SOCS3 Gene: Insulin Resistance, IFN resistance

[MKAndrew]

For six years, I believed there was a single-source connection between interferon resistance and interferon resistance.  It is, as I suspected, a gene.  The gene is SOCS3 - Suppressor Of Cytokine Signaling-3.  The discovery of this gene also sheds some light on why prior nonresponders have more trouble acheiving SVR.

1. SOCS-3 is elevated by HCV's core protein.

2. SOCS-3 elevation causes interferon resistance.

3. SOCS-3 elevation causes insulin resistance in the liver.

4. SOCS-3 depletion reduces liver insulin resistance, but causes systemic insulin resistance.

5. SOCS-3 is further elevated in people who have treated unsuccessfully.

These findings suggest a new and viable target for therapy.  

[jmjm530]

CO: You can be insulin resistant without being overweight.
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That's correct, and you can also have fatty liver without being overweight -- but that was not my point. The fact that you can have fatty liver without being overweight does not mean that IF you're overweight, one should necessarily dispense with first line treatment, i.e. weight loss and lifestyle changes. And as far as I know, this prinicple holds true whether the IR is caused by Hep C or not. That's why good liver specialists have (and still are) recommed weight loss and lifestyle changes to their overweight patients.

And to be clear, as the sub-text of some of these posts may suggest to some -- I am not against treating IR whatever means is deemed appropriate, not do I have any pic with the current studies, not do have any illusions that the medical profession as a whole has been on top of this situation.

Quite the contrary. The medical profession as a whole has been behind the curve on both IR as well as many other issues, and that's one of the reasons why a place like this is such a valuable resource. It's also why I, and others, always urge people to seek out the best possible liver specialist they can reasonably find, because top line liver specialists tend to be ahead of the curve, not behind it.

So please, let's not turn this into an argument, because I'm not sure what we're arguing here, unless you don't believe that recommending weight loss and lifestyle changes to an overweight patient with IR is not a reasonable first approach.

-- Jim

[CoWriter]

That's right.

Co


Association among cigarette smoking, metabolic syndrome, and its individual components: the metabolic syndrome study in Taiwan.

Chen CC, Li TC, Chang PC, Liu CS, Lin WY, Wu MT, Li CI, Lai MM, Lin CC.
Division of Endocrinology and Metabolism, Department of Medicine, China Medical University Hospital, Taichung 404, Taiwan.

Insulin resistance is a common feature of metabolic syndrome. Smokers are at great risk of developing insulin resistance. Theoretically, smoking status should be associated with metabolic syndrome. This study aimed to explore the association among cigarette smoking, metabolic syndrome, and its individual components. Information of participants regarding previous and current diseases, family history of disease, smoking habits, alcohol consumption, betel nut chewing, and physical activity status were gathered from self-reported nutrition and lifestyle questionnaires. The fasting plasma glucose, triglyceride level, high-density lipoprotein cholesterol (HDL-C) level, blood pressure, and anthropometric indices in each patient were measured. Data of 1146 male subjects were analyzed. Individuals who currently smoked had a higher prevalence of metabolic syndrome than those who had never smoked and those who had quit smoking. The adjusted odds ratios of current smoking amount showed a statistically significant dose-dependent association with metabolic syndrome, high triglyceride level, and low HDL-C level. Current smokers who smoke > or =20 pack-years have a significantly increased risk of developing metabolic syndrome, high triglyceride level, and low HDL-C level. The higher risk of development of metabolic syndrome, high triglyceride level, and low HDL-C level was insignificant in former smokers. In conclusion, this community-based study supports the view that smoking is associated with metabolic syndrome and its individual components. Smoking cessation is beneficial to metabolic syndrome and its individual components.

http://www.ncbi.nlm.nih.gov/pubmed/18328358?ordinalpos=6&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

[CoWriter]

The insulin resistance caused by Hep C is actually hepatic hyperglycemia.  It's not the same as the simple antagonism of PPAR gamma of adipose tissue associated with Type 2 diabetes.  

In some people, Hep C causes the liver to disgorge huge amounts of glucagon.  This kind of sugar infusion would overwhelm most people's ability to produce enough insulin to control it.

You can be insulin resistant without being overweight.  

[jmjm530]

JM: .."many liver specialists having been asking patients to lose weight for some time prior to treatment -- so even without specific studies they have been connecting the dots..."
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Really?  Let's see.  Here's what a couple of hepatologists said in response to these questions back in Sept 2005.....
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Yes, "really" MS sarcastic one these days.  

Please read again my statement, and your response. BOTH doctors you quote (from 2005) suggest weight loss.

I was talking about "connecting the dots" and again, specifically to weight loss recommedations.  The first doctor connected the dots by recommending gradual weight loss for overweight patients. Hmmm (sacrasm unecessarily added) Hmmmm (why not over do it) isn't that exactly what I said? Hmmmm

Second doctor you noted ALSO suggests weight loss and you speculate on whether or not he would recommend weight loss in overweight patients without fatty liver. He agrees with the first doctor so just because he might go for weight loss and metaformin with fatty liver biopsy does not mean he "only" does it in those cases.

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CO:
Realistically....how many people will loose weight if they're given no education?
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Not sure what you mean by this. All I am saying is that weight loss has been suggested by good liver specialists for some time now, and that -- along with lifestyle changes such as exercise, stopping smoking, etc, -- rightly should be the first line attack for IR. This is not to criticize using drugs like Metaformin if first line measures do not work. And yes, a number of people here have lost signficant weight prior to treatment because their doctors told them to. "Gauf" is one example. When someone has something as serious as Hep C can be, and their doc tells them that losing weight will help SVR, that can be a real motivation.

[CoWriter]

Go get 'em CO!!

"That's right.  The women did much better than the men."  

____________________

High five sista!

Co

[CoWriter]

"I am curious have any studies been done if IR is a leading factor for Non Response to interferon treatment"  
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It is now the MOST important host factor......



"Thus, insulin resistance emerges as THE MOST IMPORTANT host factor in the prediction of response in non-diabetic patients treated with the best available option -peginterferon plus ribavirin. Interestingly, insulin resistance has been found a common denominator to the majority of features associated with difficult-to-treat patients. Patients with cirrhosis, obesity, HIV coinfection and Afro-American showed all insulin resistance."

http://scielo.isciii.es/scielo.php?pid= ... ci_arttext



"of all the Non Responders How many are Insulin Resistant? From what I am reading seems Many?"

We don't know exactly.  Most of the doctors do NOT test people with Hep C for insulin resistance.  Even though we've known for years that insulin resistance lowers SVR.  According to some of the studies, up to two thirds of Hep C patients have IR.



" Why after all these years of the Interferon treatment  is this only now coming to light??"

(I've been asking that for years).

Because even though they knew that IR lowered SVR, they hadn't done any studies (until recently) using medications to lower the insulin resistance.



"Diabetics with Chronic HCV  is that different than insulin resistant?  Or are Diabetic conditions the same as Pre Diabetic"


First comes PRE-DIABETES (a fasting blood sugar above 100)....When you start becoming insensitive to insulin, your blood sugar starts to go up.  A study showed that a blood sugar above 100 lowers SVR.

Then the insulin resistance gets worse.....and for a long time your pancreas works fast and makes extra insulin, so it's able to keep your blood sugar in the normal range even though you're insulin resistant..  

But eventually, you become more insensitive to insulin and the pancreas can no longer keep working so fast.....slows down....sugar goes above 126....and you're now considered a diabetic.

So that means that you have to be insulin resistant before you can become a diabetic.  All diabetics type 2 are insulin resistant.



"and do people with Diabetes on tx do they SVR "

I believe CS and I created a monster...LOL

Great question.

Years ago, I used to work with both diabetics and people with Hep C.  And I noticed that many diabetics didn't clear.  If their blood sugar was kept under very strict control they did better.  But the problem is that treatment can also make the diabetes worse.  

Don't stop asking.....

Co