ITIS -- It's the Insulin, Stupid (pt 2/8)

Warning: This is a ridiculously long post. I was going to break it up into two, but I figured, what’s the difference between one really long post, and two semi-long ones? You can always read a couple paragraphs and then come back later if you don’t have time to read it all at once.

Also: My blog has a very eclectic audience. I have physicians, PhDs, and others well-educated in biochem and A&P reading this, but I think the bulk of my readers are interested laypeople. I try to tailor my posts to the laypeople, keeping in mind that they are of above-average intelligence, and certainly above-average knowledge about all this low-carb, high-fat, Paleo, and ancestral health "stuff." Just wanted to remind everyone of the diverse audience here, because this post, in particular, contains simplified explanations of complex processes, and I apologize if any of the pros find themselves bored. :-/ 

OKAY! Now we come to the next part of why all of this insulin stuff is so important. (Missed the first part? Click here. And you’ll notice I’ve changed the title of this post to say it’s part 2 of I-don’t-know-how-many. In starting to write part 3, I realized this is going to be more like 5 or 6. I am learning new things about this every day that I feel are important enough to write about, and the number of posts it will take to include them keeps rising.) 

Here we go...




Insulin is elevated, and it’s elevated for a prolonged amount of time. I wouldn’t be devoting so much (unpaid!) time to writing about this if elevated insulin, in itself, weren’t such a big threat to good health. It’s even worse when coupled with elevated glucose, but it’s got some pretty nasty effects all on its own. So let’s break this down. Some of this you’ll be familiar with, but some of it might surprise you. Make no mistake, though, what Dr. Tim Noakes said is true:

That's why insulin resistance most important medical condition of our day. Yet we (doctors) pretend it doesn't exist https://t.co/Rb1ogX1JB5

— Tim Noakes (@ProfTimNoakes) September 13, 2015 

The only point on which I disagree with Dr. Noakes is that insulin resistance (IR) is a “medical condition.” I would say it’s a pathological physiological state, for sure, but I don’t know if I’d call it a medical condition, as in, something that needs to be treated with medication. Insulin resistance is a medical condition in the same way a broken leg is a medical condition: it can come about due to forces beyond someone’s control, or it can come about because of misguided lifestyle practices. A broken leg, for example, can result from a freak car accident (forces beyond one’s control), or it can be the result of running with the bulls in Pamplona and getting trampled (misguided lifestyle practice). Insulin resistance can result from being born with very strong genetic and epigenetic propensities toward IR almost no matter what someone eats or how they live (forces beyond one’s control), and we currently hypothesize that it can result from a long time of overconsuming carbohydrates (and potentially all food), being sedentary, being chronically stressed, and not getting adequate sleep (misguided lifestyle practices).

But I’m no zealot. I’ll give a little and acknowledge that there are, indeed, individuals who need medication to help decrease their insulin resistance. There are plenty of people out there for whom a LCHF diet, exercise, better sleep, less stress, and the whole rest of the package just doesn’t take them all the way. Maybe these people really do need metformin, or, on the non-prescription side, maybe berberine, chromium, and alpha-lipoic acid. (And let’s not underestimate the power of vinegar!) But I still don’t know if I’d call IR a “medical condition.”

But that is neither here nor there. I am usually a stickler for semantics, but let’s not get hung up on the details this time. Whether it’s a medical condition, metabolism gone awry, or just one heck of a problem, insulin resistance is no joke. 

And I don’t think we can say with certainty what actually causes IR. I suspect it’s multifactorial. There are probably many factors in diet and lifestyle that combine in a “perfect storm” to wreck physiology and metabolism. So I don’t think it’s just excess carbohydrates. If it were, then a low-carb diet, by itself, would help everyone who’s insulin resistant, and while it is that simple for many people, I have clients who can confirm it’s often more complex than that. 

It probably looks something like both of these cascades:

Order might rather be: oxidative stress => mitochondrial dysfunction => IR => hyperinsulinaemia => inflammation => cancer, CVD, T2DM, etc.

— Gabor Erdosi /erdoke (@gerdosi) September 13, 2015

(In fact, I have written extensively about the role of mitochondrial dysfunction in cancer. See here and here.)

But back to insulin.

When it comes to the role of increased small intestinal permeability (a.k.a. “leaky gut”), the scientific literature indicates that a leaky gut might be the driving force for health effects far and wide in the rest of the body. At the very least, there’s a gut-skin axis; a gut-brain axis, and a gut-joint axis. And I am hereby proclaiming that we can make a case for a glucose-insulin-every-system-in-the-body-axis.

After digging through this stuff for a while, I have come to the following conclusion:

THERE ISN’T ONE BODY SYSTEM THAT IS NOT ADVERSELY AFFECTED BY CHRONICALLY ELEVATED BLOOD GLUCOSE AND/OR INSULIN.

Just off the top of my head, here are six body systems that take a very gnarly hit from chronic hyperglycemia and/or hyperinsulinemia:

Reproductive system

It is fairly well established that polycystic ovarian syndrome (PCOS) is related to hyperinsulinemia. Not in every case, but in a great many. Additionally, hyperinsulinemia, hyper- and hypoglycemia may cause PMS to be darn near unbearable, partly because of insulin’s effects on sex hormones, but also for the much more obvious reason of wild blood sugar ups and downs causing mood swings and irritability. But it’s not all about the women. Oh, no, fellas, you’re not immune to the effects of elevated insulin on your precious gonads. Y’know all those commercials pushing pills and potions for “low T”—i.e., low testosterone? Well, there are lots of reasons your “T” could be low, but one of the biggies is hyperinsulinemia. See, insulin upregulates an enzyme called aromatase, and aromatase converts androgens into estrogens. The more aromatase activity a man’s body has, the less testosterone and the more estrogen he probably has floating around in his bloodstream. Elevated estrogen—and, really, just messed up hormones in general—in men can lead to all sorts of nasty stuff, including gynecomastia, benign prostatic hypertrophy (BPH), prostate cancer, and infertility. Elevated PSA (prostate-specific antigen) levels? Is it cancer, or hyperinsulinemia? “Man boobs?” Maybe that guy needs a low-carb diet. Shooting blanks? Maybe that calls for some insulin-lowering lifestyle interventions. “The up-regulation of aromatase produces increased intracellular oestradiol […] in combination with insulin, to cause aberrant downstream transduction signaling, and thus induce metabolic syndrome and mitogenic prostate growth.” Right. “Mitogenic prostate growth.” That’s science-speak for enlarged prostate, which it seems like tons of older men are being “diagnosed” with. Is there something wrong with the prostate gland, itself, or is it hyperinsulinemia? The author of this paper concludes that these conditions are a result of excess insulin & estrogen, rather than “low T.” 

Bottom line: High insulin is bad sexual health & fertility juju for both sexes.  (Know someone struggling to get pregnant? Tell them to contact me!)

Cardiovascular system

According to Dr. Kraft, “Those with cardiovascular disease not identified with diabetes are simply undiagnosed.” Can you imagine? This sh*t has nothing to do with cholesterol. Cholesterol is accumulating in the blood vessel walls in order to repair the microdamage inflicted by all the glucose & insulin! Sure, arteries being “blocked” by a buildup of plaque can lead to ischemia (reduced blood flow) and infarction (total lack of blood flow and resultant tissue death), but rather than getting rid of the cholesterol by any and all means possible, the question should be, WHAT is CAUSING the plaques to form in the first place?

Okay, now that I’ve gotten the rant out of the way, let’s look at some of the ways in which hyperglycemia and insulin resistance affect the cardiovascular system:

Glycation:  I sprinkled the term “hemoglobin A1c,” or just A1c, throughout part 1 of this series. A1c is “glycated hemoglobin,” and it’s an approximate measure of your average blood glucose during the past 3-4 months. Glycation happens when a sugar (such as glucose) gloms onto a protein (such as hemoglobin in the blood) and doesn’t let go. It’s an irreversible process. Think of it like an unwrapped lollipop accidentally left on a car dashboard in a closed-up car in the dead of summer. That sugar is going to melt and get sticky, hard, and brittle, and it’s going to be darn near impossible to remove it. I am simplifying here for the sake of explanation, but if your A1c is elevated, think of it like your blood being sticky and gunky. Its consistency/viscosity has gone from watery to more like maple syrup or molasses. But hemoglobin isn’t the only protein that can become glycated. Any protein—including structural ones in blood vessels—can also get glycated. The result is, they become hard and brittle. They go from soft-ish, rubbery hoses that are quite accommodating (meaning they can expand and contract easily), into something more like glass tubes. They’re brittle and fragile. So when you have chronically elevated BG, and your A1c is high, instead of water flowing through a nice, rubbery hose, we have thick, dense molasses being forced through a brittle glass tube at a high pressure (due to hypertension…more on that in a sec). The extremely logical and semi-inevitable effect of this is the high incidence of all the cardiovascular complications so many diabetics experience, many of which are the results of compromised blood vessels: stroke, heart attack, burst blood vessels in the eyes, poor circulation, kidney failure, loss of feeling in the extremities (diabetic neuropathy)—particularly in the feet, and more. So I have to agree with Dr. Kraft: people with cardiovascular disease not seemingly related to diabetes are probably the exact people I talked about in part 1: people with diabetes in-situ. Undiagnosed diabetics, who remain undiagnosed because the only things their doctors are looking at are A1c and fasting glucose.  

Okay, now that we’ve covered the cardiovascular system, let’s go one step further and connect this back to reproductive function. With what we just discussed about the effects of hyperglycemia on the blood vessels, another very common problem among men of all ages, but particularly older ones, emerges: erectile dysfunction. Informed doctors will confirm that erectile dysfunction is, for many men, the first sign of heart/cardiovascular problems. Why? What does the southern brain have to do with heart function? Easy-peasy. Erectile dysfunction isn’t typically caused by lack of desire. The man wants to perform; it’s that damn little soldier who’s not following orders, right? Well, failure to get and/or maintain an erection may well be due to impaired blood flow to the penis. If blood circulation is compromised, and the body has to do triage, despite what men might think, the penis is not his body’s most important organ. In fact, the penis is probably one of the first places the body would stop sending adequate blood to if it had to prioritize. (So you can see why ED really can be an early sign of heart trouble, particularly in the absence of other indicators.)

Check out this post from Dr. Gerber for a closer look at the cardiovascular connection to hyperinsulinemia, and why the traditional way of measuring heart disease risk is way off the mark.

Bottom line: High glucose & high insulin are bad cardiovascular juju.

Eyesight  

I hate to start sentences with “everybody knows,” but really, everybody knows poorly managed type 2 diabetes can cause complications with vision, the most serious of which is straight-up blindness. The retina contains teeny, tiny blood vessels, and we just reviewed what happens to blood vessels in the sustained presence of lots of glucose. It’s bad enough when large, strong, hardy and usually accommodating blood vessels, such as arteries, are glycated. Imagine what happens when itty bitty ones in the eyes become brittle and unforgiving. Burst vessels all over the place. (My mother had poorly managed type 2 diabetes, and she experienced these all the time.) Hence the term “diabetic retinopathy.” There are people whose diabetes was initially diagnosed not by a family doctor or endocrinologist, but by an ophthalmologist! Eye doctors can look directly at your retina, and they might be the first person to notice that you’ve got a problem with blood glucose.

Bottom line: Hyperglycemia is bad eyesight juju.

Kidney Function

As well-known as eye problems are among individuals with poorly managed T2D, it is equally acknowledged that poorly managed T2D has horrible, fatal implications for kidney function. There are two main reasons for this:

1. The renal tubules, which are the parts of the kidneys responsible for filtering the blood, contain teeny, tiny blood vessels, just like the retinas do. And at the risk of beating you over the head with it at this point, you know what happens to blood vessels—particularly very small ones—when constantly exposed to high glucose. If these little blood vessels in your renal tubules go kaput, you will be in serious trouble. There’s a reason so many diabetics end up on dialysis. (But don’t forget the role of cholesterol-lowering drugs in statin-induced renal failure!) Hence the term “diabetic nephropathy.”
2. Insulin has a huge influence on sodium dynamics in the body. More insulin ---> more sodium retention. And more sodium retention ---> higher blood pressure. (Note: this doesn’t mean you need to avoid salt. If anything, reducing sugar and other carbohydrates will be more effective for curing managing hypertension than cutting back on sodium. Hypertension has so little to do with salt in the diet, it’s not even funny. I keep saying I have a sodium series planned for after the series on the metabolic theory of cancer is done. Frankly, I think it’ll blow your mind.) How does increased sodium retention cause an elevation in blood pressure? Well, there’s a phrase in physiology that says “water follows sodium.” If the kidneys are holding onto more sodium, more water will naturally be drawn back into the body. More water means more water in the blood, raising the blood volume. So we have a greater volume of blood flowing through the same amount of blood vessels, which will cause the pressure to increase. The increase will be even greater if the blood vessels are somewhat glycated, because then, instead of being able to expand/dilate easily to accommodate the increased blood flow, these vessels are hard and unforgiving. And remember: when it comes to diet-induced hypertension, it is insulin that is driving the train far more than it is sodium. 

Healthy kidneys should be able to reabsorb or filter out sodium as needed. But when some other, more powerful regulatory force—such as insulin—exerts its effects, this process can be overridden. “Hyperglycemia potentiates insulin antinatriuresis through an effect on the proximal tubule (sodium-glucose cotransport).” (“Antinatriuresis” is a fancy medical word for “preventing the excretion of sodium.” The Latin word for sodium is natrium, hence its symbol on the periodic table being Na.) And guess what else? “Insulin antinatriuresis is accompanied by a reduction in the urinary excretion of uric acid.” And, “In hypertensive patients, higher uric acid levels and lower renal urate clearance rates cluster with insulin resistance and dyslipidemia.” And y’know what reduced excretion of uric acid means, right? Yes: gout. Gout is likely not a result of too many dietary purines; it’s looking more and more like yet another of these conditions driven by hyperinsulinemia. (You may have heard that gout is strongly linked to fructose consumption. Indeed, this is probably due to the effects of fructose on insulin. See, fructose doesn't elevate blood glucose much, but it does raise insulin. Dr. Fung explains starting about 17 minutes into this video.)

Okay, so there’s hypertension, and there’s kidney function. What’s the connection? Well, hypertension is very hard on the kidneys. The kidneys are responsible for filtering the blood—every last drop. They filter out “toxins” as well as the harmful byproducts of normal metabolic processes, and they also decide how much of which minerals and electrolytes to get rid of, and how much to reabsorb. High blood pressure makes this harder to do. (So does dehydration. Remember: thick, sludgy blood forcing itself through tiny, brittle blood vessels.) 

Bottom line: Hyperglycemia & hyperinsulinemia are bad kidney juju.

Brain Health & Cognitive Function

Hello? I wrote a whole friggin’ book about the connection between elevated insulin and Alzheimer’s disease. I also talked about Alzheimer’s as “diabetes of the brain” or “type 3 diabetes” on podcasts I recorded with Jimmy Moore on the Livin’ la Vida Low Carb show, and Robb Wolf, on The Paleo Solution Podcast. In my conversation with Robb (still can’t believe I talked to him…squee!), I made a point to mention Kraft’s work (and Ivor’s), and that many people with cognitive impairment or Alzheimer’s disease have exactly what we’ve been talking about here: “normal” fasting BG, and “normal” A1c, but they are insulin resistant out the wazoo. (As I mentioned in both shows, the more insulin in the blood, the more the amyloid plaques accumulate.) These people are not type 2 diabetics, because they lack the elevated FBG and A1c that would trigger a diagnosis. What they do have is raging hyperinsulinemia, or what we can now call “diabetes ­in-situ.” 

Bottom line: Hyperinsulinemia is BAD brain juju.

Cochleovestibular disorders

(affecting inner ear & balance) 

After learning all this fascinating stuff about diabetes in-situ and hyperinsulinemia, I wrote a post about it for my freelance gig. I specifically looked at cochleovestibular disorders. (A handful of the many conditions that fall under this category are vertigo, tinnitus, Ménière's disease, and mal de debarquement syndrome.) In fact, medical doctors in the ear, nose, and throat (ENT) specialty were among the first people to note the connection between these seemingly “idiopathic” conditions and elevated insulin. (“Idiopathic” means no one knows what the hell causes it.)

Now, the thing is, I don’t know the mechanism at work here. But I’m sure there is one. (I’m not well-versed in inner ear anatomy & physiology, nor the mechanisms that underlie postural balance.) And unfortunately, I have recently lost easy access to the full-text of most articles on PubMed, so I will simply hypothesize here. (If anyone out there is well-informed on this stuff, and can explain this better, please email me privately, or chime in in the comments!)

Okay. We know insulin affects renal sodium retention, and, therefore, fluid dynamics throughout the whole body. Might there be a role for insulin in influencing fluid balance in the inner ear? Some healthcare practitioners have made the case that, for some individuals who are sensitive to gluten, the ONLY manifestations of the sensitivity will be outside the GI tract (i.e., non-celiac gluten sensitivity). For example, there’s “gluten ataxia” – a (supposedly) gluten-induced state of general clumsiness. And there seem to be other neurological, dermatological, and other systemic effects from gluten, wherein the affected parts of the body are the only indications that there’s a gluten sensitivity. So, what if some of these cochleovestibular conditions are the only manifestation of someone’s hyperinsulinemia? Because, remember, we are talking about individuals who have normal fasting blood glucose, normal A1c, and a normal response to an OGTT. (All of which look only at glucose.) But if they are hyperinsulinemic, you’ve got to think the glut of insulin is wreaking havoc somewhere in the body, no? And maybe, just maybe, the only place it’s doing so is the inner ear. On the same theme, for individuals with normal BG and normal A1c, maybe hypertension, or infertility, or BPH, or reduced GFR [glomerular filtration rate -- an indicator of kidney function], is the only manifestation of insulin resistance.

This is an area supremely ripe for research employing low-carb or ketogenic diets as therapy, for the same reason they are so desperately warranted for Alzheimer’s: these are conditions for which pharmaceutical drugs are either nonexistent or woefully ineffective. Millions of people have their quality of life crushed because of these weird, freakish-seeming conditions of “unknown origin.” It’s like Robb Wolf says every time someone asks him if a Paleo diet works for “x” rare autoimmune condition they have, and he says, “Couldn’t hurt to try!” For goodness' sake, people, TRY low-carb/keto!

To their credit, as I mentioned, some physicians in the ENT specialty were among the first to realize that Dr. Kraft might be onto something, and they started investigating hyperinsulinemia among their patients. And lookie, lookie, at what they found:

• Hyperinsulinemia: The Common Denominator of Subjective Idiopathic Tinnitus and Other Idiopathic Central and Peripheral Neurootologic Disorders. (By Dr. Kraft!)
• Glucose and insulin profiles and their correlations in Ménière’s disease: This study’s authors went so far as to call hyperinsulinemia “the metabolic change most often involved in the pathogenesis of cochleovestibular disorders.” It’s involved in the pathogenesis. This means it is a causative factor, and isn’t just “associated” with these issues.
• Glucose, insulin and inner ear pathology: “Hyperinsulinemia was the most frequent abnormality and was found to constitute the determining factor of the inner ear disorders.” Again, the authors are saying hyperinsulinemia is the determining factor. Meaning, this is causation, NOT just “association.”
• Metabolic disorders in vertigo, tinnitus, and hearing loss: “such disturbances of glucose metabolism as diabetes mellitus and hyperinsulinemia may be responsible for inner ear diseases.”
• Blood levels of glucose and insulin in Meniere’s disease.

HOLY COW, right? Why have none of us ever heard of this before? (BTW: Dr. Naiman has mentioned that a patient of his was cured of tinnitus after adopting a LCHF diet. Just sayin’.) 

Bottom line: Hyperinsulinemia is BAD inner-ear and balance juju.

I mentioned a Dr. Kenneth Brookler in part 1, and I said we’d come back to him. Well, here he is. He’s an otolaryngologist, and was one of the first physicians to understand the importance of Kraft’s work. He made a lot of headway in uncovering the link between hyperinsulinemia and these “idiopathic” inner-ear disorders. Again, big thanks to Ivor Cummins, the Fat Emperor, for interviewing Dr. Brookler and making the video available to all of us: 

• Interview with Dr. Kenneth Brookler

Here’s what’s coming next time:

You’ll note that, in all of this discussion about diabetes, glucose, and insulin, I have not said a single thing about obesity. The reason I wanted to address weight after all the other things we covered today, is that, frankly, a little bit of excess adipose around the ol’ hips and gut is the least of the issues that can come from elevated insulin and glucose.

Nevertheless, no blog series on insulin would be complete without a look at the role of insulin in fuel partitioning and the regulation of adipose tissue. So that’s where we’ll go next.

Until then, remember: OBESITY IS AN EFFECT, NOT A CAUSE, OF METABOLIC DYSFUNCTION AND DISEASE.

P.S. In case it wasn’t clear from our discussion of erectile dysfunction, heart disease, kidney failure, Alzheimer’s, loss of vision, and inner-ear disorders, BEING THIN DOES NOT AUTOMATICALLY MEAN YOU ARE HEALTHY!! For sure, millions of thin people have Alzheimer’s, tinnitus, vertigo, heart disease, kidney failure, infertility, and more. Having been LUCKY enough to not become obese does not imply you do not have rip-roaring problems with glucose & insulin. Obesity is simply one manifestation of insulin resistance, but because it’s the one we can see most easily, it’s the one that everybody thinks is causing everything else. If we could see someone’s serum triglycerides, someone’s renal tubules, someone’s arteries, or someone’s fasting insulin, all the fat-shamers out there would SHUT UP PDQ. (Sorry...this is a huge, huge sticking point for me, professionally and personally.)

Continue to part 3 in this series: http://www.tuitnutrition.com/2015/10/its-the-insulin-3.html

Remember: Amy Berger, M.S., NTP, is not a physician and Tuit Nutrition, LLC, is not a medical practice. The information contained on this site is not intended to diagnose, treat, cure, or prevent any medical condition.