Aa
Understanding Non Response
As many already know I am a G3a 2x non responder. Twice never been UND.
Not bad for an apparently easy to treat geno type.
Now if you are a non G1 non responder there isn’t much out there specific to your genotype.
If fact looking for reasons for non response in non G1s just does your head in.
Below is what I have learnt about NR. I don’t look at Genotype much now I look more at what the virus does to us and how we contribute. I look for what is common among NRs and what is different between NRs and SVRs. Genotype doesn’t have much to do with that.
There are numerous virologic and host factors have been identified that impact the likelihood of SVR.
Viral factors impacting SVR
• Treatment Response (RVR, cEVR)
• HVL -HCV RNA above 800,000 IU/mL
More recent studies suggest above 400,000 IU/mL impacts SVR
• Genotype 1
Among host characteristics, that been demonstrated to decrease the rate of SVR
• Age
• Age at Infection
• Length of Infection
• Sex
• Cirrhosis,
• African American race
• Hispanic race
• Bodyweight/Obesity
• Hepatic Steatosis
Other factors that decrease response rates
• Alcohol
• Iron Overload (Hemochromatosis)
• Oxidative Stress
• Insulin Resistance
Below is what I have discovered about each of these negatives
Alcohol
Virology Journal http://www.virologyj.com/content/2/1/89
Effect of ethanol on innate antiviral pathways and HCV replication in human liver cells
Infection with Hepatitis C virus is a significant cause of morbidity and mortality throughout the world. With a propensity to progress to chronic infection, approximately 70% of patients with chronic viremia develop histological evidence of chronic liver diseases including chronic hepatitis, cirrhosis, and hepatocellular carcinoma.
The situation is even more dire for patients who abuse ethanol, where the risk of developing end stage liver disease is significantly higher as compared to HCV patients who do not drink [1,2].
Moreover, HCV-infected patients who abuse alcohol have extremely low response rates to IFN
therapy, but the mechanisms involved have not been clarified.
To model the molecular mechanisms behind this phenotype, we characterized the effects of ethanol on Jak-Stat and MAPK pathways in Huh7 human hepatoma cells, in HCV replicon cell lines, and in primary human hepatocytes.
High physiological concentrations of acute ethanol activated the Jak-Stat and p38 MAPK pathways and inhibited HCV replication in several independent replicon cell lines.
Moreover, acute ethanol induced Stat1 serine phosphorylation, which was partially mediated by the p38 MAPK pathway.
In contrast, when combined with exogenously applied IFN-a, ethanol inhibited the antiviral actions of IFN against HCV replication, involving inhibition of IFN-induced Stat1 tyrosine phosphorylation.
These effects of alcohol occurred independently of
i) alcohol metabolism via ADH and CYP2E1, and
ii) cytotoxic or cytostatic effects of ethanol.
In this model system, ethanol directly perturbs the Jak-Stat pathway, and HCV replication.
Ethanol did not appear to have significant effects on ISRE activity at 25 and 50 mM concentrations.
However, at concentrations of 100 and 200 mM, ethanol caused statistically significant 3.0 (p = 0.03) and 5.0 (p < 0.001) fold increases in ISRE reporter gene activity, as compared to cells not treated with ethanol.
The data suggest that high physiological doses of acute ethanol activate the ISRE, an IFN responsive promoter.
This study is interesting because it implies a number of things
1.If you drink while on TX then you have to wait until your liver breaks down the alcohol and clears it before IFN starts working again.
2. The Anti-Viral effect of Alcohol is probably Oxidative Stress related. Not Good.
3. This could happen with other substances
4. The Don’t drink cause its like throwing fuel on to a fire brigade have some basis for their views other than the cr@p on alternative treatment sites, They may actually have a point, although the effects of Alcohol on the IFN signalling pathways were dose related, with very little impact at the lower concentrations.
So once again it appears to be the quantity of alcohol not just alcohol per se.
5. Alcohol activates CYP2E1
Not bad for an apparently easy to treat geno type.
Now if you are a non G1 non responder there isn’t much out there specific to your genotype.
If fact looking for reasons for non response in non G1s just does your head in.
Below is what I have learnt about NR. I don’t look at Genotype much now I look more at what the virus does to us and how we contribute. I look for what is common among NRs and what is different between NRs and SVRs. Genotype doesn’t have much to do with that.
There are numerous virologic and host factors have been identified that impact the likelihood of SVR.
Viral factors impacting SVR
• Treatment Response (RVR, cEVR)
• HVL -HCV RNA above 800,000 IU/mL
More recent studies suggest above 400,000 IU/mL impacts SVR
• Genotype 1
Among host characteristics, that been demonstrated to decrease the rate of SVR
• Age
• Age at Infection
• Length of Infection
• Sex
• Cirrhosis,
• African American race
• Hispanic race
• Bodyweight/Obesity
• Hepatic Steatosis
Other factors that decrease response rates
• Alcohol
• Iron Overload (Hemochromatosis)
• Oxidative Stress
• Insulin Resistance
Below is what I have discovered about each of these negatives
Alcohol
Virology Journal http://www.virologyj.com/content/2/1/89
Effect of ethanol on innate antiviral pathways and HCV replication in human liver cells
Infection with Hepatitis C virus is a significant cause of morbidity and mortality throughout the world. With a propensity to progress to chronic infection, approximately 70% of patients with chronic viremia develop histological evidence of chronic liver diseases including chronic hepatitis, cirrhosis, and hepatocellular carcinoma.
The situation is even more dire for patients who abuse ethanol, where the risk of developing end stage liver disease is significantly higher as compared to HCV patients who do not drink [1,2].
Moreover, HCV-infected patients who abuse alcohol have extremely low response rates to IFN
therapy, but the mechanisms involved have not been clarified.
To model the molecular mechanisms behind this phenotype, we characterized the effects of ethanol on Jak-Stat and MAPK pathways in Huh7 human hepatoma cells, in HCV replicon cell lines, and in primary human hepatocytes.
High physiological concentrations of acute ethanol activated the Jak-Stat and p38 MAPK pathways and inhibited HCV replication in several independent replicon cell lines.
Moreover, acute ethanol induced Stat1 serine phosphorylation, which was partially mediated by the p38 MAPK pathway.
In contrast, when combined with exogenously applied IFN-a, ethanol inhibited the antiviral actions of IFN against HCV replication, involving inhibition of IFN-induced Stat1 tyrosine phosphorylation.
These effects of alcohol occurred independently of
i) alcohol metabolism via ADH and CYP2E1, and
ii) cytotoxic or cytostatic effects of ethanol.
In this model system, ethanol directly perturbs the Jak-Stat pathway, and HCV replication.
Ethanol did not appear to have significant effects on ISRE activity at 25 and 50 mM concentrations.
However, at concentrations of 100 and 200 mM, ethanol caused statistically significant 3.0 (p = 0.03) and 5.0 (p < 0.001) fold increases in ISRE reporter gene activity, as compared to cells not treated with ethanol.
The data suggest that high physiological doses of acute ethanol activate the ISRE, an IFN responsive promoter.
This study is interesting because it implies a number of things
1.If you drink while on TX then you have to wait until your liver breaks down the alcohol and clears it before IFN starts working again.
2. The Anti-Viral effect of Alcohol is probably Oxidative Stress related. Not Good.
3. This could happen with other substances
4. The Don’t drink cause its like throwing fuel on to a fire brigade have some basis for their views other than the cr@p on alternative treatment sites, They may actually have a point, although the effects of Alcohol on the IFN signalling pathways were dose related, with very little impact at the lower concentrations.
So once again it appears to be the quantity of alcohol not just alcohol per se.
5. Alcohol activates CYP2E1
thanks for all those great answers. Your case for metformin is formidable, my only question is do you know which oral med would be less taxing on the liver, P450 and so forth? It would seem wisdom to have approached my tx this way is view of the stats, but maybe at stage 3/4 the docs were weighing benefit vs. risk, I don't have HIV, but stage 3/4 is pretty late to start tx.. Don't know, but it did take me forever to get UND.
thanks for the GH article too. They did ease me very slowly up to a therapeutic dose, and my diet as I said was arduous. Both of these were attempts to reverse my IR and they seem to have worked.
Fatty acids and lions and bears, oh my. Well, yes, but we can get overly concerned here if we forget the liver will make it's own cholesterol if we don't eat enough. So any way we slice it there are going to be fatty acids to contend with. To lipid or not to lipid,,,that is the question.
I', not sure my GH results are optimum here as I have been so anemic that I'm viturally frozen in space and time. The procrit is only just keeping me at 10,, and so excercise is hanging up 5 blouses, and then collapsing. Hence I've lost no weight in spite of limiting calories because I'm unable to move more than 20 ft without becoming breathless. Hopefully this will get better after tx.
The thought that HCV has crossed the blood brain barrier has been around, and worrying me since my MRI. Unfortuantely my doc never even diagnosed me with anything all the years I complained. So my first guess was chronic fatique, second guess fibromyalgia, 3rd pituitary dysfunction. The latter 2 were confirmed but the first oas a real as real gets. Who knows what all can cause demylinazation....for that matter, pituitary dysfunction itself could cause such a domino throughout the body could it not?
I mean, I have neuropathy elsewhere, maybe failure to repair tissue brough on by GH deficiency causes all these changes. Maybe HCV or polio, or another virus would be the trigger, but in the end the cure needs to be kill the virus AND replace or return the gladular secretions to normal. Right?
However my HGH got down to 20% of normal we do know if cells are not replaced with healthy new cells as they need to be that eventually complete shutdown, multiple gland and organ failure, and death will follow.
It will be interesting to see if in a few years they'll have a special brain cocktail taylored to each individuals faulty signal pathways, thus rewiring via chemical pathways around the whole disease processes. Won't that be a breathe of fresh air.
it's not the getting old that's ever bothers me, it's the getting helpless and sick that nobody wants. It'll be fun to see that go by the wayside. I hope our children at least will live to see it, and get to be productive for twice as long as we've been.
You know, I read about shaken baby, whiplash, and even radiation (I grew up near the Nevada test site) causing pituitary failures, but that article was the first one to suggest viral origins. For that matter...who is to say they won't yet discover MS starts with a yet to be discovered virus.
Well, now at least when I break into Scarecrow mode...singing "If I only had a brain" we'll all know why, ain't it the truth!! LOL
thanks for the good imput!! me want imput......(short circuit loves stephanies)
mb
thanks for the GH article too. They did ease me very slowly up to a therapeutic dose, and my diet as I said was arduous. Both of these were attempts to reverse my IR and they seem to have worked.
Fatty acids and lions and bears, oh my. Well, yes, but we can get overly concerned here if we forget the liver will make it's own cholesterol if we don't eat enough. So any way we slice it there are going to be fatty acids to contend with. To lipid or not to lipid,,,that is the question.
I', not sure my GH results are optimum here as I have been so anemic that I'm viturally frozen in space and time. The procrit is only just keeping me at 10,, and so excercise is hanging up 5 blouses, and then collapsing. Hence I've lost no weight in spite of limiting calories because I'm unable to move more than 20 ft without becoming breathless. Hopefully this will get better after tx.
The thought that HCV has crossed the blood brain barrier has been around, and worrying me since my MRI. Unfortuantely my doc never even diagnosed me with anything all the years I complained. So my first guess was chronic fatique, second guess fibromyalgia, 3rd pituitary dysfunction. The latter 2 were confirmed but the first oas a real as real gets. Who knows what all can cause demylinazation....for that matter, pituitary dysfunction itself could cause such a domino throughout the body could it not?
I mean, I have neuropathy elsewhere, maybe failure to repair tissue brough on by GH deficiency causes all these changes. Maybe HCV or polio, or another virus would be the trigger, but in the end the cure needs to be kill the virus AND replace or return the gladular secretions to normal. Right?
However my HGH got down to 20% of normal we do know if cells are not replaced with healthy new cells as they need to be that eventually complete shutdown, multiple gland and organ failure, and death will follow.
It will be interesting to see if in a few years they'll have a special brain cocktail taylored to each individuals faulty signal pathways, thus rewiring via chemical pathways around the whole disease processes. Won't that be a breathe of fresh air.
it's not the getting old that's ever bothers me, it's the getting helpless and sick that nobody wants. It'll be fun to see that go by the wayside. I hope our children at least will live to see it, and get to be productive for twice as long as we've been.
You know, I read about shaken baby, whiplash, and even radiation (I grew up near the Nevada test site) causing pituitary failures, but that article was the first one to suggest viral origins. For that matter...who is to say they won't yet discover MS starts with a yet to be discovered virus.
Well, now at least when I break into Scarecrow mode...singing "If I only had a brain" we'll all know why, ain't it the truth!! LOL
thanks for the good imput!! me want imput......(short circuit loves stephanies)
mb
wow, I really appreciate you putting this altogether, and think what with CW chiming in it's turned into a great thread. My only concern is regarding the tapering in of INF.
I've read a bit on tapering, most of the studies were done before Riba was even available, and the benefit on tapering in or while on was proven to lower rates of SVR. In fact the study I read no one SVR'd. Of course INF being the only drug back then, the results may not apply as well now, yet still they are telling.
The verdict on tapering off INF at treatments end has a different set of issues and may be of great benefit, as outlined in the discussion Headed up by HR in another thread in Medhelp.
http://www.medhelp.org/posts/show/393732
if you are tapering in could you share your thinking or research on that please?
mb
I've read a bit on tapering, most of the studies were done before Riba was even available, and the benefit on tapering in or while on was proven to lower rates of SVR. In fact the study I read no one SVR'd. Of course INF being the only drug back then, the results may not apply as well now, yet still they are telling.
The verdict on tapering off INF at treatments end has a different set of issues and may be of great benefit, as outlined in the discussion Headed up by HR in another thread in Medhelp.
http://www.medhelp.org/posts/show/393732
if you are tapering in could you share your thinking or research on that please?
mb
this reminds me of the rife machine crowd material.
Infra red has been used for years in physical therapy, the benefit of penetrating heat can be helpful for certain conditions.
However, the rub on LED's is 2 fold,
1. they lose half their strength in the first 30 days of use, all Leds do, and they continue to decline from there so the benefit if any is short lived unless diodes are replaced monthly....
2 they are being marketed to people who are desparate, trying to suck several thousand each out of people with advanced diseases who haven't been helped or cured by modern medicine is the mark of a scam.
Don't beleive me? Go search for home LED light therapy machines and see what they cost. Then try to find even any lisenced medical professionals (beside chiropractors which don't count as they'll push anything) who will even use them, much less try finding a legit doc who will tell you they'll cure HCV. (When you do find the one nut out there, ask him for his research and then double check with each publication to see if it was ever even published. I've been there done that...Get back to me, I'm dying to hear your results.
mb
Infra red has been used for years in physical therapy, the benefit of penetrating heat can be helpful for certain conditions.
However, the rub on LED's is 2 fold,
1. they lose half their strength in the first 30 days of use, all Leds do, and they continue to decline from there so the benefit if any is short lived unless diodes are replaced monthly....
2 they are being marketed to people who are desparate, trying to suck several thousand each out of people with advanced diseases who haven't been helped or cured by modern medicine is the mark of a scam.
Don't beleive me? Go search for home LED light therapy machines and see what they cost. Then try to find even any lisenced medical professionals (beside chiropractors which don't count as they'll push anything) who will even use them, much less try finding a legit doc who will tell you they'll cure HCV. (When you do find the one nut out there, ask him for his research and then double check with each publication to see if it was ever even published. I've been there done that...Get back to me, I'm dying to hear your results.
mb
The clinicaltrials.gov entry for r7128 specifies the following eligibility criteria
"Genotype 1 Patients who are HCV treatment-naive, with no history of exposure to interferon, ribavirin, or direct antivirals; OR Genoytpe 2 or 3 patients who have previously been treated with interferon."
since this is marked as phase II and "recruiting" I had assumed it covers the new IIb trial as well but perhaps not - it's worth checking with them.
Overall, if ifn isn't effective, a tx regime that relies on it as little as possible seems advisable. One of the pleasant surprises from the NS3a trials was they showed improvement even among non-responders - that is even a poor ifn response was sufficient to deal with escape mutations. For r7128 that situation will improve further because of the lower level of evasion.
"Genotype 1 Patients who are HCV treatment-naive, with no history of exposure to interferon, ribavirin, or direct antivirals; OR Genoytpe 2 or 3 patients who have previously been treated with interferon."
since this is marked as phase II and "recruiting" I had assumed it covers the new IIb trial as well but perhaps not - it's worth checking with them.
Overall, if ifn isn't effective, a tx regime that relies on it as little as possible seems advisable. One of the pleasant surprises from the NS3a trials was they showed improvement even among non-responders - that is even a poor ifn response was sufficient to deal with escape mutations. For r7128 that situation will improve further because of the lower level of evasion.
Regarding your white brain spots.....
White spots found on MRI in the brain's myelinated neurons, similar but smaller than those on the brains of multiple sclerosis patients....are also found on Polio survivors and Chronic Fatigue Syndrome patients.....and are related to Growth Hormone deficiency.
Co
http://books.google.com/books?id=t8i4e_q3Gj0C&pg=PA289&lpg=PA289&dq=growth+hormone+deficiency+and+white+brain+spots&source=web&ots=i22g7qnk1C&sig=h432hU-84L35IisVrq1-lyhcYSA&hl=en&sa=X&oi=book_result&resnum=2&ct=result
"I love the idea in theory that an oral med could reduce insulin resistance and increase EVR. However, I was interested in this prior to treatment and told by my endocrinologist, GP, and hepatologist that these were all very hard on the liver and should not be considered for liver diseased patients."
----------------------
Actually, some studies have shown that insulin sensitizers are safe for HCV patients (but Metformin is not recommended for patients with HIV because of the risk of lactic acidosis). From AASLD Nov 2008......
Assessing Hepatotoxicity of Thiazolidinediones (TZDs), Metformin, and/or Statin Therapy in Chronic Hepatitis C (HCV) Patients
H. Han, A.S. Boxer, M. Adler, J.L. Matloff, D.C. Carriero, M. Vachon, D.T. Dieterich, , Mount Sinai Medical Center, New York, NY;
Purpose: Patients over the age of 40 with Hepatitis C (HCV) have a three-fold higher prevalence of Type 2 diabetes (T2DM) than those without HCV. In addition, glucose abnormalities are associated with a poorer virologic response in chronic HCV patients. Attempts to improve insulin sensitivity prior to or during combination pegylated interferon and ribavirin therapy may result in a higher rate of viral response to HCV treatment. The aim of the study is to assess hepatic safety of insulin sensitizers such as TZDs and metformin, and/or cholesterol lowering agents like statins when used in patients with chronic HCV, prior to HCV treatment. Methods: IRB-approved, retrospective chart review from 2002 to 2007 of patients at a liver clinic in our center with chronic HCV treated with at least one of the study medications. We examined variations in ALT, AST, GGT, HDL, LDL and total cholesterol, triglycerides (TG), HbA1C, and calculated HOMA-IR at baseline and after 3 to 6 months of therapy. The Student T-Test was used to compare pre-treatment and post-treatment parameters. Results: Fifty-two patients (73% males, ages 36-68), of which 32 were on TZDs, 14 on metformin, and 6 on statins, were included for analysis. Compared to the pre-treatment, the post-treatment group evidenced a decreased trend in all biochemical parameters except for TG and HDL cholesterol. There was a statistically significant (p<0.05) decrease in calculated HOMA-IR from 7.37 (8.28) to 2.40 (0.87) after 3 to 6 months of treatment, and HbA1C declined from 5.44 (1.11) to 5.29 (0.82) %. ALT, AST, and GGT levels improved from 83.56 (82.47) to 65.92 (46.04) IU/L, 78.44 (66.76) to 65.77 (42.11) IU/L, and 139.48 (132.60) to 136.84 (202.38) IU/L, respectively. Total and LDL cholesterol also showed a trend downwards from pre-treatment (167.63 [37.69] and 82.65 [29.73] mg/dL, respectively) to post-treatment (162.55 [35.16] and 77.86 [27.21] mg/dL, respectively). TG and HDL values trended up from 163.85 (97.52) to 171.04 (127.99) mg/dL and from 49.59 (17.91) to 49.93 (19.99) mg/dL, respectively. There was no significant change in BMI from pre-treatment, 28.38 [5.72], to post-treatment, 28.04 [4.24] kg/m^2. No patients discontinued medications because of liver-related side effects. Conclusions: The decreasing trends in ALT, AST, GGT, and total cholesterol with the use of TZDs, metformin, and/or statins demonstrate the relative safety of these agents in HCV patients. The significant decrease in calculated HOMA-IR with insulin sensitizers given before HCV therapy may indicate a role for them in improving treatment response in HCV patients. A randomized study is underway.
"This is important in that getting to the root cause or the missing hormone most likely to be the culprit in causing diebetes makes more sense than insulin replacement"
------------------------
Untreated GH deficiency is associated with insulin resistance....but short-term (<6 months) GH replacement can decrease insulin sensitivity further.
GH replacement therapy increases lipolysis, thereby increasing circulating free fatty acid (FFA) concentrations. These increased FFA concentrations may decrease the uptake of glucose in skeletal muscle.
Therefore, the increased lipolysis induced by GH replacement therapy seems to be a sword with two edges in terms of insulin sensitivity. The short-term effect, with increased lipid oxidation and increased circulating free fatty acid levels, deteriorates insulin sensitivity. The long-term effect, with a reduction in body fat, is beneficial for insulin sensitivity.
"Growth Hormone Replacement Therapy and Insulin Sensitivity"
http://jcem.endojournals.org/cgi/content/full/88/4/1453
You know....the same fatty acids used by the Hepatitis C virus to make its outer coating.
In cellular metabolism, glucose (sugar) can be converted into fatty acids. Many viruses use these fatty acids to build their viral envelopes, or outer coatings, which help the viruses penetrate and infect human cells.
When the Hepatitis C virus gets into your body, it tries to increase your metabolism so that it can reproduce more quickly by using fatty acids to build protective outer coatings which will help it penetrate and infect your liver cells.
And one of the ways to create more glucose that can be converted into fatty acids, is by making you insulin resistant and eventually turning you into a diabetic.
BTW, you don't treat insulin resistance with insulin. Insulin resistance leads to hyperinsulinemia ...too much insulin (which makes interferon ineffectve). The last thing you would want to do is increase the insulin even more.
"I will say I also watched my diet rather arduously for the first few months, but I did an experiment at chistmas, and an increase in sugars caused not one bump in my BS levels."
-----------------------
When the Hepatitis C virus makes you insensitive to insulin, the pancreas has to produce larger amounts of insulin to keep your blood sugar under control (and sometimes, it makes too much, that's why some people have transient hypoglycemia) ....and you end up with hyperinsulinemia.....TOO MUCH insulin.....and having too much insulin, makes interferon ineffective
The problem isn't really the sugar you eat but the large amounts of insulin that are produced every time you eat all that sugar. So don't do that again.
So I'm fairly convinced insulin resistance has more than one possible way of being corrected. The question now is how to convince the medical community that one therapy may be superior and less toxic than another.
----------------------
First we have to convince them to test people to see if they have insulin resistance, and so far we're not doing well with that. And as I'm sure Jim would say, diet and exercise are not toxic...LOL and they should be the first measures used to improve insulin resistance.
Co
----------------------
Actually, some studies have shown that insulin sensitizers are safe for HCV patients (but Metformin is not recommended for patients with HIV because of the risk of lactic acidosis). From AASLD Nov 2008......
Assessing Hepatotoxicity of Thiazolidinediones (TZDs), Metformin, and/or Statin Therapy in Chronic Hepatitis C (HCV) Patients
H. Han, A.S. Boxer, M. Adler, J.L. Matloff, D.C. Carriero, M. Vachon, D.T. Dieterich, , Mount Sinai Medical Center, New York, NY;
Purpose: Patients over the age of 40 with Hepatitis C (HCV) have a three-fold higher prevalence of Type 2 diabetes (T2DM) than those without HCV. In addition, glucose abnormalities are associated with a poorer virologic response in chronic HCV patients. Attempts to improve insulin sensitivity prior to or during combination pegylated interferon and ribavirin therapy may result in a higher rate of viral response to HCV treatment. The aim of the study is to assess hepatic safety of insulin sensitizers such as TZDs and metformin, and/or cholesterol lowering agents like statins when used in patients with chronic HCV, prior to HCV treatment. Methods: IRB-approved, retrospective chart review from 2002 to 2007 of patients at a liver clinic in our center with chronic HCV treated with at least one of the study medications. We examined variations in ALT, AST, GGT, HDL, LDL and total cholesterol, triglycerides (TG), HbA1C, and calculated HOMA-IR at baseline and after 3 to 6 months of therapy. The Student T-Test was used to compare pre-treatment and post-treatment parameters. Results: Fifty-two patients (73% males, ages 36-68), of which 32 were on TZDs, 14 on metformin, and 6 on statins, were included for analysis. Compared to the pre-treatment, the post-treatment group evidenced a decreased trend in all biochemical parameters except for TG and HDL cholesterol. There was a statistically significant (p<0.05) decrease in calculated HOMA-IR from 7.37 (8.28) to 2.40 (0.87) after 3 to 6 months of treatment, and HbA1C declined from 5.44 (1.11) to 5.29 (0.82) %. ALT, AST, and GGT levels improved from 83.56 (82.47) to 65.92 (46.04) IU/L, 78.44 (66.76) to 65.77 (42.11) IU/L, and 139.48 (132.60) to 136.84 (202.38) IU/L, respectively. Total and LDL cholesterol also showed a trend downwards from pre-treatment (167.63 [37.69] and 82.65 [29.73] mg/dL, respectively) to post-treatment (162.55 [35.16] and 77.86 [27.21] mg/dL, respectively). TG and HDL values trended up from 163.85 (97.52) to 171.04 (127.99) mg/dL and from 49.59 (17.91) to 49.93 (19.99) mg/dL, respectively. There was no significant change in BMI from pre-treatment, 28.38 [5.72], to post-treatment, 28.04 [4.24] kg/m^2. No patients discontinued medications because of liver-related side effects. Conclusions: The decreasing trends in ALT, AST, GGT, and total cholesterol with the use of TZDs, metformin, and/or statins demonstrate the relative safety of these agents in HCV patients. The significant decrease in calculated HOMA-IR with insulin sensitizers given before HCV therapy may indicate a role for them in improving treatment response in HCV patients. A randomized study is underway.
"This is important in that getting to the root cause or the missing hormone most likely to be the culprit in causing diebetes makes more sense than insulin replacement"
------------------------
Untreated GH deficiency is associated with insulin resistance....but short-term (<6 months) GH replacement can decrease insulin sensitivity further.
GH replacement therapy increases lipolysis, thereby increasing circulating free fatty acid (FFA) concentrations. These increased FFA concentrations may decrease the uptake of glucose in skeletal muscle.
Therefore, the increased lipolysis induced by GH replacement therapy seems to be a sword with two edges in terms of insulin sensitivity. The short-term effect, with increased lipid oxidation and increased circulating free fatty acid levels, deteriorates insulin sensitivity. The long-term effect, with a reduction in body fat, is beneficial for insulin sensitivity.
"Growth Hormone Replacement Therapy and Insulin Sensitivity"
http://jcem.endojournals.org/cgi/content/full/88/4/1453
You know....the same fatty acids used by the Hepatitis C virus to make its outer coating.
In cellular metabolism, glucose (sugar) can be converted into fatty acids. Many viruses use these fatty acids to build their viral envelopes, or outer coatings, which help the viruses penetrate and infect human cells.
When the Hepatitis C virus gets into your body, it tries to increase your metabolism so that it can reproduce more quickly by using fatty acids to build protective outer coatings which will help it penetrate and infect your liver cells.
And one of the ways to create more glucose that can be converted into fatty acids, is by making you insulin resistant and eventually turning you into a diabetic.
BTW, you don't treat insulin resistance with insulin. Insulin resistance leads to hyperinsulinemia ...too much insulin (which makes interferon ineffectve). The last thing you would want to do is increase the insulin even more.
"I will say I also watched my diet rather arduously for the first few months, but I did an experiment at chistmas, and an increase in sugars caused not one bump in my BS levels."
-----------------------
When the Hepatitis C virus makes you insensitive to insulin, the pancreas has to produce larger amounts of insulin to keep your blood sugar under control (and sometimes, it makes too much, that's why some people have transient hypoglycemia) ....and you end up with hyperinsulinemia.....TOO MUCH insulin.....and having too much insulin, makes interferon ineffective
The problem isn't really the sugar you eat but the large amounts of insulin that are produced every time you eat all that sugar. So don't do that again.
So I'm fairly convinced insulin resistance has more than one possible way of being corrected. The question now is how to convince the medical community that one therapy may be superior and less toxic than another.
----------------------
First we have to convince them to test people to see if they have insulin resistance, and so far we're not doing well with that. And as I'm sure Jim would say, diet and exercise are not toxic...LOL and they should be the first measures used to improve insulin resistance.
Co
"R7128 is *finally* moving to phase IIb. The trial, as was the case for phase I, will enroll previous non-responders but only G2/G3s"
----------------
It says the trial will enroll naive Genotypes 1 and 4.....
"The phase 2b trial is anticipated to enroll about 400 treatment naive, genotype-1 or genotype 4 HCV-infected patients."
Co
----------------
It says the trial will enroll naive Genotypes 1 and 4.....
"The phase 2b trial is anticipated to enroll about 400 treatment naive, genotype-1 or genotype 4 HCV-infected patients."
Co
have to confess I haven't been following the insulin vs non-response issue at all, so this may not be applicable. However, if you haven't already seen this, you may want to take a look of the new Roche/Pharmasset press release
http://investor.pharmasset.com/releasedetail.cfm?ReleaseID=358626
R7128 is *finally* moving to phase IIb. The trial, as was the case for phase I, will enroll previous non-responders but only G2/G3s. IMHO, R7128 is the most promising PI candidate out there. The RVR stats speak for themselves (90% RVR among G2/G3 non-responders in phase I).
http://investor.pharmasset.com/releasedetail.cfm?ReleaseID=358626
R7128 is *finally* moving to phase IIb. The trial, as was the case for phase I, will enroll previous non-responders but only G2/G3s. IMHO, R7128 is the most promising PI candidate out there. The RVR stats speak for themselves (90% RVR among G2/G3 non-responders in phase I).
Susan
Some info for you from the American Diabetes Association.
Standards of Medical Care in Diabetes—2009
American Diabetes Association
http://care.diabetesjournals.org/cgi/reprint/32/Supplement_1/S13
Diagnosis of pre-diabetes
Hyperglycemia not sufficient to meet the diagnostic criteria for diabetes is categorized as either
(IFG) impaired fasting glucose
(IGT), impaired glucose tolerance
depending on whether it is identified through the FPG or the OGTT:
● IFG = FPG 100 mg/dl (5.6 mmol/l) to 125 mg/dl (6.9 mmol/l)
● IGT = 2-h plasma glucose 140 mg/dl (7.8 mmol/l) to 199 mg/dl (11.0 mmol/l)
IFG and IGT have been officially termed “pre-diabetes.”
Both categories of prediabetes are risk factors for future diabetes and for cardiovascular disease (CVD) (7).
Insulin Resistance and Pre-Diabetes
http://diabetes.niddk.nih.gov/DM/pubs/insulinresistance/
How are insulin resistance and pre-diabetes diagnosed?
Health care providers use blood tests to determine whether a person has pre-diabetes but do not usually test for insulin resistance. Insulin resistance can be assessed by measuring the level of insulin in the blood. However, the test that most accurately measures insulin resistance, called the euglycemic clamp, is too costly and complicated to be used in most doctors' offices. The clamp is a research tool used by scientists to learn more about glucose metabolism.
If tests indicate pre-diabetes or metabolic syndrome, insulin resistance most likely is present.
Diabetes and pre-diabetes can be detected with one of the following tests:
• Fasting glucose test. This test measures blood glucose in people who have not eaten anything for at least 8 hours. This test is most reliable when done in the morning.
Fasting glucose levels of 100 to 125 mg/dL are above normal but not high enough to be called diabetes.
This condition is called pre-diabetes or IFG.
People with IFG often have had insulin resistance for some time.
They are much more likely to develop diabetes than people with normal blood glucose levels.
• Glucose tolerance test. This test measures blood glucose after people fast for at least 8 hours and 2 hours after they drink a sweet liquid provided by a doctor or laboratory.
A blood glucose level between 140 and 199 mg/dL means glucose tolerance is not normal but is not high enough for a diagnosis of diabetes.
This form of pre-diabetes is called IGT and, like IFG, it points toward a history of insulin resistance and a risk for developing diabetes.
Frequently Asked Questions about Pre-Diabetes
American Diabetes Association
http://www.diabetes.org/pre-diabetes/faq.jsp
Q: How does the FPG test define diabetes and pre-diabetes?
A Normal fasting blood glucose is below 100 mg/dl. A person with pre-diabetes has a fasting blood glucose level between 100 and 125 mg/dl. If the blood glucose level rises to 126 mg/dl or above, a person has diabetes.
Q: How do I know if I have pre-diabetes?
A: Doctors can use either the fasting plasma glucose test (FPG) or the oral glucose tolerance test (OGTT) to detect pre-diabetes. Both require a person to fast overnight. In the FPG test, a person's blood glucose is measured first thing in the morning before eating.
Q: Which test is better?
A: According to the expert panel, either test is appropriate to identify pre-diabetes.
Risk factors for diabetes or pre-diabetes.
These include:
high blood pressure,
low HDL cholesterol and high triglycerides,
a family history of diabetes,
a history of gestational diabetes or giving birth to a baby weighing more than 9 pounds, or belonging to an ethnic or minority group at high risk for diabetes.
CS
Some info for you from the American Diabetes Association.
Standards of Medical Care in Diabetes—2009
American Diabetes Association
http://care.diabetesjournals.org/cgi/reprint/32/Supplement_1/S13
Diagnosis of pre-diabetes
Hyperglycemia not sufficient to meet the diagnostic criteria for diabetes is categorized as either
(IFG) impaired fasting glucose
(IGT), impaired glucose tolerance
depending on whether it is identified through the FPG or the OGTT:
● IFG = FPG 100 mg/dl (5.6 mmol/l) to 125 mg/dl (6.9 mmol/l)
● IGT = 2-h plasma glucose 140 mg/dl (7.8 mmol/l) to 199 mg/dl (11.0 mmol/l)
IFG and IGT have been officially termed “pre-diabetes.”
Both categories of prediabetes are risk factors for future diabetes and for cardiovascular disease (CVD) (7).
Insulin Resistance and Pre-Diabetes
http://diabetes.niddk.nih.gov/DM/pubs/insulinresistance/
How are insulin resistance and pre-diabetes diagnosed?
Health care providers use blood tests to determine whether a person has pre-diabetes but do not usually test for insulin resistance. Insulin resistance can be assessed by measuring the level of insulin in the blood. However, the test that most accurately measures insulin resistance, called the euglycemic clamp, is too costly and complicated to be used in most doctors' offices. The clamp is a research tool used by scientists to learn more about glucose metabolism.
If tests indicate pre-diabetes or metabolic syndrome, insulin resistance most likely is present.
Diabetes and pre-diabetes can be detected with one of the following tests:
• Fasting glucose test. This test measures blood glucose in people who have not eaten anything for at least 8 hours. This test is most reliable when done in the morning.
Fasting glucose levels of 100 to 125 mg/dL are above normal but not high enough to be called diabetes.
This condition is called pre-diabetes or IFG.
People with IFG often have had insulin resistance for some time.
They are much more likely to develop diabetes than people with normal blood glucose levels.
• Glucose tolerance test. This test measures blood glucose after people fast for at least 8 hours and 2 hours after they drink a sweet liquid provided by a doctor or laboratory.
A blood glucose level between 140 and 199 mg/dL means glucose tolerance is not normal but is not high enough for a diagnosis of diabetes.
This form of pre-diabetes is called IGT and, like IFG, it points toward a history of insulin resistance and a risk for developing diabetes.
Frequently Asked Questions about Pre-Diabetes
American Diabetes Association
http://www.diabetes.org/pre-diabetes/faq.jsp
Q: How does the FPG test define diabetes and pre-diabetes?
A Normal fasting blood glucose is below 100 mg/dl. A person with pre-diabetes has a fasting blood glucose level between 100 and 125 mg/dl. If the blood glucose level rises to 126 mg/dl or above, a person has diabetes.
Q: How do I know if I have pre-diabetes?
A: Doctors can use either the fasting plasma glucose test (FPG) or the oral glucose tolerance test (OGTT) to detect pre-diabetes. Both require a person to fast overnight. In the FPG test, a person's blood glucose is measured first thing in the morning before eating.
Q: Which test is better?
A: According to the expert panel, either test is appropriate to identify pre-diabetes.
Risk factors for diabetes or pre-diabetes.
These include:
high blood pressure,
low HDL cholesterol and high triglycerides,
a family history of diabetes,
a history of gestational diabetes or giving birth to a baby weighing more than 9 pounds, or belonging to an ethnic or minority group at high risk for diabetes.
CS
Susan
http://care.diabetesjournals.org/cgi/reprint/32/Supplement_1/S62
Diagnosis of diabetes
Current criteria for the diagnosis of diabetes in nonpregnant adults are shown in Table 2.
Three ways to diagnose diabetes are recommended at the time of this statement, and each must be confirmed on a subsequent day unless unequivocal symptoms of hyperglycemia are present.
Although the 75-g oral glucose tolerance test (OGTT) is more sensitive and modestly more specific than the fasting plasma glucose (FPG) to diagnose diabetes, it is poorly reproducible and difficult to perform in practice.
Its boring but I wouldn’t say its difficult to perform.
It’s the waiting around for 2 or 3 hours that’s the main issue with it. Bring something to read.
Because of ease of use, acceptability to patients, and lower cost, the FPG has been the preferred diagnostic test.
Though FPG is less sensitive than the OGTT, the vast majority of people who do not meet diagnostic criteria for diabetes by FPG but would by OGTT will have an A1C value well under 7.0% (6).
Vast Majority is not everyone. You might be able to use this.
Though the OGTT is not recommended for routine clinical use, it may be useful for further evaluation of patients in whom diabetes is still strongly suspected but who have normal FPG or IFG (see Section I.C).
http://care.diabetesjournals.org/cgi/reprint/32/Supplement_1/S13
CLASSIFICATION AND DIAGNOSIS
Patients with IFG and/or IGT are now referred to as having “pre-diabetes” indicating the relatively high risk for development of diabetes in these patients. In the absence of pregnancy, IFG and IGT are not clinical entities in their own right but rather risk factors for future diabetes as well as cardiovascular disease.
They can be observed as intermediate stages in any of the disease processes listed in Table 1. IFG and IGT are associated with the metabolic syndrome, which includes obesity (especially abdominal or visceral obesity), dyslipidemia of the high-triglyceride and/or low-HDL type, and hypertension.
Now you don’t have Metabolic Syndrome, which is why your Dr’s don’t see you as having a problem. But you need to understand we are not trying to diagnose Diabetes here.
What we need to know is how Insulin Resistant we are so we know what our IFN response is likely to be.
Once you know you are IR then you can do something about it. Now you are already doing the classical things such as diet and exercise and they aren’t doing much.
Why because it’s the virus that is causing your IR.
You can reduce this by taking the following supplements
Resveratrol, ALA, NAC, Tarine. Astragalus and Stevia would also be good.
Most of HR’s other sups would be a good idea as well. But not PPC it goes off to easy.
Now you need an Insulin test done.
I have no idea why Insulin tests are so hard to get but they are.
Its going to be up to you to convince your Dr’s that you need this.
Actively manage your own care, so to speak.
Try and get them to give you an Oral Glucose Tolerance Test (OGTT).
And make sure insulin is being done with it.
This is used to diagnose Diabetes but will give us useful information, as well.
Your FPG is high enough to make this a worthwhile test.
It is more accurate than FPG but more expensive and time consuming.
Remember your Doctor is trying to diagnose Diabetes we are not.
CS
http://care.diabetesjournals.org/cgi/reprint/32/Supplement_1/S62
Diagnosis of diabetes
Current criteria for the diagnosis of diabetes in nonpregnant adults are shown in Table 2.
Three ways to diagnose diabetes are recommended at the time of this statement, and each must be confirmed on a subsequent day unless unequivocal symptoms of hyperglycemia are present.
Although the 75-g oral glucose tolerance test (OGTT) is more sensitive and modestly more specific than the fasting plasma glucose (FPG) to diagnose diabetes, it is poorly reproducible and difficult to perform in practice.
Its boring but I wouldn’t say its difficult to perform.
It’s the waiting around for 2 or 3 hours that’s the main issue with it. Bring something to read.
Because of ease of use, acceptability to patients, and lower cost, the FPG has been the preferred diagnostic test.
Though FPG is less sensitive than the OGTT, the vast majority of people who do not meet diagnostic criteria for diabetes by FPG but would by OGTT will have an A1C value well under 7.0% (6).
Vast Majority is not everyone. You might be able to use this.
Though the OGTT is not recommended for routine clinical use, it may be useful for further evaluation of patients in whom diabetes is still strongly suspected but who have normal FPG or IFG (see Section I.C).
http://care.diabetesjournals.org/cgi/reprint/32/Supplement_1/S13
CLASSIFICATION AND DIAGNOSIS
Patients with IFG and/or IGT are now referred to as having “pre-diabetes” indicating the relatively high risk for development of diabetes in these patients. In the absence of pregnancy, IFG and IGT are not clinical entities in their own right but rather risk factors for future diabetes as well as cardiovascular disease.
They can be observed as intermediate stages in any of the disease processes listed in Table 1. IFG and IGT are associated with the metabolic syndrome, which includes obesity (especially abdominal or visceral obesity), dyslipidemia of the high-triglyceride and/or low-HDL type, and hypertension.
Now you don’t have Metabolic Syndrome, which is why your Dr’s don’t see you as having a problem. But you need to understand we are not trying to diagnose Diabetes here.
What we need to know is how Insulin Resistant we are so we know what our IFN response is likely to be.
Once you know you are IR then you can do something about it. Now you are already doing the classical things such as diet and exercise and they aren’t doing much.
Why because it’s the virus that is causing your IR.
You can reduce this by taking the following supplements
Resveratrol, ALA, NAC, Tarine. Astragalus and Stevia would also be good.
Most of HR’s other sups would be a good idea as well. But not PPC it goes off to easy.
Now you need an Insulin test done.
I have no idea why Insulin tests are so hard to get but they are.
Its going to be up to you to convince your Dr’s that you need this.
Actively manage your own care, so to speak.
Try and get them to give you an Oral Glucose Tolerance Test (OGTT).
And make sure insulin is being done with it.
This is used to diagnose Diabetes but will give us useful information, as well.
Your FPG is high enough to make this a worthwhile test.
It is more accurate than FPG but more expensive and time consuming.
Remember your Doctor is trying to diagnose Diabetes we are not.
CS
Susan
http://care.diabetesjournals.org/cgi/reprint/32/Supplement_1/S62
Diagnosis of diabetes
Current criteria for the diagnosis of diabetes in nonpregnant adults are shown in Table 2.
Three ways to diagnose diabetes are recommended at the time of this statement, and each must be confirmed on a subsequent day unless unequivocal symptoms of hyperglycemia are present.
Although the 75-g oral glucose tolerance test (OGTT) is more sensitive and modestly more specific than the fasting plasma glucose (FPG) to diagnose diabetes, it is poorly reproducible and difficult to perform in practice.
Its boring but I wouldn’t say its difficult to perform.
It’s the waiting around for 2 or 3 hours that’s the main issue with it. Bring something to read.
Because of ease of use, acceptability to patients, and lower cost, the FPG has been the preferred diagnostic test.
Though FPG is less sensitive than the OGTT, the vast majority of people who do not meet diagnostic criteria for diabetes by FPG but would by OGTT will have an A1C value well under 7.0% (6).
Vast Majority is not everyone. You might be able to use this.
Though the OGTT is not recommended for routine clinical use, it may be useful for further evaluation of patients in whom diabetes is still strongly suspected but who have normal FPG or IFG (see Section I.C).
http://care.diabetesjournals.org/cgi/reprint/32/Supplement_1/S13
CLASSIFICATION AND DIAGNOSIS
Patients with IFG and/or IGT are now referred to as having “pre-diabetes” indicating the relatively high risk for development of diabetes in these patients. In the absence of pregnancy, IFG and IGT are not clinical entities in their own right but rather risk factors for future diabetes as well as cardiovascular disease.
They can be observed as intermediate stages in any of the disease processes listed in Table 1. IFG and IGT are associated with the metabolic syndrome, which includes obesity (especially abdominal or visceral obesity), dyslipidemia of the high-triglyceride and/or low-HDL type, and hypertension.
Now you don’t have Metabolic Syndrome, which is why your Dr’s don’t see you as having a problem. But you need to understand we are not trying to diagnose Diabetes here.
What we need to know is how Insulin Resistant we are so we know what our IFN response is likely to be.
Once you know you are IR then you can do something about it. Now you are already doing the classical things such as diet and exercise and they aren’t doing much.
Why because it’s the virus that is causing your IR.
You can reduce this by taking the following supplements
Resveratrol, ALA, NAC, Tarine. Astragalus and Stevia would also be good.
Most of HR’s other sups would be a good idea as well. But not PPC it goes off to easy.
Now you need an Insulin test done.
I have no idea why Insulin tests are so hard to get but they are.
Its going to be up to you to convince your Dr’s that you need this.
Actively manage your own care, so to speak.
Try and get them to give you an Oral Glucose Tolerance Test (OGTT).
And make sure insulin is being done with it.
This is used to diagnose Diabetes but will give us useful information, as well.
Your FPG is high enough to make this a worthwhile test.
It is more accurate than FPG but more expensive and time consuming.
Remember your Doctor is trying to diagnose Diabetes we are not.
CS
http://care.diabetesjournals.org/cgi/reprint/32/Supplement_1/S62
Diagnosis of diabetes
Current criteria for the diagnosis of diabetes in nonpregnant adults are shown in Table 2.
Three ways to diagnose diabetes are recommended at the time of this statement, and each must be confirmed on a subsequent day unless unequivocal symptoms of hyperglycemia are present.
Although the 75-g oral glucose tolerance test (OGTT) is more sensitive and modestly more specific than the fasting plasma glucose (FPG) to diagnose diabetes, it is poorly reproducible and difficult to perform in practice.
Its boring but I wouldn’t say its difficult to perform.
It’s the waiting around for 2 or 3 hours that’s the main issue with it. Bring something to read.
Because of ease of use, acceptability to patients, and lower cost, the FPG has been the preferred diagnostic test.
Though FPG is less sensitive than the OGTT, the vast majority of people who do not meet diagnostic criteria for diabetes by FPG but would by OGTT will have an A1C value well under 7.0% (6).
Vast Majority is not everyone. You might be able to use this.
Though the OGTT is not recommended for routine clinical use, it may be useful for further evaluation of patients in whom diabetes is still strongly suspected but who have normal FPG or IFG (see Section I.C).
http://care.diabetesjournals.org/cgi/reprint/32/Supplement_1/S13
CLASSIFICATION AND DIAGNOSIS
Patients with IFG and/or IGT are now referred to as having “pre-diabetes” indicating the relatively high risk for development of diabetes in these patients. In the absence of pregnancy, IFG and IGT are not clinical entities in their own right but rather risk factors for future diabetes as well as cardiovascular disease.
They can be observed as intermediate stages in any of the disease processes listed in Table 1. IFG and IGT are associated with the metabolic syndrome, which includes obesity (especially abdominal or visceral obesity), dyslipidemia of the high-triglyceride and/or low-HDL type, and hypertension.
Now you don’t have Metabolic Syndrome, which is why your Dr’s don’t see you as having a problem. But you need to understand we are not trying to diagnose Diabetes here.
What we need to know is how Insulin Resistant we are so we know what our IFN response is likely to be.
Once you know you are IR then you can do something about it. Now you are already doing the classical things such as diet and exercise and they aren’t doing much.
Why because it’s the virus that is causing your IR.
You can reduce this by taking the following supplements
Resveratrol, ALA, NAC, Tarine. Astragalus and Stevia would also be good.
Most of HR’s other sups would be a good idea as well. But not PPC it goes off to easy.
Now you need an Insulin test done.
I have no idea why Insulin tests are so hard to get but they are.
Its going to be up to you to convince your Dr’s that you need this.
Actively manage your own care, so to speak.
Try and get them to give you an Oral Glucose Tolerance Test (OGTT).
And make sure insulin is being done with it.
This is used to diagnose Diabetes but will give us useful information, as well.
Your FPG is high enough to make this a worthwhile test.
It is more accurate than FPG but more expensive and time consuming.
Remember your Doctor is trying to diagnose Diabetes we are not.
CS
http://care.diabetesjournals.org/cgi/reprint/32/Supplement_1/S62
Diagnosis of diabetes
Current criteria for the diagnosis of diabetes in nonpregnant adults are shown in Table 2.
Three ways to diagnose diabetes are recommended at the time of this statement, and each must be confirmed on a subsequent day unless unequivocal symptoms of hyperglycemia are present.
Although the 75-g oral glucose tolerance test (OGTT) is more sensitive and modestly more specific than the fasting plasma glucose (FPG) to diagnose diabetes, it is poorly reproducible and difficult to perform in practice.
Its boring but I wouldn’t say its difficult to perform.
It’s the waiting around for 2 or 3 hours that’s the main issue with it. Bring something to read.
Because of ease of use, acceptability to patients, and lower cost, the FPG has been the preferred diagnostic test.
Though FPG is less sensitive than the OGTT, the vast majority of people who do not meet diagnostic criteria for diabetes by FPG but would by OGTT will have an A1C value well under 7.0% (6).
Vast Majority is not everyone. You might be able to use this.
Though the OGTT is not recommended for routine clinical use, it may be useful for further evaluation of patients in whom diabetes is still strongly suspected but who have normal FPG or IFG (see Section I.C).
http://care.diabetesjournals.org/cgi/reprint/32/Supplement_1/S13
CLASSIFICATION AND DIAGNOSIS
Patients with IFG and/or IGT are now referred to as having “pre-diabetes” indicating the relatively high risk for development of diabetes in these patients. In the absence of pregnancy, IFG and IGT are not clinical entities in their own right but rather risk factors for future diabetes as well as cardiovascular disease.
They can be observed as intermediate stages in any of the disease processes listed in Table 1. IFG and IGT are associated with the metabolic syndrome, which includes obesity (especially abdominal or visceral obesity), dyslipidemia of the high-triglyceride and/or low-HDL type, and hypertension.
Now you don’t have Metabolic Syndrome, which is why your Dr’s don’t see you as having a problem. But you need to understand we are not trying to diagnose Diabetes here.
What we need to know is how Insulin Resistant we are so we know what our IFN response is likely to be.
Once you know you are IR then you can do something about it. Now you are already doing the classical things such as diet and exercise and they aren’t doing much.
Why because it’s the virus that is causing your IR.
You can reduce this by taking the following supplements
Resveratrol, ALA, NAC, Tarine. Astragalus and Stevia would also be good.
Most of HR’s other sups would be a good idea as well. But not PPC it goes off to easy.
Now you need an Insulin test done.
I have no idea why Insulin tests are so hard to get but they are.
Its going to be up to you to convince your Dr’s that you need this.
Actively manage your own care, so to speak.
Try and get them to give you an Oral Glucose Tolerance Test (OGTT).
And make sure insulin is being done with it.
This is used to diagnose Diabetes but will give us useful information, as well.
Your FPG is high enough to make this a worthwhile test.
It is more accurate than FPG but more expensive and time consuming.
Remember your Doctor is trying to diagnose Diabetes we are not.
CS
Diagnosis of diabetes
Current criteria for the diagnosis of diabetes in nonpregnant adults are shown in Table 2.
Three ways to diagnose diabetes are recommended at the time of this statement, and each must be confirmed on a subsequent day unless unequivocal symptoms of hyperglycemia are present.
Although the 75-g oral glucose tolerance test (OGTT) is more sensitive and modestly more specific than the fasting plasma glucose (FPG) to diagnose diabetes, it is poorly reproducible and difficult to perform in practice.
Its boring but I wouldn’t say its difficult to perform.
It’s the waiting around for 2 or 3 hours that’s the main issue with it. Bring something to read.
Because of ease of use, acceptability to patients, and lower cost, the FPG has been the preferred diagnostic test.
Though FPG is less sensitive than the OGTT, the vast majority of people who do not meet diagnostic criteria for diabetes by FPG but would by OGTT will have an A1C value well under 7.0% (6).
Vast Majority is not everyone. You might be able to use this.
Though the OGTT is not recommended for routine clinical use, it may be useful for further evaluation of patients in whom diabetes is still strongly suspected but who have normal FPG or IFG (see Section I.C).
http://care.diabetesjournals.org/cgi/reprint/32/Supplement_1/S13
CLASSIFICATION AND DIAGNOSIS
Patients with IFG and/or IGT are now referred to as having “pre-diabetes” indicating the relatively high risk for development of diabetes in these patients. In the absence of pregnancy, IFG and IGT are not clinical entities in their own right but rather risk factors for future diabetes as well as cardiovascular disease.
They can be observed as intermediate stages in any of the disease processes listed in Table 1. IFG and IGT are associated with the metabolic syndrome, which includes obesity (especially abdominal or visceral obesity), dyslipidemia of the high-triglyceride and/or low-HDL type, and hypertension.
Now you don’t have Metabolic Syndrome, which is why your Dr’s don’t see you as having a problem. But you need to understand we are not trying to diagnose Diabetes here.
What we need to know is how Insulin Resistant we are so we know what our IFN response is likely to be.
Once you know you are IR then you can do something about it. Now you are already doing the classical things such as diet and exercise and they aren’t doing much.
Why because it’s the virus that is causing your IR.
You can reduce this by taking the following supplements
Resveratrol, ALA, NAC, Tarine. Astragalus and Stevia would also be good.
Most of HR’s other sups would be a good idea as well. But not PPC it goes off to easy.
Now you need an Insulin test done.
I have no idea why Insulin tests are so hard to get but they are.
Its going to be up to you to convince your Dr’s that you need this.
Actively manage your own care, so to speak.
Try and get them to give you an Oral Glucose Tolerance Test (OGTT).
And make sure insulin is being done with it.
This is used to diagnose Diabetes but will give us useful information, as well.
Your FPG is high enough to make this a worthwhile test.
It is more accurate than FPG but more expensive and time consuming.
Remember your Doctor is trying to diagnose Diabetes we are not.
CS
I appreciate all your research you've done. As far as my using any kind of diabetes medications with my next treatment, that's going to have to be left up to my doctors. My internal medicine doctor has had my A1C done numerous times and I'll be getting another one in Feb. He's pretty much stayed on top of things with it because my sister had Type II and sero-converted into Type 1, but she's very obese and does not closely control her diet, nor exercise as much as she should. My Dad had Type II and aggressively followed his diet and exercise and lost a bunch of weight. He did so well that his doctor told him that he was no longer diabetic and took him off of all his diabetic medicine. I exercise just about every day of the week. My weight is in the perfect range as far as my BMI. My past 2 biopsies showed no steatosis, even though I do have the bridging fibrosis. My triglycerides are not real high, not to the degree even where they would give me medications for them. My cholesterol has been within normal limits. My liver doctor told me point blank that he doesn't think that I fit the profile for insulin resistance. So, I'm at a loss there. If neither of the 2 doctors seems to be going there, I don't know that there's much more that I can do. When you go into clinical trials, they are very specific on what you can take and what you can't so, if my next treatment is in a clinical trial, I don't see that I'd be able to use Metformin or any insulin. If my A1C gets into the high range then, I think that they would probably be more inclined to further investigate this theory. I do agree that my fasting blood sugar is slightly high... As I said, I am listening to your words of advice but, since I'm now into an HMO and have to use the doctors that accept my insurance, financially speaking, I can't really go several different doctors to find one who will pursue this, you know? At least now, I finally have prescription drug coverage. Susan400
You need to get a copy of the test results
Without that its all a bit of a guess.
CS
Without that its all a bit of a guess.
CS
Not sure what happening with the test in Dec, all I knew about was the IR test, which was a fasting blood test = 6.8.
Dont know where the specialist got the 6.3 as I didnt have any GGT done that day.
Dont know where the specialist got the 6.3 as I didnt have any GGT done that day.
Cowriter and CS and HR
I spoke to specialist and GP, both say that I dont have Insulin Resistance.
The specialist wont do HOMA-IG, says its meaningless.
I decided to go on the supplements CS is taking, and delay treatment for a couple of months, April.
Here are my blood test done in November.
Any info or comments would be appreciated.
*Haemoglobin= 157g/L (115-155)*
Platelets= 263x10/L (159-400)
AFP= 3 (<7) - AFP is of use in the diagnosis and monitoring of hepatocellular carcinoma and germ cell tumors.
RBC=5.13x10 (3.80-5.20)
*PCV=0.46L/L (0.35-0.45)*
MCV=90.4 fl (80.0-98.0)
MCH=30.6 pg (27.0-33.0)
MCHC= 338 g/L (3315-355)
RDW= 12.8% (11.5-15.5)
White Cell Count= 8.44x10/L (4.00-11.0)
Neutrophils= 57.4% 4.84x10/L (1.80-7.50)
Lymphocytes= 34.1% 2.88x10/L (1.00-3.50)
Monocytes=5.2% 0.44x10/L (0.20-0.80)
Eosinophils=3.1% 0.26x10/L (0.02-0.50)
Basophils=0.2% 0.02x10/L (0..00-0.10)
*Glucose= 6.6 (3.8-5.5)fasting.* - IR test in Dec=6.8, glucose=6.3
ALT=77 (0-55)
*Total Triglycerides= 2.7 (0.3-2.0)
Total Cholesterol=4.8 (<5.5) desirable
HDL Cholesterol=1.4 (1.0-2.2)
I spoke to specialist and GP, both say that I dont have Insulin Resistance.
The specialist wont do HOMA-IG, says its meaningless.
I decided to go on the supplements CS is taking, and delay treatment for a couple of months, April.
Here are my blood test done in November.
Any info or comments would be appreciated.
*Haemoglobin= 157g/L (115-155)*
Platelets= 263x10/L (159-400)
AFP= 3 (<7) - AFP is of use in the diagnosis and monitoring of hepatocellular carcinoma and germ cell tumors.
RBC=5.13x10 (3.80-5.20)
*PCV=0.46L/L (0.35-0.45)*
MCV=90.4 fl (80.0-98.0)
MCH=30.6 pg (27.0-33.0)
MCHC= 338 g/L (3315-355)
RDW= 12.8% (11.5-15.5)
White Cell Count= 8.44x10/L (4.00-11.0)
Neutrophils= 57.4% 4.84x10/L (1.80-7.50)
Lymphocytes= 34.1% 2.88x10/L (1.00-3.50)
Monocytes=5.2% 0.44x10/L (0.20-0.80)
Eosinophils=3.1% 0.26x10/L (0.02-0.50)
Basophils=0.2% 0.02x10/L (0..00-0.10)
*Glucose= 6.6 (3.8-5.5)fasting.* - IR test in Dec=6.8, glucose=6.3
ALT=77 (0-55)
*Total Triglycerides= 2.7 (0.3-2.0)
Total Cholesterol=4.8 (<5.5) desirable
HDL Cholesterol=1.4 (1.0-2.2)
I love the idea in theory that an oral med could reduce insulin resistance and increase EVR. However, I was interested in this prior to treatment and told by my endocrinologist, GP, and hepatologist that these were all very hard on the liver and should not be considered for liver diseased patients.
Fortunately I had discovered on my own that I had every symptom of pituitary dysfunction which was subsequently confirmed as working at 10-20% of normal output.
this is common in HCV people by the way, somehow the virus causes Pituitary changes and shutdown.
My therapy was controvercial, I went on HGH injections to return my pituitary to normal levels of human growth hormone for my age. This in turn returned my IGF=1 to normal levels, (insulin growth factor). This in turn returned me to normal AC1 (4.6) from highs of 6.9-7.2)
Even though the literature suggests HGH and INF can both cause insulin resistance and/or diebetes, this has not been my experience. In fact the addition of HGH returned my cells to normal metabolism and compensated for the damage that HCV (or something else) had done to my pituitary. This is important in that getting to the root cause or the missing hormone most likely to be the culprit in causing diebetes makes more sense than insulin replacement, at least in my mind because it spares all the fluctuations and possible complications that both hyper and hypoinsulemia can cause.
I will say I also watched my diet rather arduously for the first few months, but I did an experiment at chistmas, and an increase in sugars caused not one bump in my BS levels. So I'm fairly convinced insulin resistance has more than one possible way of being corrected. The question now is how to convince the medical community that one therapy may be superior and less toxic than another. At this point HGH is as expensive as insulin injections, but several companies are working on an oral secretouge which should bring the cost and benefit to a whole new generation of sufferers.
mb
Fortunately I had discovered on my own that I had every symptom of pituitary dysfunction which was subsequently confirmed as working at 10-20% of normal output.
this is common in HCV people by the way, somehow the virus causes Pituitary changes and shutdown.
My therapy was controvercial, I went on HGH injections to return my pituitary to normal levels of human growth hormone for my age. This in turn returned my IGF=1 to normal levels, (insulin growth factor). This in turn returned me to normal AC1 (4.6) from highs of 6.9-7.2)
Even though the literature suggests HGH and INF can both cause insulin resistance and/or diebetes, this has not been my experience. In fact the addition of HGH returned my cells to normal metabolism and compensated for the damage that HCV (or something else) had done to my pituitary. This is important in that getting to the root cause or the missing hormone most likely to be the culprit in causing diebetes makes more sense than insulin replacement, at least in my mind because it spares all the fluctuations and possible complications that both hyper and hypoinsulemia can cause.
I will say I also watched my diet rather arduously for the first few months, but I did an experiment at chistmas, and an increase in sugars caused not one bump in my BS levels. So I'm fairly convinced insulin resistance has more than one possible way of being corrected. The question now is how to convince the medical community that one therapy may be superior and less toxic than another. At this point HGH is as expensive as insulin injections, but several companies are working on an oral secretouge which should bring the cost and benefit to a whole new generation of sufferers.
mb
"Wheres the study that shows Meformin makes any difference."
------------------
Here's the Metformin study I owed you ; )
Co
In Chronic Hepatitis C (HCV), Pretreatment with Thiazolidinediones (TZDs) or Metformin Decreases Insulin Resistance (IR) and HCV Viral Load and Increases Early Virologic Response (EVR)
M. Adler, J.L. Matloff, A.S. Boxer, H. Han, M. Vachon, D.C. Carriero, D.T. Dieterich, , Mount Sinai School of Medicine, New York, NY; M. Vachon, D.C. Carriero, D.T. Dieterich, Division of Liver Diseases, Mount Sinai School of Medicine, New York, NY;
Background: Chronic HCV is associated with increased incidence of insulin resistance (IR), which leads to a lower rate of sustained virologic response (SVR) following treatment with peginterferon plus ribavirin (IFN + RBV). Romero-Gomez et al. reported an SVR rate of 32.8% in genotype 1-infected patients with IR (HOMA-IR > 2) compared to 60.5% in those without IR. In addition, IR is associated with increased liver fibrosis and is characterized by a higher viral load, two other independent risk factors for decreased response to treatment. A recent study showed 0/5 EVR in patients with IR who were given a TZD at initiation of IFN + RBV. It is unknown if therapeutic intervention to improve insulin sensitivity prior to anti-viral treatment increases response to HCV treatment. Aim: To evaluate the effect of treatment with TZDs or metformin on IR and viral load prior to IFN + RBV and the impact on EVR. Methods: IRB-approved, we retrospectively reviewed charts of patients with chronic HCV from a liver clinic in our center. We included patients with IR treated with either metformin or a TZD for at least 3 months prior to initiating IFN+RBV. We compared HOMA-IR, HCV viral load, liver enzymes and BMI at baseline, after treatment with an insulin sensitizer (IS), and at week 12 of HCV treatment. Results: 17 patients met inclusion criteria. 10 were co-infected with HIV. The average age was 52.2 years, and 82% of patients were genotype 1. 11 patients were treatment-naïve to IFN+RBV. The mean stage of fibrosis was 2.7 on Metavir score in 12 patients. 11 patients received a TZD and 6 received metformin. The mean HOMA-IR decreased from 7.99 to 6.06 after treatment with an IS to 4.60 at 12 weeks of IFN + RBV. There was a significant mean decrease of 0.52 log in HCV viral load on each patient after treatment with an IS (p<0.01). An EVR was achieved in 12 patients (71%). The mean ALT value decreased from 86.2 at baseline to 72.5 (p=0.02) after treatment with an IS to 34.1 IU/L (p=0.01) after 12 weeks of IFN + RBV. BMI significantly decreased from 27.9 to 26.8 kg/m2 (p=0.02) following treatment with an IS. Conclusion: The use of a TZD or metformin improved insulin sensitivity prior to treatment with IFN + RBV. The baseline viral load, a risk factor for decreased response to treatment and until now referred to as an unmodifiable factor, was also significantly lowered. This intervention allowed a 71% rate of EVR in a population of mono and co-infected patients, the majority being genotype 1. This small pilot study suggests that targeting insulin resistance prior to treatment may enhance the chance of response to traditional treatment for chronic HCV.
------------------
Here's the Metformin study I owed you ; )
Co
In Chronic Hepatitis C (HCV), Pretreatment with Thiazolidinediones (TZDs) or Metformin Decreases Insulin Resistance (IR) and HCV Viral Load and Increases Early Virologic Response (EVR)
M. Adler, J.L. Matloff, A.S. Boxer, H. Han, M. Vachon, D.C. Carriero, D.T. Dieterich, , Mount Sinai School of Medicine, New York, NY; M. Vachon, D.C. Carriero, D.T. Dieterich, Division of Liver Diseases, Mount Sinai School of Medicine, New York, NY;
Background: Chronic HCV is associated with increased incidence of insulin resistance (IR), which leads to a lower rate of sustained virologic response (SVR) following treatment with peginterferon plus ribavirin (IFN + RBV). Romero-Gomez et al. reported an SVR rate of 32.8% in genotype 1-infected patients with IR (HOMA-IR > 2) compared to 60.5% in those without IR. In addition, IR is associated with increased liver fibrosis and is characterized by a higher viral load, two other independent risk factors for decreased response to treatment. A recent study showed 0/5 EVR in patients with IR who were given a TZD at initiation of IFN + RBV. It is unknown if therapeutic intervention to improve insulin sensitivity prior to anti-viral treatment increases response to HCV treatment. Aim: To evaluate the effect of treatment with TZDs or metformin on IR and viral load prior to IFN + RBV and the impact on EVR. Methods: IRB-approved, we retrospectively reviewed charts of patients with chronic HCV from a liver clinic in our center. We included patients with IR treated with either metformin or a TZD for at least 3 months prior to initiating IFN+RBV. We compared HOMA-IR, HCV viral load, liver enzymes and BMI at baseline, after treatment with an insulin sensitizer (IS), and at week 12 of HCV treatment. Results: 17 patients met inclusion criteria. 10 were co-infected with HIV. The average age was 52.2 years, and 82% of patients were genotype 1. 11 patients were treatment-naïve to IFN+RBV. The mean stage of fibrosis was 2.7 on Metavir score in 12 patients. 11 patients received a TZD and 6 received metformin. The mean HOMA-IR decreased from 7.99 to 6.06 after treatment with an IS to 4.60 at 12 weeks of IFN + RBV. There was a significant mean decrease of 0.52 log in HCV viral load on each patient after treatment with an IS (p<0.01). An EVR was achieved in 12 patients (71%). The mean ALT value decreased from 86.2 at baseline to 72.5 (p=0.02) after treatment with an IS to 34.1 IU/L (p=0.01) after 12 weeks of IFN + RBV. BMI significantly decreased from 27.9 to 26.8 kg/m2 (p=0.02) following treatment with an IS. Conclusion: The use of a TZD or metformin improved insulin sensitivity prior to treatment with IFN + RBV. The baseline viral load, a risk factor for decreased response to treatment and until now referred to as an unmodifiable factor, was also significantly lowered. This intervention allowed a 71% rate of EVR in a population of mono and co-infected patients, the majority being genotype 1. This small pilot study suggests that targeting insulin resistance prior to treatment may enhance the chance of response to traditional treatment for chronic HCV.
Is the 6.8 the result of a fasting blood sugar? If it is, that means that you are pre-diabetic/insulin resistant. A reading above 5.5 means pre-diabetes.
Don't start treating until you resolve the insulin resistance because that will decrease your chances of SVR.
"Glucose above 100 mg/dl (same as 5.5 mmol/l) Reduces Interferon/RBV SVR"
http://www.natap.org/2008/HCV/031008_01.htm
"Also, what do you think the chances of getting Alinia added to combo therapy? In australia of course."
---------------------
CS got his doctor to approve it. I'm sure he'll be happy to share the info he used to back up his request. (he will also be predosing the Riba).
Co
To CS....we're even....LOL
Don't start treating until you resolve the insulin resistance because that will decrease your chances of SVR.
"Glucose above 100 mg/dl (same as 5.5 mmol/l) Reduces Interferon/RBV SVR"
http://www.natap.org/2008/HCV/031008_01.htm
"Also, what do you think the chances of getting Alinia added to combo therapy? In australia of course."
---------------------
CS got his doctor to approve it. I'm sure he'll be happy to share the info he used to back up his request. (he will also be predosing the Riba).
Co
To CS....we're even....LOL
Gday CS, I had my blood test done for IR, it came back 6.8, which is in the normal range, so now i know I dont have Insulin Resistance. And we were so sure that I did werent we.
So now I dont have to worry about that when I start the tx again in Feb/March. Just have to lose a few kilos, get the weight down.
Been hearing about taking Riba for a couple of weeks before I start the interferon.
Also, what do you think the chances of getting Alinia added to combo therapy? In australia of course.
Linda
Geno 3, relapser/ fibrosis 2, tx 2004
So now I dont have to worry about that when I start the tx again in Feb/March. Just have to lose a few kilos, get the weight down.
Been hearing about taking Riba for a couple of weeks before I start the interferon.
Also, what do you think the chances of getting Alinia added to combo therapy? In australia of course.
Linda
Geno 3, relapser/ fibrosis 2, tx 2004
epi...I feel your pain...and just when we thought it was safe to come out from under our rock....but I still think a little fat w/riba is a good idea...just saying overall maybe a reduction in lipids might be wisdom...might be.....and then a return to healthy lips once the virus is clear....well.....it's just a theory, remember that. There's no absolute proof that virions couldn't steal fat from what already exists in your fat stores, so it's just a theory....but if my blood is rich in lipids, that certainly wouldn't make them have to work very hard to improve their own lipid shell would it?
Come to think of it...HR said it's the harder lipid shells that are the RESISTANT vrions, so I'm just wondering why would I offer these things a raincoat AND galoshes??
Just this month a study showed rats (closest to us genetically in reaction to food stuffs) had a much higher rate of fibrosis if on a diet rich in folic acid (green things)...
so again, normally one thinks..eat yer broccoli...but in this case, with this disease, all bets are off and we need to llok at the science of virion killing first, and then at all the rest. just my opinion.
CS....yes, please do let us know....it would be curious to see if there is a tie in somewhere. We do now know that diebetes is tied as much to lipids as to sugars, and plaque formation is also more insulin related than once thought, it wouldn't surprise me to learn that eating more healthy fats might just have been the overkill the virus needed to survive. Wouldn't that be a freakin' kicker.
mb
Come to think of it...HR said it's the harder lipid shells that are the RESISTANT vrions, so I'm just wondering why would I offer these things a raincoat AND galoshes??
Just this month a study showed rats (closest to us genetically in reaction to food stuffs) had a much higher rate of fibrosis if on a diet rich in folic acid (green things)...
so again, normally one thinks..eat yer broccoli...but in this case, with this disease, all bets are off and we need to llok at the science of virion killing first, and then at all the rest. just my opinion.
CS....yes, please do let us know....it would be curious to see if there is a tie in somewhere. We do now know that diebetes is tied as much to lipids as to sugars, and plaque formation is also more insulin related than once thought, it wouldn't surprise me to learn that eating more healthy fats might just have been the overkill the virus needed to survive. Wouldn't that be a freakin' kicker.
mb
I too have had some strange results from resent blood tests.
I'll post on the lipid thing after i get the results of a PCR test back.
Next week end most likely.
All the Best
CS
I'll post on the lipid thing after i get the results of a PCR test back.
Next week end most likely.
All the Best
CS
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