Wednesday, December 5, 2012

Myths, Metabolism, & Appetite Part 2b

Continued from part 2a...

Muscle fiber type distribution in Type 2 Diabetics
One of the more intriguing attributes of people with obesity and Type 2 Diabetes is that they have a higher percentage of Type IIx muscle fibers and a lower percentage of Type I fibers (5, 6, 7, 8, 9, 10).  When we look at the 3 muscle fiber types, the IIx fibers are the most insulin resistant, followed by the IIa and, finally, the type I fibers are the least resistant to insulin(11).  Obviously a person with a higher percentage of muscle fibers that are insulin resistant will be more prone to insulin resistance and the conditions associated with it.  Looking at this merely on the surface, one would be inclined to believe that people born with a higher percentage of Type IIx muscle fibers may be particularly prone to these conditions.  While the data shows that genetics probably plays a large role in your percentage of Type I vs Type II fibers, it probably has little to do with Type IIx fiber distribution.  When you look at all of the information that is out there, it appears more likely that this is an adaptive response by the body to the environment presented to it.  In other words, it is a classic gene/environment interaction that develops within people who have a higher percentage of Type II muscle fiber types.

Muscle Fiber Type Conversion
It has been well established that all training, whether it be cardiovascular/aerobic or resistance training/anaerobic, causes a change in type IIx muscle fibers by either converting them to type IIa fibers or causing them to take on the characteristics of the more intermediate IIa fibers(12,13).  This is a positive adaptation in that it allows you to do more work before fatigue sets in by increasing the amount of energy the fiber can store and the amount of energy it can make.  In addition, once training ceases for more than a week, the IIa fibers revert back to IIx fibers.  In fact, all sedentary people experience this conversion whether they are prone to diabetes/obesity or not. 

Knowing that the IIx fibers are primarily driven directly by ATP and have low glycogen, it makes sense that they would be insulin resistant because they fill up with glycogen faster.  As an adaptive response to training, they increase glycogen storage and mitochondria content while at the same time receiving an increase in blood flow via an increase in capillaries serving the fiber, which is basically the same thing as taking on IIa fiber characteristics.  This improves their insulin sensitivity both by using the glycogen content of the fibers as well as increasing their capacity to store glycogen, improving their ability to dispose of glucose from the blood.  It also improves their ability to generate ATP from fatty acids given that is the primary role of the mitochondria.  In other words, they burn more fat.

So, what drives this adaptation, is it simply a use it or lose it scenario or is it caused by some environmental factor?  Interestingly enough, it appears this adaptation may be driven hormonally, specifically by our good friend insulin.  In a study performed on rats, induced hyperinsulinemia caused IIa to IIx conversion (14).  In another study performed on humans, inducing hyperinsulinemia on 10 young male subjects for 3 hours increased MHC IIx gene expression by 40% when compared to control conditions in each subject (15).  This means the subjects were beginning to make Type IIx muscle fibers as a response to high insulin levels.
It makes sense that this could be the body adapting to the environment you are providing it, insulin only gets high when you secrete a lot of it.  If you eat a ton of carbohydrates and don’t exercise you will create tons of insulin to deal with that glucose.  If you eat the same amount of carbohydrates and exercise a lot you will be using exercise as your method of getting glucose in to cells, insulin will stay low, and this conversion will not happen.  This provides support for the notion that Type 2 diabetes is a reversible metabolic state.  If you activate IIx muscle fibers they convert to IIa fibers, become more sensitive to insulin, and are capable of disposing of more gulcose in the event blood glucose gets too high.  If you stop using them they will convert back to IIx fibers, become more insulin resistant, and become relatively worthless with regard to disposing of glucose.  The end result is elevated blood insulin levels to force the glucose in to the lower threshold Type I fibers and eventually, fat cells.  A high percentage of Type II fibers in general is a very strong risk factor for Type 2 Diabetes, and it makes sense since they will switch from IIa fibers to the more insulin resistant IIx fibers with disuse. 

Type IIx fibers have often been referred to as the default fiber type, but this is not something that has been studied extensively.  Given that the modern diet is, by default, high in carbohydrate, it would be interesting to see the effects of a high fat diet on muscle fiber type conversion.  Would a high fat environment induce the opposite effect?  In other words, if you consumed more fat would this cause fiber type changes that favor fat oxidation, a conversion to Type I fibers?  While the effect of a high fat diet on fiber type has not been studied directly, there have been studies that show physiological adaptations via gene expression to burning fat from a high fat diet (16) and endurance exercise (17).  It is highly unlikely that eating a high fat diet would induce a fiber type change from Type IIx to I given that IIx fibers have a very limited blood supply, but the latter study did show an increase in genetic expression of genes responsible for the creation of mitochondria from exercise.  A limited blood supply means ingested fatty acids probably wouldn’t make their way to the IIx fiber, but if these fibers converted to IIa fibers via exercise the blood supply may become sufficient enough to go from IIx to IIa to I. 

There is the possibility that a high fat diet could induce a Type IIa to I fiber conversion given the good blood supply to IIa fibers.  The general consensus is that fibers may convert in the following ways:
Type IIx<------------>Type IIa<------------>Type I
There is plenty of evidence of IIx to IIa and IIa to IIx conversion in multiple studies, but the lack of studies on conversion of either Type II fiber types to Type I fibers makes any notion that this conversion is possible speculative at best.  In addition, given that fiber type is dictated by the type of nerve that fires the muscle fiber, this conversion is unlikely.

Since we know people who are prone to obesity have a higher percentage of these Type IIx fibers, getting them to convert to IIa fibers is a potentially good intervention.  In order to get IIx fibers to take on the characteristics of the IIa fibers, you have to activate them on a regular basis, which means meeting their force activation threshold or fatiguing the muscles recruited before them to the point the IIx fibers need to kick in.  Given the high force threshold for activation of IIx fibers, this is not likely to happen with distance running or aerobics, the exercise should be glycolytic and short in nature with appropriate rest between exercise sets.  The best options that meet these criteria are high intensity resistance training, plyometrics, and sprints.  While it is certainly possible that you could eventually activate IIx fibers via endurance exercise once the Type I and IIa fibers run out of fuel, the speed you would need to run at or the amount of time you would need to run for make it an unappealing option.  However, no matter which dietary approach you decide to use, low carbohydrate or low calorie, diet will have no effect on increasing the blood supply to IIx fibers, underscoring why it is so difficult to get rid of insulin resistance once you have it.

When we look at what happens to people as they age, we see the same adaptation as we see in sedentary people, a conversion from IIa to IIx muscle fibers and eventual atrophy of the IIx fibers, making them even insulin resistant.  As a result, the risk of Type 2 Diabetes doubles when you reach the age of 65 and doubles again when you reach 80.  When we look at studies involving older people and resistance training, we see nearly identical improvements in muscle fiber type characteristics and measures of insulin resistance as we do in younger people (18, 19, 20) that we would not expect to see in endurance training unless it were progressive in nature.  In other words, if you can run 5 miles at a pace of 10 minutes/mile, your fiber type characteristics will improve a little and then stop unless you increase your speed to 9.5 minutes/mile.  Then, the adaptations would stop until you increase your speed even further.  This is something that a competitive endurance athlete does that your typical gym-goer does not.  A much better option is to induce this fiber conversion via high intensity resistance training, which takes less time, is more pleasant, and is unlikely to cause an overuse injury provided it is done properly and progressively.

Glycogen depletion during exercise
During high intensity exercise, glycogen is depleted equally among the muscle fiber types.  This makes sense given that during high intensity exercise, all muscle fiber types are recruited.  During aerobic exercise, most of the glycogen depletion during the onset of exercise comes from the Type I muscle fibers.  Given that these fibers have a low glycogen storage capacity, they run out of glycogen relatively quickly.  Once this happens, the Type II fiber types will start to kick in to allow exercise to continue.  But wait, we mentioned above that Type II fibers have a high contraction threshold, why would they be activated at a lower threshold?  To provide fast acting glucose to the Type I fibers which will fatigue without it, and the process is actually pretty cool.

Recall that the glycogen within a muscle fiber has to be metabolized by that fiber.  If this is the case, how can the Type II fibers provide glucose to the Type I fibers?  The answer, aka loophole, is lactate.  If you have ever exercised for a long period of time, you have probably felt the burn associated with lactate/lactic acid.  This burn actually comes from the high levels of hydrogen ions that are created alongside lactate.  While glycogen cannot be passed on from fiber to fiber, lactate can.  As lactate accumulates in a muscle fiber, it is shuttled out of the fiber and in to the blood where it goes to the liver and is converted to glucose.  Now, this glucose is free to go wherever it is needed.  But what happens once exercise ceases?

Glycogen Storage
One concept that is important to grasp with regard to exercise and it’s effect on insulin sensitivity is that the improvements in insulin sensitivity are not permanent, they only last for a limited period of time.  This is probably variable based on the amount of exercise you do, the type of exercise, and the amount of carbohydrate you consume afterwards, but is typically about 36 hours following exercise.  During the recovery period following exercise, the body preferentially stores glycogen while increasing fatty acid oxidation, even when it is primarily carbohydrate being consumed.  The hormonal environment post-exercise primes the muscles to store glucose rather than burn it (21, 22, 23). 

The body’s drive to replenish glycogen is so great that even during fasting after exercise it tries to replenish muscle glycogen stores, provided they were used during the exercise period(22).  What the body uses to replenish glycogen stores post-exercise in the absence of food is primarily dictated by the intensity and duration of the exercise.  If the exercise was intense and of short duration, the lactate generated during exercise is used to replenish glycogen.  If the exercise was of moderate intensity but long duration (Long distance running anyone?), amino acids are the fuel, i.e., your muscles (22).

In addition, even if you are performing physical activity, your body will replenish glycogen in the muscle fibers you are not using (22).  Active recovery is a recovery modality where you continue to do low intensity activity like walking or lower intensity exercise after a period more of intense exercise.  During active recovery following exercise, even though Type I fibers are still using glucose, some of the glucose being made in the liver from lactate is actually shuttled to the Type II fibers that are not being used to replenish glycogen stores (22).  This is, of course, contingent on those fibers depleting their glycogen stores first.  If the intensity of exercise prior to the recovery was not sufficient enough to engage the higher threshold IIx fibers, they will not need glycogen.  However, the Type IIa fibers, which have a lower contraction threshold, are probably being activated to provide the lactate that is converted in the liver to glucose to fuel the Type I fibers, so their glycogen content would be depleted to some extent.

The science vs “conventional wisdom”
The evidence appears to support the notion that we are dealing with a mismatch between the primary type of fuel consumed and the type of activity performed, at least in obese people and Type 2 Diabetics.  Given that obese/diabetic people have more IIx fibers and that glycogen is preferentially directed to these fibers even during fasting and physical activity, these fibers will typically be insulin resistant unless used regularly.  In people with a higher percentage of these fibers that also tend to over-consume carbohydrate and not perform physically demanding activity, it appears that we are seeing a classic gene/environment interaction that is driving the obesity epidemic.  This same interaction occurs in non-obese people as well via a conversion of IIa fibers to IIx.

Taking all of this data in to consideration, performing intense physical activity on a regular basis is obviously something important for anyone who wants to maintain insulin sensitivity throughout life.  In people who are Type 2 Diabetic or obese as well as their children, it is absolutely critical while carbohydrate is a significant part of the diet.  It is also important to make sure this activity is performed with both the lower AND the upper body as well as with a full range of motion.  In order to improve insulin sensitivity even further, it would also be smart to vary your exercises frequently to make sure that you are hitting as many muscle fibers in as many muscle groups as possible.  So, let’s compare what the science shows to the route most people are recommended to take by the medical establishment.

If you go in to the Doctor’s office and get a diagnosis of Pre-diabetes or Type 2 Diabetes, you are told that you need to change your diet and start an exercise regimen.   The general theme of the discussion will center around the fact that you need to lose weight.  While this is true, the extra weight doesn’t cause Diabetes, the extra weight is an effect of Diabetes caused by insulin resistance.

If you lose some fat you are improving insulin sensitivity via exercise and diet because if you weren’t you wouldn’t be able to release or burn body fat.  The problem is you are doing it indirectly by focusing on creating an energy deficit.  More often than not the exercise portion of creating this deficit is long distance running, a spin class, or some other aerobic activity.  This will take forever and require a massive amount of effort given the IIx fibers are not recruited for this type of activity so they can’t convert to IIa fibers.  Given that you would still have a higher percentage of insulin resistant muscle fibers, the insulin resistance is probably still there, and unless your diet is spot on and very low carbohydrate you will continue to have problems with your blood glucose. 

In fact, you may be able to maintain normal blood glucose levels as long as you keep your carbohydrates low or exercise for hours per day.  If you go wild and hammer in to carbohydrate-heavy food or stop running, your blood glucose will shoot through the roof along with your insulin levels.  This doesn’t even consider the fact that very few people who run long distances do so with a full range of motion, progress it properly, and that running and spinning do little to nothing for the upper body.

At this point you are probably going, “Wait a second, I know a bunch of people who do long distance running or spinning and they aren’t overweight.”  While this is certainly true, chances are these people aren’t prone to Type 2 Diabetes or obesity.  They probably have a higher percentage of Type I fibers so they are better suited to distance running, or they may not have the genetic predisposition to store body fat.  While the former would make them far less likely to develop Type 2 Diabetes, neither prevents them from developing insulin resistance.  Anybody can become insulin resistant at any time, and you don’t have to have an outwardly obese appearance to have either Type 2 Diabetes or insulin resistance.  It would certainly be much more difficult for a person with a high percentage of Type I fibers to become insulin resistant, but it is possible.  Whether you are Type 2 Diabetic or not, insulin resistance is a bad scene.  A small list of the diseases/issues associated with insulin resistance includes cancer, heart disease, high blood pressure, stroke, fatty liver disease, metabolic syndrome, Polycystic Ovarian Syndrome, and Type 2 Diabetes/Obesity.  So, don’t think you’re safe just because you are lean.

If you get anything from part 2 of this series, it’s that insulin sensitivity is NOT a 1- trick pony.  With exercise, you have something you can do that mimics the primary effect of insulin while at the same time lowering your resistance to insulin provided you do it properly.  In the context that most people approach exercise, I agree with Gary Taubes, that it has little effect on fat loss.  But, in the proper context with the proper modalities it not only helps improve insulin sensitivity in a way that diet cannot (You will not empty glycogen from a muscle fiber with diet, only activating it via activity will do that), it gives you leeway in the event you want to consume some higher carbohydrate meals.

Now that we have looked at the science behind obesity and diabetes, it seems the exercise prescription given by the medical establishment is way off base.  While capable of attaining short-term success, it comes at the expense of long-term health.  At the end of the day, this approach is unsustainable.  You will be exercising 8 days a week and eating rice cakes all day which is not even remotely necessary.  You will be hungry, irritable, and won’t be able to think straight.  You will be constantly preoccupied with food and tired until you just give up.  You will also enter an overstressed state and become either sick, injured, or not be able to sleep.  Does this sound familiar?  There are very specific reasons why all of this happens, and most of it is dictated by hormones.  

In Part 3 we will answer why all of this occurs and how to adjust your diet to prevent it.

(Having problems publishing the references, I'll plug them in later today)

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