochondria by a process of oxidative stress and the same may be true for insulin resistance, are you recommending anti-oxidants and if so, what amount?

Since aerobic exercise helps produce more mitochondria and a high- protein diet boosts the benefit of exercise, possibly decreasing insulin resistance, are you recommending compensated patients do this and if so, how much protein?

As a diabetes educator, I find the subject of insulin resistance
fascinating. Thank you for your input.

Sources:
Insulin resistance impairs sustained response rate to peginterferon plus ribavirin in chronic hepatitis C patients.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15765399&query_hl=1 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15765399&query_hl=1

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14976002&dopt=Citation

Is oxidative stress the pathogenic mechanism underlying insulin resistance, diabetes, and cardiovascular disease? The common soil hypothesis revisited.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14976002&dopt=Citation

Liver steatosis is an independent risk factor for treatment failure in patients with chronic hepatitis C.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15674091&dopt=Citation
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15674091&dopt=Citation

Protein-rich diet boosts benefit of exercise.
http://www.eurekalert.org/pub_releases/2005-08/epr_pdb082505.php

RESPONSES TO DATE (9/15/05):

The issue of metabolic syndrome in patients infected with HCV is quite interesting. It seems that HCV patients with components of metabolic syndrome (diabetes mellitus, central obesity, insulin resistance) can have more advanced liver disease as well as lower response to antiviral therapy.  The exact mechanism of this interaction is not well known but could involve insulin resistance (IR), adipokines (adiponectin, leptin), cytokines, and associated oxidative stress.

Despite this interesting data, I don't routinely check HCV patients  for IR.  However, assessing IR in patients with nonalcoholic disease (NAFLD), a fasting serum glucose and serum insulin can provide an easy method to calculate HOMA (HOMA >2.2=IR).

Although theoretically it makes sense to use medications/ strategies to improve IR and oxidative stress, there are currently no convincing data that these treatment strategies (including amount of protein intake) improve outcomes in patients with HCV.

However, for overweight HCV patients, I do recommend gradual weight loss. .....

Zobair Younossi, MD, MPH
Director, Center for Liver Diseases
Medical Direcor, Liver Transplant Program
Inova Fairfax Hospital
Co-Director, Center for the Study of Genomics in Liver Diseases
Affiliate Professor of Biomedical Sciences
George Mason University
Fairfax, Virginia .

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MUST READ!
Insulin resistance is a cause of steatosis and fibrosis progression in chronic hepatitis C  ...insulin resistance is the cause rather than the consequence of steatosis and fibrosis in genotype 1 patients...
 

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