In Memoriam

Today (Monday, May 31, 2010) is Memorial Day, and this day was formally established by Congress to commemorate U.S. soldiers who died while in the military service. While most Americans view this holiday weekend as the unofficial start of summer, we should at least try to respect the intention of this as a national holiday. Some Americans take issue with the claim that Memorial Day is to honor Americans who died "protecting Americans' Freedom" because virtually no military engagement the U.S. has been involved with since World War II was a result of the U.S. being directly attacked, therefore American freedom was arguably not really threatened -- at best, one could claim soldiers in those conflicts died serving American "interests", which is frequently defined more by politics than it is military interests.

But regardless of your personal views on that, taken in a broader context, Memorial Day is a time to reflect on those who have died as the result of military conflict, or merely remembering those who meant something to us personally, whether they served in the military or not.

For my post today, I'd first like to acknowledge two efforts (one of which is no longer operational) designed to acknowledge individuals who have died (either directly, or as is more often the case, indirectly) from diabetes.

One was a site my friend Deb Butterfield operated for nearly a decade, and although in 2005, she decided to discontinue the DiabetesPortal family of web sites, nevertheless, there was a page there that some individuals set up to honor family members that died of diabetes. We should remember that no current diabetes treatments are 100% effective in preventing complications; these treatments are merely the best thing medicine can offer, but they are not now, nor will they ever be as good as a cure. It is important to acknowledge that no matter how diligent we may be, treatments do not eliminate the disease, therefore some people always suffer from complications in spite of receiving state-of-the art treatments for their diabetes. To visit the now archived Insulin-Free World's Memorial Site, please visit here and have a look at some of the memorials established there.

The second site is one that was featured in Diabetes Health magazine (see here for details) back in 1999, and the site is still operational today. Arlene Shapiro created this virtual diabetes memorial back in 1997 which can be found here.

These sites are a sobering reminder that modern insulins and fancy, $7,000 insulin pumps are still only life support. While it's admirable to talk about preventing diabetes, it's a bit too late to stop a diabetes epidemic that's already well underway. Now, the focus needs to shift away from costly ongoing treatments which are bankrupting our healthcare "system" (a term I use very loosely) and shift our focus towards cures.

Bowersox: "We Both Win"

I have remained completely mum on the entire American Idol competition, although as a number of fellow diabetes bloggers have noted, Crystal Bowersox, a native from the Toledo, Ohio area, was among the final two remaining contestants in the competition. Bowersox has type 1 diabetes, and she even spoke about it during the competition following a health incident early in the competition. Many in the diabetes community felt the title should have gone to her. Based on her performance and that of her rival (and the 2010 American Idol winner) Lee DeWyze, a Chicago-area native, I was inclined to agree on the basis of their Tuesday evening performances alone.

But that didn't happen.

Instead, Crystal Bowersox got the unglamourous title of runner-up, while DeWyze got the title. Some (OK, many) are lamenting the final outcome, we should be asking "does it REALLY even matter?"

After all, this competition has always been a popularity contest that occasionally has proven to have little to do with actual musical talent or liklihood of success. One look no further than a few years ago during Season 6 when a contestant named Sanjaya Malakar remained in the competition for far longer than anyone would have predicted. At that point, it became widely known that automated computer-controlled telephone dialers (some of which were rumored to be physically located in India) had influenced the vote outcomes (for more on the auto-dialer conversation, see here for details) keeping Malakar in the competition. Last season, there was also some question as to whether the actual Idol winner, Kris Allen, was indeed more talented than his rival, Adam Lambert. Many critics suggested that it was Allen's cute face and charming demeanor that endeared him to many young girls who called in and texted votes for their favored competitor, in spite of rival Lambert's very highly-regarded competition performances.

However, I'd like to go on record saying that in the end, it's largely irrelevant.

History has proven that in many cases, the Idol non-winners have gone on to become far more successful recording artists and entertainers than the winners. A number of prominent Idol "losers" have achieved stunning success, among them Academy-award winner Jennifer Hudson (best supporting actress in "Dreamgirls"), Chris Daughtry who is perhaps one of the most successful American Idol contestants of all time based on sales, behind only Kelly Clarkson and possibly Carrie Underwood, both of whom won their respective seasons. There are a number of others, including: Katharine McPhee (recording), David Archuleta (recording), Clay Aiken (Broadway, recording), Constantine Maroulis (Broadway), Adam Lambert (recording), and probably a few others I have forgotten to include on this list.

On the other hand, there are also a few Idol winners whose success has been far more modest than their win might have suggested they could or should be, among them: Ruben Studdard, Taylor Hicks, and Jordin Sparks.

The simple reality is this: Crystal Bowersox is likely to get a recording contract anyway, and depending on what she chooses to record, could ultimately do as well (if not better) than Lee DeWyze -- Idol success does not necessarily translate into recording success. As the entertainment inudstry has learned, there is plenty of gold to be mined from the entire cast of American Idol, sometimes even more from the losers in the competition!

Bowersox perhaps said it best herself on this clip from MTV, in which she stated "we both win.":

On the upside, this season on television, diabetes (type 1 in particular) has garnered a lot of attention from American Idol, and Brett Michaels on Celebrity Apprentice, not to mention the vetting of Supreme Court Justice Sonia Sotomayor (who kept a regular Sprite with her as she spoke before the Judiciary Committee in Congress). Health issues made their presence known in some subtle, and in other cases, not-so-subtle ways. This brought attention to the fact that in spite of existing palliative treatments, it remains a never-ending challenge to achieve the balance that ordinary people with diabetes don't even have to think about. Even so, people with diabetes are proving themselves in increasingly prominent public roles, and we are likely to be hearing more from Crysal Bowersox in the not-too-distant future.

Why the Mysterious Absence of Diabetes Man-Bags?

Most women carry purses, while I don't know any men (gay or straight) who do. Now, truth be told, I have to agree with this guy when I say that a bag really needs to "be big enough to be useful -- that is, to hold substantially more stuff than a wallet, or for that matter one's pockets -- but not so big that you might as well be carrying a briefcase instead". They should also have a shoulder strap that's adjustable in length. At one time, it was a social faux pas for a man to carry anything other than a briefcase or gym bag around, except maybe a backpack if you were on a college campus. But those days, thankfully, are now history. In fact, today, there are a number of startups by people with diabetes including Myabetic, StickMeDesigns and Adorn Designs that sell well-designed bags for people with diabetes that have special compartments specifically designed to hold testing supplies, vials of test strips, a tube or two of glucose tablets, and all the other miscellaneous other d-stuff that PWD's are expected to carry around 24/7/365.

But in spite of these social advances, virtually ALL of these products are desgined for women exclusively (based solely on the designs and color schemes of these products) while men with diabetes are pretty much left to fend for themselves, and let me add, the pickings are pretty slim!! That really needs to change.

For a number of years, I used a "half backpack" I bought at either the Gap, Old Navy, or Eddie Bauer, which was a lot smaller than a regular backpack used by kids in school, but did the job and wasn't too much of an embarrassment to carry around. But eventually, after about 4 years of daily use, it ripped from wear-and-tear, and I was forced to find some kind of replacement.

By the late 1990's, the advent of the "messenger bag" or "courier bag" emerged, which were frequently used by bicycle delivery couriers/messengers in big cities like New York and San Francisco (see here for some more background), thus the name. It became more acceptable for guys to carry a bag other than a cheap old grocery sack around. I guess we can thank metrosexuality for that not-so-small advancement, although truthfully, many things that carry the name "messenger bag" today are really just inexpensive briefcases in terms of size, and I should note that I don't need yet another bag to carry my laptop around in, thank you very much!

But I do have to carry a bunch of diabetes crap around everywhere in some kind of bag (although likely carry more stuff than I really need, but inertia is the main reason I haven't cleaned my bag out recently), including: my primary glucose meter, as well as a smaller, secondary meter I can use as a back-up in a pinch, a replacement meter battery (and when I wore my insulin pump, some batteries for the pump, as my Animas pump had an alarm that sounded like a fire engine's siren), some lancets, a syringe or two, and a bunch of pen needles. When I wore a pump, I also carried a new infusion set, IV prep and a container of Skin-Tac adhesive as well medical tape or a patch to cover the infusion set to ensure I'd get more than a single day from it (I either take long showers, or the adhesive just is inadequate). These days, it's an insulin pen, and maybe a second if the pen is approaching empty. I also have a prefilled syringe case for my evening dosage of NPH, which eliminates the need to carry a vial of insulin around with me and takes about the amount of space as an insulin pen. I use the disposable insulin pens these days, but I will give hats off to Novo Nordisk for the soft cases they include with the Novopen Junior, which has room for another cartridge of insulin as well as three pen needles. With disposables, I need to carry the pen needles separately. I also carry some hand sanitizer around (I prefer the Lysol Healthy Touch foam hand sanitizer over gels, because it doesn't leave a gross feeling or smell after using it and dries almost instantly) but I haven't found it in my local stores lately, possibly because flu season has finally passed. In the absence of that, I'll have a spray hand santizer that's about the size of a ballpoint pen, but I don't really like those as much because they don't last very long (like 5 uses and they're empty). I also carry a box of 100 test strips (which I draw from throughout the week), a pair of reading glasses and a pair of bifocals just in case I lose a contact lens or my eyes bother me, some contact lens drops, and a full container of 50 glucose tabs so I'm never without some (1 tube might be exhaused treating a single low if I don't get to eat after treating a low, because tablets don't usually provide permanent low relief, only rapid relief for me, meaning I'll have to eat more tabs in about a half hour if I don't eat something. And it has a pocket on the outside for both my cell phone and iPod. All of that's an enormous amount of crap to carry around, and its nice to have it all together in a central location so I don't have to search around gathering all the pieces every day.

What do I use to carry all this around? Well, I've historically had pretty decent luck in finding relatively small and inexpensive messenger bag with an adjustable length strap at H&M in such basic colors as black or army green. But even there, those items are usually only carried by H&M during the back-to-school rush in August and September, then they regularly disappear until the next school year begins. I've learned to buy a backup bag after the zipper on my first beloved black messenger bag died one year. Fortunately, my mother is a great seamstress and she was able to replace the zipper on her sewing machine without much difficulty, but if she wasn't around to do it for me, I would have been s#!t out of luck!

On Sunday, at a diabetes meetup I went to in New York City, a few people including the women from Act1 Diabetes, were discussing what they liked about the different Stick Me Design and Myabetic bags. I chimed in on the conversation by showing my beloved but well-worn army-green messenger bag, which frankly is showing normal wear-and-tear, although I think I can survive without a replacement until August. But that prompted some questions for me, specifically 2 things:

#1) What do other guys with diabetes use to carry all their diabetes crap around?

and

#2) Why aren't any of these entrepeneurs interested in the men with diabetes market, who constitute roughly half the market? Our needs aren't complex, but stick with basic colors like black, blue, brown, and gray -- not pink paisleys or flowers!

Anyway, with that diatribe, I'd love to hear from others, even the women who have done business with the folks at Stick Me Designs or Myabetic to see whether they've considered the needs of the other half the potential market for these products! What are things you look for in a bag? What would you like to see changed? Guys, what do you use to carry all your diabetes stuff around?

Day 7: The Awesome C-Word!

Sunday 5/16 - Dream a little dream - life after a cure. To wrap up Diabetes Blog Week, let’s pretend a cure has been found. We are all given a tiny little pill to swallow and *poof* our pancreases are back in working order. No side effects. No more insulin replacement. No more diabetes. Tell us what your life is now like. Or take us through your first day celebrating life without the Big D. Blog about how you imagine you would feel if you no longer were a Person With Diabetes.

Like many of my readers, I've been hearing the "we're 5 to 10 years away from a cure" for what will be 34 years in July. I know a line of bull$#!t when I hear it. But I also keep close tabs on developments that even hint of the C-word (that word being "cure"). But I'm going to spin this topic a little first, because I actually DO believe there are a number of very promising developments that might actually cure type 1 diabetes in the not-too-distant future, and they're closer than many of you might think, although no one is testing them together yet, and if and when they are approved, it seems certain that someone will then start to test the idea of combination therapies.

In essence, the approach will be a kind of drug/treatment "cocktail", and it will likely require several different steps to actually finish the job, and it seems that its not likely to be a pill (at least initially), but a series of IV injections before we'll be able to kiss diabetes goodbye. But it is not at all inconceivable that one treatment may be able to fix the autoimmune response that destroys the insulin-producing beta cells, and that would essentially set the scaffolding for a cure, then another, second step would be needed to restore lost beta cell function to restore insulin independence.

Before continuing, I should introduce the doom & gloom scenario to get that out of the way. In November 2009, the fine (a term I use jokingly) doctors at the American Diabetes Association published a disturbing little "consensus statement" (see here to read it) co-authored by a dozen or so self-proclaimed "experts" on the subject of diabetes and a few other diseases were included for good measure. In essence, this group, which included former ADA President Dr. John B. Buse proclaimed that no form of diabetes will ever be cured; they said it's more appropriate to call it remission. To me, that's splitting hairs; call it whatever the f*%& you want to, if I don't have to deal with the day-to-day crap-o-l-a involved in managing blood glucose levels 24/7/365, even if it DOES require periodic refresher treatments, that's a cure in my book. Interestingly, the folks at the ADA who wrote this article did not seek a single iota of input from a single individual who actually HAS diabetes to see how they might define a cure, and frankly, I think this is one group whose contribution might be an important one to include the next time they decided to come up with a "consensus statement" about a cure, or lack thereof!

I should also note that the efforts for a type 1 cure may have relatively little impact on type 2 diabetes, which frankly is a tougher nut to crack because the etiology for that disease is poorly understood, and frankly, that's a much bigger cash-cow than type 1 is likely to be anyway. But even those patients may benefit from regenerative and/or islet replacement therapies, although solving the insulin resistance challenge remains unsolved.

With all of that aside, I'll give a quick scenario, followed by my ideas for life post-diabetes!

Imagine it's the year 2095, and your 5 year old child (who is now in kindergarden, and has been potty-trained for several years already) has started wetting the bed a lot lately, so you bring him in to see the doctor. The doctor takes a small blood sample with a fingerstick the office and delivers the diganosis a few minutes later: your son has type 1 diabetes, an autoimmune disease where the body's immune system screws up and destroys the vital pancreatic beta cells, rending him without the primary hormone needed to regulate blood glucose levels, and it is hyperglycemia leads to polyuria, thus the bed-wetting. He gives the child a SmartInsulin injection to reduce his super-high blood glucose levels right now which has been designed to last for about 4 weeks -- this should stop the bed-wetting tonight and make him feel better until he's all fixed up. The doctor tells you he can cure the disease, but it will require very careful adherance to a drug regimen or "cocktail" for 2 weeks, although the SmartInsulin injection should tide him over until he's cured. You sigh, willing to do what's necessary to restore your child's health, but you ask the doctor "isn't there an easier way?"

The doctor responds by saying this cure is an absolute cakewalk compared to what people with type 1 diabetes lived with back as recently as 2010, and absolutely mindblowing compared to what people in the 1920's had to endure. Back then, type 1 diabetes was a burdensome, ridiculously-complex, costly and never-ending treatment regimen that helped to stave off long-term complications but still failed to provide perfect blood sugar control, and the demanding treatment protocol frequently caused clinical depression in countless patients.

In hindsight, he admits, "it was almost inhumane treatment, but it was better than death." All you'll need to do is take a few pills on schedule for 2 weeks, the pills taken during the first week will re-educate the immune system, then the pills taken in the second week will regenerate new beta cells to restore the cells that were destroyed. He comments "Imagine a lifetime of bloodtests, injections or wearing a huge insulin pump (the size of today's pagers) that has to be refilled every few days, costly supplies before there was universal healthcare coverage for all, regular doctors visits, routine glycemic variation including dangerous episodes of hypoglycemia (often without symptoms that some believe was due to imperfect folding of the biosynthetic proteins made by bacteria and yeast in those days), high blood sugars that drained you of energy and caused dry mouth syndrome ... the list of daily burdens on the patient and long-term adverse events was almost endless!" He adds that once curative therapies emerged, there were many tests that needed to be done to determine which autoimmunity treatment and regenerative therapy worked best for which patients, so there was often trial-and-error going on -- today, the treatments address all bases. Now, however, a combinantion therapy works to cure almost everyone.

You respond, "I guess this IS much better than life in the dark ages of diabetes care, but it's still a nuisance, and those pills are so big for a 5 year-old!"

About 3 weeks later, after following the drug cocktail, you bring your son in for a final checkup, telling the doctor that there has been no incidence of bedwetting since your initial visit. Another fingerstick test provides a C-Peptide count and an fructosamine test run in the office reveals that glycemic control has been perfect since the last visit. The cure has been successful, and the doctor comments "I hope the cure wasn't too much of a burden -- researchers are working on a single pill that can do everything, but it's still in pre-clinical trials right now."

With that, your child is cured of what was once a lifetime of expensive and burdensome, and sometimes ineffective treatment, and a death sentence prior to 1921. What's more, this low-cost treatment is now so easy that it's available even in remote parts of the world because it's so cheap (as a generic drug) and it's also easy to deliver, and type 1 diabetes at least has been relegated to the medical history books.

Sci-Fi or Reality TV?

Is this sci-fi, or could this someday be reality? Well, there are a number of elements that suggest we are moving in that direction, although there are a number of hurdles that must be addressed first.

First, the hardest element to address seems to be the autoimmune response that causes type 1 diabetes in the first place. But at present, there are 2 drugs entering Phase III human clinical trials that might arrest the autoimmune response. There are at least 3 that I am aware of, and all are in late-stage (meaning Phase III clinical trials). Lilly and Macrogenics have one called Teplizumab (which is good for Lilly, as it's share of the insulin market continues to slide, since they offer only Humalog which makes the company a one-trick pony in the insulin biz). And GlaxoSmithKline also has a very similar product called Otelixizumab in the pipleline, along with development partner Tolerx, whose CEO writes a blog the entitled "The Green Chair" that you can read here which may be only slightly further ahead in development. You can be damn sure both greedy big-pharma partners will push, push and push more to make these treatments applicable for almost anyone with type 1, using the same method they've used to introduce costly new drugs using stacked studies, many of which aren't even blinded. And there's little doubt they'll charge handsomely for the product, we're probably talking like $15,000 for it. The downside of these anti-CD3 treatments seems to be recurrent mononucleosis in some patients (its not understood exactly why yet), but even that seems a small price to pay all things considered, as the daily risks of insulin treatment alone are almost as severe. We may also see the Swedish company Diamyd come into play here (see my interview with them here), and their treatment may ultimately prove superior to anti-CD3 treatments, although only time will tell for sure.

To solve the second half of the type 1 diabetes problem, there are several different approaches in development. One is islet transplantation, and there are several companies pursuing that, including New Zealand/Australia-based LCT (Living Cells Technology). Others including Geron Corp. as well as the company that the recently-stepped down CEO of the JDRF, Alan Lewis, ran which is now known as ViaCyte, are pursuing stem-cell therapies to regenerate islets that can be transplanted into patients whose islet cell autoimmunity has been eradicated. The idea there is that they can generate islets using our own DNA and create the beta cells in a lab and assuming the autoimmune response is gone, there will be no other immune reaction.

Then there are the regeneration companies, among them Exsulin, which counts Dr. Alexander Fleming, who formerly ran (for 12 years) the U.S. FDA's Metabolic Group (which included ALL diabetes treatments) as a leader, so this guy can navigate the FDA perhaps better than anyone else on earth. And the Toronto company JDRF seed funded known as Transition Therapeutics has another regenerative therapy in development. David Mendosa in 2008 wrote that it looks like Exsulin's approach could cost about $20,000 (the best I can tell), although with changes in the insurance business looming, it's not as if one company will incur anything different than the others, plus the cost will still likely be less for them to pony up for this than to continue paying for ongoing care for people with type 1 diabetes. And it seems most likely that the cost for all of this will come down significantly, though, so by 2095, the cost for both treatments will be pretty cheap. And refinements will make the side effects by then to be pretty minimal, as the companies try to one-up one another with better and better products.

I'm not naïve; not all of these options will make it to commercialization, and its quite possible that even if one or more DOES make it, one treatment may not work in all people with type 1 diabetes, or may be more effective in some people but not in others. But that's waaaaaay closer than we are right now! We may ultimately find that certain cure approaches (e.g. transplantation vs. regeneration) work better in different groups of people, but in another eighty-five years, that should all be sorted out!

So what about the kick-@$$ party?

We've heard about beach parties catered by Crumbs and oompa loompas, the latter of which gave me the idea that realistically, a celebratory trip Hershey Park might be a realistic place to hold a kick-@$$ celebration party, and the Diabetes Online Community is all invited. Instead of being tempted (or taunted) with chocolate and not being able to enjoy it, we can actually enjoy it this time without too much thought! But the first thing I'm doing is enjoying a pizza, and I won't have to worry about extended boluses or morning hyperglycemia. Although I don't expect any pharmaceutical company to pitch in a dime for this, as we we're their cash cows, and now that little party is over, but I agree that we'll all have a boatload of money that we'll be free to enjoy after this crap is over. And having a bonfire of meters, pump supplies, insulin pens, and all the other crap also seems in order (I wonder if Hershey will let us do that onsite?). But the thing I'm most looking forward to getting rid of is the test strips and meters, which companies ranging from Abbott, J&J and Bayer and the rest who have been milking this forever will take take a pleasant financial hit on. Too f'ing bad, IMHO. They're sure to find something else to bilk for billion$ before too long, we can be sure. But if a few go under in the process, we can laugh about it!

But at the risk of sounding too pleasing, we can't just eat to our hearts content for long, lest our waistlines pay the price. But the initial party will be worth it! We probably will have periodic reunions before we have some other health ailments to worry about, but realistically, I honestly believe that new treatments that address the disease itself, rather than continued palliative treatments to address the SYMPTOMS of diabetes, might not be too far away. And I like to think the party will be awesome, and life post-D will take some getting used to, but if anyone can handle it, it's the people with diabetes. Realistically, the commeditization for these treatments seem very appropriate. And I hope an occasional reunion might be in order once this party is over!

2-In-1: Diabetes Blog Week Topics

Yesterday's Diabetes Blog Week topic (Friday 5/14) was Let's get moving. Exercise ... love it or hate it? Do you have a regular exercise routine? Or do you have trouble finding your exercise motivation? How do you manage your insulin and food to avoid bottoming out during your workout? Today is the day to tell us all about your exercise habits, or lack thereof. I'll get to that in a second.

Friday Blog Hiatus

My Friday was really busy at work, so I didn't have time to blog about anything, nor did I even log into Twitter until about 9:00 PM, at which point, the only thing I did was share the news that JDRF's CEO, Alan Lewis, had stepped down (see here for the press release on that) in spite of being on the job for a little over a year.

I won't pretend to be terribly upset about his departure. I was only luke-warm about his taking the job in the first place, mainly because I wasn't sure if JDRF required him to liquidate any ownership he may have had from when he was the CEO of Novocell (which incidentally just changed it's name to ViaCyte, see here for the press release on that). JDRF has never been very forthcoming about whether they had any conflicts-of-policy for senior executives that I am aware of (or could find evidence of on it's website). My concern was if he, as a former CEO stood to gain financially for decisions he could make as the new CEO of JDRF, such as using his influence with JDRF to fund projects that might lift the value of Novocell/ViaCyte as a company. (As it is, ViaCyte has already received important support from the both California Institute for Regenerative Medicine [CIRM] which is the Prop 71 stem cell initiative that JDRF helped to get passed into law, and direct funding from the JDRF, although most of this pre-dates Mr. Lewis' taking the role as CEO of JDRF), so I don't think it's an unreasonable question to ask. There was no detail in the press release on WHY he decided to step down, leaving us to wonder if he did so voluntarily.

Anyway, with that, first I'll address part 1, which was Friday's topic. Exercise. I won't pretend to get off on endorphins, and I've never been really keen on team sports involving balls (except soccer). But I've always enjoyed hockey (maybe I should be Canadian?) and also enjoy solo sports, such as walking or swimming. But I don't do nearly what I should be, and as middle-age has set in, my metabolism isn't quite what it was when I was 25. Truthfully, I'm looking forward to being in my new office at 120 Broadway in Manhattan (for a photo, see here), because it's proven that people who work in the suburbs get less exercise than urban dwellers/workers because to get to anything in the suburbs, you have to use a car, while in the city, you can usually walk to just about anything. Plus, I didn't want to get tied down to a gym membership near work only to not be able to use it for remaining half the year. Anyway, we're moving the weekend of July 3rd, so I might get settled into a new routine then.

Exercise is, in my opinion, best when it's part of something else, not made to be a task unto itself. If you walk a few blocks each day to and from work, you don't even notice it. Ditto if your job involves some activity (this seldom applies to office workers, but if you work in a job that involves physical activity, chances are you don't even notice the calories you burn as part of your regular activity). I don't really enjoy hanging out at the gym, either, but the reality is that I neither have the space for expensive equipment at home, nor do I want to own this stuff. Once upon a time, I actually owned a treadmill, and it was the biggest dust collection device I ever owned. There were just too many distractions at home, whereas in a gym, you're there to work out, without the temptations of the computer or TV to lure you away.

Saturday's Topic: Wild Card, Blood Sugar Nirvana or Moronic Moment.

Moving on to Saturday's topic ... today was supposed to be Diabetes Snapshots/Photos. Inspired by the Diabetes 365 project, the idea was to snap a few d-related pictures to share today. Post as many or as few as we'd like. Instead, I'm going to rely on the Wild Card topic of the week, because I don't have many photos nor do I pay for hosting on Flickr, so I don't think I can really add anything to that topic.

Instead, I'll blog about the time I ate a meal that tended to spike me to the moon, but my perfectly calculated and timed insulin dosage kept your blood sugar happy. Or tell you about that time my brain had a little diabetes-blip and I did something you think is "stupid". (Because chances are, anyone with diabetes has done it too!!)

We've all had both scenarios, because the reality is that dosages are really NOT scientific. The body has other hormones that can interfere with insulin requirements, and there are other factors that may also influence this. This is why the idea of calling this glycemic "control" is such a joke to me, and many others.

But last Thanksgiving, I actually enjoyed blood sugar nirvana, and it was really a crap shoot that turned out great! My family makes Thanksgiving mostly an all-day-event, with cousins coming in from out of state. The day begins around 11:00 AM, at which point, it's appetizers galore. Dips, chips, nuts not to mention a pre-meal happy hour with my now departed grandfather's Scarlet O'hara's, which is really 2 parts 100 proof Southern Comfort, 1 part cranberry juice, and a splash (or packet) of sour mix mixed in a blender with some ice. Under normal circumstances, that drink is pure sugar (excluding the sweet Southern Comfort cordial, which is mostly alcohol). I've been making them with Ocean Spray Diet Cranberry drink and sugar-free sour mix (a few places sell it, but it's great if you can find it someplace). No one even noticed that it was sugar-free and contained far less calories than the original, and after about 3 or 4 blenders full was consumed (not by me alone), and countless hors d'oeuvres, I tested and corrected with a few units but life was pretty good.

Then came dinner. All the typical stuff turkey, stuffing, mashed potatoes, cranberry sauce, some other vegetables or veggie dish. Then desert ... the holiday's make it damn near impossible to manage blood glucose levels, no matter how diligent or good at carb counting one may be. I estimated what I'd be eating and dosed accordingly, worried about the nasty outcome a few hours later. Would it be enough? Not enough? I just said screw it and took a wild-ass-crazy guess and dosed, hoping for the best.

A few hours after our mid-day dinner, I tested, and was prepared for the worst. Instead, I was delighted with a reading of 117 mg/dL. WTF? I totally guessed and this turned out sooooo much better than I could ever have guessed. But next year, I might not be so lucky, so I'll enjoy the gifts when they are given!

Carbo-licious or Carbo-idiotic? Problem solving is key, not costly pumps.

Today's topic is to carb or not to carb. We've been asked to blog about what we eat. And perhaps what we don't eat. Some believe a low carb diet is important in diabetes management, while others believe carbs are fine as long as they are counted and bolused for. Which side of the fence do you fall on? What kind of things do you eat for meals and snacks? What foods do you deem bolus-worthy? What other foodie wisdom would you like to share?

There is a debate among people with diabetes, particularly among those with type 1 diabetes (and/or their caregivers) about whether carbohydrates (referred to herein as "carbs") should be severely restricted in order to maintain normalized glucose levels. Theoretically at least, it makes sense.

While it's true that carbs have the most immediate impact on blood glucose levels because they are readily converted into blood glucose, contrary to what many have been taught to believe, other nutritional components, especially proteins, do in fact also raise blood glucose levels. The main difference is that while a piece of bread will show up in your blood glucose test results within a matter of minutes, protein usually takes anywhere from 6 to 8 hours before hitting your bood glucose. Most practitioners will say that theoretically at least, basal insulin is supposed to address this, but I disagree. First, the reality is there's not really any such thing as basal insulin in normal physiology, instead the beta cells respond whenever there's a bodily need for insulin, which makes artificial insulin replacement such a challenge (insulin supplementation, which is often the case with type 2 diabetes, does not have the exact same issues). In any event, metabolism is highly individualized, so claims that half of your total daily insulin dosage should be comprised of basal insulin have little if any scientific fact to validate those claims. Some people may require a constant stream of a small amount of insulin, others do not require it.

It took quite some time for me to figure all of this out and prove it, as it was conveniently excluded from any and all diabetes and nutritional education I had ever received, but after much experimenting and testing, I proved it unequivocally to myself. I probably would not have learned it if I wasn't wearning an insulin pump. Back when I did wear an insulin pump (I wore the
Animas IR1000, which was the company's first generation pump), I performed (and repeated) a number of dietary experiments and proved that most land-sourced proteins have a rather significant impact on blood glucose, while poultry had less of an impact, fish had almost no impact, and eggs had none that I could discern, yet ALL are called proteins.

For example, one evening for dinner (I usually eat dinner about 7:00 PM, incidentally), I ate a measured piece of meat (although I don't usually eat beef because I don't care for it, this was an experiment for the purpose of science) only, in this case, steak, and sure enough, the next morning I woke up with hyperglycemia. When I ate no protein, just some vegetable soup which was mostly water and vegetables containing some carbs (carrots, potatoes, and the fruit that tastes and acts like a vegetable, tomotoes) as well as more fibrous veggies such as celery (which is mainly salt and water), and some green beans, plus some breadsticks (which are pure carbs with, a glycemic index of 100). I kept my basal rate unchanged, and woke up hypoglycemic by the middle of the night. The next time, I ate protein-only again in the same amounts, and increased my basal rates (I ended up having to increase my basals by 60% if that tells you anything) until I woke up with perfect numbers. Then I tried it with different types of proteins, and found slightly different but still consistent results. For example, after beef, pork (such as ham) has a very similar effect, although it is metabolized slightly faster than beef (at least for me). By comparison, measured portions of chicken or turkey had a far less significant impact. And two proteins, notably eggs (which I ate as Spinach Quiche, which admittedly had a few extra ingredients such as Spinach which really added flavor more than anything else, and cheese which is mostly fat and a small amount of carbs -- I made crust-less Quiche in case you were wondering) and fish of any type (whether it was freshwater or seawater fish; shellfish, or lean fish steaks such as Chilean Sea Bass or Tuna Steaks), had virtually no impact at all, and again, I woke up in the middle of the night with hypos. I tested this over a lengthy period of time, and repeated the both what I ate, my basal configurations, and the timing, and found the results worked exactly the same way each and every time, so it was not a one-time fluke of nature, as is often the case with diabetes.

After documenting all of this, I then I asked both my CDE and nutritionist about it, and neither denied the impact that protein can have, instead saying that basals "usually" cover it (but they don't with every person), and that I did everything I should have to investigate the issue, and that both of them (both my CDE and nutritionist at the time had type 1 themselves and wore insulin pumps) would have recommended doing exactly the same thing. In effect, I was rewarded with a compliment for what I had done to test my theory and validate the findings and I suppose the knowledge would reward me for many years to come, but to me, that seemed like a cop-out. Why hadn't anyone advised me of this in training? Why did I have to go through several weeks (or months, if you consider the daily fasting highs I dealt with, only to be told that I should try raising my basal rates, to which I responded, "Uh duuuuuh, thanks for that extremely valuable recommendation" (that's saracasm ... can someone remind me again what the hell my insurance company is paying these people for if I'm doing all the work myself)?

The reason I mention all of this is because first, I do believe that wearing an insulin pump enables people with diabetes to problem solve that isn't always possible with a traditional short/long-acting insulin regimen. In that regard, even if one returns to MDI (multiple daily injections) as was the case for me, I still believe that my experience in wearing a pump was valuable because I was able to learn so much. I believe everyone should try it for themselves at some point.

On the other hand, I did not find wearning a pump to be my salvation, as many had suggested it would be, nor did it eliminate hypos as many salespeople are only too willing to suggest. On the other hand, wearing a pump did teach me problem solving, and that expertise, which I gained from the experience that helped me most. On the other hand, the pump was a costly impetus that I really did not require, and there are many people who can do just as well without a pump. The notion of claiming everyone with type 1 diabetes is an example of how wasteful the healthcare "system" has become. The tools themselves are not a panacea, rather the notion of problem-solving really is the key to good glycemic management, not the costly devices. To be sure, pumps can make life easier for many patients, and at the very least, patients with chronic diseases like diabetes should be allowed access to these costly tools, but I firmly believe that the devices themselves are an example of inherent waste that's been firmly built into the system. Some people do much better with a pump, especially children whose insulin needs can vary widely, or anyone who can benefit from the level of precision in dosages that only a pump can provide. Usually, that is people whose basal rates vary widely benefit most over the course of a day, or people whose sensitivity to insulin remains high, but I do believe that the device itself is behind that.

So what does this mean for insulin dosages?

Well, first of all, the more carbs a patient consumes, the more widely their insulin dosages will vary throughout the day. That, I think, is amounts to a fact. And one element I agree with is that the a diet that is loaded with carbs will amount to glycemic instability. One way to improve control, therefore, is to reduce the consumption of carbs. But that does not equate to elimination, as many seem to suggest, especially those who are on the paleo diets or similar types of dietary restriction. Does that improve glycemic control? Absolutely it will, but to those who suggest that you should eat a meat-only diet, I think they're nuts.

When one drastically reduces their consumption of carbs, I believe they will see dramatically improved glycemic "control", although I think that word control should be dropped in favor of "management" or "influence", but for many people, that's an exercise in semantics. On the other hand, I do not subscribe to the belief that carbs should necessarily be restricted. To do so day after day, for a lifetime, amounts to what I would argue is cruel and unusual punishment. Carbs are fine in moderation, and should be consumed carefully so that insulin can be dosed accordingly. But carbs are part of a varied diet that I believe IS a part of a rich part of life. I will give the (in)famous Dr. Bernstein appropriate credit where due: he's 100% correct about the law of small numbers. His law of small numbers is basically the less medicine (of any type) you take, the less risk of something terrible going wrong and the greater the likelihood of the medication (and that's especially true with injected insulin) working in a consistently reliable fashion. Therefore, anything you can do to reduce the amount of insulin required will be beneficial, but within reason, naturally.

But complete carb restriction, especially over a lifetime, is not necessarily something I would recommend to anyone, because it amounts to a lifetime of restrictions that are neither desirable nor sustainable. For example, we know that in people with impaired kidney function, an all-protein diet would amount to an accelerated death, besides who really wants to live a life like that? Not me. So the key, in my humble opinion (IMHO) is to try and minimize insulin dosages as much as feasible, but one shouldn't have to avoid bread to do it.

All By Myself? No, as K2 and Hillary Note, It Takes A Village. And A Pussy.

Karen's topic du jour for those of us participating in "Diabetes Blog Week" was to write about our biggest supporter. Just one? Geez, that's really an exercize in futility, because there's no way I can name just one.

First, because I have 2 parents (a mother and a father), that alone would force me to choose just one parent, and it's not going to happen. Ditto with siblings. And grandparents.

When I became an adult with type 1 diabetes, I was supposed to be able to take care of myself without the need for outside support, but even then, I had my super pussy Phyllis who is remarkably well-versed (even for a cat) in supporting me when I lived all by myself. At this point, you can listen to the 1977 sappy song "All By Myself" by Eric Carmen for the proper effect, yes, Celine Dion did remake it, but I'm usually a sucker for the original version. Phyllis usually sleeps at the foot of the bed (except when I'm not home, in which case, it becomes HER bed), and she can usually sense if my blood sugar is dropping, and she has proven quite skillful (for a cat) at helping me in these situations, in much the way that service dogs also serve this function. For example, one night I was having a hypo, and because people with type 1 usually don't wake from hypos, Phyllis sensed something wasn't quite right -- maybe I breathed or snored differently, but whatever it was, she knew. So to fix things, she began making a pest of herself, first by walking on my head and meowing. Evidently, that wasn't enough, and I continued to sleep. So Phyllis jumped on top of my chest, and when that didn't wake me, she took out the claws and began to gently kneed me. At that point, and if memory serves me correctly, it was around 3:00 AM, I got up and grabbed my meter from the nightstand. Sure enough, it was 45 mg/dL. The pussy cat had fixed the situation, and all was well with the world. (Phyllis actually won a price for being the smartest CAT in Queens, NY, although she's the third-smartest animal in the borough of 2.5 million residents ... read her glowing story from the Queens Chronicle here).

These days, I have a partner who is perhaps my main supporter, which has alleviated the hefty responsibilities from Phyllis who is now kind of a senior citizen (for a cat, anyway). So Phyllis might do something to wake one of us, but her de facto responsibilities are not as demanding these days. But as Hillary Clinton, Kelly Kunik and others eloquently note, "It Takes A Village"!

Day 2: Making the Low Go

As I noted yesterday, I've decided to participate in the Diabetes Blog Week, which my friend Karen at Bitter-Sweet suggested last week in her post here. A full list of diabetes bloggers who are also participating can be viewed here. Today's topic: Making the low go.

Tuesday 5/11 – Making the low go. Tell us about your favorite way to treat a low. Juice? Glucose tabs? Secret candy stash? What's your favorite thing to indulge in when you are low? What do you find brings your blood sugar up fast without spiking it too high?

For me, hypos (or lows) are a major inconvenience. When I was a kid, I viewed lows as opportunities to enjoy the candy or juice that I was routinely denied on a day-to-day basis, but now that I'm older, I view hypos as just a major PITA (I think you can probably guess what the acronym stands for). For one thing, they are an unwelcome distraction from more important things, whether that's work, sleep or something else. They always happen at an inconvenient time (when ARE they convenient?), and treatment sucks a good 15 minutes away from productive time I'd rather be spending on something else.

The irony of hypos is the fact that they are more often caused by insulin than any other diabetes treatment, and yet again, the drug industry sees nothing wrong with that, and has instead made it's priority to make insulin last longer, but with little effort to address hypos. If insulin were discovered today, I have little doubt the FDA would probably not approve it without a blackbox warning label because of the safety concerns and the fact that insulin causes more than 58,000 Emergency Room visits each year. Another historical irony is that the ONLY reason insulin is delivered subcutaneously is because that was the only practical way in 1921, but because artificially replaced insulin is never delivered in a physiological manner, the risks for overdosage remains a permanent risk of insulin treatment, although the costly boondoggle known as the artificial pancreas project involving an insulin pump and a continuous glucose monitor hopes to make insulin a bit more fool-proof, but until insurance coverage can be assured, it will be a costly effort that many will still struggle to attain coverage for, even with exapnded healthcare coverage.

In terms of treatments for lows, I know everyone has their personal fav's, and what works for me will be totally inappropriate for someone else, and the reverse is true, too. Personally, I HATE, HATE, HATE, HATE fruit juice of any kind as a hypo treatment. Some people claim they carry juice boxes around to treat lows, but that just doesn't work for me -- they're too bulky and I hate the taste. My disdain for fruit juice as a hypo treatment is especially true for orange juice, a beverage that the mere smell of makes me want to gag and barf (sorry to offend, but you get the point) -- the pulp and texture and the taste is equally as gross to me -- I really hate oranges (the Anita Bryant endorsement did little to help change that opinion). On the other hand, I love grapefruit juice, so I have nothing against citrus fruit, just oranges. I don't mind apple or grape juice, but not as a treatment for a low, because I don't ever buy either, and these would literally grow penecillin in my refrigerator. Besides, both are loaded with empty calories, and I find them cumbersome to measure making the risk for overtreatment (which is as bad as the hypo) quite real.

I almost always rely on premeasured dextrose (which Americans call glucose, even though they are actually dextrose), although my reliance on Glucose Tablets has practically ended. For one thing, Glucose Tablets are way overpriced even though they are usually branded with the store's name, not the biggest brand in the business Dex4. I have long favored Smarties (catch a recent post here), as 2 1/2 rolls works out to exactly 15 grams of carbs. Lately, I have migrated to Mega Smarties, which are a larger sized tablet sold in the same cellophane rolls, but each Mega Smarties roll contains 15 tablets (each tablet is exactly 2.5 grams of carbs) that sell for $1.79 at my local 7-11, while a roll of glucose tablets containing only 10, 4-grams of carbohydrate tablets sell for the exact same price at my neighborhood Walgreens. That means for the same price, I get about 5% more glucose, and they're very easy to work with, as 15 grams equals an even 6 tablets of Mega Smarties (by comparison, regular Glucose Tablets cannot even be measured evenly into the ADA's recommended treatment for a hypo, which is strange). The only thing they really need is a plastic container to store them in so they don't crumble in pockets or purses, but beyond that, they are fully functional and even better, I never get strange looks from people on the street for eating Smarties!

Sure, they have the chalk-like consistency that gives many PWDs the same reaction I get from Orange Juice - nausea, but as I said, this is very much a personal option, and I have always avoided fruit juice at all costs for the reasons previously noted. So that's how I make the lows go, but for a person with type 1 diabetes, the only real way to make lows go away is to do away with insulin replacement, which means finding a cure, not trying to improve a flawed treatment protocol that is delivered in a non-physiological manner!

OK, that's today's diatribe. Did you expect me to be cheering life with diabetes? How silly of you!

A Day In the Life With Type 1 Diabetes

I've decided to participate in the spontaneous Diabetes Blog Week, which my friend Karen at Bitter-Sweet suggested last week (catch her post here for the details). To have a look at the other diabetes bloggers who are participating, visit here.

I first met Karen face-to-face a few years ago at a diabetes blogger meetup in New York. We had an instant bond of sorts not only because of life diabetes (as if we needed any other), but she happens to live in a town that's literally a few miles from where my parents live (and where I grew up). If I recall correctly, she also graduated from the same university as I did (of course, it was known as a college when she and I attended, but a few years ago, they became a full-fledged university). Anyway, the main reason I agreed to do this was because there are really no rules, no blog length, nothing other than a suggested topic du jour So without further delay, here is today's topic, along with my posting on that subject.

Monday 5/10 - A day in the life ... with type 1 diabetes. Take us through a quick rundown of an average day and all the ways in which diabetes touches it. Blood tests, site changes, high and low blood sugars, meal planning, anything that comes along. This can be a log of an actual day, or a fictional compilation of pieces from many days.

This posting will likely garner two types of responses: 1) for people who live with diabetes (and/or their caregivers), they may nod their heads in agreement with different components, while 2) for anyone who have no personal connection to life with diabetes (including the many, many, many doctors and diabetes educators who may have extensive training in the subject, without having a second of personal experience or even a clue what life with their prescribed treatment entails other than the over-simplified basics they outline). For the latter group, I hope this provides just a glimpse at the day to day s#!t people with diabetes (PWDs) must deal with until we die. (Or until some vast improvements are made to prescribed treatment protocols.)

On any given weekday, I usually get up pretty early to get ready for work, not unlike millions of other Americans who do the same. But the similarities end there. To begin with, my morning ALWAYs, without fail, begins the exact same way it ended the night before. By cutting myself with a razor-sharp device called a lancet in order to make myself bleed enough to conduct a blood glucose test, which is as barbaric as it sounds because we haven't done any better than that yet. The results nowadays are quick, usually within 5 seconds or so, but my day has only about a 60% chance of starting out great -- the remainder of the time, the number is either too low which is pretty easily fixed by eating one or more glucose tablets to raise the number to an acceptable level (although if it drops too low, I might not be coherent enough to do that) before I can even begin the rest of the getting ready routine.

On the other hand, if my number is too high, then my morning is effectively ruined, and I am likely to be incredibly p!$$ed off, which is ironic, considering I followed all the rules of good diabetes care and usually go to bed with good numbers for a PWD, but there are more things that can influence blood sugar levels than insulin, exercise and food intake, which are the ONLY elements a person with type 1 diabetes actually has control over. Pattern recognition helps me avoid this many times, but if there's one thing a person with type 1 diabetes must adjust to more than anything else is that diabetes math means that 1+2 DOES NOT always = 3, sometimes it = 5, sometimes it equals 10, and sometimes it = 0.5. The very notion of calling this diabetes CONTROL is frankly one of the medical profession's cruelest jokes (and biggest lies), and I am being way too kind when I call it complete bullshit that anyone can expect someone to gleefully do this day after day until they die -- its really bulls#!t. Control means absolute power over the outcome, and I have yet to meet anyone with type 1 who actually has control of their diabetes. Why does it ruin my morning? For one thing, I'll need to dose insulin to bring the number down before I can even have a cup of coffee, and although patent-protected, genetically-engineered insulin-like molecules known as insulin analogues are supposed to start working within 15 minutes, they never work that fast for me ... I have to wait an hour before it BEGINS to come down, and it won't be normalized for close to 3 1/2 hours. No coffee (that would send the numbers even higher) which really ruins mornings for many people. No food for hours, even if I'm starving.

Only then I will be able to jump into the shower and proceed with the commute to work (I am now counting down to when I can do like mostly everyone else in the largest U.S. metropolis where I live does, and rely on public transit to wisk me into work -- it's just 8 weeks away ... wooo hooo! Until then, I rely on traffic-choked freeways that are overcrowded and often, falling apart with holes, car bumbers in the break-down lane (where one actually exists) on what has been dubbed the world's longest parking lot. But that's a tangent to the topic du jour. All of this happens before 8:00 AM EST.

When I arrive at work, my day is a lot like anyone elses; I work in a consulting firm, so some days are chaotic, others are quiet depending on projects we are engaged to do, people's travel schedules, etc. However, my colleagues waltz into the office at random times, so I find my mornings to be by far my most productive hours; the phone hasn't yet starting ringing, and the interruptions are fewer. I actually like working in the morning because of that, plus by that time, if I haven't been able to eat, I can actually do so from my desk at work. The funny thing is, I'm by no means a morning person, and for me, I'd much rather sleep late then get up early and face the day with a cheerful smile on my face ... in my dreams, maybe!!

Usually, by 1:30, my uninvited friend and co-worker, also known as type 1 diabetes (which has overstayed its welcome by more than 31 years for me) starts to makes itself known. Usually, I need to eat lunch by then or I'm ready to crash. I might not be hungry, but I'm still obliged to eat something, although for me, often a cup of soup might work, other times, I'm really starved and might need something more. I would really like to enjoy one of life's simplest pleasures someday, which is to be able to eat without having to premeditate bolus meal doses, time-activity profiles of insulin, or anything else except maybe calorie counts.

By afternoon, I normally have my day filled with various things I have to do before I can call it a day. That may consist of follow-up phone calls, perhaps a meeting and/or conference call, seeking out deliverables from colleagues, etc., etc., etc. By 6:00 PM, I'm done with work, unless I have a deadline that I need to stay to finish. At present, I still work in the suburbs, so I might stop by the large supermarket located down the street from my office to pick up any grocery items I've run out of. That usually consists of fresh produce items which are both more plentiful, fresher and much less costly in the suburbs than they usually are in NYC. Even though I live fairly close to a supermarket, it is so overrun with shoppers that the store often runs out of items unless I arrive first thing in the morning.

My evenings are pretty calm; make dinner, watch the evening news, possibly catch something on TV, and maybe catch up with some follow d-bloggers on Twitter before going to sleep for the evening. I no longer wear an insulin pump, so I use NPH overnight (by choice) because I actually require a bit of a peak (I still would prefer Lente, but that's a separate diatribe) and have had absolutely horrendous results with Lantus, which works way too long into the next day, yet ironically still failed to cover my digestible proteins consumed with dinner. Of course, with generics looming in the not-too-distant future, we might actually see a resurrection in the Lente series, which most doctors considered superior to NPH. The reason: NPH works well in premixed insulin varieties sold primarily to the type 2 audience (not that premixed gives them better glycemic control, but it's easier for primary care doctors to prescribe, thus the world's worst medium-length insulin is the only one now on the market. I'm not at a point where I'm ready to reconsider pumping because I went through a HUGE hassle with my insurance company just to get my test strips covered, and don't have the stomach to endure another lengthy appeals process on a pump, even if the pump company does all the work. It's just not worth the effort for me, as when I did wear a pump, I did not have better glycemic control. Whatever ... the bottom line is that this crap is par for the course in the day of the life with type 1 diabetes.

I have come to the realization that I will be denied the simple pleasure of ever being able to eat without pre-planning, an innocent pleasure that the average person has absolutely no appreciation for unless this disease is cured. Frankly, given how long treatment advances take to get approvals, I may never see it. But if one believes in karma, then ME and my fellow PWDs will be able enjoy this forever more in the afterlife, while everyone else will have to suffer with this bulls#!t (of course, I could be paying for transgressions in a previous life with this today) but as long as I have the ability to influence the day to day numbers for life with diabetes, then I also plan to use my influence to fund research towards a CURE (that means funding for the JDRF or the DRI, two organizations with an explict goal of eradicating type 1 diabetes.

Interview With Diamyd Medical AB

I've always had great respect for the Swedes, for a host of different reasons. For one thing, Sweden has continually reinvented itself. Sweden was also the first European country I ever visited, back in 1987, although I've returned a number of times since then. Aside from being one of Europe's most affluent and prosperous countries, it's also one of the most Internet-penetrated countries on earth, and I follow a number of Swedish diabetes bloggers even though I don't speak any Swedish (thanks to Google translate for that!). Beneath the surface, I think relatively few Americans realize that Sweden is the third largest cultural exporter in the world, surpassed only by the US and the UK. For example, all of Britney Spears' early hits were written by Swedish songwriters. The country has given us many popular musicians and/or bands, including ABBA ("Dancing Queen", countless others), Europe (perhaps known for the song "The Final Countdown"), Neneh Cherry ("Buffalo Stance"), Ace of Base ("All That She Wants"), Roxette ("Listen to Your Heart", among others), The Cardigans ("Lovefool") and countless others, yet few Americans even realize these artists come from Sweden. Countless female (and male) models have hailed from Sweden. The country rules ice hockey (although the Canadians might beg to differ). Sweden gave us IKEA and H&M, and countless modern designers. Even reality TV was invented in Sweden; as "Survivor" was actually invented by Swedish television, not Hollywood execs. That's a pretty impressive track record considering the fact that the country has fewer than 10 million residents, and English isn’t even a native language!

I also doubt that many Americans realize that Sweden had its own real estate bubble that went bust in the 1990's, yet the country did a much better job of implementing necessary reforms than, say, Japan, for example, as some in Japan call the 1990's as "the lost decade"). In 2008, a New York Times journalist wrote "Stopping a Financial Crisis, the Swedish Way", although the U.S. has so far failed to follow the Swedish reform model, which I think is probably a mistake, but only time will tell. But Sweden also ranks near the top in terms of type 1 diabetes prevalence (exceeded only by neighboring Finland), so the country has particular interest in eradicating this type of diabetes and its complications. I continue to seek out information about how Swedish biotechnology companies are working to change diabetes treatment. One is Creative Peptides, which is pursuing approval for C-Peptide, once believed to be a useless byproduct of insulin synthesis, but subsequently proven to have a number of therapeutic benefits in its own right, such as helping to prevent and/or eradicate neuropathy and possibly as a factor in cardiovascular disease prevention. But this article isn't about Creative Peptides; it's about another Swedish biotech firm that I think could have an even more profound impact on treatment for type 1 diabetes.

Interview With Diamyd Medical AB: A Swedish Biotech Company With A Bold Vision For Type 1 Diabetes

A little over month ago (on March 26, 2010), I had the pleasure of speaking with Peter Zerhouni, who is the Director of Business Development at Diamyd Medical AB (the "AB" is akin to what we in the U.S. call "Inc.", that means it's legal entity that's incorporated) which is based in Stockholm, Sweden. For those of you who aren't familiar with Diamyd, it's a biopharmaceutical company in the field of diabetes, with particular focus on type 1. More specifically, the company’s current research and development concentrates on autoimmune diabetes and complications related to diabetes. The company’s vision is to one day be able to prevent AND cure the autoimmune form of diabetes, which makes them a bit different from other companies who are pursuing treatments to arrest autoimmune diabetes. The ultimate objective is to be able to treat children, adolescents and adults with type 1 diabetes and to vaccinate those at risk in order to prevent the disease from breaking out. After several years of successful research and good results, the company believes that the diabetes vaccine they call Diamyd® significantly slows the disease process, but I’m not sure how many PWD’s (persons with diabetes) are aware it also has potential to be applied not only to the not yet diagnosed or newly diagnosed, but also those with longstanding type 1 diabetes.



Diamyd For Dummies?

I am most likely over-simplifying things quite a bit for clarity, but the Diamyd vaccine pretty much accomplishes the same thing as some of the other autoimmune treatments for type 1 diabetes now in development do (among them antibody treatments Macrogenics’/Lilly’s teplizumab, Tolerx’s/GlaxoSmithKline’s otelixizumab AND even the TB vaccine [BCG] being trialed by Dr. Denise Faustman and David Nathan at Massachusetts General Hospital which aims to do the same). Unlike these other, now-in-development autoimmunity treatments for type 1 diabetes, which work by killing off the autoreactive T-Cells responsible for beta cell destruction (as well as some innocent bystanders along with them), Diamyd is thought to stimulate another class of T-Cells (regulatory T-Cells) that selectively calms down their autoreactive friends. This means Diamyd may be a more specific route to correcting the body's errant immune system that causes type 1 diabetes in the first place. For this reason, it is viewed by a number of researchers as more than simply a vaccine – the prescription (assuming it is ultimately approved by the FDA) could also potentially be expanded to longstanding patients as well. The mechanisms on how each of these autoimmunity treatments these work specifically is best reviewed in the companies’ scientific literature, but that’s my general understanding as a layman (thanks to some valuable input from Peter Zerhouni at Diamyd!).

At its core, the Diamyd vaccine is based on what’s known as glutamic acid decarboxylase (GAD). What’s that? Well, the active substance in Diamyd® is what’s known as GAD65 (technically, it’s the 65 kDa isoform of glutamic acid decarboxylase, which probably means nothing to any of my readers, but I digress …). That’s essentially a human enzyme that has an important role in the nervous system and in several nervous system diseases (e.g. Parkinson’s disease and chronic pain). But endogenous GAD65 is also found in the insulin-producing beta cells of the pancreas, although its function at this site is not yet been fully established, as well as in nerve and brain tissues. As noted, its role in beta cells is not fully understood, but researchers do know that GAD65 catalyzes the conversion of the amino acid glutamate to GABA, which is a neurotransmitter, in nerve cells. GAD65 is also considered an important candidate drug in several neurological diseases, including Parkinson’s disease and chronic pain.

One need not know the precise role of GAD65 in the beta cells to understand how it impacts the autoimmune response to those cells. It’s clear that GAD65 is one of the most important targets when the immune system attacks the insulin producing beta cells in autoimmune diabetes, thus its use as a type 1 diabetes vaccine among at-risk patients. By introducing the enzyme to the immune system before it wreaks havoc on a person’s beta cells, the vaccine can potentially induce what’s known as "self-tolerance" to their own beta cells, which is THE core problem in type 1 diabetes, not a lack of insulin per se. Treatment with Diamyd® is believed to induce tolerance to GAD65, thereby intervening in the autoimmune response/attack and therefore preserving the body’s capacity to produce at least some of their own insulin in patients with autoimmune diabetes, i.e. type 1 diabetes and LADA.

In summary, GAD65 is known to be a major autoantigen in autoimmune (type 1) diabetes. The Diamyd® vaccine is intended to induce immunotolerization in patients with autoimmune diabetes to slow or prevent the destruction of pancreatic beta cells going forward, and to maintain some endogenous secretion of insulin, which has been proven unequivocally to have long-term patient benefits by enabling easier glycemic control, and providing significant protection from hypoglycemia, a major problem that plagues many patients with type 1 diabetes (but is far less common in type 2 diabetes due to residual counterregulatory function).

Diamyd: An "Orphan" Drug? Yes, According to the FDA!

In any event, I reached out to Diamyd to discuss a fairly recent development that culminated with a press release announcement last month that Diamyd’s type 1 diabetes vaccine had been granted a designation by the U.S. Food and Drug Administration as an "Orphan Drug" intended to treat rare diseases. This development is important for a number of reasons.

Historically, the approval time for Orphan Drugs has been shorter than the approval time for other drugs in the U.S. Although the approval criteria is NOT different than it is for other drugs, applicants for orphan drugs do have the added benefit of having an ongoing dialogue with the FDA, which helps applicants to avoid sometimes lengthy delays in the application that might occur in the event that there is a question on the application or on the clinical trial results, and what those actually mean. There is also a staff at the FDA that can assist orphan drug developers through the entire application process. Plus, if approved, the drug gets 7 years’ exclusivity from the FDA on top of any patent protection that the product may be eligible for. It also eliminates FDA filing and registration fees, and provides tax incentives for as much as 50% of the clinical development costs.

But Type 1 Diabetes Isn’t Exactly "Rare", So Why The Designation As Such?

Although there are some 7,000 rare diseases according to the FDA’s definition, the reason this designation for Diamyd is so noteworthy is because ordinarily, a rare disease is one that affects fewer than 200,000 individuals. In the case of type 1 diabetes, depending on whose estimates one uses (the U.S. Centers for Disease Control does not gather information based on diabetes type, and there is no nationwide registry for people with the disease, so solid statistics are clearly lacking) there are anywhere from 1.5 million to 3 million Americans living with type 1 diabetes in the U.S. today (and we know that the incidence is growing) – far more than most other rare diseases according to the FDA's definition. The orphan drug designation usually involves a very limited subset of patients, and in the case of type 1 diabetes, that is most often newly-diagnosed patients. But if the Diamyd treatment is approved, it is foreseeable that the applicable patient universe for the treatment could possibly be expanded to include patients with longstanding type 1, which is fantastic, because any research analyst will confirm that it’s faster, easier and usually cheaper to expand the applicability of an already-approved drug to other groups of patients than it is to get a brand new drug approved.

Diamyd isn't exactly alone in getting Orphan Drug designation for a type 1 autoimmunity treatment in development. Right now, there are a few other drug candidates that have also received an orphan drug designation, among them teplizumab which was developed by Macrogenics, Inc. along with it's big Pharma partner Eli Lilly & Co., and otelixizumab which was developed by Tolerx, Inc. with big Pharma partner GSK/GlaxoSmithKline. In the case of teplizumab and otelixizumab (both of which are anti-CD3 antibodies meant to address the autoimmune response responsible for type 1 diabetes), these drugs have been granted the orphan drug designation only for "new onset" or "recent onset" type 1 diabetes patients.

"With Residual Beta Cell Function" Is VERY Different From "Newly Diagnosed"

Diamyd’s orphan drug designation differs from both of them in that it has been granted orphan drug designation for individuals with type 1 diabetes "with residual beta cell function", which is a very important difference, as it could potentially be expanded to include certain any patients with longstanding type 1 diabetes provided they have some remaining beta cell function. Now, I should advise that my impression is that other autoimmunity treatments in development might need to submit additional clinical trial data in order to reclassify their eligible universe for the treatments, or else have doctors prescribe it off-label (doctors can already do that on virtually any FDA approved drug), a practice that the FDA has recently cracked down on after years of widespread abuse by the pharmaceutical and biotechnology industries, but I should point out that Mr. Zerhouni did not suggest this, rather that is merely my personal impression of how these definitions differ slightly.

Mr. Zerhouni did tell me that the FDA has not specified exactly how that beta cell functionality must be measured, but would most likely use C-Peptide level and possibly some other criteria.

On a related tangent, it is worth noting that Exsulin/Kinexum Therapeutics' Dr. G. Alexander Fleming, who was for 12 years the Head of the Metabolic Group including diabetes at the FDA, and was involved in the approvals for ALL diabetes drugs approved by the FDA during the 1990’s and also led professional education at the FDA's CDER [Center for Drug Evaluation and Research] knows only too well, the FDA has struggled with defining criteria for evaluating the efficacy of curative therapies for type 1 diabetes (see his paper here for more details) for a number of years, and the FDA has yet to specify exactly what it will need to consider to measure residual beta cell function. In my personal opinion, the reason for this is because the FDA has overwhelmingly relied on using "surrogate" endpoints for diabetes treatments which has been measured almost exclusively by using HbA1c, rather than taking a more global view of how medicines for this disease should really be evaluated.

But there seems to be growing pressure from within the medical community on the FDA to change that review criteria. This was prompted, at least in part, by a commentary article published in the September 29, 2007 edition of The Lancet entitled "Patient-important outcomes in diabetes—time for consensus" in which the authors, largely from the Mayo Clinic, reported that a majority of diabetes clinical trials in the U.S. ignore virtually everything except glycemic control (see my previous post on this topic here). Similarly, the FDA has rightly been criticized for looking only at HbA1c, especially to fast-track approvals on drugs like Avandia to treat type 2 diabetes, in spite of the FDA having some evidence that Avandia actually killed certain patients, suggesting the use of surrogates alone is deeply flawed. It is my hope that this growing pressure on the FDA, combined with the advent of new treatments that address the root cause rather than simply the symptoms of the disease, will result in clearer review criteria going forward.

However, to confirm Mr. Zerhouni's presumption, a 2001 workshop did seem to validate the use of C-Peptide as an appropriate measurement (see here for that paper) of residual beta cell function. However, because orphan drugs have more guidance from FDA regulators, this will likely be decided as the Phase III human clinical trial results are analyzed and reviewed.

Diamyd and LADA

Another difference with Diamyd seems to be the LADA (latent autoimmune diabetes in adults) patient audience because Diamyd has already studied this group with GAD in its earlier trials. Since this group has a slower progression of beta cell destruction, Diamyd has learned a lot about the effects of GAD working for LADA patients in the earlier Phase I and Phase II trials, and that could potentially have implications for future trials helping this group as well.

Diamyd has already finished both Phase I and Phase II human clinical trials successfully, reporting positive results from a completed 30-month randomized double-blind placebo controlled Phase II study of 70 children and adolescents with type 1 diabetes. In the Phase II trial, significant long-term efficacy was demonstrated in preserving ongoing beta cell function, i.e. endogenous insulin-producing capacity. The treatment was also reportedly well-received by patients, their doctors and family members. The results also strongly support the safety of Diamyd, with no serious side effects related to the treatment reported. The study was published in the fall of 2008 in The New England Journal of Medicine.

Steady Progress In Enrollment for the Phase III Trial



In March 2010, Diamyd announced that it had recruited 100 study participants at 33 diabetes centers in the USA (and more sites will be added) in the ongoing U.S. Phase III study, called DiaPrevent, which is part of a global Phase III program with the company's lead drug candidate. Collectively, Diamyd has already enrolled more than 430 children newly-diagnosed patients with type 1 diabetes in Europe and the USA.

In the meantime, Diamyd, like all biotech startups, is losing money, but angel investors tend to view progress towards the company’s business goal(s) as a more important measure of the company’s success thus far. The Phase III trial is largest trial required thus far, but Mr. Zerhouni mentioned that most parents they speak with seem gratified by their child’s participation in the study. Given that, if I had to surmise, I would not expect any major delays in recruiting participation in this trial.

Elisabeth Lindner, President and CEO of Diamyd Medical, said in an April 2, 2010 statement:

"We have exciting times ahead of us with only one year to go before we have the results from our European Phase III study. Our hard work starts to pay off. Besides our ongoing partnership discussions, we will primarily focus on completing the Phase III studies and prepare for market launch of Diamyd®."

I think all of us should look for great things to come from this company, and I personally wish them success, not only from a financial perspective, but also for having a product that could benefit all people with type 1 diabetes. I expect great things from Diamyd!