Friday, June 4, 2010

Rx: Bike

Rx: Bike

I am not a medical doctor. But if you have been diagnosed with Pre-Diabetes, or if your Doctor has said you have Type II but that you don't yet have serious complications such as vascular damage (e.g. kidney or eye problems)...then I have a prescription for you: ride a bike. Seriously. It just may be the most effective medical treatment you can seek out. It can completely reverse your symptoms. You can be drug free if you are bike-ful. And I'm about to tell you why. But I have to tell you some things about diabetes first, and some things about me.

Why Should You Listen to Me?
As I say above, I am not a medical doctor. But I've done a lot of thinking and reading about diabetes since being diagnosed with Type II (with numbers just over the diagnostic guidelines for pre-diabetes) in 2006. At the time, I didn't know what it meant to have diabetes: not clinically, in terms of what was going wrong (or right) in the body, or practically, as in what was I doing wrong (or right) in my day to day life.

So I treated this like a research problem. No surprise there. I am a researcher, after all. And a doctor of sorts (a Ph.D.) with access to and the ability to understand the studies underlying diagnosis and treatment of both Pre-Diabetes and Type II. These are really two different literatures: 1) those studies related to pathology or the origins of the disease and how it causes metabolic disruptions that lead to damaging results, and 2) those studies that test interventions (forms of treatment) to see which produce better outcomes in relation to the known damaging results. Your medical doctor, a clinician, is likely to know about and follow guidelines based on some combination of both types of studies. But it is not uncommon for clinicians to be uninformed about the state of the art in one or the other area. This is not shocking. Doctors are busy and General Practitioners, in particular, cannot possibly keep up with all the research on all the disorders they must offer treatment for on a day-to-day basis.

But even the best informed clinicians will tell you, if they trust you enough, that there is still a great deal we do not know about the disease formally known as Diabetes Mellitus. So let me tell you what I think we know about the disease today. Some of this may surprise even those who are familiar with Type I and Type II Diabetes.

What is Diabetes Mellitus?
Recently, I posted much of what follows in this section on a website discussion board at Diabetes Self Management. The thread is about Type I and Type II, and the misconceptions associated with the two. Much confusion and not a little anger ensued from folks who have or are associated with both conditions. Here's what I said to try and bring things together a bit.

There are clearly misconceptions on both sides [when it comes to the nature of Type I and Type II diabetes], and this is no surprise. This is in part due to the fact that the pathology of diabetes mellitus (all types) is not clear.

What all of the various types have in common is an inadequate insulin response. The body simply doesn’t regulate blood glucose (BG) normally, causing a risk of highs and the associated damage of high BG.

Type I diabetes is usually diagnosed when a person cannot make insulin. Type II, when a person cannot make enough or use enough…or when another metabolic process is out of control (e.g. the liver dumping too much into the bloodstream). This last thing, by the way, is what metformin treats for: liver function. In newly diagnosed Type II patients, insulin resistance may also be present, but it is often another metabolic process that is responsible for high fasting glucose numbers overnight that trigger some form of treatment.

What is not known, completely, is what causes a person to have an inadequate insulin response. Some people can present with many of the metabolic syndrome risk factors and still have a relatively normal insulin response.

Insulin resistance, inadequate insulin production due to beta cell loss (autoimmune or otherwise), and improper liver calibration (I like to think of it as a broken thermostat) can all play a role in all types of diabetes, depending on the individual. And those are just the main three that we know about and have common pharmaceutical interventions for. This is diabetes mellitus.

So What is Pre-Diabetes Then?
Pre-Diabetes is a relatively new diagnostic category, created to help clinicians and patients address the risk factors associated with developing diabetes (and the most serious complications of the disease): elevated blood glucose, elevated blood pressure, elevated cholesterol & triglycerides, and being overweight. These risk factors increase the liklihood of heart disease, stroke, and even cancer, and so there is good reason to treat them.

What Pre-Diabetes does, as a category, is group all of these together so that they can be treated in a coherent fashion. This, despite the fact that not all of the cause-effect relationships among these are well-understood. There are theories about how these factors are interrelated, most notably "syndrome X" or "Metabolic syndrome," and I will come back to this in a moment. But in the world of clinical practice, we needn't understand all of the pathology in order to treat patients and see positive results.

Pre-Diabetes, then, is useful. It may even be a positive thing in that it helps both doctors and patients take a whole group of life-threatening, negative trending symptoms and treat them together rather than addressing some and not others. But Pre-Diabetes is also a product of the market for pharmaceuticals. It creates an even larger group of people to whom a class of drugs may be marketed than existed before. How much bigger? According to statistics published in the National Diabetes Fact Sheet (most recent data is from 2007), about 17.9 million Americans are diagnosed with diabetes (Type I and II). Another 5.7 million likely have it, but are undiagnosed. And – get ready – an estimated 57 million have Pre-Diabetes. That more than doubles the size of the market.

This week (June 2, 2010), a study published in the Lancet and sponsored by drug maker Glaxo Smith Kline (1) found that low doses of two drugs - Avandia and Metformin, combined in a product marketed under the name "Avandamet - make it less likely that people diagnoses with Pre-Diabetes taking the drugs would go on to develop Type II diabetes. Good news for Glaxo, as it creates a broader market for a product that has seen its sales slip as the drug ages and approaches the time when it will be available as a generic. Good info for clinicians too, as it offers them another choice for treatment of patients with metabolic syndrome. it the best available choice?

Of course, the best choice depends on the individual patient. But here's what we know: a bike will do the same thing, only better. But your doctor may not tell you that. Why? Because he assumes you won’t make the effort and so a drug intervention is probably more likely to produce a better outcome. True enough.

But here’s what I’d like to propose to all clinicians. Please say to your patients something like this:

“before I give you this prescription, what if I told you that there is something that works twice as well? Something that might even cure you rather than just hold your symptoms in check. Would you want that instead?”

Even better would be to have someone wheel in a nice, shiny new bike…but perhaps that’s a step too far.

So here is what we know, to put it in clinical terms: "lifestyle modifications" - meaning, in one particular study, diet and exercise changes that result in weight loss of 7% of total body weight - are nearly twice as effective as drugs for preventing onset of Type II diabetes. This study in the New England Journal of Medicine looked at lifestyle changes vs. metformin (2). Another published in the Journal of the American Board of Family Medicine (3) looked at the effect of lifestyle intervention on the range of risk factors associated with metabolic syndrome, and found similar results. Drugs are about half as good as exercise & diet modifications leading to a loss of as little as 7% of total body weight.

But why do lifestyle changes work?
Neither of these studies talk about why lifestyle interventions work. That's just not what clinical studies tend to do. These studies just show that they do. And neither say what kind of exercise is preferable over others. I've said, already, that I think it should be a bike. And I’m about to explain that claim. But I have just a bit more explaining to do about Diabetes, Pre-Diabetes, and Metabolic Syndrome first.

When folks are diagnosed with Pre-Diabetes or Type II, there is usually evidence of one or two conditions that underlay the diagnosis. Neither has much to do with the condition that we most readily associate with Type I diabetes: an impaired ability to make insulin due to beta cell loss or dysfunction, though this may be present in Type II patients as well. One of these conditions you’ve likely heard about – insulin resistance - and one you’ve likely not heard about much at all – insulin signaling defects. Both, together, can be characterized as problems regulating glucose levels in the blood and using the insulin the body makes. But the body “uses” insulin in two ways. One way that insulin functions is as a helper molecule that permits glucose to move and break down into energy that a cell can use. Another important use, though, is as message system. Insulin levels communicate the need for more or less energy. This is the magic of hormones, generally: they are “smart” chemicals that do stuff and, at the same time, facilitate feedback. When insulin’s communicative functions malfunction, all kinds of weird things can happen in the body. Medications that treat Type II often address these insulin signaling defects. Let’s take a closer look, though, at both kinds of problems mentioned above. By doing so, we can get a sense of why the diabetes risk factors can be grouped together under the heading “metabolic syndrome.”

One way to think about glucose is as a substance that is fuel for the body. Glucose isn’t pure energy, though, but rather a format for storing energy for use in the short term. Fat stores energy too, and is a long-term storage format. There’s one in the middle of these: glycogen, housed in the liver. That’s a simplistic picture, but it helps to reveal one important piece of information that can be difficult to understand. The body stores excess energy as fat if there is no immediate need for it. The body makes sugars into fat, in fact, for this purpose. This is why you can get fat eating stuff that doesn’t have fat in it. It’s also why it is hard to get fat eating things that don’t have much sugar (carbohydrates) in them. Try to get fat eating celery, for example. Hard to do. And the reason is that the amount of carbohydrates as compared to water and fiber is very low. Celery is a low octane fuel.

When you are active, your body calls for more energy. It takes that energy from a number of places, including available ATP in muscle cells (that’s the basic essential energy molecule for us humans), glucose in the bloodstream is next, followed by glycogen stores in the liver that break apart to raise blood glucose levels. And then there is fat. Fat gets “burned” when all the above levels are sufficiently depleted and the body is still using energy.

Perhaps now it makes sense why I talk about insulin signaling defects as “thermostat problems.” There are sensors in the body that ask for more energy (more heat) and then a communication system (hormones) that carry that message to the parts of the body involved in raising the level of available energy (blood glucose is a pretty good approximation of this). If either the sensors or the communication system fail to work properly, the body is stressed and kicks off other processes designed to compensate for the malfunctions. The liver might be getting a signal for more energy when the body is at rest, for example, causing blood glucose to rise. The problem could be with any one part of that transaction: the liver, the hormone messages or the glands that produce them, etc.

Insulin resistance is a problem that we are only starting to understand in a detailed way (4). But what we think happens does so at a cellular level. Consistent high blood glucose forces adaptations in the body to store the surplus energy as fat. These adaptations change the nature of tissues that send and receive insulin signals. As a result, the signals don’t get through, and so neither does glucose. The body may be making insulin, but the sensing tissues aren’t as able to use it (in both ways that it can be used) as they should be.

What happens over time is still very speculative…but most think that the progression of Type II Diabetes is a vicious cycle: the body’s insulin signals get more out of whack, the concentration of glucose in the blood continues to be too high so the stress in the overall system from the potential negative effects of this continue to force cellular-level changes, the beta cells in the pancreas try to compensate by making more insulin (to make the signal louder, etc.). Eventually, some of the beta cells may poop out from being worked to hard, or they may change, causing the body to see them as cells gone awry that need to be attacked by the immune system. Less insulin production, impaired insulin signaling, increased insulin resistance…and so the spiral continues.

Metabolically, things are messed up. Hence the name: metabolic syndrome. What started the chain reaction may never be clear in any one individual. But once the chain of events starts, what seems clear is

A) a source of stress: elevated blood glucose causes the body to
B) adapt in order to maintain equilibrium, a “new normal”

For some people, equilibrium is reached. Bodies adapt. This is why there are people who are overweight who don’t have diabetes. This is also why you can’t simply eat your way into the disease, despite what you may have heard. Some bodies can adapt and find the balance point even when there is a huge energy surplus. Some, maybe even most, cannot.

Lifestyle interventions work to reverse metabolic syndrome because they force adaptations in the body that counter the risk factors. It is not just because during a workout you burn calories and use up carbs consumed that day. That helps, but the more significant effects happen when

A) a source of stress: exercise (both cardiovascular & resistance) causes the body to
B)adapt in order to maintain equilibrium, a “new normal”

Ok, but still: why bikes?
Bikes are an excellent way to apply the right type of stress needed to reverse metabolic syndrome. Specifically, bikes allow users to apply consistent, short but intense doses of both cardiovascular and resistance exercise with relatively few negative side effects (e.g. joint and muscle pain); these are exactly the kinds of stresses shown to produce metabolic adaptations that reverse metabolic syndrome (5). Plus riding a bike is fun.

It is true that other forms of exercise can work too. But there aren’t many that combine low side effects with efficiency (cardio + resistance in the same workout) with easily manageable dosing (mechanical advantage of a bike allows even novice users to start and stop in short bursts as preferred in interval workouts), with just plain fun. For many people, there are very positive psychological benefits to riding a bike because it reminds you of being a kid. It still feels the same to have the wind in your hair and the sense of freedom that you experienced back then. That feeling, even if you haven’t had it for twenty years or more, always comes back.

If you want to be healthy, go ride a bike. Doctor’s orders.

Further Reading
(1)Zinman, B. et. al. Low-dose combination therapy with rosiglitazone and metformin to prevent type 2 diabetes mellitus (CANOE trial): a double-blind randomised controlled study.
(4) Shulman, G.I. (2000). Cellular mechanisms of insulin resistance. The journal of clinical investigation 106.2. 171-176.
(5) Colberg, S.R. (2007) Physical Activity, Insulin Action, and Diabetes Prevention and Control. Current Diabetes Reviews, Volume 3, Number 3, August 2007 , pp. 176-184(9).