Friday, May 21, 2010

Cortisol Versus Insulin

The man in the picture has insulin resistance and what the Heart Scan Blog" calls "wheat belly," right? Wrong. He has a hormone problem, but in this case the hormone isn't insulin, it's cortisol.

Insulin, which we discuss frequently on this blog, is a storage hormone. In response to ingestion of carbohydrates, and to a lesser degree of amino acids, the pancreas releases insulin. As a result, within minutes to hours, carbohydrates, amino acids and fats are stored after each meal.

Cortisol is a glucocorticoid hormone that is released from the adrenal glands in response to stress. The stress can be physical or emotional. The effects of cortisol in the body occur over hours to days and include suppression of the immune system, suppression of inflammation and an increase in blood glucose. When people survived by hunting, or when they were involved in combat, elevated cortisol would allow a person to ignore pain and illness in order to concentrate on the task at hand. It would also provide excess glucose in the blood, allowing the person additional energy to fuel the brain and muscles in extreme situations.

Both insulin and cortisol are powerful hormones. Too much insulin for too long will eventually result in insulin resistance, a condition in which more and more insulin must be secreted to produce normal insulin responses in tissues such as muscle, brain and liver. Too much cortisol for too long produces an increased risk of infection, reduced bone density, increased muscle weakness and excess glucose in the blood. Cushing's syndrome is the result of having excessively high cortisol for several years. Take another look at the picture at the beginning of this post. The patient looks like a person with metabolic syndrome, doesn't he? But this person actually has Cushing's syndrome.

Cushing's syndrome can be caused by an adrenal or pituitary tumor, or it may be the result of taking high doses of glucocorticoids for a long period of time. People who do not have these tumors and who do not take exogenous glucocorticoids do not have to worry about Cushing's syndrome, but the man in the picture does illustrate the point that there may be metabolic side effects from stress-induced hypercortisolism.

In a May 2010 review in the American Journal of Physiology-Endocrinology and Metabolism, Dake Qi and Brian Rodrigues described the effects of glucocorticoids on insulin-responsive tissues. Many of the studies in the review used dexamethasone, a synthetic glucocorticoid that is about 50 times as potent as cortisol and produces robust reactions in a short period of time. However, clinical experience with excess cortisol secretion supports these observations. At any rate, excess glucocorticoids will produce:
  • Decreased glucose uptake and utilization in muscle and adipose tissue.
  • Increased gluconeogenesis and glucose output by the liver.
  • Increased triglyceride storage in the liver.
  • Increased fatty acid uptake, fat synthesis and fat storage in adipose cells.

Readers of the previous post will recognize that these symptoms are consistent with insulin resistance. What makes it complicated is that there are many different molecules involved in insulin signaling, and each of these can be regulated on several levels. Any of the signaling intermediates can be synthesized more slowly or more rapidly, degraded more slowly or more rapidly, and activated or inactivated through phosphorylation or dephosphorylation by various kinases or phosphatases at numerous sites. These multiple levels of regulation mean that insulin resistance can be achieved through one mechanism when excess cortisol is involved and through another mechanism when excess insulin is involved. Consequently it is possible that both hormones working together can achieve more damage to insulin signaling pathways than one hormone acting alone.

Stress is able to produce a ten-fold increase in cortisol secretion. If the stress is chronic, it is possible that this alone could result in insulin resistance and eventually in the symptoms of the metabolic syndrome. This has been postulated by Anagnostis et al. in The Pathogenetic Role of Cortisol in the Metabolic Syndrome: A Hypothesis.

As we have noted, when primitive cultures adopt Western lifestyles, within about twenty years they can expect to begin experiencing the chronic diseases of Western civilization. While the carbohydrate hypothesis postulates that a diet of refined carbohydrates is the chief cause of insulin resistance and ultimately of the metabolic syndrome, it is also possible that the stress associated with the Western lifestyle is a contributor to insulin resistance. Stress and cortisol secretion are unavoidable, but in the absence of mammoth hunts and hand-to-hand warfare, those of us who wish to avoid the symptoms of insulin resistance would do well to avoid stress while also minimizing our intake of refined carbohydrates.


Unknown said...

Years ago this photo would have been recognized as “beer belly”; then we recognized that many of those “beer bellies” were actually “wheat bellies” expanding the term to include most gluten containing grains. Both “beer” and “wheat” bellies come with a stigma of excess intake of one or both foods. Cushing’s Syndrome adds still another avenue to becoming obese, pre-diabetic, diabetic, etc.

Those of us who have chosen to live low carb may have an advantage, but we must continue to expand our knowledge in expectation of new or additional factors that lead to metabolic syndrome. Each time an additional causal factor is identified a new sub group is also identified with the resultant corrective diet / living choices to slow, stop, reverse the harm being done to the individual’s health.

Thank you for continuing to bring to us the new, interesting, or important factors being identified that may be impacting our own or our loved one’s health. More information on Cushings Syndrome will be appreciated. I know, "a book could be written" perhaps instead, or in the interim 5 - 10 posts would be a beginning. Not necessarily in sequence, but as you have in the past one or two now, then return to a subject later.

Stargazey said...

Thanks for your comments, stormycatalyst!

I was probably unclear in my post and have revised it a bit. Cushing's syndrome usually involves a pituitary or adrenal tumor and is treated with resection of the tumor or with radiation. Endogenous Cushing's syndrome is an extremely rare condition (the incidence is about 10 people per million per year). If you have a loved one who looks like the guy in the picture, the odds are high that he suffers from "wheat belly" rather than Cushing's syndrome.

Iatrogenic (medication-caused) Cushing's syndrome is more common and can be the result of long-term use of glucocorticoids like dexamethasone and prednisone. In that case, the risks of Cushing's syndrome have to be balanced against the risks of discontinuing the drug. Central obesity and high blood sugar may be a necessary price to pay when the alternative is death from asthma or organ rejection.

Let me think a bit about doing more posts on cortisol. The topic gets into a web of interacting signaling pathways and jargon that gives joy to a molecular biologist and despair to most everyone else.

Mike said...

Thanks for putting the time into this, Stargazey! Although far from black and white, could one state that, in regards to metabolic syndrome, chronically excessive hyperinsulinism leads to chronically elevated cortisol?

One of the "topics gets into a web of interacting signaling pathways and jargon that gives joy to a molecular biologist and despair to most everyone else" (ha, I love that) would be excessive exercise (stress?)cortisol secretion, and the role of dietary question being, wouldn't a purposeful post-workout insulin spike via simple carbohydrates attenuate the rise in cortisol from training?

Stargazey said...

Mike--the Blogger software ate your comment! I'll try to answer it from memory.

As far as I know, insulin and cortisol do not "talk" to each other directly. Cortisol tends to tear down muscle and insulin tends to build it up. But both hormones have unique signaling systems, which sometimes overlap, but not always. For that reason, cortisol is not the opposite of insulin and insulin is not the opposite of cortisol.

Insulin tends to work in the realm of phosphorylation and dephosphorylation and is short-acting. Cortisol tends to work in the realm of gene expression and is long-acting.

If you consume food after exercise, insulin will be released and will allow you to replenish your glycogen stores. If you eat protein, this will also give you the amino acids needed to replace any muscle tissue that may have been damaged.

But in the long term, if you exercise very hard and very often to the point of chronic stress, the long-term effects of increased cortisol will begin to break down your muscle tissue even between exercise sessions. The body gets the signal that keeping a high blood sugar is so important for survival that it's worth losing muscle mass to do it.

One way to conceptualize this is by thinking of a paleolithic hunter. He would have had brief bouts of stress as he hunted for food and he could have compensated for those by recovering between hunts. But if he was constantly running rapidly and constantly exerting himself, his body would switch into survival mode and make the management decision that it would be worth it to sacrifice muscle mass, immune function, bone density, and the effects of high blood sugar in order to stay alive. If a modern-day person is simply exercising too much, the cortisol signaling system will not realize that and will initiate the same program, even though survival is not an issue at all.

I hope that helps. If I've forgotten to answer something you asked, or if something isn't clear, please send another question and I'll do my best to answer.

Stargazey said...

Mike--after four days in Comment Purgatory, your comment showed up again. That's never happened to me before, but it's nice to know it came back and is now sitting in its proper place in the queue. By the way, thanks for making me study about insulin and cortisol. I had forgotten that the two were so interconnected.

Alex Cahill said...

As someone with Cushing's caused by long term inhaled steroids, I know the necessity of low-carbing. At 30g a day, I'm still not able to lose the abdominal fat buildup.

Unknown said...

I have always had trouble with hypoglycemia, and have finally adopted a low-carb diet to stop the insulin spikes. But... the resulting hypoglycemia, as I begin this diet, is even worse. I'm only 5 days in.

Some people have told me it just takes time to get the body to switch over to fat-burning mode. I'm already losing weight, so I'm burning some fat, but obviously my body is still wanting to burn sugar.

However, my chiropractic neurologist pointed something else out: my body is reacting to the low-carb diet (and it also reacted to a high-carb diet) by having hypoglycemia in the night, and "fixing" it via the adrenals sending me a shot of cortisol or adrenaline, or both. I wake every night at 3am feeling very unsettled, sometimes nervous, and occasionally in a full-blown panic attack. My doc told me that if the body is going to "survival mode" via these adrenal hits, my body won't switch to fat burning on its own. Are you familiar with this problem?

Stargazey said...

Hi, Stephanie! I'm not a physician, so I'm not really qualified to answer your question. If you have trouble with hypoglycemia, it might be a good idea to see an M.D. who is familiar with treating diabetes, and preferably one who is used to using low-carb as part of that treatment.

The body doesn't really have on/off switches. The control mechanisms are more like rheostats. You may be burning some fat, but not enough to get you through the night. One thing that occurs to me is that you might be trying to do a low-fat version of low-carb. Eating fat on low-carb gets the fat-burning process started each day. If we aren't eating enough fat, the body assumes that we're in the midst of a famine and kicks in all the mechanisms it can find to keep us from dying. Eating fat lets the body know that all is well. That may be completely off the mark, so you'll want to consult with an M.D. to make sure you are working with your body and not against it. Best wishes.

Sarah said...

I watched a very interesting program by National Geographic called "Stress: Portrait of a Killer". In it a researcher who has been studying baboon troops in the wild for more than thirty years talks about his findings about how stress impacts the health of the non-alpha baboons. Evidently baboon society is, except in unusual circumstances, extremely stressful for all but the alpha types, because the alphas make it that way for the rest. This scientist has found that the alphas remain very healthy, but the stressed out non-alpha baboons develop abdominal fat and other signs of metabolic disorder.
I looked up studies of baboons on the Internet and found one comparing baboons eating human food from a dump and from gardens to baboons eating their traditional diet in the wild. Many of the baboons eating the human food started developing health problems like insulin resistance irrespective of their status in the troop. Of course the other group did not have these problems. So, these two studies to me seem to say that both diet and stress play a role in insulin resistance and metabolic syndrome.
My sixty-four year old husband has the "wheat gut" look. He is a Vietnam Vet with PTSD, so he is almost always stressed. I think in response to his stress he drinks gallons of soda a week and it can be hit or miss on any real food. I did read on the Internet a paper hypothesizing that people with hypoglycemia (not the kind caused by insulin) are prone to PTSD.

Vickie Ewell said...

I've been thinking about elevated cortisol this past week, because a round of Atkins Induction resurrected my Neuropathy once again. We had someone give us 1/2 a box of homegrown beef, and from day 1 I was itching like crazy. By day 14, I was sick, sick, sick, and in so much pain I went back onto maintenance again.

With beef a strong tie between what happened this week, and going no carb before, I did some research on allergies and food sensitivities.

I read this week in several places that allergies and food sensitivities elevate cortisol. So I guess I'm wondering if you can have chronic elevated cortisol (from eating beef and/or dairy daily) to the point that it disturbs blood glucose levels without actually going into full-blown Cushing's?

I gained 2 inches in my waist and 2 inches in my belly from a single 14 day Atkins. It's that no-carb nightmare all over again, but I was honestly doing 20 net carbs this time. Lots of veggies - but lots of dairy and beef.

I found a study that said 20% of those sensitive to dairy are also sensitive to beef. So I'm off both for now.

Stargazey said...

Wow! Two comments on a year-old post! It's great to hear from both of you.

Sarah, my heart goes out to you. It may well be that your husband is suffering from cortisol and insulin resistance issues simultaneously. One of the things I've noticed is that people sometimes try to self-medicate their emotional pain with food. Some carb-rich foods can stimulate production of serotonin and some can stimulate dopamine receptors. Once a person is aware of why he is eating for emotional comfort, he can sometimes stop, but not always. Carbs are cheap and legal, so it's easy to head for them when stress increases.

Vickie, it's great to see you again! Beef allergies? I kind of wonder if the beef came from an animal that had been given a particular drug or had eaten some sort of plant that you are allergic to. Are you usually allergic to beef?

Did you check your blood sugar during this Induction? Were you careful not to eat too much protein each day? One of the things I came across lately was that a big bolus of whey protein can spike blood sugar, too. A woman who tried Dr. Eades' 6 week cure found that out the hard way. You may be right on the allergies, though. I think of them in the context of needing to take steroids to knock them down, but maybe they do promote cortisol release on their own. It would make sense.

Sarah said...

I read your articles on dopamine and seratonin. I knew about the seratonin-food connection, but this made it clearer and I didn't know about the dopamine connection to sweets. If I weren't slightly diabetic and very aware now that I can't eat sweets without sliding down the slippery slope of doom (a little humor there), I might be slurping sodas right along with my husband. Oddly, both of us are on the same medications for depression, Wellbutrin and Adderall. The trouble for me is the Adderall helps for a while but I get less and less able to sleep. Then I feel depressed from lack of sleep, which is kind of where I'm at now, hence the temptation of dopamine. I do notice sleepiness and relaxation if I eat a little more carbohydrate foods. I'm trying to determine the amount of carbs that's best for me as far as mood goes.
From reading I have done on various Internet sites, it sounds like carbohydrates may play a role in inflammation which in turn may be the cause of depression as well as other ills. I wonder if what causes most of the inflammation is just an overwhelming number of strange germs our bodies have to fight off in this modern overcrowded world. What is your thought on that? Or is my logic wrong, because I don't know enough about it?

Stargazey said...

Sarah, I asked my husband (a behavioral neurologist) about using Wellbutrin and Adderall for depression. He says you may be receiving the Adderall for adult ADHD rather than for depression. If that's the case, there are other ADHD medications such as INTUNIV that don't cause insomnia. You might discuss this with your physician.

As far as inflammation, you might find this blogpost informative. That's just one possibility, though.

Sarah said...

Thank you for thinking about my post and offering some ideas. I have only just found your blog a few days ago, so I haven't read through it that much yet, but I know I will enjoy taking it in. I recently found the 'Cooling Inflammation blog by Dr. Art Ayers and even without that much science background I still get quite a bit out of it.

My doctor never said that he thought I had ADD. I don't think so anyway, although he may have told me around the time I had ECT treatments and anything at that time is gone from my memory. The only thing he has said about it, that I know, is that Adderall is used to boost the effect of the anti-depressant in treatment resistant cases. It could be that when a depressed person is helped by Adderall, it is due to the fact that they have ADD. Sometimes I have wondered if I don't have ADD. For instance I have a hard time pulling my thoughts together in print into what I think is a conventional organization. So, maybe another ADD medication would help. I left out the H factor as I have always been a far cry from hyperactive.

I read one of the comments after the post where someone said they are having nighttime hypoglycemia. I have that I think. I understand that it is a common problem for diabetics and that eating a protein or protein and carb snack at bedtime will probably help that. I think the Blood sugar 101 site has something about it.

Stargazey said...

You're welcome. I know Blood Sugar 101 and it's a great site. Enjoy your reading!

Vickie Ewell said...

Hi Stargazy,
I thought this would be the best place to find you. :)

I don't normally eat very much beef; it's way expensive here. Only a hamburger now and then - when I can get it marked down. So I don't know for sure if I have beef sensitivities.

It's just odd that on no carb I was eating just beef and water, and this time on Atkins Induction, I was eating beef once or twice a day. But you might be right about something given to the animal or something the animal ate. I haven't ruled that out yet.

I "am" allergic to dairy, but have been in denial about that for many years. I gave up milk years ago, but have clung to the cheese, butter, and heavy cream.

I did not take my blood sugar during Induction. I didn't have any glucose strips. We've had a hard winter financially, and I didn't realize I would need them. I thought my last craziness was due to the no carbs, too high protein, run away gluconeogenesis thing.

My Neuropathy always kicks in when my blood glucose is consistently high, but before it's taken awhile. It came back much quicker this time, only after a mere 10 days.

2 scoops of whey protein would coincide with the amount of beef I was eating on no carb, but this time since I was eating salads and veggies, I was eating way less than that. Plus I hadn't forgotten our past studies about that. But I was eating lots of dairy. As well as the beef.

Now that I'm off the dairy and beef, eating maintenance level of carbs (100 grams), the Neuropathy is healing super fast. It's been 2 weeks, and I just have twinges now and then. Last time, it took months - but then, I was still eating beef and dairy, and trying out different things.

Won't go back onto Induction until I have some glucose strips though. Thanx for your help.

Rob Wahl said...

Hi there, I just wanted to leave you a not to say this is an excellent blog post/article. With so much bunk on the web it was great to read something that made sense.

Rami said...

Excellent blog, thank you for the work! I am fascinated with insulin and cortisol. I call these hormones are "the ying and the yang" of blood sugar. Because of the critical role the two hormones play for our health and life, it is critical to reduce even avoid refined sugary foods. Excess of either hormone will make us fat, and the loss of either one will lead to our death. A human can live few days to weeks without insulin, He can not live without cortisol. The loss of cortisol will lead to a severe cardiovascular collapse and death because nor adrenaline, the major catecholamine that regulates arteriolar blood pressure can not work without cortisol. This is called adrenal crisis. It can occur with sudden withdrawal after long time oral or systematic corticosteroid treatments or after poorly treated Addison disease. A third cause is septic meningitis known as Waterhouse-Kooper syndrome. I however was surprised that using steroid inhalers may lead to Cushing's syndrome. This is rare. Thank you again Rami Hanna, MD and a graduate student at NFS Wayne State University.