Odds'n'Ends
This Discussion Forum is closed to new comments; please see the continuation: CLICK HERE.
It was the 15th in a series of Discussion Forums at Diabetes.Blog.Com, and is for almost any other diabetes-related topics that aren't covered by our existing Discussion Forums. I don't want stuff that's not related to diabetes, but just about any diabetes topic that's not covered by the other Discussion Forums will be okay here.
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Bill the diabetesdoc
wwq@diabetesmonitor.com
Diabetes.Blog.Com is a blogcompanion to our main website, the Diabetes Monitor, which you can find at www.DiabetesMonitor.com.
Sorry to blab on so long - thanks for the new site and all the help. (Comment this)
It (hair loss) has decreased dramatically since I started using a conditioner. I have NEVER had to use a conditioner because of the oily skin/hair that comes from the insulin resistance.
I take spironolactone for my blood pressure and after about 3 months on it, I noticed that the facial hair had decreased dramatically because it has an anti-androgen (blocks male hormones) effect. I haven't noticed any change since starting the Byetta, but then, we haven't had a functioning bathroom since August when we started the remodeling from hell. So, I haven't spent all that much time looking for facial hair:) (Comment this)
I believe the body reacts to severe stress and weight loss by shedding hair. I had severe hair loss when I first started on metformin and was losing weight and added a really good vitamin supplement/ antioxidant regimine which stopped it cold. I'm not going to get into specific brands but look at some of the recommendations for cardiovascular or cancer patients in terms of antioxidants and supplements and that should get you in the right ball park. Ask your physicians if you have questions. (Comment this)
Here is the link for the announcement about Byetta LAR (Long Acting Release) version:
http://investors.amylin.com/phoenix.zhtml?c=101911&p=irol-newsArticle&ID=748512&highlight=
You can see the Amylin pipeline here:
http://www.amylin.com/pipeline/default.cfm
Bill wants us to discuss new drugs on his new site: Research about meds (Comment this)
The results of Phase 1 clinical trials with a small patient set (14?) were phenomenally positive as Betty reported above.
Application for a large Phase 2, 1 year study, has been made to the FDA. It is expected to be approved.
Pending Phase 2 results, Wall Street financial analysts do not expect FDA approval (even with phenomenal positive results) until late 2008 to early 2010.
So, Byetta LAR is still 3 to 4.5 years away from commercial distribution.
I'll post this at the research forum too. (Comment this)
Byetta has shown Beta cell restoration in rats. There is some speculation in the scientific community that is may also occur in humans. There are more Clinical studies are currently underway.
Medscape's Laurie Barclay interviewed diabetologist John B. Buse, MD, PhD. Dr. Buse is chief of the Division of General Medicine and Clinical Epidemiology and director of the Diabetes Care Center at the University of North Carolina School of Medicine at Chapel Hill. Here is what he had to say about this subject:
>There are lots of animal data with GLP-1 and more limited supportive data with exenatide that suggest that these agents promote islet differentiation and inhibit beta-cell apoptosis, shifting the balance toward an increase in islet mass. The only data in humans with exenatide in this regard does demonstrate an improvement in islet functioning implied by improvement in the proinsulin-to-insulin ratio.
This is obviously an area of great excitement regarding this class of drugs, as it holds the promise that these agents might be particularly effective in diabetes prevention or even cure. It is premature to speculate a great deal in this regard, as for a long time we have been able to demonstrate multiple effective techniques for islet generation in animals that have not panned out in humans. However, this is an area of active investigation.<
Here is the NIH Clinical Trial now recruiting. As you see, the NIH is doing the study and it is for Type 1 diabetics. Obviously if it works in this instance, it will work in T2s.
http://clinicalstudies.info.nih.gov/cgi/detail.cgi?A_2003-DK-0245.html
Title:
Effect of AC2993 (Synthetic Exendin-4) - Administered Alone or in Combination with Daclizumab - On Islet Function in Patients with Type I Diabetes
Number:
03-DK-0245
Summary:
This study will determine 1) the safety of AC2993 in patients with type I diabetes; 2) the ability of AC2993 to improve beta cell function; and 3) the effects of immunosuppression on beta cell function. (Comment this)
(2) Also: if you haven't yet answered our polls to tell us more about yourself, we'd encourage you to please do so:
(Comment this)BYETTA is the first in a new class of drugs for the treatment of type 2 diabetes called incretin mimetics and exhibits many of the same effects as the human incretin hormone glucagon-like peptide-1 (GLP-1). GLP-1, secreted in response to food intake, has multiple effects on the stomach, liver, pancreas and brain that work in concert to regulate blood sugar.(1) BYETTA was approved by the FDA for use by people with type 2 diabetes who are unsuccessful at controlling their blood sugar levels despite using the commonly prescribed oral medications metformin, a sulfonylurea or both. For full Prescribing Information, visit www.BYETTA.com .
About Incretin Mimetics
Incretin mimetics is a new class of therapeutics for use in the fight against type 2 diabetes. An incretin mimetic works to mimic the antidiabetic or glucose-lowering actions of naturally occurring human hormones called incretins. These actions include stimulating the body's ability to produce insulin in response to elevated levels of blood sugar, inhibiting the release of a hormone called glucagon following meals, slowing the rate at which nutrients are absorbed into the bloodstream and reducing food intake. BYETTA is the first FDA-approved agent of this new class of medications. This is taken from Dr. Bill's page http://www.diabetesmonitor.com/byetta.htm
which is of course taken from Lilly. All of who are Diabetic and or Insulin Resistant are probably burning up our Beta cells and the hopeful thing about Byetta is the possibility that at least in the animal studies thaere was some regeneration.
(Comment this)
I assume that you are familiar with the story of Dr. John Eng.
The following contain information contained in a recent article in the NY Times on April 29, 2005 which I hope briefly tells the evolution of Byetta.
Dr. Eng's research found that the saliva of the Gila monster contains a hormone that could lead to a treatment of diabetes, and then licensed the discovery to San Diego's Amylin Pharmaceuticals in October 1996.
He did studies on the hormones of guinea pigs, and later, chinchillas. Then he looked for animal subjects that might be more difficult to analyze.
Eng came across what he thought were very interesting studies done in the early 1980s by gastroenterologists at the National Institutes of Health, who noted that the venom in certain snakes and lizards caused inflammation of the pancreas, where insulin is made. Of particular interest was the hormone in the venom of the Gila monster.
Dr. Eng first discovered a new hormone in the venom of the Mexican beaded lizard, which in 1990 he named exendin-3. But this hormone was vasoactive, which means that it contracts or dilates blood vessels.
That prompted Dr. Eng to look at the venom of the Gila monster, which is not vasoactive. There he discovered a hormone, which he named exendin-4 that was similar in structure to glucagon-like peptide 1 (GLP-1). While GLP-1 regulates blood glucose and satiety, as a potential drug it has a short half-life requiring multiple daily injections. He published his key paper on exendin-4 in a 1992 issue of The Journal of Biological Chemistry.
In 1992, Eng's studies revealed that the venom contained two compounds, including one that had never been documented.
The compound seemed to have properties similar to a human gut hormone, GLP-1, that was being researched around that time by scientists at Massachusetts General Hospital.
GLP-1 was exciting to researchers because it stimulates insulin secretion from the pancreas only when blood sugar is high, Eng said. When blood sugar levels are normal, GLP-1 seems to know not to stimulate insulin, the hormone that helps cells process blood sugar.
GLP-1 seems to help the body keep the blood sugar from dropping too low, Eng said
The problem with GLP-1, however, is that enzymes in the blood cause it to degrade quickly, Eng said. If it were to be used as a treatment for diabetics, it would have to be injected into the body almost hourly, something most people would not be willing to do.
But studies Eng performed showed that the Gila monster's hormone, exendin-4, doesn't degrade for hours, making it a much better candidate for a drug.
Dr. Eng licensed the discovery to San Diego's Amylin Pharmaceuticals in October 1996 and the rest id history.
As Betty said above, BYETTA is the first in a new class of drugs for the treatment of type 2 diabetes called incretin mimetics and exhibits many of the same effects as the human incretin hormone glucagon-like peptide-1 (GLP-1).
The foregoing depicts a very brief history of its evolution.
As an aside, I picked up the following from an article in National Wildlife, Feb-March, 1998 by Bert Gildart. It is mildly relative and thought I would include it in this post. It is an odd'n'end.
>For Gila monsters, rabbits represented a gluttonous intake, and herpetologists know that such a meal can provide a Gila monster with nearly half its yearly nutritional requirements. Unused energy is stored in the large, sausage-shaped tail and drawn on as needed. A fat tail indicates a well-nourished Gila monster.
Because Gila monsters can exist on so few meals, Beck has been fascinated by the lizards' metabolic abilities. From the lab, he learned that the reptiles have an unusually low metabolism rate, but he wanted to know more. Since 1983, the scientist has implanted radio transmitters in the abdominal cavities of wild Gila monsters. From the signals--as well as laboratory measurements--he has learned that the animals' metabolic rate lowers at decreased body temperatures, thereby reducing food needs. "It means," he says, "that Gila monsters can spend up to 95 percent of their lives underground and not have to spend a lot of time foraging."
Gila monsters have the "the highest aerobic capacity of any American lizard." And more specifically, he adds, "It's the male with the highest aerobic capacity that wins the amorous contest."<
http://www.zoeticzone.com/p/articles/mi_m1169/is_n2_v36/ai_20334596 (Comment this)
About Symlin and native amylin
http://www.symlin.com/pcg/about/default.cfm
Byetta is a glp-1 analog. It is the pharmaceutical version of exendin-4, an insulin secretagogue isolated from the Gila monster. The Gila monster eats only two or three times a year and exendin-4 is part of the regulatory system for the unusual demands placed on the animals pancreas. It has been approved for type 2 diabetics who have failed to achieve good glycemic control using oral medications. When Byetta was approved, the FDA gave Amylin Pharmaceuticals strong encouragement to continue work on this drug for use as a monotherapy, even though the company had not applied for this provision. Such a reaction by the FDA is extremely rare if not unprecedented.
It has several modes of action in humans, and like Symlin is only active in the presence of high plasma glucose, giving it a very good safety profile. Byetta also slows gastric emptying and promotes a feeling of satiety, and patients using it also lose weight. In the presence of excess plasma glucose it directly stimulates beta cells to produce insulin and it suppresses glucagon expression. Byetta acts on peripheral tissues and adipocytes to improve sensitivity to insulin. The activity on the adipocytes has also been shown to decrease inflammatory markers that are often elevated in diabetes. In addition to the glucose control and weight loss effects, data presented at the 2005 American Diabetes Association meeting showed that patients using Byetta had decreased LDL cholesterol, increased HDL cholesterol, decreased triglycerides and decreased blood pressure.
Byetta as a therapy for type 1 diabetes is currently being investigated in a clinical trial run by the NIH. It has previously been shown to promote growth of new beta cells in mice, rats and rhesus monkeys, and in human embryonic and fetal pancreatic cells. The NIH study is looking at the effect of Byetta on beta cell health in type 1 diabetics either with or without immunosuppressive drugs. An independent study of Byetta in type 1 diabetics showed that it could be safely given along with insulin, and that it delayed gastric emptying, decreased postprandial glucose excursion, and suppressed glucagon expression. Other metabolic markers were not studied..
J Clin Endocrinol Metab. 2004 Jul;89(7):3469-73. Exendin-4 normalized postcibal glycemic excursions in type 1 diabetes. Dupre J, Behme MT, McDonald TJ.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15240633&query_hl=34
Additional information about Byetta can be found at:
http://www.byetta.com
In the interest of full disclosure, I have been an investor in Amylin Pharmaceuticals for many years. I have a Ph.D. in molecular biology and I contribute to the Yahoo AMLN message board. I actually do not own very many shares. Knowing that these drugs are helping peopple regain control of their lives is as important as my investment.
I wish you all the best.
Marty (Comment this)
Gwen (Comment this)
you can also find a list of the side effects reported by the blog but not necessarily in the official info here
http://www.diabetesmonitor.com/m60.htm
(Comment this)
Thanks for the posts Marty. No disclaimers necessary. The Monster has become our new best friend and being a TCU graduate you know the Horned Frog is really a Lizzard too. (Comment this)
Marty, I appreciated your imput to the question too. I want to make a disclaimer myself. I am now an investor in Amylin and so is of my sons. I figure as a patient I can always be responsive to company policies. So you see it does get more confusing as we go along. Your insights and best wishes were heart felt and you are most welcome, as Betty said, on this blog. We are in to a new era and it does not appear what will happen in the future. I am beginning my 5th month today on Byetta. No side effects, BG kind a wobblying around but for the most part in the mid range.( 116-160) Average weight loss 5lb a month. Last A1c was 6.9. More later, thanks to both of you, John (Comment this)
Many thanks (Comment this)
Phone: (800) 433-2469
Address: 20460 Gramercy Place, Torrance, CA, 90501
John Dodson (Comment this)
Do you have PCOS, knowing all that info I thought you might had. I do have PCOS and I am insulin resitant. (Comment this)
Yea, I have PCOS. I was diagnosed with it about 4 years ago but have showed signs of it for years. But no one had heard of PCOS then. That is what has lead to the diabetes. I've read all I can on PCOS and IR. (Comment this)
The concept I was struggling with in my weight loss post on the other Blog and fat reabsorbtion is the Gila Monster seems to be devouring the cellulite. The weight loss is toned and smooth as if you have been in a gym working hard. (Comment this)
As you read this, please keep in mind that I am Ph.D. in molecular biology, not a medical doctor. This is not intended to be construed as medical advice. It is meant to supply a scientific basis for understanding what happens during diabetes progression.
I also do not have diabetes, though several people I care about do. As I do not have first hand experience with the disease, I would not feel comfortable contributing to the topic-specific blogs. However, I hope that what I post here might be of help to some of you who must live with diabetes.
Best wishes,
Marty
*****
J Biol Chem. 2003 Jan 31;278(5):2997-3005. Critical reduction in beta-cell mass results in two distinct outcomes over time. Adaptation with impaired glucose tolerance or decompensated diabetes. Laybutt DR, Glandt M, Xu G, Ahn YB, Trivedi N, Bonner-Weir S, Weir GC.
Section of Islet Transplantation and Cell Biology, Joslin Diabetes Center, Boston, Massachusetts 02215, USA.
We have proposed that hyperglycemia-induced dedifferentiation of beta-cells is a critical factor for the loss of insulin secretory function in diabetes. Here we examined the effects of the duration of hyperglycemia on gene expression in islets of partially pancreatectomized (Px) rats. Islets were isolated, and mRNA was extracted from rats 4 and 14 weeks after Px or sham Px surgery. Px rats developed different degrees of hyperglycemia; low hyperglycemia was assigned to Px rats with fed blood glucose levels less than 150 mg/dl, and high hyperglycemia was assigned above 150 mg/dl. beta-Cell hypertrophy was present at both 4 and 14 weeks. At the same time points, high hyperglycemia rats showed a global alteration in gene expression with decreased mRNA for insulin, IAPP, islet-associated transcription factors (pancreatic and duodenal homeobox-1, BETA2/NeuroD, Nkx6.1, and hepatocyte nuclear factor 1 alpha), beta-cell metabolic enzymes (glucose transporter 2, glucokinase, mitochondrial glycerol phosphate dehydrogenase, and pyruvate carboxylase), and ion channels/pumps (Kir6.2, VDCC beta, and sarcoplasmic reticulum Ca(2+)-ATPase 3). Conversely, genes normally suppressed in beta-cells, such as lactate dehydrogenase-A, hexokinase I, glucose-6-phosphatase, stress genes (heme oxygenase-1, A20, and Fas), and the transcription factor c-Myc, were markedly increased. In contrast, gene expression in low hyperglycemia rats was only minimally changed at 4 weeks but significantly changed at 14 weeks, indicating that even low levels of hyperglycemia induce beta-cell dedifferentiation over time. In addition, whereas 2 weeks of correction of hyperglycemia completely reverses the changes in gene expression of Px rats at 4 weeks, the changes at 14 weeks were only partially reversed, indicating that the phenotype becomes resistant to reversal in the long term. In conclusion, chronic hyperglycemia induces a progressive loss of beta-cell phenotype with decreased expression of beta-cell-associated genes and increased expression of normally suppressed genes, these changes being present with even minimal levels of hyperglycemia. Thus, both the severity and duration of hyperglycemia appear to contribute to the deterioration of the beta-cell phenotype found in diabetes.
(Comment this)
(2) Also: if you haven't yet answered our polls to tell us more about yourself, we'd encourage you to please do so:
(Comment this)Marty, you are welcome here and anything you wish to share is appreciated. (Comment this)
I just discovered why my hair is falling out and was excited to contact you when I read you also have a thyroid problem. My Endo has taken me off Byetta, but here is what we found in the meantime. The Byetta was causing my system to not absorb my thyroid pill. Guess what a huge symptom of LOW THYROID is? You guessed it....hair loss! In addition to that I also had very dry skin, and around 12 of around 16 other symptoms listed as symptoms of low thyroid. I stopped the Byetta this past Friday.... and doubled up my thyroid pill for about three days, and guess what -- no more hair loss, my skin is silky smooth again!
Don't know if this is your answer....but PLEASE check with you doc. as to when you are taking you thyroid pill. Byetta and Thyroid meds are not a good mix unless you take them in a way where your body can absorb the thyroid med without interruption! Please let me know happens. I sure hope this helps you! (Comment this)
There is nothing about the possible interaction of Byetta with thyroid hormone pills in the Byetta label.
If you have been taking thyroid hormone, and recently started Byetta, and now are finding symptoms of hypothyroidism (such as hair loss, fatigue, dry skin -- see the list at diabetes and your thyroid), ask your doctor to run a TSH level to check how things are going. If you previously had stable normal TSH levels on thyroid hormone therapy, and now they are elevated (indicating less thyroid hormone pill effect), it's possible that the change is related to use of Byetta, as Ruth suggests.
If this string of events turns out to be true for you, please nag your physician to contact the manufacturer, and to report the time sequence of use of the thyroid pill, the Byetta, the TSH lab tests, and the results of the TSH testing.
(Comment this)
I will certainly make it a point to have it checked more often. My dry skin/hair disappeared when I started taking a daily multivitamin, so I am thinking that was caysed by the weight loss (42 pounds as of yesterday at the doctors office):) (Comment this)
Thanks
Barbara (Comment this)
I try to remember, that when I see desserts, breads and other such items, then I am looking at a poison to my system. Just as our medications would be poisons at too high a dosage, we try to remember that too much (or any) of the wrong foods will poison us just as effectively. Hang in there, Barbara!!! And, if you fall off the horse, just brush yourself off and get back on it again!!! (Comment this)