Monday, May 2, 2011

Strength training plus fasting regularly, and becoming diabetic!? No, it is just compensatory adaptation at work

One common outcome of doing glycogen-depleting exercise (e.g., strength training, sprinting) in combination with intermittent fasting is an increase in growth hormone (GH) levels. See this post for a graph showing the acute effect on GH levels of glycogen-depleting exercise. This effect applies to both men and women, and is generally healthy, leading to improvements in mood and many health markers.

It is a bit like GH therapy, with GH being “administered” to you by your own body. Both glycogen-depleting exercise and intermittent fasting increase GH levels; apparently they have an additive effect when done together.

Still, a complaint that one sees a lot from people who have been doing glycogen-depleting exercise and intermittent fasting for a while is that their fasting blood glucose levels go up. This is particularly true for obese folks (after they lose body fat), as obesity tends to be associated with low GH levels, although it is not restricted to the obese. In fact, many people decide to stop what they were doing because they think that they are becoming insulin resistant and on their way to developing type 2 diabetes. And, surely enough, when they stop, their blood glucose levels go down.

Guess what? If your blood glucose levels are going up quite a bit in response to glycogen-depleting exercise and intermittent fasting, maybe you are one of the lucky folks who are very effective at increasing their GH levels. The blood glucose increase effect is temporary, although it can last months, and is indeed caused by insulin resistance. An HbA1c test should also show an increase in hemoglobin glycation.

Over time, however, you will very likely become more insulin sensitive. What is happening is compensatory adaptation, with different short-term and long-term responses. In the short term, your body is trying to become a more efficient fat-burning machine, and GH is involved in this adaptation. But in the short term, GH leads to insulin resistance, probably via actions on muscle and fat cells. This gradually improves in the long term, possibly through a concomitant increase in liver insulin sensitivity and glycogen storage capacity.

This is somewhat similar to the response to GH therapy.

The figure below is from Johannsson et al. (1997). It shows what happened in terms of glucose metabolism when a group of obese men were administered recombinant GH for 9 months. The participants were aged 48–66, and were given in daily doses the equivalent to what would be needed to bring their GH levels to approximately what they were at age 20. For glucose, 5 mmol is about 90 mg, 5.5 is about 99, and 6 is about 108. GDR is glucose disposal rate; a measure of how quickly glucose is cleared from the blood.

As you can see, insulin sensitivity initially goes down for the GH group, and fasting blood glucose goes up quite a lot. But after 9 months the GH group has better insulin sensitivity. Their GDR is the same as in the placebo group, but with lower circulating insulin. The folks in the GH group also have significantly less body fat, and have better health markers, than those who took the placebo.

There is such a thing as sudden-onset type 2-like diabetes, but it is very rare (see Michael’s blog). Usually type 2 diabetes “telegraphs” its arrival through gradually increasing fasting blood glucose and HbA1c. However, those normally come together with other things, notably a decrease in HDL cholesterol and an increase in fasting triglycerides. Folks who do glycogen-depleting exercise and intermittent fasting tend to see the opposite – an increase in HDL cholesterol and a decrease in triglycerides.

So, if you are doing things that have the potential to increase your GH levels, a standard lipid panel can help you try to figure out whether insulin resistance is benign or not, if it happens.

By the way, GH and cortisol levels are correlated, which is often why some associate responses to glycogen-depleting exercise and intermittent fasting with esoteric nonsense that has no basis in scientific research like “adrenal fatigue”. Cortisol levels are meant to go up and down, but they should not go up and stay up while you are sitting down.

Avoid chronic stress, and keep on doing glycogen-depleting exercise and intermittent fasting; there is overwhelming scientific evidence that these things are good for you.


CarbSane said...

Ned, do you have any studies/evidence to support this statement:

Over time, however, you will very likely become more insulin sensitive.

I'm not asking to be argumentative, but rather that anecdotal evidence seems contrary to this assertion.

Richard Nikoley said...

How timely Ned. Just this morning I have been formulating plans along these lines and I have much experience with doing exercise fasted.

I'm doing a post on it later today and this will certainly help.

Helen said...
This comment has been removed by the author.
Helen said...


I think I've had this experience. When I found I had an A1C of 6.4 a year ago, I started doing high-intensity interval training. I only did it for a couple of weeks because the day after my sprints, my glucose control would be in the toilet. I researched a bit to determine if there were a benign reason for this, like the one you just described, but decided I was a prediabetic/diabetic freak whose response to the normally therapeutic things resided in Opposite Land. (For instance, I thought perhaps it released more free fatty acids and my system couldn't deal with it.)

I'm not sure I'm not that freak entirely but your post is reassuring about the exercise.

When I had that 6.4 A1C, I didn't have any other markers of metabolic syndrome, except a modest recent weight gain (my BMI was 25). My fasting triglycerides were 44, my LDL was low and my HDL was high. My blood pressure was low-normal. My fasting insulin was 7 (I can't remember the unit of measurement). My inflammatory markers were nil.

My fasting blood sugars were also higher on a low-carb diet and my glucose tolerance became abysmal. I'm still not sure if that indicates it was the wrong diet for me or if that's a normal response. My recent A1Cs were 6.0 on low-carb, followed by 6.0 a few months later on low-fat, though on low-fat, my meter readings are somewhat better. I don't know why they don't correlate with my recent A1C.

Jake said...

Your excellent post nailed me to a tee. I have done high intensity fasted weight training and Tabata sprints for 2 years .

My blood sugar rarely goes above 120 after a meal but my fasting blood sugar rarely goes lower than 95. I eat 75 grams of carbs or less a day.

However, my recent VAP and NMR tests shows that I have zero insulin resistance based upon my lipid particles. My fasting insulin level is below 4.

You have taken a load off of my mind.

Ned Kock said...

Hi CarbSane. My initial answer would be the Johannsson et al. (1997) study linked on the post; but maybe I am not understanding the question. That study is nice because it clearly shows a decrease in serum insulin occurring together with an increase in GDR, in response to GH elevation, even though FBG levels are unchanged at the end for the GH group.

Ned Kock said...

Hi Richard, thanks. I look forward to reading your post.

Ned Kock said...
This comment has been removed by the author.
Ned Kock said...

Hi Helen. It seems that yours is a sudden-onset case that might have been diagnosed as T1D, right? You may want to take a look at Michael’s blog, linked on this post. In one of his recent blog posts he talks about what seems to be a major recovery in beta cell function.

Here in South Texas most cases are T2D, the most common type by far. They progress slowly and show up first as the type of pathological IR that is part of the metabolic syndrome.

Ned Kock said...

Hi Jake. Indeed, this post is for you and a lot of people doing strength training, HIIT, paleo + IF, Warrior Diet, or even LC (in some cases).

I’ll bet that many people who see elevated FBG but no metabolic syndrome signs have higher than average GH for their age.

That would make them healthier than average, but they end up being misdiagnosed and stop a good thing from progressing.

Chris Kresser said...


Great post. I see this phenomenon quite a bit in my practice.

Have you seen any studies on what happens with post-meal blood sugars in this situation? One could assume they're also rising if both FBG and A1c is going up, but I'm curious because post-meal #s are more accurate indicators of blood sugar control and predictors of future complications.

Helen said...

Hi Ned,

I've read Michael's blog and admire it, but my diabetes isn't of that variety.

It wasn't sudden onset. I'd had gestational diabetes two years prior (though starting my pregnancy at a normal weight), and had abnormal BG readings throughout my life, though was never labeled pre-diabetic nor warned about being at risk for diabetes until my pregnancy.

I think my "outside the normal range" (both high and low) OGTT at 20, and my >100 <110 fasting sugars and abnormal spot-check (146) in my 30's were dismissed because I had a low-normal A1C then (which makes me wonder if I often had reactive hypoglycemia, which is certainly how I felt), and was thin with an "excellent" cholesterol profile, and just from general ignorance.

I now know from Jenny Ruhl that all of those were important warnings but I didn't know to heed them. Because in terms of weight and lifestyle I didn't seem high-risk, I, too, believed diabetes wasn't in my future.

I believe I may have a MODY type (monozygotic form) of diabetes. I got tested for one and didn't have it, but there are many varieties. Either that or I am highly genetically susceptible to insulin resistance.

I don't think I have LADA (late Type I). I've tested negative for GAD antibodies, and though there are other possible antibodies to test for, usually LADAs become insulin-dependent after a short honeymoon period following diagnosis. Having had gestational diabetes doesn't fit the LADA profile, either, though it does fit MODY and insulin resistance profiles.

If I were MODY 4, that might explain why my glucose seems more affected by fat than carbs. But that story should go on my own blog, if I ever do one.

Helen said...

Another thought - MODY 4 might include higher than normal GH, too, since the IPF1/PDX1 gene half-missing is a transcription factor for glucokinase, insulin, *and* somatostatin, which opposes growth hormone. All of those would be affected.

It also regulates Gpr40 gene expression. Gpr40 in turn controls the expression of free fatty acid receptors in the gut and in the beta cells, both of which stimulate insulin secretion in response to free fatty acids. If I'm deficient in this, a high-fat diet would *not* be good. And getting chubby would not be good either, which is when my glucose trouble became clinical. (I'm down to a BMI of 20 now.)

But perhaps any damage from the mild diabetes of MODY 4 would be offset by a generous level of growth hormone. I wish I'd picked the right MODY form to persuade my insurance company to test for!

Ned Kock said...

Hi Chris. With the GDR going down so steeply, I’m pretty sure the postprandials will be a bit messed up too, unless the person is LC’ing. This will remain until CA runs its course, which can take months.

After that, you may find yourself in an ideal (or close to ideal) situation: muscle is hungry for fat and rejecting glucose, adipocytes are rejecting glucose, and the liver is not letting any glucose go past it.

Chris Kresser said...

The trick is how to convince someone (including myself) that this is actually what's going to happen after 9 months of excessively high blood sugar which is toxic to organs and tissues. Obviously the long-term result is desirable, if indeed we can be relatively certain that this is what happens in most or all cases, but as a clinician I'd love to see more than a single study supporting this before I'd be comfortable putting people on a program that elevates their blood sugar above the level shown to cause complications for several months. Do you know of any other such studies?

Ned Kock said...

Hi Chris. Nearly all studies involving GH administration show an increase in BG at first, and then stabilization after a while, with the end result nearly always being increased insulin sensitivity. In some cases “overt IR” or “overt diabetes” is reported, but then the participant is removed from the study and we are left to guess what happened to him or her.

Btw, GH therapy studies show qualitatively what happens as GH goes up, but the fact that they involve exogenous administration of GH is a bit of a problem for extrapolation. The study below, which is recent, may be more in line with what I think one should expect to see in response to both glycogen-depleting exercise and IF. It involves a more “gentle” use of GH.

Another thing to bear in mind is that health complications from glycation (e.g., vascular damage, retinopathy, nephropathy) happen at much higher BG levels than many people think:

Someone who has a constantly elevated BG of 120 mg/dl throughout the day, but relatively low postprandials (e.g., lower than 160 mg/dl) may not develop those complications. Still, the A1C will look bad.

Of course, typically a FBG of 120 is an indication that BG levels are going up a lot, more often than not postprandially. But this is not always the case. By “a lot” I mean way above 200 mg/dl, which may or may not be associated with either beta cell dysfunction or another problem (alpha cell dysfunction, severe liver IR).

At those levels, complications from glycation will happen. However, they will happen over many years of constantly hitting those levels or higher, everyday.

Unknown said...

Hey Ned, I've noticed something interesting from both of these activities. I am pretty lean, I'd say 9% body fat. When I look in the mirror during an extended fast, my abs get piled by some fat. Same thing after strength training, that area looks less defined. It's as if cortisol is just depositing fat there.

After I eat some food though, it's back to normal and the fat magically disappears. But I thought perhaps it was a result of me having some adrenal fatigue or something. Do you think this is related to what you are talking about? THe high blood glucose perhaps is being stored temporarily as fat by cortisol?

Ned Kock said...

Hi Avishek. What makes you believe that the accumulation is of fat and not water?

The “piling up” feeling is consistent with water being denser than fat – more of a gravity pull.

Adipocytes, like many other cells, store water. As fat content in adipocytes goes down, it seems reasonable that the body would use the extra space for water storage, given water’s many and critical metabolic roles.

As adipocytes lose even more fat, it is also reasonable to believe that the body would recycle some of them – the ones that were formed through obesity-induced hyperplasia. But this should take some time at a low body fat level.

David Isaak said...

Medical science is so glued to the short-term numbers that it iften makes mistakes.

For many years they told people with hypertension to avoid anything except the mildest exercise--because, of course strenuous exercise raises blood pressure. They also told people with hypertension to avoid cold water immersion, for the same reasons.

Now, of course, here is growing recognition that both exercise and cold-water immersion raise your blood pressure in the short term and lower it in the longer term.

In fact, one theory of "essential hypertension"--ie the 'we have no idea what causes it' type that is by far the most common--is that the baroreceptors in the body adapt to prolonged high levels of blood pressure; it becomes a new baseline. They need to be forced above that new baseline to engage in their normal role of taking blood pressure down to normal after elevation.

Somewhat off-topic, I know--but my points are:

1) Short-term numbers and results are often in conflict with longer-term results--especially in biological systems.

2) What passes for common sense in medical science has been wrong again and again.

David Isaak said...

"Over time, however, you will very likely become more insulin sensitive.

I'm not asking to be argumentative, but rather that anecdotal evidence seems contrary to this assertion."

Like Ned, I'm a little bit confused by the question. Surely you aren't questioning that resistance training increases insulin sensitivity? If you are, just Google those two phrases. Or see: nauseum. Strength training increases insulin sensitivity in the young, the old, the obese, the lean, the diabetic and the non-diabetic.

Since even a cursory look at the literature confirms this, I assume I'm misunderstanding your question.

Unknown said...

Thanks Ned, well I don't know what to believe really I did not know adipocytes would regularly store water. Under what circumstances do they store more water?

I do not know why exactly I thought it was fat. ANother thing after a carb bloat, if I pinch my belly it feels tight. But during a fast I can pinch much more, so if it is water then that could explain it. I have no idea where the fat would be coming from, but could be the glucose

Ned Kock said...

Hi David. Ditto for IF, with very few exceptions. Mostly from religious fasting studies (e.g., Ramadan), but still …

Ned Kock said...
This comment has been removed by the author.
Ned Kock said...

Hi Avishek. I’ve heard that complaint many times – hey, I water-fasted for 24 hours and ended up with a wider waist than when I started!? And the glucose explanation comes up often; it is an Internet meme.

Think about it. What was the only thing that was consumed in the fast? Water … which is denser than fat, so it leads to a slightly bigger lower ab “bulge”.

This is quite common among obese folks who lost a lot of body fat, and is, I think, at the very source of the “loose skin” myth.

Maybe formerly obese folks tend to have more space in their adipocytes for water storage, and also more spare adipocytes that formed via hyperplasia when they were becoming obese.

When one is IF’ing the hormonal mix is such that the adipocytes are in fat release mode. The GLUT4 transporters are playing hide-and-seek. Barring any major metabolic abnormality, glucose is spared for the brain.

Jerry said...

I'm glad I saw your blog on this - I went Paleo last year and have been doing IF and glycogen depleting exercises. I have my blood tests compared to last year:
Date 1/6/2010 4/21/2011
Ttl Cholesterol 263 206
Triglycerides 305 91
HDL 40 51
VLDL 61 18
LDL 162 137

Serum Glucose 99 105

You can see my results showing exactly what your blog indicated.
I was puzzled by the glucose increase and this explains the reason for that. Thanks for clearing that up!

Ned Kock said...

Hi Jerry. Thanks for sharing, and congrats!

Rock Steady Dance Troupe said...

Ned, great post. Do you think this tells us anything about when we should eat after fasted strength training?

Ned Kock said...

Hi Rock. There is plenty of empirical evidence from the strength training literature that there is an important 2-hour window after any strength training session. It is critical to consume high quality protein within this window if you want to gain muscle.

Kareem said...

I found this article really interesting because I fast every year from dusk til dawn for a month (Ramadan) and have to really dig deep to push myself through my workouts. It's cool to see the phenomena behind this style of working out. Great read!

spider veins said...

My fasting blood sugars were also higher on a low-carb diet and my glucose tolerance became abysmal. I am still not definite if that indicates it was the wrong diet for me or if that is a standard response.

Unknown said...

spider veins: there is a discussion going on at

I do not know what that means. It's normal, as glucagon and ghrelin should be higher, but many people have posted some of their anecdotes on the blog about how their blood sugars have changed after switching to a lower-fat diet after low carbing for a while.

it may answer a few questions. Or give rise to more!!....

Online pharmacy reviews said...

I think the alterations of the human conditions can influence the body's function, to get a good health is really important to have a perfect balance.

viagra blog said...

jhmmm For many years they told people with hypertension to avoid anything except the mildest exercise--because, of course strenuous exercise raises blood pressure. They also told people with hypertension to avoid cold water immersion, for the same reasons.

angelapostea said...

Steroids-Online is the real place for steroids user, were you can buy anabolic steroids online without prescription at brands like Balkan Pharmaceuticals and SP Laboratories. Our Steroids Pharmacy offers 100% original products directly from manufacturer at the lowes prices-24 hour 7 day a week. We provide maximum security-any personal information remains private. We deliver orders in time, safe and fast (SUA, UK, Germany, France, Italy, Greece, Spain and other countres). Steroids-Online don't have a minimum order amount limit!
With so many scams it's hard to believe, if what we writing are real! You can't know it if you don't try. Make a order and convince yourself of quality our services.
We aim at all times to provide our customers a professional and efficient service, as well to improve the standards of the service which we provide.
If you have questions regarding the ordering process and how to use steroids, do not hesitate to Contact Us. Our customer support is trained to answer all your questions.
Your satisfaction is our guarantee!