The tissue at risk here are the capillaries and other small blood vessels in the choroid. These are the sources of nutrients for the retina which is the most metabolically active tissue in the body. We have a great deal of information about how diabetes changes these vessels at very early times in the disease. The early heroes who made this possible are the people who have specified that their bodies can be used for research after they die. Sadly, there are too many of them. Car accidents probably account for the vast majority along with heart attacks and cancer. People studying diabetic retinopathy put together a proposal to obtain eyes from these people after they die. Once the proposal is reviewed and accepted, specific hospitals would be set up as sources for the material and everything would be scrutinized carefully by ethics committees before the work began. Once the eyes were in hand, these researchers carefully examined the vascular structure of the choroid and compare it to the status of diabetes in the person before they died. In the present day, we have very powerful imaging tools that can examine many aspects of the retinal vasculature in the living patient – more on this later.

Those first researchers found interesting abnormalities in the vascular structure that supplies the retina and have associated this with very early times during the development of diabetes. First of all, they found that the walls of certain capillaries thicken. What do I mean by walls? Capillaries are, of course, made up of cells that create these tiny tubes through which the blood flows. However, what I am talking about is the stuff that is secreted just outside of these cells. We call this stuff “basement membrane”. Think of basement membrane kind of like a lattice of fibers. It is made up of collagen – you know…that stuff that some people inject to make their lips look fuller. Its real function is to create these lattice structures that surround tissues. All of the tissues of our body have basement membrane surrounding it. The lattice contains many important molecules that help information pass from tissue to tissue. This lattice is what gets thickened in places as diabetes progresses. Since nutrients need to pass from the capillaries to the RPE layer (see the previous post for the definition) to get to the photoreceptors it is probably no surprise that a thickening of the basement membrane will decrease the flow rate for these nutrients. This sets up a problem. Nutrients are no longer getting to the photoreceptors in that area fast enough. What happens is that the tissue begins to build up an oxygen debt – a state called ischemia. Let’s hold onto that thought for a while since we have to talk about some other changes to the vasculature.

In other capillaries researchers have found tiny ruptures (called microaneurysms). The presence of microaneurysms is considered the first sign of diabetic retinopathy in medical textbooks. We do not really know how this fits in with the pathology. Imaging can detect these microaneurysms so we can now see them in live patients and try to correlate them with the onset of diabetes and with diabetic retinopathy. The problem is that they don’t seem to correlate with any of the standard pathologies apart from the fact that we see them at the beginning of the disease.

In yet other capillaries we see something called pericyte ghosts. Pericytes are going to end up playing a big role in diabetic retinopathy so let’s spend a minute on them. Blood vessels tighten and relax. This is how blood pressure is regulated. It can let one organ get lots of blood while decreasing blood flow to another organ. In order for a blood vessel to tighten it needs a band of muscle to surround the vessel. This vascular smooth muscle is what does the job of squeezing and releasing. Really small blood vessels like arterioles, veinules, and the capillaries in between are too small. Instead they use pericytes. The pericyte surrounds the tiny tube at strategic spots and squeezes to create pressure. When they are missing we can tell. We see an outline of where they were positioned and we call this a pericyte ghost.

In still other capillaries we see a different kind of ghost. In imaging studies of patients it is possible to actually see blood flow through the capillaries. Actually, in pictures what we really see are the red blood cells in a line (the capillary is so small that red blood cells go through one at a time). In patients who are developing diabetic retinopathy we see whole capillary branches that appear empty.

So to sum up, we see lots of changes in the vascular bed of the retina long before the patient has any kind of problem with their vision. These changes are visible with current imaging techniques and unequivocally herald the onset of diabetic retinopathy. How long it takes to develop depends on how well the patient controls their glucose. Good glucose control can keep things under control for many years.

Take, for example, the cepelin — doughy, greasy potato dumplings roughly the shape of a blimp (hence the name — it’s Lithuanian for “zeppelin”), but with a density that guarantees that they would never remain airborne. Peter and I shared a serving of those the first day we were here, and I was left amazed that a. a potato could be made that gelatinous and b. the normal serving size is two. I ate only part of one, and felt like I could hardly get up from the table.

But the obsession with carbs does not stop there. No, this is the land that worships the potato, and potato pancakes (similarly gelatinous inside, but somehow better-tasting) are available at every restaurant. You’re not safe if you try to stick to, say, a salad — there appears to be a distrust of any dressing that is not sweet.  And oh, don’t get me started on the fried bread sticks. These are a national favorite beer snack, as they’re called, also available on nearly every menu — and after seeing them pop up again and again, Peter and I finally could not resist. I mean, it’s fried bread. Thanks to our biking itinerary, I had a few free carbs to spare. What better way to spend them than to eat bread — not just fried, but dipped in cheese?

It turns out that there are many better ways. Stale and greasy, the bread sticks had been dipped in some sort of ranch dressing (again with the sweet!) and then rolled, Sno-ball-like, in tasteless shredded mozzarella.

The upside of the fried bread sticks was that I was not at all tempted to eat more than one. Instead, I stuck to the cold beetroot soup (which I’ve convinced myself is healthy, though I think it may be made with sour cream). It’s bright pink, contains hard boiled eggs, and has delicious dill-spiked shreds of beet and cucumber. Yes, it comes with potatoes, but in what seems like a gift to diabetics, they’re always served on the side.

But it’s hard to get beetroot soup for breakfast on the road — one trick Peter and I have developed is to boil a bunch of eggs at the hostel or guesthouse the night before, and then take them on the road (one way to make new friends on long-distance bus rides: unpeel hardboiled eggs). When that doesn’t work, I try to stick to a banana or an unsweetened  yogurt. But sometimes even that doesn’t work — and I’m left with choices like this, the Magic Sticks. Please note the condensed milk.

Needless to say, I ate pretty light that morning.

But as I noted earlier, I’m rediscovering that one of the best ways to deal with a carb-heavy diet — or with traveling in general — is to exercise. Right now is a bit extreme — we biked 60 kilometers today, and have done roughly similar distances for five out of the past seven days. I’ve been dropping my basals to 55% while we’re on the road, drastically lowering my boluses, and still have been able to indulge the occasional ice cream cone without any diabetic repercussions to speak of. It’s making me wonder if I could work long-distance bike rides into my everyday life! (Especially if the rewards involved were greater than Magic Sticks. . . .)

I’ve also started to look at national cuisines with a more critical eye. It’s hard to read the menu of restaurants here, look at the body shapes of most Lithuanians over 40, and not think that Type 2 diabetes must be a problem. Obviously, to criticize the Lithuanian diet (or anyone’s diet, for that matter) as unhealthy — when I’m American — is a bit laughable. We are, after all, the country that invented the Double Down — a nationwide obsession with the potato might actually be an improvement. But still, observing a culture and a cuisine from the outside makes me recognize that Type 2 really is becoming a global problem, and it’s exacerbated by the way we eat, whether it’s cepelins or French Fries.

But I’m too tired to do much pontificating at the moment — tomorrow we’re off to a national park that used to house Soviet nuclear missiles (now you can take guided tours of the empty silos). My current plan is to keep biking through the Baltics, enjoy my occasional ice cream cone, keep to the beetroot soup and, above all else, avoid another favorite local beer snack: smoked pig ears. (Some of them still had hair.)

Biking on the Curonian Spit

First, the good news. After writing that last post — the one where I found out that Air Baltic had lost the bag containing all of my non-diabetic belongings for a second time, I fell into a restless sleep, full of dreams of luggage and frustration. I really thought the bag was gone. But then, surprise of surprises, I awoke in the morning to find an email from the Vilnius airport saying that my baggage had arrived. No mention of what might have happened to it in the 24 hours since last it was seen — but whatever. By lunch time, I had new pants.

I also had my biking clothes, which meant that we were finally free to set off on the next stage of our adventure: biking to Estonia. I should probably point out here that this is not the first long-distance bike ride I’ve done — after college (and three months after being diagnosed), I biked from Connecticut to San Francisco with a bunch of college friends. But there are several important differences between that trip and this one. First, it was ten years ago. Second, we had a support van — which meant not only that we didn’t have to carry our own luggage, but that on the days when I didn’t want to bike, I could get a ride. Third, we knew where we were going. And fourth, we had a place to sleep at night.

This trip? Well, it’s a little different.

We’re hauling our own luggage, to begin with, and aside from a stack of maps and (thankfully) a small GPS device, we have no idea where the hell we’re going. Oh, and also, everyone here speaks Lithuanian.

Nonetheless, we somehow managed to make our way to the lakeside town of Trakai, 25 or so kilometers from Vilnius (or 35 kilometers, if you take our route). There’s water everywhere you look, a beautiful castle, and lots of Lithuanian men in small bathing suits. We celebrated our arrival by going out for kibinas, crescent-shaped dough pockets that are similar in theory to a calzone, but come stuffed with ground meat and cabbage. This, combined with a national love of the potato, is not making Lithuania the most diabetically friendly country to visit.

I mean, seriously? I’m grateful that I’m exercising so much, because if I weren’t, my bolusing woudl be out of control (as it is, four hours a day of biking is enabling me to drop my basals to 55% and eat an entire ice cream cone with less than .5 of a unit to cover it — amazing!).

After dinner, we strolled along the river bank to check out the castle and, perhaps more importantly, to see what was going on with the two stretch-stretch-stretch-stretch white SUVs that had passed us as we ate. Turns out it was a wedding — as evidenced by a group of flouncily dressed young women who responded to Peter’s request that “Everyone, get together!” not by shooing away the creepy foreign guy, but by posing for a photo.

So here we are, at the edge of a Lithuanian lake, with tired thighs, sore butts, and a hell of a long way to go. Stay tuned.

Peter and I arrived in Lithuania, and I have two major first impressions: Vilnius, the capital of Lithuania, is both fascinating and beautiful. And second, no matter where you are traveling, never, ever check a bag that contains your diabetes supplies. When flying from Milan to Vilnius (via Riga) I did not make that mistake. Thank goodness — here’s a rough itinerary of how our day of travel turned out. (I’m borrowing this from some of our travel blog, so apologies for not getting to pancreatic issues till the end!)

1:30 am: Go to sleep

6:30 am: Pull selves out of bed, walk to train station.

7:37 am: Take express train from Turin to Milan

8:45 am: Arrive in Milan. Wander around aimlessly and irritably looking for the supposed “Malpensa Express” to the airport. Eventually learn that we are in the wrong train station.

9 am: Take Milan subway to correct station. Find airport bus.

10:30 am: Arrive Milan airport to find a sea of people in an immense check-in area, the sort of chaotic scene that actually makes JFK seem like a nice place to spend the afternoon. Discover that our check-in counter does not open for two hours.

10:30 am – 12:30 pm: Distract selves by, at least in my case, reading Michael Lewis’s The Blind Side, drinking multiple cappuccinos, waiting in line for the bathroom, and impulse buying travel items at an airport boutique (a portable clothesline AND the world’s smallest fan? Amazing!).

12:15 pm: Get stuck in bag drop-off line behind a pair of Americans who seem unwilling to believe that this is not the line for Swiss Air, despite the fact that the counter says Baltic Air, and the destination is Riga. We point out that the Swiss Air counter appears to be — nay, IS — several desks down, and that it is too early for them to check in. “So this is not the Swiss Air line?” asks the man, gesturing toward the sign that says Baltic Air. “Where are these people going? Can we wait here?”

12:30 pm: Deposit bags at drop-off counter. Peter makes sarcastic comment about how the woman at the counter does not securely affix the “transfer” tag on his bag. He reaches down to fix it. I notice the same problem on my bag and realize I should fix it, too,  but it is too late; she has sent it down the chute. I think for a moment what would happen if my bag were lost. “At least I have the computer adapter,” I say in my head. “But it sure would suck not to have any underwear.”

12:34-37 pm: Fun activity #1: Make Peter pose in front of underwear ads starring the Italian soccer team.

Activity #2: Observe a phenomenon I first noticed in China: people paying to have their bags wrapped in saran wrap. Nine euros. To have your bag wrapped in saran wrap.

2:20 – 5:45: Fly to Riga. Upon landing in Riga, try to figure out the exchange rate and then realize that we don’t know what country we’re in. Not kidding. We knew it was either Lithuania, Latvia or Estonia, but I’d been so focused on getting us to Vilnius that I hadn’t paid attention to our transfer point. This is, I might note, not the sort of question you can really ask people without feeling enormously stupid.

5:55 pm: Discover we are in Latvia. Order airport food. Learn the answer to the age-old question: how do you make a tomato unhealthy? (Answer: stuff it with goat cheese and serve it with a plate of ham — but hey, at least there are very few carbs.)

8:10-9:20 pm: Fly from Riga to Vilnius with a captain who enjoys banking to the right, then banking to the left, then speeding up, then slowing down. I begin to wonder if perhaps I should not have spent so much time focusing on the chapter in Malcolm Gladwell’s book, Outliers, that focuses on plane crashes.

9:45 pm: Customs hall. Except, there is no customs hall. We have not had our passports stamped — or indeed, looked at — since landing in Iceland. Presumably this should not be a problem, but I don’t think we’re technically supposed to be in the EU for more than three months straight. Oh well. We’ll see how it goes when we try to enter Russia.

9:50: Wait at luggage carousel four. I am so engrossed in finishing the book (and having a conversation with a Lithuanian woman about e-readers — her dream is to find one that can translate between Russian and English on the same screen) — that I do not notice that the luggage carousel has stopped. “Well, at least we got one bag!” Peter says, jokingly, pulling his over to where I am sitting.

9:55 pm: We realize that the rest of our plane-mates have all left, and what appeared to have been a pause in luggage delivery was, in fact, the end of it. My bag = nowhere to be seen.

9:56 pm: Find a friendly airport employee named, wait for it, Zilvinas Pilypas (“I’m probably going to call you later, and I’m probably going to pronounce your name wrong,” I warn him), and tell him about the bag. I also tell him, as politely as I can, that I really need the bag, you see, because in two days I am supposed to get on a bicycle and ride to Talinn (which happens to be in Estonia, two countries away). Zilvinas, who remains polite, but unmoved, types much information into the computer, then hands me a dot-matrix-printed piece of paper containing a reference number and a phone number that I can call. Zilvinas also calls a taxi for us, a kind gesture that I will be even more grateful for if and when I ever get my bag back.

10:10 pm: Get in taxi, show map and address to driver, realize that map and address do not represent the same physical location. Driver puts on glasses, squints, looks again, shrugs shoulders, hands map back, and begins to drive.

10:15 pm: We drive past the Vilnius train tracks. “I don’t think it was supposed to be across from the train tracks,” I keep saying to Peter, as the driver pulls up in front of the correct address, which is across the street from the train tracks.

10:16 pm: Get out of cab in front of a dilapidated building with only a small “Hosteling International” sign to indicate that it might, in fact, be where we are supposed to stay for the night. Adding to the confusion, the front door — which is unlocked — leads to a dark, unfinished room — lights dangling from ceiling, unfinished plasterwork, a missing front stair, and no people. Cab driver peeks inside, looks back at us, and giggles.

10:20 pm: After some exploration, we discover that the hostel is indeed there — upstairs, in fact, and empty except for a woman named Margaret who presents us with sheets and pillow cases and returns to watching the world cup finals.

10:25 pm: I try to make the bed, and then notice something that, at first, I attribute to my fatigue: the sheets, designed for a single bed, appear to be square. I try to turn them the other direction. Still square, and about a foot and a half too short for the bed. Consider asking Margaret for other ones, but, decide that since she has just let me raid the toiletries of former guests (including a half-finished bottle of “Hangover Cure” Axe body wash), that might be asking too much. Make the bed with the square sheets, leaving the exposed part down by my feet. At least I have socks?

11:15 pm: So here I am, wearing the same pants I wore on a very sweaty hike yesterday and the same shirt I slept in last night (and which was subjected to a good deal of airport sweat as well). I’m wondering where my bag could be. Surely, it made it out of Italy. But then again, our second flight was on the same plane as the first. What kind of transfer tag fuck-up does it require to lose a bag that didn’t need to go anywhere? (This, and many other questions, will be answered in the coming days.) Luckily, I was wise enough not to check the bag that contains my diabetes supplies, and so I am happy to say that my artificial pancreas is not MIA. If only the same were true for my underwear.

Post script: It is now two days later, and I still do not have my bag. Yesterday, it was found in Riga — hallelujah! — right outside of the luggage department. But today? Lost again. I’m having difficulty figuring out how you could misplace a bag on a 1/2 hour direct flight, but, well, apparently you can. And I am once again so, so grateful that I didn’t succumb to the urge to check my enormous backpack of diabetes gear. This way, the worst-case scenario is that I’m going to have to do a bunch of shopping, plus deal with Air Baltic’s claims department (surely they have nothing on Blue Shield). If, on the other hand, I’d lost the diabetes bag, I might be in the hospital (or at least an emergency clinic trying to get a prescription for needles and insulin).

The problem started at lunch, when, after a snack of bread on the bus (which I bolused for, mind you), my blood sugar was 323. That’s enough to make me want to scream to begin with, but it also happened to be lunch time, and I had fought my way through a large crowd of tour groups and CERN scientists, and wasn’t about to not eat. (After all, we were looking at another 5-hour bus ride home, and I was already starving.) So I double bolused, for lunch and for the correction, even adding a little more since I knew that my inactivity and already high blood sugar were going to make me really insulin resistant.

Then, as one does, I went to check out the hydron collider. Or, rather, I followed my group to a huge warehouse where they store the extra magnets. Now, I’m not really one for particle physics to begin with, but we had a jovial British tour guide who was used to groups of school children, which meant that I actually could understand what he was talking about. I followed along for about 45 minutes and then decided to check my blood sugar, just to see what was going on. This seems crazy in retrospect, but I was a little worried it might drop too low — I’ve had some really scary ones recently that came on unannounced, and I’ve been getting paranoid.

Well, no need to worry this time, because when I pricked my finger, the result came back at 447.

No, that’s not a typo. That is four hundred and forty seven mg/dl and is, quite literally, higher than it was when I was diagnosed nearly 10 years ago. Freaking out, I took a huge correction bolus, waited a few minutes, and checked again. 475.  Twenty minutes later? The glucometer stopped giving me numbers and simply said “Hi.”  Surely that was wrong — so I checked on my backup glucometer. “Hi.” My blood sugar was so out of control that it didn’t even register on the machine.

I was horrified, frustrated, scared, confused — pretty much any diabetes-related adjective you could think of. What was going on? What had I eaten — what had I possibly done — to make my blood sugar go this high? The only possible explanation I could come up with was that I had somehow tugged on the tubing/insertion site when we’d stopped at a rest stop on our way to Switzerland and had pulled the tubing out from my skin — but, thanks to the ingenious design of the Quick-Set, I couldn’t actually see if anything was wrong.

Thank god that I had had the foresight to bring another insertion site — I usually am not good at remembering to do that, and in this situation, it would have meant at least 7 hours more with outrageously high blood sugar. (I had a backup syringe, but no humalog b/c I didn’t want the vial to denature — starting tomorrow, I’m going to pack one anyway.) As our tour guide spoke to our group about how the refrigeration system of the hadron collider worked, I carefully (very carefully) unwrapped the set and plunged it into the skin of my opposite hip, making sure that I could feel the needle going in, before reattaching the pump on my other side. I then took off the problematic site, pulling the adhesive slowly so that I could see if the cannula had indeed come loose.

Nothing. The cannula was securely in my skin. Sure, I had my typical “donut” of puffy tissue left over from the Quick-Set, but there was nothing otherwise unusual that I could tell from the surface. Meanwhile, I checked again — still “hi.”

I’m almost embarrassed to say what happened next — but here goes: as the rest of the group went off to see something called the ATLAS project, I stayed behind in the visitor’s center and . . . burst into tears. I’m not talking like, a little sniffle. I’m talking about full-on crying, the type that is so intense you need to lock yourself in the handicapped bathroom so that you can sob against a wall (and then you need to wear dark sunglasses on your way out so as not to show your red-rimmed eyes to the world). I’ve been frustrated by my blood sugar pretty much continuously on this trip, and this was a tipping point, one of those moments where all the tiny details of diabetes come crashing down on you all at once — the self-control and the attention to detail and the thought required for every single bite of food. As I stood there, alternately crying and talking to myself, I could only really say one thing, a phrase I return to every time the emotions of diabetes get the best of me: “I am so tired of this. I am so, so tired.” And then, something new: “I am so angry about having diabetes.”

It was a funny and surprising thing to hear myself say, because the vast majority of the time I’m really *not* angry about it. It just seems so pointless — who would I be angry at? Whose fault is it? No one’s. What can I do about it? Nothing. But today, all the frustration I’ve been feeling boiled over into a genuine anger at having to live with this goddamned disease every day of my life, with no end in sight. Suffice it to say, by the time I got out of that bathroom and snuck outside to take a walk, I really needed those sunglasses.  And I also couldn’t help but notice the irony of being at a research laboratory that is attempting to recreate the conditions of the Big Bang — and we still haven’t been able to figure out the secrets of something as close to our hearts (literally!) as the human pancreas. If only JDRF had a 20-country partnership and over a billion dollars a year.

As it turned out, it took more than sixteen units of insulin to get my blood sugar to go back down — which it did after nearly six hours. It even threw in a fun trick where, after not working at all for the entire afternoon, the insulin kicked in and I dropped from 293 to 69 in an hour — despite the fact that the insulin technically should have been nearly out of my system.

Anyway, I’m now back in the hotel room, I ate a tomato salad for dinner, and I’m looking forward to collapsing into bed. But I’m confused and upset that, for reasons I still don’t understand, my blood sugar was higher this afternoon than it’s ever been since I was diagnosed — and that it took so much to get it to go down (even the walk did nothing). I have never, and I mean never, gotten that “hi” message on my glucometer. But then again, as my husband pointed out, at least it didn’t say “Bye.”

As I researched Saxl’s life, I was particularly struck by the mention of prejudice against diabetics–all the more so because it seemed removed from my own experience. Although diabetes isn’t my conversation opener of choice, I’ve never had a problem explaining my condition if I need to. Until recently, if someone had asked me if I felt the need to hide my diabetes, I would have thought: Why should I? It’s not my fault that I have diabetes, and there are many situations in which it could be important for other people to be aware that I’m diabetic.

A few days ago, however, my brother Julian and I discussed the fact that even though we aren’t embarrassed to admit we have diabetes, non-diabetics often make us feel as though we should be. Once, when I went to have blood drawn before an endocrynologist appointment, a nurse asked me if I had a phobia of needles. I joked that it would be tough if I did, since I had type 1 diabetes and needed to give myself several injections every day. “It’s so sad how young people are getting diabetes these days,” she said, and launched into a discussion of child obesity and the benefits of whole grain versus white bread. It took me a few minutes to realize that she wasn’t just discussing diabetes in general, but was trying to give me advice that she felt I needed. My brother complained that when people find out that he has diabetes, they often exclaim: “But you’re in such good shape!” or “You don’t look like you have diabetes.” Both of us have also encountered the shock of friends or relatives if we eat anything sweet, or the admonishing “Are you sure you’re allowed to eat that?”

Comments like these reveal some of the misconceptions that many people still have about diabetes. The nurse lectured me about healthy eating because she thought that bad dietary habits had caused my diabetes. People are surprised that my brother is fit and athletic because they assume that diabetics must be overweight. Most of these false impressions can be explained away with little effort. Nevertheless, they have the potential to be extremely irritating. Why are they able to make us feel guilty or defensive when we have nothing to be ashamed about?

When Julian and I thought about it, we realized that all of these misconceptions boil down to one assumption: that you, the diabetic, have brought on diabetes yourself. This belief–which seems to have persisted from Saxl’s time–allows the non-diabetic to take the moral high ground. Even if we correct a specific misunderstanding (such as yes, type 1 diabetics can eat dessert sometimes), it’s hard to counteract the underlying impression that the diabetic is somehow at fault.

With all of the advances in diabetes research, it might seem strange that this misconception still exists. I feel that part of the problem has to do with the lack of differentiation between type 1 and type 2 diabetes. Type 2 diabetes, unlike type 1, is in part based caused by factors like weight, eating habits, and lack of exercise. Because type 2 is much more prevalent than type 1, it’s likely that if a non-diabetic has any contact with a diabetic, it will be with a type 2 diabetic. It’s also inevitable that most advertising about diabetes products is geared towards type 2 diabetics. Even Oprah’s recent episode on diabetes focused mainly on type 2. Keeping this in mind, it’s hardly surprising that most people are unaware of the differences between the two forms of the disease. However, it would also be an oversimplification to make an equation like: type 1=not your fault, type 2 = your fault. Type 2 diabetes is in part triggered by a person’s habits, but many type 2 diabetics also have a genetic predisposition towards the disease.

Ultimately, no one should assume that any type of diabetic deserves the blame for their disease. But this fact isn’t widely understood by our society. It seems to me that the only way to counteract the stigmatization of diabetics is not to hide the fact that you have diabetes, but instead to follow in Saxl’s footsteps and openly correct misconceptions whenever you encounter them.

I was alerted to this by Bob Fenton, another diabetes blogger (http://bobsdiabetes. blogspot.com/). He sent me a piece from the Telegraph, a newspaper published in Briton which described the work of Dr. Karen Porter. I pulled up the research paper and found it to be quite interesting. Dr. Porter is looking at why patients with diabetes fare so poorly with heart disease. Not only do they need more procedures such as bypass surgery but the outcomes of these surgeries are often quite poor. For example, the saphenous vein (a big vein found in the thigh) is often used for coronary artery bypass grafts. The graft gets plugged surprisingly quickly when the patient has diabetes and is taking insulin; a process that gets the fancy name “intimal hyperplasia”. The plugging of the graft is not due to atherosclerotic plaque but rather due to the proliferation of the cells of the graft itself (hence the word, hyperplasia). The new cells can only grow inward and so the hole gets plugged and heart disease returns.

It is possible to examine theses cells in a tissue culture dish and this is what the research team did. They obtained bits of saphenous vein from non diabetic patients who had heart disease and were getting a coronary bypass graft (and volunteered for the study). These bits of tissue were placed into tissue culture dishes containing a liquid maintenance medium in the presence of either insulin or C-peptide or neither or both. Now it has been known for some time that insulin can act as a growth factor for some cells and others had demonstrated that insulin will promote the growth of the cells of the saphenous vein. What this group found was that C-peptide reversed the effect.

Insulin is cleaved within the secretory granule from which it will be released. Thus upon release, not only is insulin entering the blood stream but also an equal amount of C-peptide. Diabetes patients who do not make their own insulin do not get any C-peptide since it is not included in synthetic human insulin preparations. This leads to a lot of interesting and important questions. Would heart disease decrease for diabetes patients taking insulin if C-peptide was present? The present work suggests that after a saphenous vein graft cardiac bypass graft, C peptide might have a positive effect but we do not know how it will work for a patient whose heart is still healthy. As a pharmacologist, I would like to know how C-peptide works. Is there a separate receptor for C-peptide? Does C-peptide bind to some part of the insulin receptor and modify its function? Would the addition of C-peptide improve other diabetes complications?

At least some of these questions have been answered. A company called “Creative Peptides” is promoting the use of C-peptide in diabetes and has funded a clinical trial. The results were published in 2007 by Drs Karin Ekberg and colleagues from the Karolinska Institute in Stockholm. They found that a replacement dose of C-peptide resulted in an improvement in diabetic neuropathy. Others have shown that C-peptide can bind to membranes from endothelial cells, kidney cells, and nerve cells, indicating that a receptor for C-peptide exists and is probably different from the insulin receptor (which is found on many if not all cells). While the receptor has not yet been identified researchers have identified several signaling pathways that are altered when C-peptide is present. These result in the production of a chemical called nitric oxide (NO) which helps with blood flow as well as an increase in the activity of the pump that keeps the electrical gradient that powers neurons. C-peptide has also been shown to increase the secretion of neurotrophic factors which function to protect neurons. Within the symphony of the body, this is not a trivial part.

Can we expect to see C-peptide on the market any time soon? After mucking around on the web I found the beginnings of an answer in good old Wikipedia. A US company called Cebix has secured patents for the manufacture of C-peptide. According to the Cebix website they will be performing another phase II clinical trial which will start in 2011. Should you be interested in seeing if you qualify for this trial, keep an eye on the clinical trial web site www.clinicaltrials.gov. If indeed, insulin alone promotes a degree of discord, it is satisfying to know that harmony will be restored.

It would be impossible to do everything — there are four sessions a day with six simultaneous talks, not to mention the lunchtime lectures, the late afternoon lectures, the site visits, the science parties and the scientific events going on around the city — so I’ve had to pick and choose. Perhaps unsurprisingly, a lot of my interest centers around human health — I went to a really interesting discussion yesterday on how people respond differently to the same exercise regimens (it appears that there’s a genetic component to whether or not exercise will actually improve your health — who knew?). I’ve  also been interested to see that while there are plenty of talks about climate change and a ridiculous number about the Big Bang (CERN is involved in the conference, and seems a little defensive), there is nothing exclusively devoted to diabetes. Obviously I’m biased, but given its worldwide explosion, I would have expected there to be more. Oh well. I’ve already got one pancreas to deal with — perhaps I don’t really need more.

So I’ll leave the conference updates to Karmel (keep them coming!), and instead write an update on our trip so far, since our itinerary has been so hectic that I’ve hardly had a chance to reflect on the whole diabetic aspect of traveling the world.

My first thought? It’s hard. In fact, I’ve been surprised by how difficult it’s been. I know what you’re thinking — you’re away from your normal diet and exercise patterns — of course it’s going to be hard! But hear me out: I’ve done numerous trips since being diagnosed, most notably six weeks in Europe after college, and two months in China a few years later, land of dumplings and rice. I don’t remember either of those trips as being particularly diabetically disastrous. I also spent the summer after I was diagnosed biking across the United States. Sure, I can remember weeping hysterically in a church basement somewhere in Pennsylvania, but I also remember getting to eat DQ shakes without problems (biking 70 miles a day gives you a bit of flexibility).

Right now I’m in Italy, and I’ve had a relatively good couple of days, probably due to the fact that I have been hoarding hardboiled eggs from the hotel breakfast buffet (there’s one in my bag right now, and I’m really hoping it doesn’t break). But in France, some combination of a lack of exercise, a bad cold, and, let’s face it, baguettes, meant that I was a diabetic disaster. I went high after nearly every meal — and then, if I tried to preempt the highs by taking extra insulin, I’d drop too low. I woke up one night drenched in sweat because of a miscalculation at dinner; I even had a scary low in the middle of the Louvre (I’ll attach a photo when I get home). If there’s one thing that can make that museum even more stressful, it’s having your blood sugar drop to 47 somewhere between the Mona Lisa and the Venus de Milo.

I was assuming this was mostly my fault — I don’t normally eat so many sandwiches — but then several days ago, things seemed to regulate back to a relatively normal state, despite my increased bread consumption. It’s yet another trick of diabetes — even when you’re certain you know the cause, there are other variables working behind the scenes. Luckily at  the moment, they seem to be in my favor — but it was a rough few weeks.

On a separate note, before we were in Paris, my husband and I spent two weeks volunteering at a French dairy farm, a location I chose primarily because they produce cheese and yogurt — both delicious and low-carb. The first night at dinner (which included  bread, pasta and rice) I was sitting at the table with the family and pulled out my Symlin needle. I saw the father — a hardy French farmer named Laurent, whose daily activities include tasks like delivering baby cows — blanch.  “Are you okay?” I asked him, jabbing my needle into my stomach as he literally turned away and covered his face with his hands.

“In a minute,” he said. His wife and daughter rolled their eyes and laughed.

He turned out to be the first person I’ve met — in the almost 10 years I’ve had diabetes — who had genuinely been known to faint at the sight of  needles. It became a running joke between us that became especially relevant when, several days later, he had to give a goat a shot of antibiotics in the neck.

Also,  a note on my preceding kitten video post. That was the cat of the family on the farm. In addition to playing with my pump, she also enjoyed being put in plastic bags. (Not kidding.)

For many of us in the West, we have our sights set clearly on finding a cure, while millions of people in developing countries live day to day hoping for diabetes medicines and care so their child with type 1 or a parent with type 2 can live a better life, longer.

The International Insulin Foundation (IIF) in Southeast Asia

David Beran (right) with the father of a child with type 1 diabetes (left)

The last time I spoke with David Beran, Project Coordinator for the IIF since 2002, I focused on the IIF’s work in Africa in 2006. Now that I live in Hong Kong, I wanted to know what key differences for diabetes existed in Asia. David pointed out three conditions that make the focus on diabetes in Asia imperative:

1. Development and westernization of Asia is much further along than Africa, especially in urban areas such as Hanoi and further north or south in Bangkok (Thailand), Shanghai and Beijing (China) so the incidence of diabetes is growing at a faster rate. To support this theory, Vietnam, once a recipient of food aid, became “a net exporter of surplus food” and shifted to a more western diet. Since 1990 “consumption of meat and fat has doubled.” It’s hard for westerners to understand how any country could have a double burden of disease – but both malnutrition and obesity exist in rural communities and urban areas in Asia today.
2. Asia’s epidemiological transition is occurring at a faster rate which means that the burden of communicable diseases such as HIV-AIDS is far less than the current burden of non-communicable diseases (NCDs) like diabetes. NCD’s are now 62% of the total disease burden in Vietnam. Asia is quickly catching up with the USA and Europe in this regard and cannot pay for the costs associated with care, patient education or professional training.
3. Health care systems in many places in Asia, like Vietnam, are decentralized. Treatment pricing is managed by powerful hospitals which are also under-resourced. Most all primary and specialized care is delivered through provincial hospitals with some areas roughly providing 6.2 doctors per 100,000 patients. Vietnam (a Communist state) provides insurance to civil servants, state employees, private corporate employees and children under 6 – but it doesn’t cover all essentials for diabetes. Without any centralized purchasing scheme for medicines, prices are inflated and random. (In Africa, care is centralized, and often free – yet, admittedly – also under-resourced.) The number one reason why patients are not adhering to treatment or receiving proper care is the financial burden of the cost.

The Impact?

“In both Type 1 and Type 2 diabetes the result of inadequate care (elevated levels of blood glucose) lead to serious health complications such as blindness, kidney failure, nerve disease, limb amputation, heart attacks, strokes and premature death.”
(The RAPIA Study – Vietnam)

The IDF estimates that children in Vietnam diagnosed with type 1 diabetes have an average life expectancy of 7.2 years, and close to 80% have elevated HbA1cs over 9% – but for many the test is not available. With these statistics at hand and with many patients not formally registered it is hard to know just how many have been diagnosed. The International Diabetes Federation estimates 431 total type 1 patients living in Vietnam. In another study, nearly 40% of all children with type 1 have complications such as eye or kidney disorders at an early age.

Taeng has type 1 diabetes

Dr. Tan Trieu Phuong Dong worked at Children’s Hospital No. 2 in Ho Chi Minh City last year (he is now studying in Taiwan) but in Vietnam he cared for 30 children with type 1 diabetes out of an average caseload of 80-90 general pediatric patients per day. He witnessed two children die from ketoacidosis and infection. The cause? “There is just not enough (patient) knowledge to deal with this complicated disease.”

There are approximately 1,296,400 patients with type 2 diabetes in Vietnam, but the rate of undetected diabetes is high with an estimate of 1 person diagnosed out of every 8 people with diabetes. Another study found more than half of all adults were living with a complication of the disease. In Vietnam, diabetes is listed as the 8th cause of death, but again, with Ischaemic Heart Disease at number 1 and a contributing factor of diabetes – it’s hard to know how to identify the real cause of death.

The RAPIA

The IIF is a non-profit organization established by leading diabetes academics and physicians whose aim is to prolong the health of people with diabetes in resource poor countries by improving the supply of insulin and education. “We do not provide insulin to any country,” David clarified for me when I asked him if he worked with any of the Pharmaceutical companies. “We get most of funding through grants and a small proportion through donations (5-10%).” The RAPIA study in Vietnam was supported, in part, through a grant provided by the Lilly Foundation.

The RAPIA (Rapid Assessment Protocol for Insulin Access) is a series of questionnaires designed to help the IIF clarify what constraints and barriers exist to providing adequate diabetes care and education in developing countries. It occurred to me to ask David why the IIF focused their efforts in Vietnam – a country with a small type 1 population – if access to insulin was a key factor in study objectives. The reasons were varied: IDF partnership and the need for updated diabetes information in Asia, and local cooperation and collaboration with other on-the-ground NGOs which makes information gathering easier. (It might surprise some to learn that only 0.3% of total insulin needs in Vietnam are used for the Type 1 population, and that roughly 30% of all type 2s utilize insulin.) Once the study has been executed, the IIF makes recommendations to government authorities and clinicians based on RAPIA findings from categories including:

• Health service structure with regards to procurement of diabetes medicine and management
• Diabetes policies written and enacted
• Reported and observed practice for diabetes management

(and so on)

It also occurred to me as I began to think about westernized patient care and education why the RAPIA couldn’t be used for policy making in the West –especially by, let’s say the US Federal Government or in States like California and New York where the burden of diabetes cost is high? The National Institute for Health and Clinical Excellence (NICE) in the United Kingdom provides guidance and sets quality standards and laws for specific diseases and illness. In the United States, with decentralized healthcare, there is no part of the government that currently provides rules regarding patient care, standards or laws supporting diabetes patient rights and information – although the Obama Administration has been making efforts in changing this. Unfortunately, it will take time. When I read patient exchanges regarding serious diabetes health related questions on internet chat boards and in forums (“my feet are numb, will this go away if I take my insulin?” Patient Forum, Tu Diabetes) – it makes me realize how most of the world is still trying to figure out how to manage diabetes without professional advice – whether you live in Hanoi or Brooklyn, New York.

I asked David Beran how people can help if they would like to support the IIF, and here is what he had to say:

“I think the temptation is always to find a quick fix. Some organizations do this by “sponsoring a child” or donating insulin. This is easy, has an immediate impact, but is not sustainable. I know that many people reading this may have diabetes, know of someone who has diabetes or if not, have an interest in diabetes. What has always surprised me is how there is no real global diabetes community and that often people with diabetes in the developed world are focused on the cure, which is so important, but forget that their contemporaries in many developing countries still suffer and even die because of lack of access to insulin, a drug that was discovered in 1921.

However, what has become so apparent through the IIF’s work is that insulin is only part of the “diabetes puzzle” so to speak,. It is a key element, but alone it will not lead to good diabetes care. Programmes need syringes, trained healthcare workers, and patient education. The HIV/AIDS community has been able to develop a global community and I would hope that people with diabetes will Unite (to use the IDF UN resolution) to address the myriad of challenges that people with diabetes face.”

* Unless otherwise noted, all statistics in this article have been pulled from the Report on the Rapid Assessment Protocol for Insulin Access in Vietnam 2008.

Cross-posted on diabetes24-7.com

For example: within a block of the apartment where we’re staying, there are four (4!) bakeries. I can barely walk out the door before I’m hit with the sweet smell of freshly baked bread. I thought I’d be inured to this by now — after all, California has a number of high quality bakeries, and I never was particularly tempted to go out and buy baguettes. But note to California (and all of the US): when it comes to boulangerie science, we will NEVER beat France. There is a secret to French bread making, and it’s probably under guard somewhere in the national archives, with a squad of soldiers who have sworn to protect it to the death.

Point being, those baguettes are damn good. And my resistance is weak.

With avoidance disqualified as an option, yesterday, Peter and I figured out a more extreme bread mitigation strategy than merely walking around: we went for a run. Who cares that I have arthritis under both knee caps and am now having difficulty getting out of bed? We jogged down to the Champs Elysees, took a victory lap around the Arc de Triomphe, and made it back to the apartment just in time for a fresh baguette and a croissant. It was delicious and, dare I say it, totally worth the insulin.

Though that’s the thing about France: it’s pretty much all worth the insulin. I’m hoping I’ll reach a point where my standards for baguettes become so high that, after leaving France, I’ll never want to eat one again. So far, that has not happened. So in the meantime I’m trying to find indulgences that are a little less carb-tastic (cheese, vegetables, even pate), and toting — when it comes to sampling carby foods without guilt — what must be perhaps the best diabetic accessory of them all: a husband who’s willing to share.