The Doctor Weighs In

by Pat Salber

I was pretty shocked when I first heard about diabulemia. This is a practice some teens and young women with Type 1 diabetes, are using in order to lose weight. They purposely underdose their insulin allowing their blood glucoses to skyrocket. The excess blood glucose is eliminated in the urine. “Traditional” bulimics purge excess calories by forcing themselves to vomit. Diabulimics purge excess calories by underdosing on insulin and peeing out unmetabolized glucose.

Girls and young women with diabulimia will tell you they feel really crummy as their glucose levels increase and they increasingly rely on metabolizing fatty acids for energy instead of glucose. The end result of underdosing insulin is a state known as diabetic ketoacidosis, that is characterized by high blood glucose and increased acidity of the blood -- a potentially fatal condition.

Here is how one young woman describes (on the internet) what it feels like to be chronically hyperglycemic and ketotic:

“…I skipped all my insulin but two units at night, sometimes only one. I would consume up to 40,000 calories a day, purge maybe half, and pee the rest out. My muscles deteriorated. My hair fell out, and many nights I couldn't breathe.

In February (2003) I had a heart attack after taking up to 80 laxatives a day for three months, so I knew I had to quit that. Even Standford [sic] didn't know what to do. They sent me home and told my Mom to expect to find me dead in my bed one day soon.

My days became consumed with EKGs, getting labs taken, and doctor visits. I was so dehydrated that if I did venture to take my insulin I would gain so much as fifteen pounds of water overnight, so I quit trying.

I became too weak to go anywhere. I would cry for no reason, low cries, because I could barely breathe from all the acid in my lungs. My heart constantly raced, I developed G.E.R.D. [reflux], my labs were always off, and I was very weak. I would sleep 20 hours a day, the other 4 hours I spent between the kitchen and the bathroom, eating , drinking, peeing and sometimes puking. My speech became slower, and it was an effort to even think.

The scariest day was when I lay awake in bed, too weak to move, and I heard my Mom whisper to my brother, "go make sure your sister is breathing".

I didn't know it at the time, but they were planning my funeral.”

Overtime, continual underdosing of insulin also contributes to the development of complications of diabetes, such as retinopathy (diabetic eye disease), nephropathy (diabetic kidney disease), and neuropathy (diabetic nerve damage). It is no laughing matter. Diabulimia is as serious as other, more “traditional” eating disorders such as anorexia and bulimia.

Here is an internet quote from “Jennie,”a women who has “practiced” diabulimia for more than 10 years:

“ I have been suffering for diabulimia for 10 years now.I became diabetic when I was 17 and quickly found out on how to keep my weight down by not taking my shots. 2 years ago I went into diabetic coma for 3 days. The doctors made my family come in and say goodbye because I was not suppose to make it. I thought that would wake me up but it hasn’t. I am 6 feet 1 inch and weighted 130 pounds for the past 10 years. I see the pain in my family eyes but for some reason I just cant get my diabetes under control. I have so much damage to my body that I feel more like a 90 year old instead of a 27 year old. I have completely ruined my chances of ever having children and I have to take a pill everytime I eat in order to digest my food. I have tried many times to get my diabetes under control but everytime I start taking my insulin regularly I gain about 20 pounds of water weight. This gets so frustrating that I just give up. If any one knows a solution to the water weight gain, PLEASE let me know. I take water pills that my doctor gave me but it does not help.”

Like anorexia and bulimia, diabulimia is a body image disorder. Girls and women with this disorder need specialized help to overcome this serious, and potentially fatal, condition. Not all doctors, diabetes educators, or behavioral therapists are adequately equipped to help individuals with diabulimia. If you are suffering from this disorder or if you have a loved one or friend with this disorder, you need to seek help from experts.

The National Eating Disorders Association (NEDA) has an information and referral hotline (800-931-2237). You can also find therapists by using the referral form on their website. Parents, family, and friends can a learn how to support their loved one with an eating disorder through the Parents, Family, and Friends Network.

I did not find any specific reference to diabulimia on the National Eating Disorder Association website, so I suggest interviewing the therapists to find out if they have expertise in this disorder prior to making an appointment. In addition, it is crucial to involve your treating endocrinologist so that he/she can help provide support for management of diabetes and any complications.

Readers, if you have other ideas please post them in the comments section.   Your suggestion could save a life.

By Dov Michaeli MD, Ph.D

Here are three headlines from today’s paper:

1. Front page: “GOP Losing Grip On Core Business Vote”. For obvious reasons.
2. Opinion page: “Immigration Losers” by Richard Nadler, President of Americas Majority Foundation, a Midwest public policy think tank (and I might add, a Republican organization in the mold of the Taft dynasty): “ …Republicans need to repudiate… the immoral, uneconomical goal of mass deportation”.
3. Opinion page: “The Future of Bioenergy”, by Juan Enriquez, managing director of Excel Medical Ventures, cofounder of Synthetic Genomics, and founding director of Harvard Business School Life science Project.

The first article Chronicles the takeover of the Republican party by the social conservatives, and the virtual disappearance of the fiscal conservatives/social moderates from the party. The second decries the xenophobic and punitive stance of the Republican party with regard to immigration issues. The last one calls for innovative approaches, using biology to solve the energy and global warming dilemmas we are confronted with.

Quiz: which newspaper was I reading?

1. The New York Times.
2. The Washington Post.
3. The Los Angeles Times.

Answer: none of the above. It was the Wall Street Journal, the bastion and mouthpiece of conservative (read: regressive) ideology, and a fierce opponent of anything liberal, such as fiscal responsibility and global warming. The editorial page had labeled the global warming issue as a liberal hoax, a figment of liberal scientists’ imagination, invented out of whole cloth and computer models.

But the purpose of this posting is not to harangue one particular political view. I want to highlight the salient points made in Enriquez’s article as to what Biology can bring to the table in solving our energy and climate problems. I had intended to write about this issue for a long time and this article was the catalyst.

A paradigm shift

One of the deepest thinkers of the history of science was Thomas Kuhn who, in 1962, published his seminal book “The Structure of Scientific Revolutions”. In it he argued that we all share a certain view of the world (paradigm) at a given time, on which the science of the time is based. But then and insight occurs, which shakes the foundation of our old world view and on which a new paradigm is founded. For example, until the 17^th century Anatomy and Medicine were based on the writings of Galen, a Greek physician from the 2^nd century. For 15 centuries scientists and physicians did not bother to dissect an animal in order to observe and verify the Galenic dogmas handed down to them since antiquity. But then William Harvey, a British physician, had an insight: why not observe how blood flows-- which led to the discovery of the circulation. But more happened: the demonstration that Galen’s writings about blood flow were wrong led other scientists to question his other assertions, test them through direct observations- which led to the modern sciences of Anatomy and Physiology. In fact, the revolution did not stop there; people learned to view with suspicion “received wisdom” handed down by higher authorities. These momentous changes in world view were a “paradigm shift”.

We are changing our world view,again

When our agricultural practices, inherited from the time we began to cultivate crop plants about 10,000 years ago, no longer sufficed to feed an exploding population we invented better ploughs, bigger machines, synthetic fertilizers, powerful insecticides. But this solution finally reached its inherent limitations. In the 20^th century the world could not feed the hungry multitudes of China, India and Africa. Malthus was triumphant. But then another revolution took place.

‘We began to apply more Gregor Mendel and less Henry Ford. Plant geneticists like Nobel Prize winner Norman Borlaug found that altering plants biologically was even more powerful and efficient than brute-force mechanical solutions. By altering seeds, harvest cycles and climate range, Mr. Borlaug and his colleagues launched the green revolution. Poor farmers in China and India, who could never afford a mechanical solution, became net exporters using a biological solution.’

The new world view is that the cleanest and most efficient solutions to our environmental and energy problems will be provided by Biology.

Consider coal, the most abundant and most polluting source of energy we have. Hydrocarbons are, in essence, sunlight concentrated in plant, animal or bacterial matter. Be it coal, gas or oil, what we are extracting and burning is bioenergy concentrated in carbon. Molecular Biology, the science that launched a thousand medical advances, is now enabling us to convert coal into ethanol in the ground; no more mining, no more environmental degradation, no more millions of tons of carbon emission, no more global warming.

And how is this miracle going to be accomplished? By genetically engineering bacteria that will break down the hydrocarbons of coal (or oil, for that matter) and convert it into ethanol. This is eminently doable, the technology is already here—all we need to do is change our thinking from big engineering solutions to clean and elegant biological ones.

You ain’t seen nothing yet

In the August 3 2007 issue of Science, an article titled “ Genome Transplantation in Bacteria: Changing One Species to Another” was published by scientists from the Craig Ventner Institute in Bethesda Maryland . (In its previous incarnation as the Celera Corporation, it was one of the two teams that deciphered the human genome). The article begins thus: “ As a step toward propagation of synthetic genomes, we completely replaced the genome of a bacterial cell with one from another species by transplanting a whole genome as naked DNA” (italics mine).

The significance of this simple statement is hard for the layman to fathom. In fact, it is almost impossible to grasp the enormity of the consequences of such a statement. What it means is that it will be possible in the not too distant future to synthesize new organisms. Not preexisting ones—completely synthetic new species! Now think of it:

· Synthetic bacteria whose whole mission in life is to convert coal and oil into ethanol at a rate faster than we could extract the hydrocarbons from the ground. And much cleaner and enormously cheaper, to boot.

· Synthetic bacteria that will consume any pollutant or toxic material we manage to create.

· Synthetic bacteria that will consume prodigious amount of carbon dioxide from the atmosphere, and convert it into ethanol—a two’fer.

· Synthetic bacteria that will course our blood vessels and convert LDL into HDL particles, and consume triglycerides while they are at it.

· Synthetic bacteria that will be able to sense glucose levels in the blood and release the appropriate amount of synthetic insulin in response.

Need I go on? The possibilities of this scientific revolution are mind boggling. Our world view will become totally biological. Sounds like science fiction or at least a distant dream: not at all. In an interview Craig Ventner stated that his team will have the first synthetic bacterial “species” in 5-10 years!

There is an ancient Chinese curse “may you live in interesting times”. Science will convert the curse into a blessing.

Dov Michaeli MD, Ph.D is in the Biotech industry.

As I wrote earlier, President Bush has vowed to veto the bipartisan Stem Cell Research Enhancement Act, SB5, when he returns from his European trip. This bill offers hope of a cure or, at the very least, more effective treatments for many chronic illnesses, including Types 1 and 2 diabetes, Parkinsons, Alzheimers and many others.

In an eloquent Op-Ed in the San Francisco Chronicle, Dwight Holing, a member of the national Board of the American Diabetes Association, explains why this bill is so important. (I have had the pleasure of serving as President of the SF Bay Area's ADA Leadership council with Dwight serving, until recently, as Chairman.  When Dwight speaks on the subject of diabetes, we all should listen.)

Here are some excerpts from his opinion piece [with my comments inserted in brackets]:

Dwight Holing, ADA board member"Like his failure to take global warming seriously, President Bush's decision to [once again] ignore science and veto the recently passed bipartisan bill that would permit federal funding of embryonic stem cell research within an ethical framework spotlights an inconvenient truth. All Americans, not just those who have diseases such as diabetes, Parkinson's and Alzheimer's, will pay the price."

[This bill will provide hope to millions of Americans with diabetes]

"Take diabetes, for example. Leading scientists say embryonic stem cell research holds great promise for finding better treatments and a cure for the nearly 21 million Americans, including 2 million Californians, who have the disease. And that's not to mention the 54 million who have pre-diabetes, meaning their blood glucose levels are higher than normal and they're at increased risk of developing the disease.... "

[And it is not just about hope, it is also about economics]

[Stem cell research will provide valuable information that could change the future for the billions of people on earth who have incurable chronic illnesses. Think of it!]

[So what can you do? Plenty. Read on.]

[Take action now!]

If you agree that we need to expand Stem Cell research, then please click on the following link and tell your Senators to override Bush’s Veto of SB 5, the Stem Cell Research Enhancement Act:

http://main.diabetes.org/site/VoteCenter?page=voteInfo&voteId=6101&JServSessionIdr010=fc4b0wmv21.app20b

Posted by Pat Salber, MD

Good news!  The SF Chronicle reports that charges against Mr. Universe related to a hypoglycemic episode have been dropped.

According to the story, "prosecutors initially insisted Burns needed to provide more medical evidence that he was a Type I diabetic suffering from insulin shock at the time. "  Come on!  A history of Type 1 diabetes, taking insulin, and ER documentation of a glucose of 29...I'd say that pretty much cinches the diagnosis. 

I hope the end result of this fiasco is that the San Mateo police get  a lesson from the local American Diabetes Association Leadership Council on manifestations of low blood sugar.  How about it guys?

Pat Salber, MD

Mr. Universe, Doug Burns got arrested and has to go to trial. Why? Because he was acting drunk and, supposedly, resisted arrest. Why? Because his blood sugar was 29! Why? Because he is a Type 1 diabetic and he was experiencing a “low” related to a mismatch between his insulin dose and his insulin need.  This happens sometimes.

Low blood sugar can have many different manifestations. Sometimes people pass out. Some people just get jittery and nervous. And, it is not uncommon for people to become confused and seem like they are drunk when their blood sugar gets too low. That is what happened to Doug. Unfortunately, Doug’s low occurred in a public place – a movie house – and police thought they had a public drunk on their hands. They arrested him and placed him in handcuffs despite the fact that a bystander suggested it could be low blood sugar that was causing the problem.

Despite having his low blood sugar confirmed in the emergency room and having had numerous physicians and other diabetes experts provide testimonials, the Redwood City District Attorney has insisted on taking this case to trial. That’s right. He is trying to criminalize low-blood sugar-related confusion. They are calling it “criminal assault and resisting arrest” even though only Doug initially reported any injury during the scuffle. (According to journalist Amy Tenderich, a week and a half later, a policeman involved in the episode reported a “strained arm and shoulders.”

Come on, guys. Is this a case of “I have my story and I am sticking to it – reason (and science) be damned?

Doug’s pre-trial conference is today. I suggest we follow Amy’s advice (from an email sent by Amy Tenderich 5/29/07:

“For all of you who are as incensed as I am over the Mr. Universe Going to Trial issue, I now have the information* on how you can speak up today:

Please place phone calls with your objections/support to

- Chief Deputy District Attorney Steve Wagstaffe
(650) 363-4752

and

- Assistant District Attorney Morley Pitt
(650) 363-4785

Please leave angry messages! The idea is to rattle their chain here, and put some pressure on the DA's office to drop the charges, as well they should.

*These contacts come directly from Doug Burns' lawyer, Micah Jacobs, of Jacobs & Ferraro, LLP, in San Francisco, which has donated its services free-of-charge to show its support for the diabetes community.

Mr. Jacobs filled me in on a few other key details you might like to know:

- The police report documents Doug's blood sugar at 26, at the time it was checked in ER following the incident.

- The initial police report also makes no mention of any violence -- solid evidence that Doug did not fight with the officers or attack them in any way.

- The theater security guard apparently escorted Doug outside the theater, and then called the cops when he stood there looking dazed, rather than leaving.

"It's one thing if he would have harmed someone, and could later prove that it was a medical issue," Jacobs says. "But nothing even happened, AND he can prove it was a medical issue. It's absurd to press ahead with these charges. Their personnel need to be better trained to distinguish a medical emergency from a real threat of harm."

Amen, Mr. Attorney, Sir. Now let's go make some noise about this!!”

- Amy Tenderich
Diabetes Mine blog www.diabetesmine.com
Know Your Numbers, Outlive Your Diabetes book http://amytenderich.vox.com/

2006 Winner, LillyforLife Achievement Award for Diabetes Journalism

.

Antibodies are an important defense mechanism against all kinds of foreign invaders, be it bacteria, viruses, or toxins. Without this defense we couldn’t survive very long. Remember the ‘bubble boy’? He was a kid who had a genetic defect that deprived him of antibody protection. He had to spend his life in a sterile plastic bubble in order to survive.

How do antibodies do it?

We are endowed from birth with a library of antibodies that are structurally designed to recognize and bind to these foreign invaders; each antibody recognizes a specific molecule of organism, or something structurally very close to it. This raises several obvious questions:

• How can the antibody recognize a certain organism from birth, not having seen this organism before? The answer is that the repertoire of antibodies we are born with is directed against invaders that our species has encountered in its evolutionary history, probably from as long ago as when the first vertebrates trod the earth.
• Does that mean that we are born with all the conceivable antibody specificities we are likely to ever need? Absolutely not. Immunological research has shown that our immune response can create antibodies to almost any molecule one can synthesize. Well, now we are talking about many millions of possible molecular structures, and the sheer number of genes required to make so many antibodies would overwhelm the capacity of our DNA.
• If our immunological memory recognizes ancient organisms that attacked us millions of years ago, is it not reasonable to assume that those organisms evolved during the eons, and thereby changed some of their structure? The answer is: yes, and consequently the antibodies we have in our library bind only loosely to the invader. This kind of binding is not very effective in neutralizing the action of the virus or the bacteria.

GOD to the rescue

These two questions occupied immunologists for almost a century. If we cannot accommodate all the possible antibody specificities in our genome, how do we create antibodies to almost anything imaginable? And if the antibodies that we do have can only loosely bind to the microorganism, and don’t do a very good job at neutralizing it—how are we to be protected?

It was demonstrated early on that once we are exposed to a new antigen, be it a microorganism, a virus or a simple molecule, an explosive increase in antibody synthesis occurs. But not just any antibody. The gene that codes for the antibody that recognizes the offending antigen becomes super activated and churns out huge amounts of antibodies. But if all these antibodies originate from the same gene, aren’t they supposed to be identical, and hence only loosely bind to the antigen just like the original antibody?

Here we have to introduce the hypothetical concept of GOD. No, it is not the religious kind; It is the theoretical mechanism that immunologists invoked to explain the infinite diversity of antibodies. This hypothetical Generator Of Diversity (come to think of it, could be a nice attribute to describe the religious kind as well) creates somehow, during this explosive expansion of antibodies, a whole range of antibody specificities, all very similar, but not identical, to the original antibody that recognized the antigen.

This concept is theoretical no more. In a paper published in the May issue of the Journal of Experimental Medicine (vol. 204, pp. 1145-1156, 2007) Raphael Casellas and his colleagues at NIH tagged with fluorescent dyes an enzyme called AID (no, it has nothing to do with AIDS), which stands for Activation-Induced Cytidine Deaminase. This enzyme has long been suspected as the hypothetical GOD.

How does GOD/AID work?

It randomly attacks the nucleic acid base Cytidine in the antibody gene, and converts it to another base called Thymine. In other words, it causes a mutation in the code for the antibody, which in turn would result in an antibody molecule of a slightly altered structure. Since there are hundreds of cytidine bases in the gene coding for the antibody, you can see that the number of possible permutations is mind boggling, all of them only slightly different from the original antibody structure. Now this is an ingenious way to create diversity.

Enter Darwin

Now we are left with the task of selecting the most effective antibody, that is to say the one that binds most tightly to the antigen. And here come Darwinian competition and selection in all its glory. The antibody that has the highest affinity (or binding) to the antigen will obviously have an advantage; even if another antibody, with lesser affinity, binds first to the antigen- it will be displaced by the more avidly binding antibody. And if later on another antibody comes along, with yet higher affinity, it will displace the lesser binding antibody. And so on and so on, in a process that ends up with highly specific, high affinity antibodies binding to the antigen and neutralizing it. The whole process takes 1-2 weeks,and is called antibody maturation. This is the reason why vaccination does not work instantaneously; protection is acquired only  7-10 days post vaccination.

The importance of the Casellas paper is that tagging the AID enzyme with fluorescent dyes will allow scientists to visualize it in vivo (in life), and follow its actions as it performs them. In fact, they have already saw (yes, actually saw) the enzyme doing its GODly work in the region of the chromosome where the immune response genes reside.

Why is it important?

This is important  from a basic science point of view, because it allows us to understand how immunity, so basic life, operates.  But wait, there is more; Immunity also plays a major role in health and disease.When the immune response goes awry and recognizes the body’s own tissues as foreign invaders, an autoimmune disease ensues. Such attacks on self tissues cause diseases such as rheumatoid arthritis, lupus, autoimmune thyroiditis, Diabetes type 1, and many others. It will now be possible to investigate these diseases on a much more detailed level, and hopefully find their root causes. It will then be infinitely easier to devise therapies to these debilitating diseases.

Isn’t science fascinating?

Dov Michaeli MD, Ph.D

Maggots. They are fly larvae. Yuck, you think. Double yuck, if you have ever seen them. But, wait a minute, we have known for a long time that maggots can clean infected wounds. It’s just darn hard to explain to a patient and his or her family.

“Hi, Mr. Smithy, you have a nasty infection there, but we have just the treatment for you. We’ll just smear some fly larvae in your wound and let them have their way.”

There are reputable studies of this practice. To pretty it up, however, the researchers have come up with names that make it seem more sophisticated than it really is. One article used the term “maggot debridement therapy,” no doubt referred to as MDT. A recent article in the well-respected and well-read journal, Diabetes Care, has cleaned up the name even more in an article titled: “Larval therapy: A Novel Treatment in Eliminating Methicillin-Resistant Staphylococcus aureus from Diabetic Foot Ulcers.”

Let me translate – overuse of antibiotics has led to a proliferation of bacteria that are resistant to commonly used antibiotics. One such bacterium, Staphylococcus, is a common cause of skin infections. Methicillin-resistant Staphylococcus aureus (aka MRSA) is a serious infection that is hard to treat with conventional methods. Diabetics are prone to getting foot ulcers because they have compromised circulation to the lower extremities and because they often have nerve damage so they don’t feel the initial injury. When a diabetic gets an ulcer infection that is hard to treat, such as a MRSA infection, the end result can be amputation -- sometimes it is just a toe or two, sometimes it is the foot or even the entire lower leg. This is a serious problem that requires aggressive treatment.

So back to the Larval Therapy article. It is actually pretty interesting even though it is only an observational study, and not the gold standard in medical research, the randomized clinical trial. The researchers, led by Frank Dowling, a podiatrist at the University of Miami School of Medicine in Florida, applied “sterile, free-range” (free-range?) larvae of the green bottle fly Lucilla sericata to MRSA colonized ulcers in 13 diabetic patients. 12 of the 13 people who received this treatment were MRSA free after an average of three such treatments over about 19 days.

Caveats here are that this is not a randomized controlled trial (RCT). Something other than the maggots could have coincidentally been responsible for the elimination of MRSA colonization. But it is intriguing. Eradication of a serious bacterial contaminant from a diabetic wound with a simple, non-invasive (albeit yucky) treatment catches your eye. Hopefully, researchers will follow-up on this early report with well-designed clinical trials.

In the old days….

When I trained in endocrinology many moons ago, we used to categorize diabetes as either “juvenile-onset” or “adult-onset.” We knew it wasn’t a perfect classification scheme  since a small number of older individuals contracted juvenile diabetes  -- a disorder characterized by immune destruction of the pancreatic islet cells (in particular, the Beta cells that produce insulin). People with this type of diabetes cannot make insulin and, therefore, require exogenous insulin, such as insulin injections, for long term survival.

Then, we really didn’t think the adult-type diabetes occurred in kids…but now it is found in children of all ages, even toddlers. What we called adult-onset diabetes, at that time, is actually a form of diabetes commonly found in overweight or obese individuals. At least initially, people with this type of diabetes have higher than normal levels of insulin.  It just doesn't work as well because these individuals are insulin resistant.

Insulin dependent vs insulin taking

Because individuals with the juvenile form of diabetes can’t make insulin, and therefore have to take insulin shots to survive, we started calling this form “insulin-dependent diabetes mellitus” or IDDM. Since people with the adult form of diabetes did not die quickly without administered insulin, we started calling it “non-insulin dependent diabetes mellitus” or NIDDM. (The mellitus part of the name refers to the fact that both forms of diabetes are characterized by having glucose in the urine….mellitus means honey.)

We changed the names of these conditions again because many people with NIDDM were found to eventually require insulin for good glucose control. Some people got confused by this and incorrectly labeled insulin-taking NIDDM patients as insulin-dependent. Are you following all of this?

Changing names again: Type 1 and Type 2

As a result of the confusion about dependence vs. use, it was decided to change the names again. IDDM became Type 1 diabetes. And NIDDM became Type 2 diabetes.

The problem is, however, that some individuals whom appear clinically to have Type 1 diabetes, do not have the immune markers associated with pancreatic islet cell destruction – a feature that is considered characteristic of that disorder. The American Diabetes Association has proposed calling this type of diabetes, Type 1b with “true” autoimmune diabetes mellitus being called Type 1a.  

In addition, some people who initially look like Type 1 diabetics – because they have diabetic ketoacidosis (DKA) [*]  and serologic markers of islet cell autoimmunity at the time they are initially diagnosed -- eventually go on to resolve their insulin deficiency.  Unlike "true Type 1 diabetes, the insulin insufficiency in these individuals appears to be reversible.

Yet another classification:  The AB classification of ketosis-prone diabetics

Now, it is proposed that we adopt yet another classification scheme. And this one makes a lot of sense on  paper. In the December 2006 issue of Diabetes Care, Ashok Balasubramanyam, MD and colleagues make the case for placing certain types of diabetics -- those who have ketosis at the time of their initial diagnosis -- in new categories depending on their immunologic status and beta cell function.

They propose an “AB” classification scheme comprised of four categories. The categories are based on whether or not the individual has immune markers related to destruction of their beta cells (that's the “A” component”) and whether or not their beta cells are able to produce the hormone insulin (that's the “B” component).

Here are the categories:

KPD type 1A (for ketosis-prone diabetes). These individuals would be labeled A+B-. The A+ means they have immune markers, evidence of immunity to their own pancreatic islet cells (aka, “autoimmunity”). The B- means they have complete and permanent loss of beta cell function. KPD type 1A diabetics must take insulin treatments for life.

KPD type 1B individuals are A-B-. Like people with type 1A, these folks cannot make, and therefore must take, insulin for life. Unlike 1As, they do not have serologic evidence of autoimmunity to their islet cells.

KPD type 2A individuals are A+B+. They have preserved beta cell function at the time of diagnosis, but they also have evidence of autoimmunity. Their prognosis varies. Some appear to have a reversible form of beta cell dysfunction and are able to eventually discontinue insulin shots. Others progress to full beta cell failure, and like Type 1 individuals will then require insulin treatments for the rest of their life.

KPD type 2Bs are A-B+ patients. They have preserved beta cell function and also lack any markers of islet cell autoimmunity. Although they initially had ketosis when diagnosed, they ultimately do not behave like people with true Type 1 diabetes. Most will be able to discontinue exogenous insulin therapy. In this respect, they are similar to “pure” Type 2 diabetics who do not require insulin for long-term survival.

Although this new classification system is not perfect, at first glance it seems better than the current Type 1, Type 2 dichotomy even with the addition of the catch-all, Type 1B:

• It is easy to understand.
• It provides information related to prognosis (although you have to wait a while to confirm exactly which category someone finally falls into).

But is it practical?

An editorial accompanying the article, written by Guillermo Umpierrez, MD, points out that this new classification scheme may be hard to operationalize in clinical practice. It is not easy to measure insulin secretion outside of research settings and it can be costly. Dr. Umpierrez points out that more than half of blacks and Hispanics with Type 2 diabetes present with ketosis. He suggests instead of the AB classification, simply modifying the current ADA classification so that Type 1b patients are called “ketosis-prone Type 2 diabetes.”   Perhaps, he should also suggest that they be called Type 2 b instead?

Regardless of what the final outcome of this debate is, the paper by Balasubramanyam and the accompanying editorial helps to remind us that the clinical condition we call diabetes mellitus, in fact is much more complicated that it seemed 30 years ago.

[*] (DKA is a life-threatening condition characterized by having a build-up of “ketone bodies” in the blood stream. It occurs when there is not enough insulin to process glucose normally. The body begins to use fatty acids (FA) as an energy source instead. When FAs are metabolized, the end result is the production of ketone bodies. Thus, the term ketosis.)