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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.
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96938 tn?1189799858
One more time, thank you.  I'll see the journal and go to the protein.
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568322 tn?1370165440
Diabetes questions are never the wrong questions.

I think what you're thinking is that Metformin lowers your blood sugar....and that is not so.  Metformin makes the cells in your body more sensitive to insulin but it doesn't lower your blood sugar 40 or 50 points.  It doesn't do that.

On my journal, which you can access through my profile, there's an explanation of diabetes and there's a section on how Metformin works.  I think it will help you understand what Metformin does.

Your HgA1C is the average fasting blood sugar over the last 3 months.  How can you lower the fastin g blood sugar?  By having a protein snack half hour before you go to bed so the liver won't give you any sugar during the night.

Co
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Avatar universal
Bill, Mike : thanks for the information; seems the DB-control dividend from svr is real but by no means conclusive..

Co: so is there a supplement that promotes phosphorylation of stat1 to take along with the SAMe? I'm starting to repeat myself here, but I still think the Magdalena S-F paper show fixing  ifn signaling is only going after a part, and possibly not the most significant part, of the problem. Even after those 200 or so ISG get translated and go about their business they're still not getting the job done in NRs.

As a card-carrying member of the Alinia fan club, I found the following
http://www.ncbi.nlm.nih.gov/pubmed/18710916
(referenced in a CME review Jim posted recently) to be very good news. Though cells saturated with the stuff can lose their response to NTZ, the virus cannot mutate away from it and the cells actually become significantly *more* responsive to ifn. There's no real reason to *not* take the SAMe, but I think adding the Alinia is likely the more significant factor. (also:
http://www.ncbi.nlm.nih.gov/pubmed/19135998
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96938 tn?1189799858
Thanks again, and I promise to give the meals a better effort.  Nuts and cheese are doable.
But it brings me to another question. Based on the transitory life of meformin, I'm beginning to think that even a religious adherence to the daily dosing of metformin will have no affect on an a1c test over time.  And, short of a steady diet of riba the only thing that can impact the a1c results for me is diet, exercise, several meals a day including nuts and cheese. Am I correct about metformin and a1c, or am I asking the wrong questions?
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568322 tn?1370165440
His HOMA was below 2.  His diet is good and he exercises.  He followed a plan like CS's.  AND his side effects are not bad at all.  Some of the supplements seem to work very well in preventing side effects.

Co
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568322 tn?1370165440
Yes, it is.  Because you will be doing the same thing every day.  What your doctor wants to see is PATTERNS.

So you can't eat 5 small meals a day?  

I once saw a patient on a referral.  He worked at a car wash on commission.  So obviously, he couldn't stop to eat whenever he wanted.  After I explained to him that having meals on a regular schedule was one of  the most important things in obtaining glucose control, he said he would try.  

Next time I saw him he was very happy.  His blood sugar was great and with a big smile on his face he told me that he was taking a sandwich or a burrito to work....and when it was lunch time, he would hide between the cars and quickly eat the food he'd taken with him.

For some reason, I think about him every time somebody says, "I can't".  Eating a snack simply means eating a few nuts or a cheese stick.  

Co
Helpful - 0
479244 tn?1271563659
"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). "

question - did this person have insulin resistance??  And if so, did he take metformin before and during tx??

Just wondering....

bandman
Helpful - 0
96938 tn?1189799858
Thank you. Now for a follow-on.  The doc asks me to take readings, he suggests taking a fasting reading (upon waking) and on alternating days two hours after lunch.  (I usually have three meals a day, can't manage  5-6 small feedings per day).  If I take the met. with breaksfast (after the fasting reading) and take the pm metformin with dinner (7 PM) am I getting a reliable reading if I take the reading after lunch which would be 7.5 hour after AM dose and 4.5 hours before PM dose?
Helpful - 0
568322 tn?1370165440
Half life of Metformin is very short 6.2 hours and it's excreted in the urine.

Metformin should be taken with meals.  For example, if you take it twice a day, then it should be taken with breakfast and dinner.

Co
Helpful - 0
96938 tn?1189799858
I am wondering if you are familiar with the 'life' of metformin.  Using riba as an example, it works up to a saturation level over time and eventually reaches a steady state.  Is it the same for metformin, or is the life of metformin much shorter. And further, is dosing of metformin strategic in terms of meals? Thanks.
Helpful - 0
568322 tn?1370165440
Thanks for posting the link.  Very interesting.  According to the Gomez-Romero study, Blacks are considered "difficult to treat" because they are IR.  So it seems that the topic of IR just got alot more complicated and alot more interesting.

Thanks again!

Co
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568322 tn?1370165440
I sent you the full text of the initial study MYS posted.

Anybody else who would like a copy please contact me via PM.

Co
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568322 tn?1370165440
Thyoid looks fine.

Co
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619345 tn?1310341421
thank you for the information here is my thyroid panel
INDICE DE TIROXINA LIBRE ITL                 2.20  %
T3 CAPTIACION                                       25.3   %
T3 TRIYODOTIRONINA LIBRE T3F       3.39  pg/ml
T3 TRIYODOTIRONINA TOTAL              108               ng/dl
T4 TIROXINA LIBRE T4F                 1.09     ng/dl
T4 TIROXINA TOTAL                           8.72   ug/dl
RTH TSH TIROTROPINA                 1.50     uUl/mL

My doctor said it was fine?
I have the Zone very good diet plan and very similar to the Insulin Resistance diet
which I think I follow pretty good but the PORTION CONTROL  is a factor for me  I am so hungry  I am eating breakfast for the first time in years
but am really starving at 11am and again throughout the day

fasting before a blood test is really hard on me to do I dread it as I feel so woosy and dizzy and feel very bad when my body is in starvation mode

there is another factor I think for some that eating time can bring anxiety from past experiences or lifestyle and I think most people in a rush do not enjoy what they eat
or how they eat  this is something I personally want to work on but always being in a hurry is a definate factor for me and with people on tx it is an anxious time as stated here as they cannot keep it down or most foods just are not appealing

Excercise I get so much bad excercise at work I am very active moving things and it is tiring and causes pain but that is part of my job decoration in my one business I love it but it tires me out to no end  
I am very strong and overdo  also being on my feet which has always been easy for me is now painful but so is laying down after sleeping there is a lot of pain upon waking
too much info???

but thanks for your post I have to admit I do not understand much of the IR Diabetes Info
just wondering if I could have both as having HCV for the length of time I have had I figure it is throughout my body rather than damaging my liver which you would think would be the case it seems to have affected my body in many ways and not my liver??
Can a person who is always in survival mode have less damage to the liver? does having HCV in your brain stem or brain cause other issues in your body?  or is it the virus in those organs?  
baja
Helpful - 0
233616 tn?1312787196
I think getting the BMI is important, much more than my doc thinks.

However, one has to be careful how one achieves that with HCV.and especially with any iron overload or IR on board.

reason being is fasting causes big issues as does too much excercsie with oxidative stress which in turn causes more liver harm.

So dieting should be renamed portion contol and excersise should be light to moderate to avoid oxidative stressand muscle acid build ups.

Because once on tx red blood cells can be cut by 30-50% of normal, activity is not always an option.

However, one can help ones blood sugar out a lot by 7 small  half meals a day.
the 7th meal should be a glass of milk and grahm cracher, or a small piece of chesse with a couple slices of apple, taken at mifnight or upon wakinf during the night,
CTUALLY EATING THAT LATE WILL HELP YOUR MORNING BLOOD SUGARS TO BE LOWER believe it or not, by having some available fuel through the night it slows the production of hormones that tend to raise BS overnight,

I'd really recommend you take a look at Barry's Sears "The Zone" diet...in paperback everywhere.
This is the only diet book I know of that explains IR and diebetes and food matabolism so that any person of average intelligence can fully understand it. His chapter on Insulin Production alone is worth the price of admission.
Even if you don't like "the point" system he used for keeping track of foods, you can still follow the principal of combining protein/carbs/fats in the right proportion is each meal or snack, and this combing alone will greatly effect IR.

mb

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Avatar universal
http://www.sciencedaily.com/releases/2009/03/090327072801.htm
Helpful - 0
233616 tn?1312787196
sevral things:

yes one could have both HCV caused and peripheral.

Your BS's are not bad but have you had your thyroid checked. The easiest way to correct for triglycerides is to be sure you stay in the .1-1.5 range, if your TSH number is 2,3,4 or higher this will rei triglycerides, so a low dose of synthroid can really help there.
It used to be a 2 or 3 was consider fine, but not anymore.

not only can you have 2 types IR, but MANY types of diebetes:

A number of other types of diabetes exist. A person may exhibit characteristics of more than one type.

For example, in latent autoimmune diabetes in adults (LADA), also called type 1.5 diabetes or double diabetes, people show signs of both type 1 and type 2 diabetes.

Other types of diabetes include those caused by

genetic defects of the beta cell—the part of the pancreas that makes insulin—such as maturity-onset diabetes of the young (MODY) or neonatal diabetes mellitus (NDM)

genetic defects in insulin action, resulting in the body’s inability to control blood glucose levels, as seen in leprechaunism and the Rabson-Mendenhall syndrome

diseases of the pancreas or conditions that damage the pancreas, such as pancreatitis and cystic fibrosis

excess amounts of certain hormones resulting from some medical conditions—such as cortisol in Cushing’s syndrome—that work against the action of insulin

medications that reduce insulin action, such as glucocorticoids, or chemicals that destroy beta cells

infections, such as congenital rubella and cytomegalovirus

rare immune-mediated disorders, such as stiff-man syndrome, an autoimmune disease of the central nervous system

genetic syndromes associated with diabetes, such as Down syndrome and Prader-Willi syndrome
Helpful - 0
Avatar universal
Willing,
I don't recall any difference in my glucose post treatment. Recently I put on some weight and that seems to have increased my BG. And, often the weight comes with increased carbohydrate intake so that played a role as well. I have lost some of the weight by abstaining from carbs and as a result my insulin requirement has decreased.
CO,
After 2 years of treatment I lost a lot of weight. I weighed between 140 & 145 lbs and I had treated with 800 mg ribavirin per day my first 2 treatments. For the third treatment my ribavirin dose was 1000 mg per day.
During my second treatment I did become undetectable but quite late in my treatment - guessing I would say between week 20 to week 28. I stopped at week 52/53 and relapsed immediately.
My third treatment I was undetectable per Heptimax at week 12 but I assume I was clear at week 11 because week 10 VL was 15 IU/ml or thereabouts.
Mike

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568322 tn?1370165440
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
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568322 tn?1370165440
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
Helpful - 0
619345 tn?1310341421
Can a person have both types of IR?
Helpful - 0
568322 tn?1370165440
Fasting 84
1 hour 119 (that was after drinking that gawdawful stuff)
2 hour 83
3 hour 76
4 hour 53

----------------

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
Helpful - 0
568322 tn?1370165440
"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."
-------------------

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 -;)) "
------------------

I, for one, like to hear what people have to say on this subject.  Thank you for jumping in!

Co
Helpful - 0
568322 tn?1370165440
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.
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