The Importance of Methodology in Curing Type 1 Diabetes or Other Disease
What’s wrong with the methodology of Phase 2 BCG study headed by
Dr. Denise Faustman? October Newsletter
This article explores how good methodology in research is crucial to the success or failure of a study. First HDIABETES.COM will introduce you to the issues of Dr. Faustman’s Phase 2 research to cure Diabetes type 1. Secondly we will show the core elements of ideal research methodology that will more likely lead to success in any study. Thirdly we will discuss add-ons to ideal methodology that apply specifically to diabetes research.
We will compare Dr. Faustman’s Phase II throughout the article so you will be able to recognize a bad methodology that is imposed on talented researchers like Dr. Faustman.
THE UNIQUENESS OF DR. FAUSTMAN’S RESEARCH
Dr Faustman has been the first in the world to have cured naturally established late-stage mouse NOD diabetes type 1. (NOD = non obese diabetic) The majority of studies have used mice that have a chemically induced diabetes type 1. ( more information) Chemically induced mice are not a reliable model to compare human Type 1 Diabetics in studies because the majority of human diabetic type 1’s have instead, a naturally established auto-immunity. Thus chemically induced Dt1 is a different disease! Dr Faustman used mice with naturally established late-stage type 1 diabetes. Therefore Dr. Faustman’s studies are more realistic than other studies, and begins with good methodology.
PROVEN EFFICACY OF BCG
The drug BCG which was used in Faustman’s Phase 1 and II, has been proven safe at multiple doses and has now been used by billions of people since it was discovered in 1854. Source: Wikipedia The many blood donations to Faustman's lab from the diabetics type 1 and the control healthy subjects showed strong efficacy of BCG to kill selectively the auto-reactive t-cells linked to diabetes type 1 auto-immune without harming the other cells.(source)
(For your information, some diabetes type 1 cases don’t have an auto-immune origin. These cases do not have an auto-immunity; that is, they don’t have auto-reactive T-cells, where the cause could be pancreatic cancer, inflammation, pancreatitis, genetic disease, Hormonal imbalance that suppresses pancreas insulin secretion, other underyling diseases or undetermined cause (idiopathic); sometimes called type 1B. Dr. Faustman’s research aims to reverse type 1 auto-immune).
It also is not because the FDA wants to hurry along a cure. Dr Faustman’s phase 1 human trial found a miniscule amount of improvement in biomarkers even with 2 dose 4 weeks apart. Why would repeating phase 1 and less for 5 years NOT be an obviously ludicrous waste of time?
Something so obviously un-scientific as the restrictions of Phase 2 makes one wonder at the ridiculousness of these parameters. One really has to wonder at the scientific training of these “experts” at the FDA. Why would they contradict Dr. Faustman’s obvious expertise? With their obvious blunders releasing many dangerous drugs, why do we hold these people in positions of authority anyway?
FDA has a lot of control regarding the approval of methodology and they could impose methodology amendments prior approval. A lot of people on the fda boards are in conflict of interests and are linked directly or indirectlty to pharma groups. So in other word, they could influence the fate of a research. If they force a bad methodology to a talented researcher, we could predict a failure before the research is even started without doubt. The UK Parliament recognized the conflicts of interests that are pervasive in every part of our current medical system: The industry is
hugely influential, affecting, every aspect of the medical world, including prescribers, patients, academics, the media,and even the institutions designed to regulate it. Source: http://www.publications.parliament.uk/pa/cm200405/cmselect/cmhealth/42/42.pdf.
PHASE II METHODOLOGY
Each dose in Dr. Faustman’s current Phase II methodology which is approved by the FDA, is identical to phase I. ( Standard BCG vaccine dosage 0.1MG) It's important to put this dosage in perspective. In a mouse study, NOD mouse diabetes type 1 was cured with a single intravenous injection between 0.25MG to 1MG of BCG.(source) Keep in mind, an intravenous injection is a lot more potent than the subcutaneous injection (intradermal) that will be used in Dr Faustman's phase II. The average weight of nod mouse is around 30 grams. ( source 1, source 2)If we use a fictional example, a Type 1 human that weighs 70KG would have received a single intravenous injection of up to 2333,333 MG of BCG. We are not suggesting increasing the dosage of BCG to this level and inject intravenously, but this is to show that 0.1 MG is low in transposing mouse dosages to human. Thus it is odd that the FDA did not allow any increase in BCG dosage from Phase 1 to Phase II.
Another comparison which shows that an increase in BCG dosage for Phase II could be a logical and safe next step, is in the current treatment of bladder cancer. In common clinical practice, 81 mg of bcg is given intravesically to bladder cancer patients without any severe side effects. (source) In private clinical practice, doctors can modulate treatment according to the needs of cancer bladder patients to use even higher dosages than 81MG. Another medical paper showed they tested up to 2000MG subcutaneously and 200 MG intravenously on cancer patients without any severe side effect.( source) The only side effect of even very high levels of BCG, as the above study shows, was a skin reaction at the injection site, avoided simply by injecting in the anterior surface of the thigh. ( source)) Therefore limiting the dosage of Phase II is not justified from the point of view of side effects
Thus instead of using one large dose of BCG like in the mouse study, a good strategy for safety’s sake is to increase both frequency and dosage using several injections per week for several weeks.
A useful tool in judging if the medication is working is the use of biomarkers. The major biomarker to show that BCG is working is the decrease of auto-reactive T cells. These are the killer cells which attack the pancreas. Other important biomarkers are T regulatory cells, anti-gad anti-bodies, c-peptides, and others which indirectly show what is happening in the body.
In the current approved Phase II methodology, Dr faustman is not allowed to adjust the dosages of bcg based on the bio-markers. Instead the FDA has allowed only a fixed dosage of 0.1mg per year (with 2 doses in the first year) for the 5 years of the study.(fixed frequency too) Ideally, BCG treatment should be adjusted according to the main bio-marker which is auto-reactive t-cells. Since the objective of Phase II is to eliminate the auto-reactive t-cells, it's important to modulate bcg treatment depending on the death rate of auto-reactive t-cells Otherwise the optimal dosage cannot be determined without knowing how the human organism is reacting to the medication. Thus the ideal methodology should include an adjustment of dosages and frequencies according to the biomarkers.
A second objective for phase II is to determine the maximum tolerance to BCG. This is because each individual could react differently to BCG based on weight, health condition and many other variables. Ideally in clinical practice, treatment should be tailored according to individual bio-markers and individual tolerance. Dr. Faustman mentioned this in her patent “The assay of step b) may also be used to tailor TNF-alpha induction therapy to the needs of a particular individual."source : Patent
However, basing dosage and frequency of BCG solely on biomarkers still leaves open the possibility of unreasonable restrictions by the FDA. In other words, a given dose based on biomarkers, still might not be enough to obtain a reversal. This is because even if the biomarkers justified an increase of dosage/frequency, and the fda still severely restricts how much BCG is given, then it still may not be at the upper limit that BCG will be effective.
To save time and money, the dosage should be dependent on the maximum subject tolerance. That is, the point at which the maximum amount of BCG is tolerated by an individual without (((severe))) side effects. (Remember that 2000 mg subcutaneously has been used in a trial without severe side effects)))
So the ideal methodology should authorize both. i.e. Adjusting BCG dosages and frequencies based on biomarkers up to maximum subject tolerance. In other words, no limit to the dosage and frequency based on biomarkers
METHODOLOGY IS CRUCIAL
Many people focus on the actual compound as a major component in research to reverse a disease, when in actual fact it is how the compound is administered that is most important. That is, the methodology.
Dr Faustman reported the importance of methodology in several interviews. As an example of bad methodology she mentioned the first research on insulin showed zero effect of insulin injections on diabetes!
As hdiabetes.com have stated previously, the most important part of an ideal methodology is a direct bio-marker linked to the disease you want to reverse. If a direct bio-marker is not available, then an indirect bio-marker also gives necessary information.
In an ideal methodology the dosages and the frequencies of the compound are not fixed in advance because the objective of research is to determine the optimal dosages and frequencies. Thus the direct bio-markers and the complementary indirect bio-markers would be used ongoingly to adjust dosages and frequencies of the compound.
Maximum subject tolerance to the compound would then be determined despite different variables in each individual. This is because variables in each individual would have an effect on how the compound reacts most effectively.
This being the ideal methodology, where optimum dosage is determined – neither too low or too high, you can see that a bad methodology, where a dosage that is too small to have effects, can readily be determined by biomarkers and maximum subject tolerance
The mode of administration must be considered as well. Different modes such as intravenous or intradermal injection,which part of the body injected, inhalation, pill swallowed, pill dissolved under the tongue, are all variables to consider in an ideal methodology. There can be different rates of absorption where the compound may be more stronger, or less so, depending on the mode of administration. Side effects may also change depending on the mode of administration as well.
Our aim in showing you core elements of ideal methodology is to allow you to go to any study and be able to discern if it has a good methodology or not.
So questions you could ask yourself about Phase II methodology are:
1. Are direct and indirect biomarkers allowed? YES
2. Is maximum subject tolerance depending on biomarkers allowed? NO
3. Is there a fixed dosage and frequency? YES
4. Are the BCG dosages and the frequencies are allowed to be adjusted based on the direct and indirect biomarkers? NO
Thus you can see that the FDA has not allowed Dr. Faustman a good methodology BY A LONG SHOT.
How much time it takes to cure a disease is unknown at the beginning of a trial. It could take from a few months to a few years. A good methodology is important to reduce the time it would take to fully reverse a disease, because much time can be wasted in ineffectual timing and dosing.
ADD-ON TO IDEAL METHODOLOGY
In addition to the above mentioned core elements of an ideal methodology that hdiabetes.com have presented so far, the following are other issues that could have an effect on the length of time it would take to reverse, specifically, Diabetes type 1, taken from other research studies
A variety of things can get in the way of blood sugar control, and thus hamper results of a trial, even if it has the core elements of ideal methodology.
ON THE REBOUND
The rebound phenomenon commonly observed in diabetic type 1's treated with insulin should be limited to a minimum with the help of a cgms/pump. A rebound occurs when untreated hypoglycemia, or a rapid decrease in blood glucose, triggers a release of counter-regulatory hormones, resulting in an episode of hyperglycemia and a period of insulin resistance that can persist for hours to days. The insulin resistance and hyperglycemia can lead to ketonurea or ketonemia. (15.)
Just one rebound could induce insulin resistance that can last several days. If a subject has several rebounds , it could maintain the subject in insulin resistance state indefinetely without proper treatment of the rebounds. Another possible issue resulting from hyperinsulinemia. Hyperinsulinemia could be caused by long-term gradual excessive usage of synthetic insulin. Likewise, hyperinsulinemia caused by insulin synthetic injections is known to cause suppression of pancreas endogenous insulin production. The loss of pulsatile insulin secretion alone is known to cause insulin resistance.(70.) The most near natural pulsatile insulin secretion treatment available is insulin pump. Moreover, it would be ideal to include a cgms/pump for every participant in order to permit tight diabetes control, because unstable diabetes hampers beta-cell regeneration. In other words, hyperglycemia, as occurring in diabetes, has a harmful effect on the function and development of beta cells.( source) Hypoglycemia that is resulting of excessive synthetic insulin injections alters the pancreas activity too. The pump/cgms will help to prevent the other issues we described as well.(rebounds,hyperinsulinemia, pulsatile insulin secretion,hyperglycemia)
Even in case of a perfectly healthy subject that would take insulin injections would result in endogenous secretion of c-peptide removed.(65)
So if one diabetic type 1 has a persistent rebound issue with resulting hyperinsulinemia it will hamper the remaining endogenous secretion of c-peptide like the healthy subject. An ideal methodology should take in consideration this reality.
In summary to promote regeneration of beta-cells, we should maintain very tight control of diabetes, in order to avoid rebounds, hyperinsulinemia and the resulting insulin resistance that decrease likelihood of success. As you understand now, hypoglycemia as hyperglycemia hampers the normal blood glucose homeostasis and in long term that could result in hyperinsulinemia.
To optimize results, we could include in our ideal methodology, an insulin reduction protocol monitored with a cgms/pump. If the treatment does indeed start to increase pancreas insulin production in the individual, then that person would be at risk for rebounds and the resulting insulin resistance. Thus an insulin reduction protocol based on continuous data supplied by a cgms would be necessary.
If no insulin reduction protocol is provided, it would leave the participants in the dark as to how much insulin to reduce and when.
Other events could effect a subject's blood sugar level, and thus potentially effect a methodology of cure. The following variables are well known to diabetic type 1's as being able to effect their blood sugars: physical, psychological, and emotional stress, plus the lesser considered sportive stress. We should not forget the importance of nutritional data that includes the quantities, the nutrients and the food groups.
As well, exposure to the sun’s UVB rays promote an immune system response which increases TNF. (6). Increase of TNF is linked to reduction of auto-reactive t-cells. The quality of sleep also effects blood sugars; the lack of sleep is associated with insulin resistance.(66)
Smoking and alcohol consumption should also be considered. Consumption of alcohol is associated with hypoglycemia, and long-term overconsumption of alcohol is associated with insulin resistance. (68) Smoking is associated with insulin resistance. (67)
These variables to blood sugar control are all well-known to diabetics, and could influence methodology of cure. They are all easily evaluable and could be logged by the participant to provide information on the effects of a medication depending of all these variables in a research setting.
As we have seen, the methodology is crucial and a strong determinant of success of any trial that aims to reverse a disease. Hdiabetes.com explored the core of ideal methodology which is to modulate the dosages and the frequencies of one compound depending of on direct/indirect biomarkers linked to disease up to maximum individual subject tolerance. Later, we showed several other variables that could be added to ideal methodology basis specifically for the diabetes type 1 researches. (Rebounds, hyperinsulinemia, hypoglycemia, hyperglycemia, insulin resistance, pulsatile insulin secretion, sun uvb, smoking, alcohol, physical as psychological stress, nutritional) Moreover, we showed Dr Faustman’s current phase II FDA approved methodology is far from an ideal methodology that could avoid wasting money and time. The methodology imposed by the FDA doesn’t permit the basic elements of ideal methodology.
We can put an end to the deceptive tactics of the FDA showing a compound is ineffective to reverse a disease when it’s in fact it could be under an ideal methodology. Hdiabetes.com delivered to you the knowledge you need to be smarter than the FDA and to know what is going behind the scenes. You can now discern yourself the bad methodologies imposed by fda now. So you will not be affected by the coming disinformation. Censoring is possible issue but feel free to share the information through all the other means and the resilient censoring networks.
We will succeed through large public pressure against a small elitism group. They are small in number compare to us. It’s time to act now. This information should be shared all over the internet through all your email contacts, social networks like twitter and facebook, forums, chatrooms,p2p and other means.. We should expect heavily censoring so don’t hesitate to copy entirely and share this information on the most resilient networks and everywhere.
For more information feel free to read the references and quotations below.
PS: If you missed June's newsletter, it contains a detailed description of Dr. Faustman's Phase II compared with Phase I. As well, it shows a media history of Dr Faustman that shows she truly wants an ideal methodology too. Click here to read.
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References and quotations:
2- One factor that has delayed the timetable is the unavailability of BCG in the U.S. As a result, Faustman’s team has set up their own small-batch production site in Bethesda, Maryland. source:http://www.thejdca.org/wp-content/uploads/2014/05/Boston-Trip.pdf
3- Faustman still does see the potential for a diabetes cure. “I would like to think it is feasible,” says Dr. Faustman. She believes people outside the scientific community can put more pressure to bear on medical science by demanding more human trials to move the possibility of a cure along. “Make [researchers] more accountable for their data,” says Dr. Faustman. source: http://www.diabetescare.net/provider_spot_detail.asp?id=445368
4- Initially we will start out with weekly BCG immunization. source: Treatment of autoimmune disease - Patent US 6599710 B1 link: Patent
5- Bcg safety : BCG vaccination have been used for more than 30 years in many countries, including Canada and in western Europe, as a vaccination against tuberculosis. The recognized side effects of BCG vaccination include mild local discomfort at the vaccination site with a papular rash developing at the site 10-14 days after vaccination and reaching a maximal diameter of 3 mm 4-6 weeks after vaccination. The rash may scale thereafter, and rarely leaves a visible scar. Local adenopathy is rarely seen in children, but almost never in adults. Rare events include osteomyelitis, lupoid reactions, disseminated BCG infections and death. The frequency of these severe reactions is between 1 in 1,000,000 and 1 in 5,000,000 vaccinations, and have occurred almost exclusively in immunosuppressed children. Most of the recent experience with BCG has been in the intravesicular treatment of bladder cancer, where weekly installations of BCG are performed for >6 weeks. Finally, BCG vaccination has been used in Type 1 diabetes without any adverse consequences noted. source: Treatment of autoimmune disease - Patent US 6599710 B1 link: Patent
6- UV Light as potential TNF increase inducer.. source: Treatment of autoimmune disease - Patent US 6599710 B1 link: Patent
7- By “maintenance of normal blood glucose levels” is meant that a mammal is treated, for example, by insulin injection or by implantation of a euglycemic clamp in vivo, depending on the host being treated. source: Treatment of autoimmune disease - Patent US 6599710 B1 link: Patent
8- The methods of the invention provide, for the first time, effective reversal of naturally-occurring (as opposed to chemically induced) mediated diseases such as type I diabetes. source: Treatment of autoimmune disease - Patent US 6599710 B1 link: Patent
9- a) treating a mammal to kill or inactivate autoimmune cells of the mammal; b) periodically monitoring the cell death rate of the autoimmune cells (i.e., by assaying the cell death rate of autoimmune cells in the mammal, wherein an increase in cell death rate of auto reactive T-lymphocytes indicates an increase in the number of functional cells of the predetermined type (i.e., resistant to cell death)); and (c) periodically adjusting the dosage of the agent based on the information obtained in step (b). The assay of step b) may also be used to tailor TNF-alpha induction therapy to the needs of a particular individual. e assay of step b) can be carried out every day or every other day in order to measure the effect of TNF-induction therapy and/or cell death inducting agents on autoimmune cell death rate so that adjustment to the administered dose, duration of treatment (i.e., the period of time over which the patient will receive the treatment) example, the in vitro monitoring of selective killing of autoimmune cells can be used to selectively grade the drug (i.e., adjust the dose administered to maximize the therapeutic effect). TNF-alpha therapy can be effective even in patients with established disease, by monitoring the elimination of autoimmune cells and optimizing the dose, duration of treatment, and/or re-treatment schedule accordingly. Thus, the assay of step b) may be used to identify an effective dose, duration of treatment, or treatment regimen of TNF-alpha source: Treatment of autoimmune disease - Patent US 6599710 B1 link: Patent
10- Therefore, I have identified and optimized a novel combination treatment for diabetes melitus. Thus, in yet another aspect, the present invention features a method of increasing and preserving the number of functional cells of a predetermined type in a diabetic patient that includes the steps of (1) ablation of autoimmune cells, (2) exposure to MHC class I and peptide, and (3) maintenance of glucose control. source: Treatment of autoimmune disease - Patent US 6599710 B1 link: Patent
11- An inexpensive approach to try to immediately rescue the pancreas would be to repeatedly perform BCG administrations, as a non-specific immnostimulant that could successfully raise the levels of endogenous TNF-alpha activity. Initially we will start out with weekly BCG immunization. With the in vitro monitoring assay, we expect to be able to identify an optimal dose. Our goal is to continue this treatment from a minimum of 40 days up to about 6 months, or until positive human C peptide is found in the blood and insulin dosing is reduced. Early signs of possible tolerance induction success might not only be the presence of C peptide but also by the absence of TNF-alpha sensitive (autoreactive) cells. source: Treatment of autoimmune disease - Patent US 6599710 B1 link: Patent
12- If the response to BCG immunization is positive, we will then start immunization with donor lymphocytes. Ideally, these lymphocyte immunizations could be from both parents and would involve weekly infusions into the diabetic child, to be administered simultaneously with the BCG immunizations. source: Treatment of autoimmune disease - Patent WO 2000053209 A1 B1 link: Patent
13- For example, one may administer BCG at least biweekly or, desirably, three times a week. Again, one skilled in the art can determine individually the dosing of the cells and TNF-alpha or BCG by analyzing a blood sample twice a week for evidence of the elimination of the phenotype of the pathogenic cell. In addition, in treating type I diabetes, it may be desirable that the patient maintains as close to normoglycemia as possible. Therefore, these patients may be placed on an insulin pump for not only the exemplary 40 days of disease reversing therapy, but also for a 120 day period to optimize the regenerative process. source: Methods and compositions for treating autoimmune diseases - US 8173129 B2 link: Patent
14- Parents at JDRF ostensibly control the organization and decide which research to fund, but a tell-tale sign of the inordinate influence that JDRF affiliated scientists exert on grant awards, is the fact that the chair of the research committee, who is on the board, did not even meet with Dr. Faustman or invite her to present her proposal at a 2004 workshop. Instead, scientists who are hostile to regenerative research, and have competing financial ties to biotech companies that favor embryonic stem cell research, were invited presenters. JDRF does not disclose the financial interests of scientists. source: full article
15- Untreated hypoglycemia or a rapid decrease in blood glucose triggers a release of counter-regulatory hormones, resulting in an episode of hyperglycemia and a period of insulin resistance that can persist for hours to days. The insulin resistance and hyperglycemia can lead to ketonurea or ketonemia. source: Westerfield J, Holcomb S, Jensen S (eds). Current Trends in Diabetes Management: A Guide for the Healthcare Professional. 7th ed. Nashville, TN: Healthways; 2008.
16- Some patients will experience a rebound reaction to hypoglycemia known as the Somogyi phenomenon . This condition almost exclusively occurs in patients who take long-acting insulin and occurs most often following nocturnal hypoglycemia . Untreated hypoglycemia or a rapid decrease in blood glucose triggers a release of counter-regulatory hormones, resulting in an episode of hyperglycemia and a period of insulin resistance that can persist for hours to days. The insulin resistance and hyperglycemia can lead to ketonurea or ketonemia .Recognition and diagnosis of the Somogyi phenomenon is difficult, and it is important that healthcare providers thoroughly assess signs and symptoms of nocturnal hypoglycemia. This can be done nicely by utilizing continuous glucose monitoring. This option involves placing a small sensor under the skin that monitors interstitial fluid . The sensor device transmits an electronic signal to a monitor every 5 minutes. These levels are stored for up to 72 hours. source: http://www.netce.com/studypoints.php?courseid=1024&printable=yes&page=printquestions
17- While drug companies actively seek out new uses for high-priced patented drugs, there are no incentives to find and test new uses for existing non-patented compounds. The reason is that if an innovator discovers a new use for an old drug, such as aspirin, the innovator would likely find it very difficult to make any profits from selling the drug. Even if the innovator could obtain a patent for the use of aspirin to treat some condition, competition in the product market would make it impossible to make profits from this patent. Given that clinical testing costs can run into the tens or hundreds of millions of dollars, the inability to make profits from existing non-patented compounds implies that they will not be tested. A good example of how this problem can operate is given by the story of Dr D. Faustman, whose approach to curing diabetes involves “an inexpensive, readily available drug.” No pharmaceutical company has been willing to invest in clinical tests, in part because it would likely be impossible to earn substantial returns even if Dr Faustman’s approach turns out to be correct. source: An Efficient Reward system for Pharmceutical Innovation,Aidan Hollis, Department of Economic, University of Calgary, Institute of Health Economics http://keionline.org/misc-docs/drugprizes.pdf
sources of financial support. A tobacco company contribution has been hidden through charity parent company source: http://www.nejm.org/doi/pdf/10.1056/NEJMe0802618
22- Direct medical costs: $116 billion
- After adjusting for population age and sex differences, average medical expenditures among people with diagnosed diabetes were 2.3 times higher than what expenditures would be in the absence of diabetes.
Indirect costs: $58 billion—disability, work loss, premature mortality
23- Quoted from UK parliament: (industry refers to drug groups)
The industry is
hugely influential, affecting
every aspect of the medical world, including
prescribers, patients, academics, the media,
and even the institutions
designed to regulate it.
24- The pharmaceutical industry is arguably the most profitable industry on our planet, with it’s profits being triple that of all of the Fortune 500 companies. Rising profits result in rising stock prices, the only way this industry can sustain this profitable momentum is by continuing to introduce new patented drugs. And since the pharmaceutical industry relies on the FDA as it’s gatekeeper to introduce these new drugs, it’s in their best interest to insure the FDA remains as compliant as possible. And since the FDA is also an office of the United States government, it’s in the government’s best interest to preserve one of it’s most powerful industries.The former editor-in-chief of the New England Journal of Medicine, Dr. Marcia Angell, has been very outspoken with the idea that... [SOURCE: Fortune 4/30/07 Company Annual Reports]
source: [Time Mag 2004]
26- Nutrition approach and reversal of diabetes type 1: a possible research exploration source: http://www.reuters.com/article/2010/07/14/idUS117589+14-Jul-2010+PRN20100714
27- Conflict of interests and the researches. A change in the culture of medicine is needed; legislation is not enough. Source: http://www.bmj.com/content/343/bmj.d5728.extract
28- Though scientists and science journalists are constantly talking up the value of the peer-review process, researchers admit among themselves that biased, erroneous, and even blatantly fraudulent studies easily slip through it. source:http://www.theatlantic.com/magazine/archive/2010/11/lies-damned-lies-and-medical-science/308269/?single_page=true
US 5886029 A link
54- www.cbc.ca/thecurrent Medical Orthodoxy program
55- http://rt.com/on-air/ Russia TV
56- http://wearechange.org/ Independant media named we are the change with mission to uncover the corruption.
57- http://www.whale.to/cancer.html Cancer alternative treatments
58- http://www.fda.gov/AboutFDA/CentersOffices/OrganizationCharts/default.htm FDA's organization chart.
59- World protests Monsanto grip on food supply chain - May 25 2014 source: http://rt.com/news/161356-anti-gmo-monsanto-protest/
69- . Results show that chronic exposure to glargine caused insulin resistance, hyperinsulinemia, and relative insulin deficiency (T2DM). source: http://joe.endocrinology-journals.org/content/221/3/469.full
70- The loss of pulsatile insulin secretion alone is known to cause insulin resistance. source: link
71- how we can measure insulin sensitivity/resistance? source: http://www.em-consulte.com/article/296652/resume/how-can-we-measure-insulin-sensitivityresistance
72- Tactics used to discredit a natural compound with a manipulated research:
- Use synthetic version of a natural compound instead of the natural form.
- Recruit the patients with the worst cases and the less healthy. ( Ex for a research on heart attack they will recruit the patients with risk of imminent heart attack)
- Use very low dosage and frequency.
- Use complex statistic formula and graphic to fit their data with the curve they want.
- Remove the patients data that don't fit in their research objective from the research results..
- Alter ther results of a research.
- Don't respect the methodology posted for the treated group and control group.. EX: They could have several people in treated group that don't take the natural compound. They could instruct to control group that they could take any quantity of natural compound studied instead to say them to avoid the natural compound..
- Use low quality natural compound.
- Withhold the research results that don't fit their objective and never publish them publicly.
73-Treatment with excess glargine(lantus insulin) led to loss of pancreatic islets(beta cells of pancreas that are responsible of endogenous insulin secretion) in healthy mouse. Results show that chronic exposure to glargine caused insulin resistance, hyperinsulinemia, and insulin deficiency in healthy mouse. source:http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4045231/
On the ketone level and fasting.
The blood ketones could increase from trace/negative to higher in level in three possible causes with Type 1 diabetes. It could either you don't have enough insulin as type 1 diabetes, you have sudden rise in insulin resistance that increase your insulin needs and you don't notice this change, so you don't have enough insulin or you fasted too long time without sugar(complex and simple sugars)
More your ketone level increase more it will induce insulin resistance. Ketone metabolism increases insulin resistance. So it will important to monitor the ketones in ideal methodology specifically for type 1 diabetes to avoid insulin resistance..
A strict monitoring with blood ketone meter will avoid you to put you in situation where you don't have enough insulin to cover your basal needs. We should not forget to monitor the fasting time. More you fast long-time without any food more it will permit to deplete the glycogen reserve and induce increase of ketone level. The best strategy to apply is avoid to fast too long time in order to avert increase of ketone level.
We should take in consideration another variable regarding energy used by basal rate of body during sleeping. If one person has insomnia or not stable sleeping pattern it will increase energy basal comsumption(faster glycogen depletion) during night consequently it will reduce fasting time one person could handle without an increase of ketone level. To remember, Ketone level is associated with higher insulin resistance.
Quotation:ketogenic – can induce “physiological” insulin resistance. Physiological insulin resistance is an adaptation, a normal biological reaction to a lack of dietary glucose. Once you’re lean and weight stable, though, very low carb diets (less than 10% of calories from carbs) can reduce insulin sensitivity.
Note: Euglycemia clamp is the best technology tool to manage the blood glucoses to reverse type 1 diabete where alll the dosages of medical drugs were tighly adjusted depending the direct bio-markers and indirect bio-markers to maximum subject tolerance. Euglycemic clamp is medical tool in restricted to hospital settting that monitors all the bio-markers intravenously with a catheter on constant basis and that provides at same time all the medical drugs in pulsative fashion on continual base. Certains euglycemic clamp automates the dosage adjustment depending of the bio-markers but everything could be monitored by a team of scientist, 7 days week and 24 hours a day to adjust the dosages of the medical drugs depending of bio-markers.
They showed in the researches more the blood glucose is tighly controlled more it stimulates the regeneration speed of pancreas and increase reversal rate in mouse that had a naturally occuring late-stage diabetes type 1 auto-immune contrary to induced chemical one new onset. It just confirms how core of ideal methodology is crucial to reverse a disease. This euglycemic clamp requires the participants to be in hospital setting 24hours a day.. So it could an option for short-term study group like the participants should stay 1 week at hospital.. It could give a lot of data that could be used to improve methodology with the ambulatory technologies available like CGMS and insulin pump.