Where I Left Off

Where I’m Going
But: Novolog, Novo Nordisk’s rapid-acting insulin, maintains a high degree of solubility even with a pH in the mid sixes. So the question that’s up next is, can the pH of Symlin be raised sufficiently such that the two solutions can remain soluble and effective while mixed in a single pump chamber?

The pH of Symlin
The first part of determining whether it is safe to alter the pH of Symlin is to determine why it is manufactured with such a low pH to begin with. Most insulins are made with a pH in the 7 range to ensure maximal solubility; is the same true for Symlin in the 4 range?

According to Amylin and research reported in “Kinetics of Pramlintide Degradation in Aqueous Solution as a Function of Temperature and pH,” the standard pH of Symlin has less to do with solubility of the peptide, and more to do with degradation over time. The isoelectric point of Symlin, as I mentioned in the last installment, is above 10.5, so Symlin has a lot of upward mobility before the molecules lose their charge and therefore motility.

However, the Symlin solution naturally degrades and becomes less potent over time, and this degradation happens at a rate that depends heavily on both storage temperature and pH. This particular study found that at a pH of 4.0, Symlin maintains potency for about two years at 5ºC (i.e., in a refrigerator) and for about one month at 25ºC (i.e., at room temperature). In contrast, at a pH of 5.0, the Symlin solution was found to degrade about three times faster. Similar results were published in a patent held by Amylin, in which the pH of 4.0 is selected as the most stable formulation of the solution, as, as the graph to the right shows, the rate of reaction increases rapidly with increasing pH.

But What About Me?
Clearly, for sale and commercialization of Symlin, long shelf life and solution stability is important. But I only need to the Symlin to maintain potency for as long as it lives in my pump plus the small amount of time it takes upon entering my body to be absorbed. So, thirty days at room temperature is probably more than I need. I could do with a week at room temperature, and that would still give me some wiggle room.

So let’s say– let’s say I mixed my Novolog and Symlin in a ratio that would be appropriate for my bolusing needs generally (that, of course, I would have to determine…), and added a weak base to raise the final pH of the solution to somewhere in the 6.5 – 7.0 range. Let’s say. Would I be able to get at least a week of solubility out of the insulin? And a week of potency out of the Symlin?

It certainly seems possible. And the reward if it works– the ability to use Symlin without separate injections or a second pump– is indeed tempting, enough that I will have to run at least a few tests to determine the feasibility of this.

Tests? Like, Human Tests?
Eventually, if everything goes as planned, I will have to try out any resulting mixture on myself, since I’m pretty sure it’s not legal to run ad hoc lab tests on pet store mice. That said, I’m certainly not going to just mix insulin and Symlin, load up my pump, and see what happens; a few test-tube trials are in order first.

My plan is to acquire some Symlin, some sodium acetate trihydrate (the weak base used to buffer and modify the pH of Symlin, according to Amylin’s documentation; fortunately, this is a standard sodium acetate, and even available from Amazon.com), and a pH meter. The pH meter may be a bit tricky, since meters with a decent level of accuracy are at least $100 (perhaps someone I know locally will have one to spare?). After I collect these materials, I will be able to mix and monitor the pH of various combinations and ratios.

I’ll keep my mixtures around for a while, and see if I get any obvious precipitation, clouding, or other corruption. Exact solubility and potency of each solution will be much harder to measure given my lack of lab equipment (anyone have a chromatograph I can borrow?), but… well… I’ll figure that one out when I get there.

Assuming any formulation of my mixture appears to maintain clarity for at least a week, and assuming I don’t get cold feet, I can consider moving on to stage two, where I become my own lab rat.

(Let me pause for a moment here and say: if you are a medical professional, Amylin employee, Novo Nordisk employee, or other knowledgeable party, and have reason to believe I might do some serious harm to myself, please, please, let me know.)

Why Hasn’t Anyone Else Done This Yet?
Now, that plan sounds pretty fun to me, but I must ask: if it’s so easy, why hasn’t someone done this? Why isn’t Amylin or Novo Nordisk all over this, marketing a mixable formulation? I have far too much faith in the power of the free market, human innovation, scientific inquiry, etc. etc. etc. to believe that no one’s thought of selling a mixable formulation!

And indeed, after some research, I found that as I suspected, Amylin and others are indeed all over this problem. On top of the studies mentioned earlier on mixing pramlintide and insulin, and on formulations of Symlin at different pHs, I came across a few patents that reassured me that my home-brew method will likely be made obsolete soon enough. Amylin Pharmaceuticals has a number of patents covering different formulations of pramlintide, one of which speaks specifically about solid formulations for pills, polymerized formulations for nasal or pulmonary delivery, and, most interesting for my purposes, formulations that were mixed with insulin and tested for solubility and potency. According to the tests cited in the patent, pramlintide was mixed with Regular insulin and alsp 70/30 Regular/NPH combinations. The resultant solutions had pHs in the upper-six to seven range, and, according to the cited tests, maintained insulin solubility for up to 33 days at 30[0][C]. Not bad! And, very promising for my upcoming home trials.

The obvious question is, why isn’t this on the market yet? And that I must admit I do not know; I don’t know enough about the pharmaceutical pipeline and FDA regulations to know what it takes for an idea, tests, and a patent to come to the shelves. (Any Amylin employees out there want to weigh in?)

More promising still, Amylin is not the only player in this game. In addition to patent applications for dual-chamber pumps, I came across a very interesting series of applications from Novo Nordisk for their own proprietary amylin agonist, and formulations based upon it. According to the application, their version of the peptide is more stable than Amylin’s version, with a longer action time in the body, and also reduced chance of degradation and fibrillation at higher pH levels. This allows for more easy mising with Novo Nordisk’s own insulins, and thus is a very promising prospect for us diabetics. The applications are from early 2009; so I’ll keep my eye out, but I certainly won’t hold my breath, given that the Patent Office and the FDA are two notoriously slow regulatory agencies standing in the way of any new drug.

To Be Continued
So, clearly, the free market is out there, working to create the next drug I will happily purchase, but until then, it looks like I’m on my own. I admit, part of me isn’t really disappointed; I’m pretty excited about my home-chemistry project. It’s been a while since I’ve gotten to play with pH buffering!

And One Last, Really Interesting but Only Tangentially Related Addendum
In the course of my patent search, I came across one other Amylin patent for Symlin uses that I found particularly notable: “Amylin agonist for treating depression, anxiety disorder and schizophrenia.” Apparently, Amylin Pharmaceuticals has found that

amylin is shown to share properties of anxiolytic, antidepressant, and antipsychotic agents in behavioral testing. Thus, it has now been discovered that amylin and amylin agonists may have the surprising ability to treat psychiatric disorders. Psychiatric disorders that can be treated include mood disorders, anxiety disorders, schizophrenia and other psychotic disorders, substance-related disorders, sleep disorders, somatoform disorders, and eating disorders. These compounds may be particularly effective in treating psychiatric disorders that have elements of metabolic disturbances, e.g., eating disorders, or in treating patients with a psychiatric disorder or those with a psychiatric disorder and who also suffer from a metabolic disturbance.

Allegedly, according to a number of animal tests that Amylin has done, amylin and amylin agonists like Symlin have been shown to reduce anxiety and stress, perhaps by modulating the corticotropin-releasing factor and glucocorticoid pathways. The pathways proposed in the patent are known to play a role in the intricate and delicate interactions of the hormones of the brain and endocrine system, stopping along the way at the hypothalamus and metabolic processing. Plus, unlike other psychiatric drugs out there, pramlintide tends to cause weight loss rather than weight gain, so that would be one less side effect to worry about.

Clearly, this has not been proven effective or commercialized yet, but it’s an interesting idea and an interesting read, especially if you, like me, are fascinated by the interdependencies of metabolism, endocrine hormones, inflammation, and various incarnations of depression and anxiety.

Please note: I am not a doctor, or a medical professional, or even a chemist. The above is intended to be purely informational, and is based on my own research; it has not been independently verified, and is not medical advice.

image from www.wikipedia.org

When I saw this movie for a high school assignment, I hadn’t yet been diagnosed with diabetes, but my brother had. My mom made a reassuring assessment of the movie’s plotholes (Once Leonard has given his wife several injection, wouldn’t she finally realize he’s not faking his condition and drink some orange juice? If Leonard saw his wife going into a coma, wouldn’t he call an ambulance?) Still, I found the movie very disturbing. It reminded me that diabetics are constantly vulnerable, despite every attempt to manage their condition as well as possible.

After watching Memento, I’ve never felt the desire to watch another movie about a diabetic. This is partly just my taste; while some people find it comforting to watch movies that address their health issues, I’m usually more of an escapist–I’m not sure I’d seek out a movie about a diabetic character even if the portrayal wasn’t depressing. Still, watching Memento made me curious. Were there any other movies about diabetics?

My google search of “diabetics” and “movies” yielded a list from dLife.com of several movies with diabetic characters. From the accompanying short description of each, I found out that there are films with diabetic characters in all different genres. You can see the full list here.

In most thrillers, like Memento, diabetes is introduced as a fatal flaw for other characters to exploit. As you can probably imagine all too well, inducing hypo- or hyperglycemia in a diabetic is an effective way to put that character’s life in danger. In Big Nothing, an agent is killed when he is force-fed sugar by his nemeses. In The Panic Room, a girl has a seizure induced by low blood sugar while trapped in the panic room without her glucagon. In Con Air a convict’s syringes are destroyed in the middle of an airplane flight and the convict is unable to take a necessary shot of insulin.

Dramas also explore the hardships associated with diabetes, albeit less sensationally. The problems mentioned in many of these movies are ones with which many people, including me, can empathize. Bread & Roses portrays a woman in financial difficulties because of her husband’s diabetes. In Mad Money the protagonist’s coworkers mistakenly believe she’s a drug addict after seeing a syringe fall from her purse. In Chocolat (the one movie on dLife’s list I’ve seen besides Memento), Judi Dench plays a grandmother with diabetes. Despite pressure from her daughter to stick to a diet, Dench’s character secretly buys hot chocolate at the the newly opened chocolate shop in town. dLife includes a quote by Dench about the grandmother’s role in the film: “At the end, through the metaphor of chocolate, people are able to embrace a free lifestyle and sexual freedom and reject repression of all kinds. And that wasn’t available to the woman with diabetes. Well, it was, but at a price.” This price, eventually, is death. Nevertheless, the film isn’t moralistic. While the chocolate shop contributes to the deterioration of the grandmother’s heath, it also heals her emotionally and prompts her to take a new interest in her grandson and the other townspeople.

If the depiction of diabetics’ weakness in most films depresses you, you might appreciate the fantastical superpowers somehow attributed to diabetics in horror flicks. In Scarecrow Gone Wild, a diabetic boy goes into a coma and emerges as a scarecrow bent on taking revenge on the football players who’ve tormented him. In The Warlock, a syringe is a diabetic girl’s weapon of choice when she destroys the warlock. (Apparently an injection of salt water is lethal to warlocks. Who knew?) At least it’s gratifying that a character’s diabetes condition empowers her to defeat an evil character, and not vice versa.

I’m curious as to what other people think about movies with diabetic characters. Do you enjoy or avoid watching them? Are there portrayals of diabetics from certain movies that you find especially accurate or moving? Which movies with diabetic characters would you recommend to others?

12 voted that Avandia should be withdrawn; 10 voted that its sales should be restricted and the warnings on its label enhanced; 7 voted only to support enhanced warnings on the drug’s label; and 3 voted that the drug should continue to be sold with its present warnings unchanged
(F.D.A. Panel Votes to Restrict Avandia, New York Times, 14 July 2010)

Now FDA leadership must make the final decision by reviewing all data supporting or opposing the sale of Avandia on the US market.  Where is that one simple defense (study, report, mandate) that shows the public proof in numerical value and without question that Avandia was safe to approve in 1999?  Where is the proof that without Avandia the world would be a poorer place – lives would be lost – people would suffer?  What exactly are the unique benefits of Avandia?

They don’t exist.

It won’t come as any surprise to some that I, having worked for many years inside the pharmaceutical industry alongside doctors, scientists and technicians; finance executives, marketers and  government liaisons, heard off-the-cuff justifications for getting the product “on the market” quickly — patients are gonna die anyway – we’re just delaying the inevitable.

No harm done then, eh?  Attitude aside – this is the big business of drugs.  The pharmaceutical business ’sees’ millions of patients;  a doctor has many patients but sees only one patient at a time.  The pharmaceutical industry has been strategizing for years to develop a similar relationship with their customers.  “YOU are important to us!” they shout, and we believe it.  What is happening this week in the debate to keep or withdraw Avandia is both the public’s denial that health care business is an industry tied to big profits versus the business of ‘caring’ and the regulator environment, medical community and industry’s need to keep that public trust intact.  The myth is cracking.  People are angry and worse, dead; opinion leader physicians are outraged; studies are “deceptive” and “incorrect.”  It’s been a real shake-up, but unfortunately the public must depend on the same agency, who erroneously approved Avandia 11 years ago, to decide it’s fate today.

What about all those Avandia prescribing doctors? I read in online comment zones.  What is their role in this debacle? There are a lot of not-so-good doctors in our world – just like their are a lot of not-so-good politicians, bankers, lawyers, and sadly, oil industry executives.  The FDA doesn’t regulate doctors; it approves products for the US market.  Regulating doctor decisions for standardized patient care is an entirely different issue and so far out of reach at this moment that it is not even worth discussing.  How about patients who have been successful on Avandia? If I am a patient prescribed a copycat drug (meaning easily replaced with alternative) and succeeding but fully aware that hundreds of patients are dying from the same drug – would I want that drug to remain on the market given the fact there were other equivalent options for me?  Ignore this suspect cry from the peanut gallery.

The FDA won’t be looking at any anecdotal evidence anyway.  The agency requires particular data for approval and Avandia maker, GlaxoSmithKline, knows exactly how much of a percentage point they need to cover.  It’s a symbiotic relationship that has developed over years of deregulation.  More importantly today, what is reflected in this split decision is the FDA’s determination to elevate self-preservation (and saving face) over the safety of the public.

For patients, it’s good to know.

Representatives for the FDA panel on the news broadcasts looked more like dozens of blind chickens before the slaughter.  And now these same FDA folks may believe that what’s at stake is saving their careers, or promises made, or reputations on the line for approving the drug in 1999 (and re-approving in 2007), and forgetting the reason they exist is:

for protecting the health of all Americans and providing essential human services, especially for those who are least able to help themselves. (Department of Health and Human Services)

Well, they haven’t.

Even if FDA leadership withdraws Avandia from the market in the days ahead – it’s too late.  GlaxoSmithKline said it will book a legal charge of $2.4 billion to settle long-standing cases related to Paxil (anti-depressant) and Avandia, but somehow that doesn’t make me feel much better either.  The US Department of Health and Human Services has some cleaning up to do in the FDA leadership closet and until then, my trust is gone.  But what is the practical take away for any consumer or patient?  Be aware, ask questions and stay informed.  If the side-effects for a medicine sound too great – they probably are.  Use caution in beginning a new course of treatment.  Don’t be swayed by glossy promises for a better life with X drug – look at the facts.  Be intelligent.

For those individuals who can’t or won’t take caution – the misinformed, the woefully too sick to think – they will suffer the most.  Pity them because these are the people the FDA should be protecting, but aren’t.

For more stories by this author see diabetes 24-7.

Symlin (also known by the generic name pramlintide acetate) is Amylin Pharmaceutical’s patented and commercially available synthetic analog of the naturally occurring endocrine hormone amylin.

Amylin is circulated throughout the body and helps to control post-meal glucose levels by impeding the release of glucagon from the liver and simultaneously slowing the rate of gastric emptying and subsequent intestinal uptake of carbohydrates. In short, amylin works in tandem with insulin to mitigate the effects of glucose that is ingested.

This close concert of amylin and insulin, however, does not stop with their joint functionality: amylin is made by the beta cells in the pancreas, and secreted in conjunction with insulin. And to all of us familiar with type 1 diabetes, this is where we say, “Alas and avast,” because, sadly, my body makes neither insulin nor amylin.

So that’s where Symlin comes in. Symlin has been available commercially for a number of years now, and an increasing number of type 1 and type 2 diabetics are augmenting their insulin-replacement-therapy with Symlin. The use of both hormones has been shown to reduce postprandial glucose spikes and reduce HbA1c measurements overall for patients, implying better glucose control.

I like this idea, and I want me some Symlin to replace my amylin.

But there’s a problem. Like insulin, Symlin can’t be taken orally. And it can’t be mixed with insulin in its synthetic formulation. So taking Symlin means either separate injections using something like Amylin Pharmaceutical’s Symlin Pen, or wearing a second pump to inject the hormone subcutaneously.

Some people I’ve spoken to say Symlin pumps work better, as they mimic more closely the natural flow of amylin throughout the body. But that would mean adding another hole to my already assailed body, and, frankly, I’m running out of space to stick things.

On the other hand, I’m not keen about the idea of injections either. Been there, done that, moved on. The thought of carrying around pen needles, and having to take shots before meals again… ugh. And ow.

So I’m back to square one, it seems. So much for Symlin.

Pause. Wait. Why isn’t anyone saying anything? This is where you’re supposed to say, “What, and give up that easily?”

And I respond, “Wait a minute, you’re right. Where’s my inner rebel when I need her?”

Take a look a few paragraphs up. Here’s what I said: “But there’s a problem. Like insulin, Symlin can’t be taken orally. And it can’t be mixed with insulin in its synthetic formulation.”

The skeptic in you should have complained at that point. You should have said, “Well, who says you can’t take it orally? Who says you can’t mix them?”

But that’s OK; I’ll say it for the both of us: Who says Symlin has to be such a pain-in-the-abdomen?

Claim 1: Symlin must be injected, and can’t be taken orally.
This one I can’t really get around; like insulin, Symlin needs to be circulating throughout the bloodstream in order to work properly, and science has not yet found a reliable way with either insulin or amylin to create a synthetic, oral version for type 1 diabetics. The complexities of digesting a drug that must in turn be used to monitor and manage the act of digestion have not yet been surmounted by the major drug players yet. Bummer.

Claim 2: Symlin and insulin cannot be mixed.
This claim gives us a bit more wiggle room. I’m not going to try drinking insulin or Symlin, but mixing them seems like it _should_ be an option, right? Figure out a standard ratio that works for me, include both in the pump reservoir, and use as if they were being simultaneously secreted by my stand-in pump pancreas?

So what’s the problem? People say the two shouldn’t be mixed. But who trusts an internet forum, right? Well, the prescribing information for Symlin says the two should not be mixed as well. Hm. But who trusts a drug company, right?

I look deeper, and find an American Journal of Health-System Pharmacy article from April 2005 called “Properties of pramlintide and insulin upon mixing.” Perfect. Written by a number of clinicians and directors at Amylin, this paper makes clear the issue with mixing Symlin and insulin:

“Pramlintide and insulin formulations interact primarily through their buffering systems. Most insulins have an isoelectric point in the range of 5–6 and are formulated at a pH of around 7. Pramlintide has an isoelectric point of >10.5 and is formulated at a pH of 4. The interaction of pramlintide and insulin formulations at different pHs (with different buffering capacities) potentially could result in precipitation of soluble insulin components or solubilization of crystalline insulin components. In vitro studies with pramlintide and short- and long- acting insulin formulations found substantial variability in insulin solubility when various quantities of insulin were mixed with fixed quantities of pramlintide.” (p. 821)

Darn. What does this mean? Synthetic insulin formulations, with the exception the long-lasting insulin glargine, like to live at a pH of about 7.4. This is because the isoelectric point of these synthetic insulins is about 5.4. The isoelectric point is the point at which the molecules of insulin in solution have no electric charge; at and near the isoelectric point, then, the insulin molecules are no longer active and ionic, and they become very stable. This stability, unfortunately, means that the insulin precipitates; the active insulin molecules bind and form a powder-like substance that falls out of the solution. The insulin molecules, no longer dissolved and distributed, cannot be absorbed or used by the body, and so the insulin is at worst useless and at best unpredictable.

By keeping insulin at a pH in the 7.0 – 8.0 range, then, manufacturers can ensure that that the insulin will not acidify and precipitate out of solution. This, clearly, is important to the potency and usefulness of insulin, but it makes mixing insulin with another solution that has a pH of 4.0 very questionable indeed.

In the 2005 study, mixing the two within a syringe that was used immediately seemed OK, and did not seem to decrease the solubility and absorption rates of the insulin, but the authors caution that the study did not test the many insulin types (just Regular and long-acting insulin), and that in vitro studies imply precipitation might occur, and that insulin’s pharmacokinetic properties are so variable according to person and environment that they can’t say for sure that the slightly longer time-to-max-effect of insulin in some of the trials was not caused by the mixing of insulin and Symlin (p. 821).

Plus, the study was conducted using syringe injections, which present a different set of problems than my hope of mixing the two in an insulin pump. The syringe concoction only has to last as long as it takes to inject and be absorbed by the body; mixing the two in a pump requires that the insulin remain soluble and uncorrupted for several days in the reservoir. Additionally, even a small amount of precipitation can have large effects in a pump, since the precipitated insulin can clog up tubing and infusion sites. In fact, though the prescribing information for both Humalog and Novolog says that “Hydrochloric acid 10% and/or sodium hydroxide 10% may be added to adjust pH,” they also specifically warn that the insulin “should not be diluted or mixed with any other insulin when used in an external insulin pump.”

Vive la resistance!
So, as many of us know from experience, insulin is a finicky little chemical, and does not like to have its pH changed. But, importantly, not all insulins are created equal; the pH sensitivity of different insulin formulations varies, according to the 2005 paper “Precipitation of Insulin Products Used for Continuous Subcutaneous Insulin Infusion.” (Note: this paper is written by chemists at Novo Nordisk; take it with a grain of salt if that’s your style.) The study compared the relative amount of precipitation at varying pHs for insulin aspart (Novolog), insulin lispro (Humalog), and Regular insulin. As you can see in the chart they produced, the solubility curve on each type of insulin is very steep; that is, there is a region in which they are not soluble at all, a region in which they are nearly entirely soluble, and then a very short region of transition between the two where the insulin is variably soluble. And, Novolog, Novo Nordisk’s own rapid-acting insulin, doesn’t start precipitating until a pH as low as about 6.0.

And here I run to the refrigerator, and check which brand of insulin I am issued by Kaiser. Novo Nordisk Novolog. Sweet. That gives me some leeway. I don’t like the idea of messing with the temperamental insulin’s pH, but if I’ve got from the neutral pH of 7.2 – 7.6 all the way down to the minimal allowable pH of 6.0, then perhaps, if I can bring up the pH of Symlin to between 6.0 and 7.0, then I can safely mix them.

So– the next set of questions– why is Symlin kept at such an acidic pH? Can it be safely kicked up a notch or two? What would that require?

I have begun to investigate these questions, and the preliminary answers are promising; but there’s more research to do before I advance to step two: Fun with Home Chemistry! And, if all goes well, step three: Karmel becomes her own lab rat! So, we’ll continue this conversation in the next installment of this Symlin saga.

Please note: I am not a doctor, or a medical professional, or even a chemist. The above is intended to be purely informational, and is based on my own research; it has not been independently verified, and is not medical advice.

I just returned from Roche’s second annual social media summit. Last year 29 of us diabetes bloggers and broadcasters were flown to Roche HQ in Indianapolis for an open exchange. Roche was putting its toe in the water. Wanting to learn from us how to enter social media as a good “citizen.” We were given carte blanche to have our say about big pharma.

A day’s dialogue resulted in Roche hearing our needs and wants as patients, and we delivered a Roche-map for “Social Media Do’s and Don’ts.” For instance, Do: Keep It Real, Educate and Earn Trust. Don’t: Spam, Sell or Self-Promote.

A week ago we were invited back for a second summit. This time the group was larger, 37 bloggers and broadcasters, and the meeting was designed largely for our benefit. Of course I’m of the mind either way you slant it, a pharma better understanding the experience of living with diabetes and doing something with that knowledge can only benefit all concerned.

The meeting kicked off with Lisa Huse, Roche Director of Strategic Initiatives/Diabetes Care, giving a recap of four initiatives Roche enacted based on our recommendations last year:

1) “Keep It Real” – Display the real experience of diabetes, the real blood sugar numbers we get, and teach patients what to do with them. ACCU-CHECK’s “Testing in Pairs” and “360″ View are two such tools.
2) Address Diabetes Costs – ACCU-CHECK now offers a 15% prescription discount card and Patient Assistance Program.

3) Advocate For the Diabetes Community – That’s happening through the Diabetes Care Project: A coalition of like-minded organizations improving care for those living with diabetes.

4) Help the Diabetes Community Amplify Its Voice – Clearly evident through this year’s exchange between us and the American Diabetes Association (ADA) and the American Association of Diabetes Educators (AADE).

And that’s what the rest of the meeting consisted of–an open exchange with representatives from the ADA and AADE.

The ADA was invested. They showed up with six representatives including David Kendall, Chief Scientific & Medical Officer. They were extremely open about the need and desire to turn their battleship organization around to be more representative of, and better serve, patients’ needs including type 1s. And, they agreed there’s a need for more transparency. Kendall cited the ADA’s “Stop Diabetes” campaign as a first step in becoming more patient-centric, and each participant felt a small bridge had been crossed.

We shared with the AADE our concern that there are not enough diabetes educators for the growing number of patients. For the current 26 million Americans with diabetes and 60 million with pre-diabetes, there are only 15,000 educators nationwide. And they are not growing in number but decreasing. We asked the AADE to advocate for more, and more direct, routes to becoming a diabetes educator. We asked about a track for patient-experts to become educators in some recognizable fashion. And we vowed to support their work, and their members, through the online community.

The day’s meeting ended with dinner and games and Roche donating $2,250 worth of game winnings, at the winners’ request, to five diabetes organizations. You could also say the meeting began short of a year ago, through the quarterly phone calls Roche held with us in-between these two annual meetings.

I am impressed by Roche, and any other company that knows the power of dialogue with customers and strives to make it happen. While we can assume this benefits Roche’s bottom line, it also benefits patients in getting products we need and want.

I also experience the Roche team as heartfelt. At the end of Lisa Huse’s talk she told us that during this past year following our blogs and having her ear on the ground with us, she’s come to understand diabetes in a way she never did her first 11 years with the company. Isn’t that what we want all companies to say?

So as I finish this article, tens of diabetes bloggers are tweeting and blogging and sending each others’ posts about the summit around the internet. And, really, what could be bad about that for Roche, and for us?

Below are all the bloggers and broadcasters who attended.

Karmel Allison, A Sweet Life
Christel Marchand Aprigliano, dLife
Brandy Barnes, Diabetes Sisters
Rachel Baumgartel, Dueling Diabetes on dLife
Gretchen Becker, Wildly Fluctuating
Chris Bishop, The Big D
Sarah Jane Blacksher, Adventures of Diabolical Diabetty
Allison Blass, Lemonade Life
Leighann Calentine, D-Mom Blog
Kitty Castellini, Diabetes Living Today
Charlie Cherry, Diabetes Power Show
Kelly Close, CloseConcerns
Beatriz Dominquez, Betizuka
Wil Dubois, Life After Dx: The Guardian Chronicles
Bennet Dunlap, Your Diabetes May Vary
David Edelman, DiabetesDaily
Elizabeth Edelman, DiabetesDaily
Bernard Farrell, Diabetes Technology
Bob Fenton, Exploring Diabetes Type 2
Riva Greenberg, Diabetes Stories
Manny Hernandez, TuDiabetes
Jeff Hitchcock, Children with Diabetes
Michael Hoskins, The Diabetic’s Corner Booth
Scott Johnson, Scott’s Diabetes Journal
Scott King, Diabetes Health
Sara Knicks, Diabetes Daily
Kelly Kunik, Diabetesaliciousness
Crystal Lane, PumpedUP
Dana Lewis, Healthcare Communications & Social Media
David Mendosa, Mendosa.com
Cherise Shockley, Diabetic_Iz_Me
George Simmons, The B.A.D. Blog
Chris Stocker, The Life of a Diabetic
Scott Strumello, Scott’s Web Log
Kerri Morrone Sparling, SixUntilMe
Amy Tenderich, Diabetes Mine
Lee Ann Thill, The Butter Compartment
Christopher Thomas Polack, Diabetic Rockstar
Ginger Vieira, Living in Progress

In full disclosure all expenses were paid for by Roche for the social media summit. I was not asked to write this article.

Originally published on Huffington Post.

If I took a poll on the one question I have had to answer the most over the past 36 years with diabetes, it’s this one:

"Does it hurt?"

“No.” I’ve answered many times. “There are worse things.” I’m not certain why I don’t tell the truth. The exercise of inserting a needle into the tips of my fingers seems very insignificant in the scheme of things.  I already have a life-threatening illness – what’s a little pin prick?

But the truth is – it does hurt -  and it can sometimes feel like the first second of a bee sting.  People with diabetes need to test their blood sugars at least 4-6 + times per day, which means that many of us have had as many as 100,000 tests in a diabetes lifetime.  For many patients, especially small children, fingers are just too delicate for the daily rounds of finger-sticking.  Others, who have been testing blood sugars for three decades, have thick callouses on their fingers from years of the blood-letting wear and tear.  Blood sugar testing is another misunderstood burden in the world of diabetes self-management.  Testing is tedious, painful, skin damaging and absolutely necessary for eating, sleeping, exercising, and even for something as mundane as driving a car.  In fact, for people who manage diabetes with insulin, testing blood sugar is often the difference between living or not.

Because testing blood sugars is such a fundamental and painful part of diabetes care, I was keen to learn more about a team of Hong Kong scientists and academics working on clinical studies for a Near-infrared (NIR) non-invasive blood glucose meter.  Professor Joanne Chung (Hong Kong Institute of Education) and her colleague Professor Thomas Wong (Hong Kong Polytechnic University)  have been developing the Near-infrared (NIR) technology since 2004.  They have conducted seven clinical studies on more than 800 patients with a high degree of success, and are currently working on their eighth study.  Benefits of non-invasive technology to measure blood sugar include a needle-free, pain-less testing system which eliminates possible infection and the high cost of current test strips prescribed today.   It would also make millions of patients more relaxed about testing and infinitely more motivated to test.

The Problem of Pain

I met Professor Joanne Chung at the Hong Kong Institute of Education, located in Tai Po in the New Territories of Hong Kong, near the border of mainland China.  Before her academic career, Professor Chung spent years working in clinical settings caring for patients in intensive care units and for people with cancer and diabetes in local hospitals and hospices.  She quickly became interested in understanding the problem of pain so much so that it became the basis of her PhD work. In fact, Professor Chung continues to run a local pain management clinic in conjunction with her full-time research work on the Near-infrared (NIR) non-invasive blood glucose meter.  Having seen such a wide spectrum of patient pain in her earlier clinical days, I wondered why she chose to focus on this aspect of diabetes.

“When you compare the pain of a pin prick to neuropathy, or cancer pain, it is very small, but the problem with blood glucose testing is how patients suffer with it every day. There is no other remedy.  It’s impossible to separate the difference between pain and suffering.  Professor Wong, myself and the rest of the team wanted to do something about this pain and suffering in diabetes care.  It was something like a dream in the beginning.” Professor Chung and the scientific team decided to move forward and outline deliverables for a non-invasive technology, and at first, assessed then current research by traveling to different countries to meet with scientists working in the field and analyzed other models such as the Glucowatch.  Then they got to work on their dream.

Near-infrared Technology (NIR)

What is NIR?  Near-infrared technology uses light spectrum with different wavelengths to detect blood sugar values and is used traditionally in animal studies for glucose measurements, but these laboratory methods are too dangerous for use on humans.  For proprietary reasons, I can’t go into a great deal of detail, but very simply, Professor Chung’s research prototype uses the NIR technology via a spectrometer light source (at a lower safe level) to detect the level of glucose in the blood with a tiny sensor (1/4 of the size of a dime) worn on a patient’s earlobe, forearm or fingertip (and here’s a practical piece of information for finger-sticking patients – the forefinger and the middle finger are the easiest to replicate).   Currently the team has succeeded in stabilizing all measurements below 8 mmol/l and above 4.2 mmol/l.  (For mg/dl, mutilply these values by 18). For blood sugars between 8  and 12 mmol/l, the research is less stable but still classified as valid or acceptable.   Because hypoglycemia is a major concern for all patients, the product is not yet ready for market although some in the industry who are more commercially eager would argue that it is.  Has the team been contacted by the pharmaceutical industry or other academic centers?  “Yes, we are working on plans for next steps today.” Why are the lower blood sugar readings a problem for the team?  Professor Chung doesn’t have the data for the lower readings because out of the 800 subjects she has tested very few patients suffer from hypoglycemia.  In other words, Hong Kong cannot provide Professor Chung with an adequate type 1 population for research.   All seven studies so far have been conducted on type 2 patients and a very small population of healthy individuals.   More studies are needed on type 1 patients, and for that, the research will have to go outside of Hong Kong.  (Hong Kong population is 7 million, type 2 population is estimated at 10%; Type 1 population is estimated around .0002).

The only  “noninvasive” glucose meter to have received U.S. Food and Drug Administration (FDA) approval was the Glucowatch in 2001 but the product was removed from the market in 2007.  The Glucowatch administered a small electrical charge to bring glucose to the surface and read by the watch  sensor, but it caused skin irritations, rashes and its overall accuracy was problematic.   Today, Echo Therapeutics, a transdermal medical device company based in Franklin, Massachusetts, is developing a wireless, needle-free transdermal continuous glucose monitoring system called Symphony tCGM, described in Scientific American Magazine earlier this year.  Like the Glucowatch, the Symphony tCGM passes tiny electric pulses into the skin using a biosensor which detects glucose as it diffuses out through the capillaries.  The readings are sent wirelessly to a handheld device.  I asked Professor Chung about the the Symphony tCGM, “The preliminary prototype has given promising results,”  she told me, but there are issues. “The longevity of the sensor, the accuracy of the device, the transdermal blood glucose variation (in terms of the time lag) and longitudinal adverse outcomes should further be explored.”

Near-infrared (NIR) Non-invasive Blood Glucose Meter’s Future

The NIR non-invasive blood glucose meter’s most promising future lies with the utilization of wireless technology and telehealth systems.
Here’s how: individual sensor results from the NIR non-invasive meter would be sent wirelessly to a mainframe system and within seconds the results from the NIR technology would be delivered via SMS mobile messaging to the patient.   In this way, the technology could be downloaded by physicians and educators for assessing  patient care and record-keeping, making it as competitive as the current CGM system without inserting a subcutaneous sensor.  The biggest challenge?  The size of the spectrometer is still too large and too costly.  With more type 1 subjects, professor Chung will have the ability to shorten the wavelengths and with that advantage, the spectrometer could become the size of a small dial, making it more cost efficient.  “We may be 2-3 years away from that. Two-thirds of the work is completed.  Our research is ongoing.  We’ll get there.”

Confidence is a powerful tool.  I believe all people with diabetes are waiting for the day when non-inasive blood sugar testing is less of a dream and more of a reality; with NIR technology, it sounds like we are getting closer.

The Roche Social Media Conference*

This may shock some of you– it is, after all, still shocking to me sometimes– but I don’t just exist on the internet; there is a live-in-the-flesh version too. And, as it turns out, all those other diabetic internet personalities out there? Also real, living people, with a few more dimensions than their several-thousand-pixel profile pictures might imply. I met a subset of the characters of the diabetes internet world for the first time at the Roche conference, and I was not surprised, but wonderfully pleased nonetheless, to meet such a friendly, interesting, and passionate group of people.

So, even if the Roche conference had just consisted of an open room for all of us to meet, I would have been happy. Even so, lucky me, there also proved to be substantive content at the Roche conference.

We began with a review of what Roche had learned from last year’s summit; having been introduced to the world wide diabetes web only within the last year, this was all news to me, but I was impressed by the extent to which Roche was able to demonstrate its ability to adapt and learn, even within a single year. The pace of change in medical and advocacy industries is often glacial, and so seeing evidence of real change within a year of new information from the conference was promising indeed.

Following the review of the prior year, we began to address as a group concerns and preferences about meter accuracy; unsurprisingly, everyone wants more accurate meters, and, also unsurprisingly, more accurate meters are harder to manufacture and sell. Notably, though, that wasn’t necessarily the point; Roche’s main drive in this area was not towards excusing meter inaccuracy so much as creating industry standards, regulated by the FDA, as to what meter accuracy even means, from allowed deviation of reported blood sugars to the nature and periodicity of trials run to ensure the proper functioning of commercial glucose meters.

It is very interesting for me to see Roche pushing for industry standards; more often than not, industry tends to reject efforts towards standardization and transparency of testing, and it is rare to have individual companies opt for more regulation. It is not unheard of, and clearly Roche, if it knows its own meters meet the set of standards they are proposing, stands to gain by raising the barrier to entry in glucose meter production and marketing. However, I am all for transparency of data and requirements– so I commend them for their efforts to at least define the rules of proper play. And, assuming the rules established are better than the current set of implied requirements, I wont hold it against Roche that they may have skewed the game in their favor.

Next up were two– oh, what shall we call them? Question and answer periods? Discussions? Grillings?– heated conversations with the American Diabetes Association and the American Association of Diabetes Educators. The social media populace expressed to both organizations their concerns, most of which surrounded the general feeling of many diabetics that neither organization puts the needs of the patient before the desire to perpetuate its own institutional stability. Overall, I felt the ADA handled the questions and comments very well, expressing understanding and commiseration without being defensive, and being willing to open the channels of communication knowing that we’re all aiming for the same end– a cure for diabetes, and better treatment in the interim. The AADE presented a less sympathetic front, but, given that I have never myself seen a Certified Diabetes Educator, and given that the whole concept of diabetes educators is relatively new to me, I will leave the commentary on that section of the conference to those more competent in this area.

And next came fun time. Dinner and conversation and the sharing of stories and the meeting of minds. And so many pumps, constantly beeping, none of them mine. It was a unique experience for me to be amidst so many diabetics, all of whom were willing to talk and discuss and collaborate for the good of the collective whole. Rock on.

From up here in the air, on the plane back to San Diego, what do I think of the Roche conference? Well, it was fun, and it was engaging. Roche handled the event very well, both logistically and in terms of the organization and productivity of events.

One of the most impressive parts to me, though, was a comparison made to last year’s event. Though I was not there, I was told that last year, the first year in which the conference was held, there was quite a bit more distrust and antagonism initially between the Roche representatives and the diabetes social media cohort. Furthermore, the day’s schedule was much more minutely managed, with more directed and formal conversations and exercises.

The thing that impresses me about this is the implied change from last year to this year– firstly in the attitude of participants, as clearly this time around the atmosphere was friendly and aimed at reaching consensus on common goals, and secondly in the structure of the day. This may seem trivial, but the fact that the design of the events was different this year pleases me greatly, as it shows to me that Roche is willing to vary, and to try different approaches, and to engage unpredictability in such a way that innovation is possible. If the Roche Social Media Conference was structured the same way every year, then it would likely quickly become another annual event of little import and much redundancy. However, the more Roche approaches the event with an attitude of, “Well, let’s try something new this time,” and, “What do you think will happen if we try this?”, the more they will be opening themselves up to the edges of opportunity and to the possibility of novel ideas.

I did not intend when I started to come full circle on this, but I suppose what I am saying in regards to both the ADA sessions and the Roche conference is– Cooperation! Collaboration! Cross-pollination! Such marvelous things to see.

* Disclosure: Flights to and from Orlando and two nights of hotel stay and meals were paid for by Roche.

In a bit more detail, some of the highlights and biggest takeaways for me:

The ADA Scientific Sessions

• The words of the hour are obesity and inflammation. Initial research is mostly into type 2 diabetes and the effects of obesity and inflammatory immune mechanisms on insulin sensitivity, cardiovascular health, thyroid functioning, and whole-body health, but clearly the funding directed toward these areas of research and resultant findings are having widespread effects on many areas of biological understanding. The mechanisms at play are still clearly unclear, but it was great to see so many researchers attacking the problem from so many different angles– from Lisa Thornton’s work into the reciprocal relationships between inflammation and depression in cancer patients; to Jens Bruening’s analysis of the role of the FTO gene in regulating energy homeostasis and fat storage; to a set of posters from Miriam Chimen and others at the University of Birmingham (UK) on the links between adiponectin, leptin, and T cell expression in type 2 insulin resistance and type 1 autoimmunity.
• Another big area of scientific growth: genetics. Despite the relative rarity in the population, many talks focused on neonatal diabetes and MODY (Maturity Onset Diabetes of the Young) because of the unique set of genetic circumstances that these two versions of diabetes present. Many other talks also looked at the genetics of type 1 and type 2 diabetes, trying to tease out the genes that play a part in disease development as well as the cellular reality that the genetics help to reveal. I found particularly compelling John Murray’s talk on the relevance and reliability of genetic testing for Celiac disease, and Jane Buckner’s look at one particular genetic variation seen in a subset of type 1 diabetics– variation in the PTPN22 gene– and how that gene in particular might participate in the development of autoimmunity in both type 1 diabetes and rheumatoid arthritis.
• How many of you type 1 diabetics out there are using Symlin? I hadn’t heard much about it, other than knowing it was a product of Amylin Pharmaceuticals. At the conference, however, I spoke to several people who touted the benefits of the multi-hormonal approach to blood glucose control. Aaron Kowalski and the JDRF spoke about the importance of dual-chamber pumps going forward, but I learned a lot more out-of-session, talking to a number of diabetics who swore by Symlin injections using the Symlin Pen or wearing two pumps. The pancreas, I was told, normally secretes both the hormone amylin and insulin, and this greatly aids blood glucose regulation. I don’t know much more than that yet, but I intend to do some reading and know more shortly!
• Cooperation! Collaboration! Cross-pollination! Such marvelous things to see. I was so happy to hear several questions that began “We are looking at a similar effect in the realm of…” and so many answers that began “You know, that is a very good question. We haven’t tried that yet– but that certainly would be interesting to look at.” One of the primary purposes of the ADA Scientific Sessions is to share research from different areas, and I am thrilled to see that “sharing” isn’t presumed to end with an informational session, but includes the advancement of our collective knowledge and abilities by means of collaborative analysis and consideration. In other words, many heads are better than one!

So, overall, a wonderful experience. Knowledge gain is a beautiful thing.

Read Part 2, my thoughts from the Roche Social Media Conference…