Diabetic Deaths Steadily Increase Thanks to Biosynthetic Insulin

I have just posted a link in the blogroll that I thought I had done a couple of months ago. This is a site reflecting the real statistics concerning diabetic complications since 1979, and like the National Diabetes Information Clearinghouse (link already in the blogroll), shows a steady increase in diabetic deaths since the introduction of biosynthetic insulin. I’m reprinting one of the pages here, to save readers time, but the whole site is well worth reading, as is the Information Clearinghouse website.

Diabetic Type 1 Org.:

We Need Beef Insulin

DEATHS SOAR CDC’s 2003 report was not complete at this posting. However, ADA has stated that in that year diabetes had risen to the 5th leading cod 1. 8/19/05 Alarming rise in diabetic Death Rates reported by the counters, Center for Disease Control www.cdc.gov 1980 – 1996 Diabetes was the 7th leading cause of death (cod).2 2000-2002 Diabetes was the 6th leading cod 2 2003 Diabetes was the 5th leading cod 1 The synthetic type of insulins combined with medical advice, based on the American Diabetic Association’s (ADA‘s) now status quo Diabetic Complication Control Trial’s (DCCT‘s) guidance has caused the condition of many diabetics to continue to worsen. In 1983 animal insulins began being replaced by synthetic human type insulin (cloned from e-coli or yeast). The last of the animal insulins in the United States was Iletin 1 (85% beef & 15% pork) Since 1998, no form of beef insulin has been manufactured in the United States. Note: Beef Insulin sales began in 1921 and to date has been the only insulin made offering a true 24 hour basal action for most healthy diabetics, with one shot a day. Synthetic Insulin sales began in 1983. The synthetics claim to offer 24 hour action. This is neither accurate nor possible for insulin dependent diabetics (idd). The pump for synthetic users is a poor answer to the synthetics lack of basal (24 hour) activity but some users think it is better than 4 to 8 shots daily. The diabetic cod remained relatively low and stable before the introduction of synthetic insulin to the market place. This left those that couldn’t function properly on the synthetics to suffer and many have already died. The 7th leading COD remained until there was no beef insulin sold in the United States, however, the charts do show a constant increase in deaths as the people were slowly switched to synthetics. Hypoglycemic unawareness (hu) is a major problem caused by synthetic insulin. Hu can be caused by any type of insulin but beef insulin is the most benign. EXPLAINATION: hu simply is when the blood glucose goes too low, and the insulin taker is unaware of the sudden drop in blood glucose. The blood glucose can dip so low that the heart stops pumping thus the person can die or go into a coma that damages the brain causing disability from that attack forward. When one dies from hypoglycemia, their heart stops and the death is usually reported as Heart Failure — cod unknown. The blood glucose must be tested within a few hours of death to reveal death from hypoglycemia and that is rarely done. Low blood glucose (bg) proof vanishes if the blood test is done too long after death. By 2002 the cod rates increased dramatically from 14.9 before synthetics in 1982 to 25.2 by 2003 as reported by the CDC. This should be alarming everyone. This is more deadly than a war. But there is a solution and it is BEEF INSULIN. The CDC told me they were behind in their counting in 2002. But I could smell the red herring when the stores ran out of Iletin I in 1999. And unfortunately I was right. Alarming! E-mail:  Margie Baker

FOOTNOTES
	1. ADA. Scroll to Understanding Diabetes, 1st para., last sentence. 2. see Charts, Stats and Policy

Correction: Type 2, not Type 1 (Yet) Potential Cure

Dear Friends, I have to report that after I sent Children With Diabetes (see blogroll) a message asking them to comment on the Imatinib/PDGF inhibition effects, they pointed out that the paper concerning Imatinib was referring to Type 2, not Type 1 subjects. This is how it was expressed in the study abstract:  “All patients had been diagnosed as diabetic at least 10 years before CML onset. Three patients were using insulin, and four patients were taking oral antidiabetic drugs for glycemic control.”

I thought it meant three Type 1s and four Type 2s, but apparently all  were Type 2s. The research is still valid, however, and may have effects on Type 1s, if it turns out the beta cells are only suppressed, not completely dead, as was indicated by the report I mentioned earlier done in the late 90s. If anyone can turn it up, I’d really like to have the citation. Also the effects of the PDGF inhibitor were faster, this was the ten-day effect as opposed to the ten-week effect of Imatinib I referred to earlier, so again this may be effective in restoring function for Type 1 beta cells. Hope I didn’t get anyone’s hopes too high up as mine were for a while, but stay positive!

23 Million and Counting

After talking with my friend Jim Yoakum about the difficulty getting accurate data regarding the number of diabetics in the US, he found a very good site, the National Diabetes Information Clearinghouse, which contains valuable statistical information regarding diabetes. It states there are 23.6 million diagnosed and estimated undiagnosed diabetics in the US, not as CBS’ Good Morning show stated on its web page a few years ago, ‘about one million.”

http://diabetes.niddk.nih.gov/

I also found a site that shows the steady increase in deaths among diabetics since the advent of biosynthetic ‘human’ insulin:

http://www.diabetictypeone.org/Charts,%20Stats%20&%20Policy1.html

I’ll add these to the blogroll tomorrow.

Oh, I mis-stated the amount of time for the PDGF inhibitor to restore beta cell function, going back over the study (see blogroll) it was ten days, not ten weeks!

Be the President Who Cured Type 1 Diabetes!

OK, here’s the thing. We now know how to cure incipient and at least suspend and perhaps cure long-standing Type I diabetes (see last three entries and blogroll). This isn’t a supposition, it has already been shown to be effective, in a drug already approved for human use, so extensive R&D isn’t necessary. The manufacturers of biosynthetic human insulin net billions each year (Lilly’s total sales for last year were over twenty billion dollars.

http://news.prnewswire.com/DisplayReleaseContent.aspx?ACCT=104&STORY=/www/story/01-29-2009/0004962536&EDATE=

Note that although they reported an actual quarterly (not yearly) loss, its first in history, that was due to their multibillion dollar purchase of another company, Imclone)

so clearly these guys are in  no rush to release a product that would remove their diabetic dependents from their customer base, one of its biggest components. In response to requests for the restoration of animal insulins, the FDA has repeatedly stated that they have no power to compel a company to produce any drug, and they will (unless the Obama administration is successful in their reform efforts, and I wish them luck), undoubtedly make the same assertion regarding the manufacture of a Type I cure.

However, there may be another way to achieve this. Most people are unaware that the pharmaceutical companies have been profiting from taxpayer funded research since the passage of the Bayh-Dole bill, in 1982, which permitted drug companies to use research from state-sponsored educational institutions, to develop and patent new products, then sell those same products back to the public at ridiculously high prices (AZT, for example).

http://www.populist.com/00.13.golden.fleece.html

The team that discovered the mechanism of curing Type I diabetes with (at first) a TK inhibitor, were all employed by the University of California at San Francisco, which is a taxpayer supported institution. Despite the fact we paid for the research, as described in the above link, they will give or sell it to a drug company, who will retain but ( I believe)  NOT USE the right to manufacture their drug that would cure diabetes. Because of their ownership, and drug patents, that is the right to a competition-free license to manufacture the drug and sell it at whatever price they choose, for a period which has grown longer and longer since the 80s, they will be able to block any other source of production of such a cure.

If the new administration is serious about reforming the FDA (and I strongly support their proposal to separate the food from the drug inspection system), then they could start by encouraging the repeal of Bayh-Dole, quickly if possible, before this drug is developed and patented, (I know this is a tall order), and the administration itself, through the NIH, for example, sponsor the development of a cure for Type I. Even without overturning B-D, a ‘Manhattan-Project’ style approach could be employed to quickly produce a cure, if it’s done before a drug company secures rights to the eventual product.  Again, the research has already been done, it’s safe for humans AND WE PAID FOR IT. There’s no need to wait. Write the White House (Sunday: just did so) and tell them you want Bayh-Dole repealed and a cure for Type I diabetes made available CHEAPLY to the public. Write The Juvenile Foundation for Diabetes and tell them the same thing. The esteemed Mary Tyler Moore appears on TV as their spokesperson, asking us to help develop a cure, well, Mary, we have one. Help us persuade someone to make it!

President Obama please step up!

Thank you.

Once again, comments are eagerly invited.

For background on Bayh-Dole and other techniques used by Big Pharma to overcharge the people who can least afford it, please read this article by Marcia Angell, published in 2004:

http://www.nybooks.com/articles/17244

Tyrosine Kinase Cure Continued

I hope everyone had a good holiday and are looking forward to a good new year. I was ill with a cold and a persistent cough, along with the usual sugar complications, but am mostly better now.

I have a few more details about Tyrosine Kinase inhibition as a cure for Type I diabetes. As detailed in the Dec 18 article from Science-Business eXchange, the key action is inhibition of PDGF, or platelet-derived growth factor. It is this action alone that is involved in suppressing the process which kills (or suppresses) the insulin-producing beta cells. Inhibiting PDGF allows, so far, young cells to resume function. The current theory (see article in blogroll) is that this will probably be effectve in recently-diagnosed patients, and less so in long-term sufferers, but this is true only if the beta cells are actually dead. and, as I mentioned earlier, a paper was released about ten years ago demonstrating they were still alive, but just suppressed. I showed it to and discussed with my Dr. at the time,  but no longer have the citation. If they can be revived, then this approach would work for long-term diabetics as well. Research is ongoing. A patent has been applied for by UCSF, who conducted the original study showing the effectiveness of this approach for the restoration of beta cell function, After that,  a PDGF-specific inhibitor (which we already have and is already approved for human use through its inclusion in the abovementioned drugs) needs to be released. We need to let as many people as possible know about this, to pressure anyone involved to release such a drug. It is seems unlikely Big Pharma will rush to eliminate a condition which nets them billions every year, so we will have to be as vocal as possible.

There is also another promising approach yielding results which address some of the issues I mentioned earlier regarding transplantation of beta cells. Take a look at the Physorg.com article about reprogramming donor cells to evade onn’e auto-immune response. Using proteins from adenoviruses (Adenoviruses infect tissues that line the respiratory tract, eyes, intestines, and urinary tract), that evade the body’s immune responses, researchers have been able to transfer this property to transplanted mouse beta cells, allowing them to function up to three months at a time, with the anticipation that this time will be significantly extended as they narrow down the choice of which specific proteins are needed. The article inclides comments from Denise Faustman, who has been conducting her own groundbreaking research into curing diabetes for at least the last decade. You can find out more about her work at Scott Strumello’s blog (see blogroll).

Type 1 Cure Discovered!

Type 1 Cure Discovered!

OK, I’ve followed up on Gleevec and its effects in causing remission of type 1 diabetes. It works by inhibiting the action of certain members of a class of enzymes called tyrosine kinases which transfer phosphates from donor to receptor cells (phosphorylation). There are twenty classes of these kinases and the 2nd class is involved with insulin production. Inhibition of one of the tyrosine kinase receptors in this group prevents cellular apoptosis, or programmed cell death, and in this case revives the function of the insulin-producing beta cells. A study came out ten years ago showing that beta cells are not actually dead, but rather suppressed, and this falls right in line with the implications of that study, that they could be reactivated. Now using Gleevec for this purpose is overkill, beacuse it contains mulitple TK inhibitors and only one is necessary for the remission of Type 1 diabetes. Also, it’s expensive as hell, looking online, it seems to average about $90. per pill and needs to be taken for about 10 weeks for lomg term remission.Check the blogroll for links to related articles.

Promising News

Having just seen a news article on NBC concerning a potential new treatment for diabetes using imatinib mesylate, sold as Gleevec ™ and made by Novartis. I’ve looked it up and initial findings are very interesting. While testing it for other conditions several years ago, researchers noted a major improvement in fasting blood glucose (FG) among their diabetic subjects. After this effect was studied, this paper was published in 2004:

Journal of Clinical Oncology, Vol 22, No 22 (November 15), 2004: pp. 4653-4655
© 2004 American Society of Clinical Oncology.
DOI: 10.1200/JCO.2004.04.217

E

Imatinib Mesylate May Improve Fasting Blood Glucose in Diabetic Ph+ Chronic Myelogenous Leukemia Patients Responsive to Treatment

M. Breccia, M. Muscaritoli, Z. Aversa, F. Mandelli, G. Alimena

University “La Sapienza,” Rome, Italy

To the Editor:

Imatinib mesylate therapy has shown significant activity against Philadelphia-chromosome positive chronic myelogenous leukemia (Ph + CML). This drug is a selective competitive inhibitor of the Bcr-Abl tyrosine kinase, but at therapeutic concentrations, it also inhibits the activity of other tyrosine kinases such as platelet-derived growth factor receptor beta (PDGF-ß) and c-kit.¹ Imatinib can be safely administered in CML patients with type 2 diabetes.

Here we report on our experience on the treatment of seven diabetic CML patients with imatinib. In six of these patients, we observed an improvement of fasting blood glucose levels (FG), which allowed a consequent reduction of oral antidiabetic drugs or insulin dosage. Of the seven patients, three were men, and four were women; median age was 66 years (range, 57 to 70 years). Four patients were in chronic phase, and all were given imatinib at 400 mg/d; of these four patients, three were resistant to prior interferon alfa (IFN-) given for a median of 25 months, while in one patient, imatinib was the first-line therapy. Three patients were in accelerated phase and were given imatinib at 600 mg/d; all of them had been pretreated with IFN- and hydroxyurea for a median time of 20 months.

All patients had been diagnosed as diabetic at least 10 years before CML onset. Three patients were using insulin, and four patients were taking oral antidiabetic drugs for glycemic control. Before starting with imatinib the median glucose level was 220 mg/dL (range, 162 to 305 mg/dL). After 3 months of therapy, six of seven patients had obtained a complete cytogenetic response. At the same time, concomitant improvement of FG with consequent reduction of antidiabetic drugs dosage was observed, although patients had apparently maintained the same lifestyle and alimentary habits. In particular, median FG was 110 mg/dL (range, 96 to 127 mg/dL), as compared with an FG of 160 mg/dL (range, 96 to 220 mg/dL; P = .0004) as evaluated after 3 months of precedent IFN- therapy. At the time of this writing, all patients have completed 12 months of therapy, six have maintained cytogenetic response and concomitant good glycemic control (median glucose level, 108 mg/dL; range, 89 to 124 mg/dL; as compared with 208 mg/dL; range, 171 to 245 mg/dL after 12 months of precedent therapy; P = .004) still on reduced antidiabetic drugs dosage. Only the accelerated-phase patient (patient 1), who was resistant to imatinib after 1 year of therapy, did not obtain a good control of blood glucose level despite increasing insulin dosages. Differences between fasting glucose concentrations before and after imatinib therapy are shown in Figure 1.

View larger version (45K): [in this window] [in a new window] Fig 1. Patient 1 was unresponsive to imatinib. Patient 3 was treated with imatinib as first-line therapy. IFN, interferon; FG, fasting blood glucose; pt., patient.

The mechanism(s) through which imatinib could improve FG in CML patients is presently not known. Boren et al² reported the in vitro evidence for decreased proliferation of Bcr-Abl-positive K562 human myeloid blast cells under treatment with imatinib at increasing doses with the concomitant reduction of glucose carbon incorporation into RNA, and of palmitate synthesis. This finding was ascribed to a direct effect of imatinib on key enzymes of glucose metabolism, such as hexokinase, glucose-6-phosphate dehydrogenase, and transketolase, which are primary targets of the drug. Further confirmatory evidence that the imatinib mechanism of action might include interference with glucose metabolism comes from the finding that the activation of Bcr-Abl tyrosine kinase is associated with the stimulation of glucose transport, and, therefore, a pivotal role by glucose metabolism may be played in the survival of stem cells in CML.³ Moreover, it has been shown⁴ that imatinib induces early functional changes in tumor glucose metabolism, which also correlate with tumor response in other cell types, such as gastrointestinal stromal tumors cells, characterized by surface expression of CD117 (c-kit).

In our experience, only patients responding to imatinib concomitantly obtained an improvement of FG; this suggests that the drug, at therapeutic concentrations, may act not only on Bcr-Abl tyrosine kinase, but also on intracellular pathways involved in peripheral insulin action in the host’s normal cells, through metabolic changes capable of influencing the normal enzyme activities in these cells as well.

In type 2 diabetes, the normal insulin signaling pathways are disrupted, and abnormal signaling in muscle, adipose tissue, liver, and pancreas leads to insulin resistance.⁵ Insulin resistance is brought about by a reduction of key signaling proteins such as insulin receptor substrate (IRS) -1 and IRS-2, and recently, a role for elevated free fatty acid concentrations and/or accumulation of intracellular lipids has been evoked in reduced-insulin sensitivity. It is possible that, as for K562 cells in vitro, imatinib also exerts its effect on normal cells in vivo by reducing fatty acid concentrations through a low rate of glucose carbon flow. However, it cannot be excluded that imatinib could interfere with any of the potentiallly disrupted molecular mechanisms downstream the IRS in the “diabetic cell,” thus contributing to restore almost normal glucose tolerance.

Another rather simplistic interpretation of our findings could be that glucose tolerance was improved in CML patients as a positive side effect of leukemic response, which could, by itself, imply reduced insulin resistance. However, this hypothesis is weakened by the clinical observation that four of the seven patients studied achieved disease remission with no improvement of FG during prior IFN- therapy.

In conclusion, we suggest that the role of imatinib on glucose metabolism warrants further investigation both in diabetic and nondiabetic CML patients. In fact, gaining insight into the yet partially unknown mechanisms of action of imatinib might, on one hand, contribute to overcoming imatinib resistance in hematologic malignancies and, conversely, help to better understand molecular abnormalities underlying insulin resistance in diabetes and other pathological conditions.

Authors’ Disclosures of Potential Conflicts of Interest

The authors indicated no potential conflicts of interest.

REFERENCES

1. Kantarjian H, Sawyers C, Hochhaus A, et al: Hematologic and cytogenetic responses to imatinib mesylate in chronic myelogenous leukemia. N Engl J Med 346:645–652, 2002[Abstract/Free Full Text]

2. Boren J, Cascante M, Marin S, et al: Gleevec (STI571) influences metabolic enzyme activities and glucose carbon flow toward nucleic acid and fatty acid synthesis in myeloid tumor cells. J Biol Chem 276:37747–37753, 2001[Abstract/Free Full Text]

3. Bentley J, Walker I, McIntosh E, et al: Glucose transport regulation by p210 Bcr-Abl in a chronic myeloid leukaemia model. Br J Haematol 112:212–215, 2001[CrossRef][Medline]

4. Van den Abbeele AD, Badawi RD: Use of positron emission tomography in oncology and its potential role to assess response to imatinib mesylate therapy in gastrointestinal stromal tumors (GISTs). Eur J Cancer 38:S60–S65, 2002

5. Rhodes CJ, White MF: Molecular insight into insulin action and secretion. Eur J Clin Investig 32:3–13, 2002
Wikipedia has an entry on imatinib, its history and use for cancer, but not diabetes.

http://en.wikipedia.org/wiki/Imatinib

I‘ve been trying to keep up with progress on a cure since the Edmonton Protocol, nearly ten years ago. That involved transplantation of donor beta cells. The problem I had with that strategy was replacing the use of insulin to control diabetes, a process that until biosynthetic insulin analogs, was fairly well understood, with a lifetime of daily immunosuppressive drugs that would greatly increase your chances of aquiring sonething much more severe, cancer, for instance, did not seem like much of a trade-off. Also, the cells came from cadavers, which while not a dealbreaker, wasn’t very appealing. I hoped that research would move into perfecting cloning for stem cells and the recovery of those pluripotent cells from the adult body of the patient, eliminating an immune counter-response. Those cells could then be implanted back into the patient. Subsequent research has indicated not only the liver but also the spleen are suitable base sites for active beta cells, suggesting that location may not be an issue, facilitating easy implantation. This approach and others similiar to it, however, all depend on the perfection of stem-cell recovery and cloning techniques.

Gotta go (left it too late)–back soon