Finding Usain Bolt, Dolphins, Eskimos, Glucose and more!

 

Among all of the labs results that I posted after my more than 1 year ongoing carnivore experience in which I’ve eaten anywhere from 4-6+ lbs of meat per day, nothing has been as controversial as my blood glucose.  Everyone seems to have an opinion and many have weighed in via private emails, tweets, DMs, YouTube videos and more.  All kinds of speculation from the vegan activists “you are clearly heading for imminent death” to the endocrinologist saying “it’s no big deal”  and to everyone in between.  Truck drivers, weekend warrior nutritionist, Keto advocates and biohackers, engineers and so on.  Everyone has a theory, everyone has a bias (including myself).  So allow me the indulgence to unpack some of this info and take you through some interesting terrain.

 

Now first of all, I am well acquainted with the horrors of diabetes.  As a military trauma orthopedic surgeon I unfortunately had to do a hell of a lot of amputations due to horrendous trauma, but the number of amputations I did for trauma pales in comparison to the toes, fingers, feet and legs I’ve cut off as a result of diabetes.  I’ve debrided countless disgusting foul smelling infections, fixed hundreds of frail diabetic bones and have seen plenty of blind diabetics on dialysis and so I am acutely aware of the destructive nature of this awful disease and thus did not take lightly the finding that my blood sugar was creeping well into the “pre diabetic” range and bordering on diabetic.

 

Now some of you have speculated that perhaps I was already diabetic and these labs actually represent an improvement.  Certainly that would make the Keto and carnivore crowd happy.  Well unfortunately, the last time I had my fasting blood glucose checked it was within normal limits and it has definitely gone up as a result of eating a carnivorous diet.  Yes, I can just imagine the vegans are dancing with glee with this information.  It’s not to say I wasn’t having clinical issues previously, in fact although my fasting glucose was normal, I was 50lbs heavier, I likely had sleep apnea, my blood pressure was elevated, my joints ached and I was constantly tired.  So this seems a bit paradoxical, I mean why would my blood sugar get worse all the while my clinical situation got dramatically better?

 

Let’s wander down a few seemingly different paths for a bit and see if we can tie everything together at the end.  

 

Let’s talk a little bit about epidemiology and Olympic gold medals.  Why do we consider 126 mg/dL to be the cutoff for calling someone diabetic? Why not 125 or 127? Interestingly up until the 1970s the number was 140.  Does this mean that if my number is 105 I’m fine? Let’s first talk a bit about the Olympic 100 m sprint to further learn a bit about epidemiology.

 

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Starting with the first modern competition in 1896, Tom Burke was the first of the US gold medalists that dominated this event 17 out of 24 times up until 2004.  If we looked at the body weight and height of every single winner we would see the tallest athlete to that point was Great Britain’s Linford Christie at 6’2.  If we were to make a prediction based on epidemiological data about the the next winner in 2008, we could predict that the winner would be American and 6’2 or less.  Now we all know what happened in 2008, Usain Bolt, from Jamaica, a country that had never before won this event, measuring a gigantic, by 100m sprinting standards, 6’5” (he was also the heaviest as well), goes onto dominant this event winning three consecutive 100m titles and destroyed the world record with a time of 9.58 seconds. Obviously he was well known to be fast and Jamaica has had many top level sprinters over the years and so his 2008 win was not that shocking, but again if we played the strict epidemiology game with out taking into account all this extra information we’d be badly mistaken.

 

So back to blood glucose.  Again the numbers we use today are based on huge population studies and don’t account for individual unique situations.  In fact you can see diabetic complication start to appear even in people that have numbers far below the cutoff values and it is one of the reason Richard Berstein, famed type 1 diabetic doctor and author of the book “The Diabetes Solution” often states that he see disease at much lower glucose levels than even the current population based guidelines suggest.  

 

Ok, let’s talk a bit more about diabetes. Elevated blood sugar has been known to be associated with diabetes for even a few thousands years, in fact one of the ways it was originally diagnosed was by tasting the urine for sweetness! Yuck, thankfully we have labs these days.  Being a doctor already has enough thankless tasks and fortunately at least tasting urine is no longer on of them.  So a basic question is what is the actual disease of diabetes?  Is it glucose in the blood the problem or is it the effects that occur in the tissues? In other words should I be worried about glucose in my blood or should I worry about damage to my kidneys, the retina in my eyes and my blood vessels.  Obviously the latter is what is really the issue and the glucose is what is associated with those problems.  Now in no way do I want anyone to think that having blood glucose at a high level is desirable or something we can disregard. In fact for the vast majority of people the higher the blood glucose the greater the risk of actual diabetic tissue disease.  That is what the epidemiology and other associational studies tell us.  Now remember the one problem with epidemiological studies is that they don’t account for the Usain Bolts of the world (uh oh, Dr Baker is going crazy comparing himself to Usain Bolt).  Is there any evidence that blood glucose Usain Bolts exist?  We’ll get that that in a bit.

 
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Before we do that we should talk a bit more about diabetic pathophysiology and the difference between glycation and advanced glycation.  Hemoglobin A1C is a relatively old test and it is widely utilized to get an estimate of average blood glucose control over a period of 8-12 weeks.  Now despite the fact that it is a widely used tool it has a few limitation and we are beginning to see that based on the recent use of continuous glucose monitors it can be off by quite a bit.  Among a number of factors that can call into question is the lifespan of the red blood cell which can potentially dramatically change the reading.  This can work both ways, for instance you may have a HBA1c reading of 4.9% but if your red blood cells are dying too early (a not uncommon event among diabetics) then the HBA1c level will be falsely too low.  Conversely if you have very long lived red blood cells then the HBA1c number may be falsely high.  Just a quick aside to talk about my own lab values showed an elevated HBA1c of 6.3 and that was paired with an also high fasting glucose of 127.  Since I have checked my blood glucose approximately 100 times since then I have a pretty good idea that the HBA1c of 6.3 is not too far off but is perhaps a slight overestimate.  My numbers tend to run at a low of about 75 to an all time high of 135 when I am eating my normal diet.  

 
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Let’s get back to talking about glycation.  Glycation occurs when glucose binds to protein.  This can occur with all types of tissues but the one most of us are aware of is the glycation that occurs with hemoglobin thus giving us our HBA1c score. A similar thing is seen with other proteins in the blood, primarily albumin and it is how we derive another estimate of 2-3 week blood sugar control via something called fructosamine.  This type of glucose to protein binding is considered stable and it requires neither an enzyme nor does it require oxidation to occur and is known as an Amadori product or a Schiff Base and is considered to be reverseable.  That is to say that the glucose can stay attached or leave depending on the concentration gradient.  Now let’s contrast this process that occurs in the blood to that which occurs at the tissue level when the so called AGEs (Advanced Glycation End Products) occur.  In this situation an unpredictable binding reaction occurs in which the protein structure is then irreversibly compromised and is largely driven by a higher oxidative stress environment.  This is where we began to see the actual damage to things like our kidneys and our blood vessels.  Interestingly when looking at advanced glycation, glucose is actually the least reactive sugar and in comparison fructose which also circulates in the blood albeit at much lower concentration is approximately 10- 20 times more reactive than glucose. This interestingly, may be part of the reason the addition of high fructose corn syrup to the modern diet has been such a disaster. There is certainly much more complexity to this stuff and we will touch on more of it, but in the end, preventing an environment that allows these advanced glycation product from accumulation is a very important concept.  

 

Ok, lets see if we can find some Usain Bolts, in other words are there examples of situations when an elevated blood glucose does not lead to diabetic complications? Well it appears there are several. We are well familiar with the concept of lowering our blood sugar to try and prevent diabetic complications and we have two general ways to do that.  One way, I’ll call it the right way, is to make aggressive diet and lifestyle changes and the other way is via pharmacotherapy using various oral medications and of course the big dog insulin.  If blood glucose were the sole driver of the diabetic problem, rather than the entire system, drugs that are very effective at reducing blood sugar should do a very good job at preventing the typical diabetic complications.  Unfortunately we have some glaring studies that show just the opposite.  The 2008 10,000 patient ACCORD study showed that aggressively lowering blood glucose levels with drugs resulted in higher death rates and higher incidence of cardiovascular diabetic complication compared to only lowering levels modestly.  That’s kind of weird and suggests that maybe just focusing on glucose and not the entire system may be a problematic strategy.  The most effective drug that lowers blood glucose is insulin, a well known issue with insulin is that it makes diabetics fat, particularly type 2 diabetics and they generally progress to greater complications the more insulin that is required to control glucoe.  So again we need to look at the whole system and that is why a focus on lifestyle reduction in glucose is such a better strategy.  The correlation between blood glucose and advanced glycation end  products and what we see is that after a certain point, HBA1c of over 7% we see a fairly decent correlation but when we are at lower levels that correlation starts to fall apart.  

 

 

Before I’m accused of trying to say I’m turning into a lion, I will talk about human evidence in just a bit.  Animal studies can be helpful and we have used them over the years to dramatically advance our understanding of physiology and medicine.  We have to realize what there limitations are.  Regardless there are a couple of very interesting examples in the animal world germane to this topic.  Carnivorous mammals that eat a higher protein all meat diet are noted to typically run a relatively high fasting blood glucose typically in the 120 range and are noted to be completely free of disease as long as they maintain their normal carnivorous diet.  Dolphins and cats have been the most widely studied animals on this topic and interestingly cats show actually a tremendous capacity to up and down regulate specific enzymes based on diet and it has been show that obligate carnivore cats can digest and tolerate a diet of up to 40% carbohydrate and absorb more than 90% of any sugar they might ingest.  Of course despite that capacity we often see modern cats with all kinds of diabetic problems that occur when they eat a diet high in carbohydrates. Nonetheless it is interesting how flexible some of the animals can be over the short term. We have a few animal examples of mammalian creatures that can run at higher glucose levels with taking any apparent damage, but what about humans?

 
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Another very interesting observation come from a group of people with a genetic disorder which leads to a glucokinase (GCK) deficiency.  The net result of this means that they tend to have a relatively high fasting blood glucose. A 2014 study in the Journal of the American Medical Association demonstrates that the 48 year long term complication rates of those with the GCK deficiency, whose average HBA1c was 6.8 was essentially no different than those with no diabetes and an average HBA1c of 5.8.  So again, we have a situation of higher blood glucose but no actual damage occurring, perhaps we have to look beyond simple univariate markers and need to consider the whole picture.  

 

A relatively recent observation in athletes using new technology in the form of continuous glucose monitors is the incidence of fairly high fasting glucose levels in high levels athletes.  One particular study observed this phenomenon occurred in around 30% of the athletes and it seemed to occur in the athletes that were exercising with the most intensity and using least carbohydrate. We don’t know what the long term implications are for these particular athletes with regards to potential complications but it does point to a potentially novel mechanistic driver of elevated glucose rather than the typical diabetic pathophysiology.

 

The last group of humans we can look at are the traditional Inuit populations of the arctic regions.  In a classic 1928 study looking at Inuit metabolism it was seen that they typically were consuming 4-8lbs of meat per day, basically zero vegetation and surprise, they maintained a fasting blood sugar of around 120mg/dL and suffered none of the complications typically associated with diabetes.  Some will argue they had a shorter life expectancy than other populations but that is very misleading and in fact if we look at pre-contact Inuit, those that hadn’t yet been exposed to flours, sugars and other modern disaster foods, we find their life expectancy to be fairly similar to other populations in the mid 1800s, particularly when we account for their very high infant mortality rates.  Later Inuit populations and indeed even those today tend to live around 10 years shorter than their non indigenous neighbors.  The primary drivers are very poor socioeconomic status, a smoking rate, particularly in women, that is double the surrounding population and the fact that they live in very cramped quarters and are more susceptible to infectious diseases due to the living arrangement, as well as a general lack of access to medical care.

 
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Why is their glucose high? Well we know that a big meal rich in fat and protein will slow down gastrointestinal transit time to allow for better extraction of nutrients.  This is especially true after particularly large meals (remember these guys are eating 4-8lbs per day).  We also know that the glucose response to a high protein bolus often peaks much later, 5 hours compared to the 30 minute to 1 hr peak with a carbohydrate meal.  We also will see a down regulation of incretin hormone (GLP-1 GIP) signaling of insulin without the GI stimulation of carbohydrate.  So essentially a slow moving bolus of meat is gradually processed and we see a long drawn out continuously elevated but not very high peak post prandial situation.  The big transporters of glucose into the large  tissues like GLUT 4 are also likely not as active because they are insulin dependent and the insulin response to meat will be short lived relative to overall big bolus digestion time. So you get prolonged glucose production but not as much tissue absorption. Remember the damage occurs not because glucose is in the blood, but because it is absorbed into the tissues and a pathological environment is in place to allow oxidative stress driven AGEs.

 

What are the potential mechanisms that allowed for them to exist at relatively high glucose numbers but be free from the complications typically associated with diabetes.  As I mentioned before, it is not the glucose itself, but rather the ability for glucose to contribute ultimately to the formation of tissue damaging advanced glycation end products.  Now if if we have an environment that limits the conversion of glucose to AGEs then we likely have the mechanism by which the Inuit were spared of the actual disease part of diabetes.  Oxidative stress brought on by high consumption of vegetable oils which were absent from the Inuit diet is one mechanism and conversely its inclusion in greater and greater quantities in the modern diet may be a potential driver of seeing diabetic complications appear at progressively lower blood glucose levels.  Carnosine, is exclusively found in meat and is one of the most powerful substance for mitigating the formation of AGEs and also was found heavily in the Inuit diet.  Additionally, as I pointed out earlier fructose, is also a fairly potent driver of AGE formation and its absence from the Inuit diet would have also helped and its inclusion in the modern diet is likely problematic.  

 

 

Mechanistically we are seeing higher intensity athletes developing a trend toward higher glucose levels and thus some might argue that training hard is a net negative and striving for top performance may result in loss of health.  When looking at my own performance I am certainly pushing the envelope athletically.  My 500m concept 2 rowing world record I set at age 50 while on my carnivorous diet was done in a time on 1 minute and 14 seconds.  To put that in perspective as to the level of effort and the extreme glycolytic physiology involved. 5 time World’s Strongest man Mariusz Pudzianowski did it in 1 minute 18.  CrossFit Champ Jason Khalipa pulled a 1 minute 20 and Olympic Rowing gold medalist Mahe Drysdale recently did a 1 minute 20 as well.  My time is among the best times ever pulled by anyone of any age and puts me way out there on the physiologic outlier spectrum and is likely one of the contributors to my seemingly discordant blood glucose, as we generally see most people that adopt a carnivore diet generally have lower blood glucose levels.  Again we do see some athletes starting to trend upwards though.  

 
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My consumption of often upwards of 6lbs of meat per day also makes me a bit of an anomaly in the modern carnivore community (but puts me in line with the Inuit) as it is uncommon for most people to consistently eat at that level and in fact the average person tends to hover closer to about 2lbs if meat per day.  If we remember that the only population that we have blood glucose data on that were essentially on an all meat diet in similar quantities that I do also see nearly identical blood glucose metrics. I will submit that the above two situations with regard to athletic output and food volume are the main drivers of my elevated glucose as opposed to underlying diabetic pathophysiology as I’ll continue to discuss next.

 

Classically we have always divided diabetes into two broad categories, type 1 and type 2 (formerly called adult onset diabetes, but since it now shows up even in little kids, that name has fallen out of favor).  

 
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Type 1 diabetes was fairly uniformly fatal and prior to the invention of exogenous insulin patients would basically die by wasting away from malnourishment as they could not get glucose into the cells of the body without insulin.  Interestingly, prior to the use of exogenous insulin therapy, type 1 diabetes was  treated with very low carb diets which significantly delayed the demise of the patient.   Pre insulin therapy Type 1 diabetics way back in the day were not dying of renal failure or heart disease like those we see today, but rather basically starved to death or died of diabetic keto-acidosis.  The fact that modern Type 1 diabetics are seeing the “typical” diabetic complications rather than the “starving to death” stuff likely has to do with insulin dysregulation rather than zero insulin.  Remember modern Type 1 diabetics are dosed with insulin daily in a “best guess” fashion and are probably constantly fluctuating from too much to too little insulin.

 

Something like 90% or more of the diabetics today fall into the category of Type 2 diabetes (there are a small percentage of unusual in between variations as well that I will mention).  Typically Type 2 diabetics have too much insulin as they try and produce higher and higher amounts in order to maintain lower blood glucose levels and then eventually at some point they cannot produce enough and then the blood glucose begins to rise.  As time goes by sometimes insulin production flags as the pancreatic Beta cells that make glucose begin to fail, one thought being that excessive AGEs can lead to this pathology. The classic Type 2 diabetic is often obese, particularly centrally obese (big belly) and often smaller extremities, although we also see a significant number of thin type 2s, but often they too tend to sport a so called “skinny fat” physique. 

 

Among the common problems with both Type 1 and Type 2 diabetes is the post prandial glucose response.  Some clinicians believe that the greatest problems occur with the often extremely high blood glucose readings that occur after a meal with numbers often above 200 and sometimes even going as high as 300 and that it might be the giant fluctuations that are leading to most of the damage that glucose can contribute to.

 

If we watch what happens to diabetics over time we will see a whole host of problems slowly worsen and this often occurs regardless of blood glucose control, particularly if control is achieved with medication.  Their blood pressure often rises likely secondary to ongoing vascular damage and subsequent inflammation. They often get put on blood pressure medications to control this.  They develop a number of orthopedic issues such as arthritis, tendinitis, nerve entrapment issues like carpal tunnel syndrome. They develop gum disease (interestingly gum disease is well correlated with serum AGE levels).  They often gain weight particularly in the midsection which often can indicate increasing visceral fat.  They tend to prematurely age and their skin tends to wrinkle more and loses its elasticity, again AGEs play a role here as well.  They lose cardiorespiratory capacity and tend to lose the capacity to exercise.  They can start to see the appearance of numerous unwanted skin growths, particularly skin tags which are associated with hyperinsulinemia.  Their libido flags and makes lose the capacity for erection, often a consequence of vascular problems. 

 

While I can’t completely ignore the fact that my fasting blood glucose is elevated and even though there is likely very plausible mechanistic reasons rather than true diabetic pathophysiology, it helps to puts things into clinical context as to regards to disease progression.  5 years ago, before I embarked on my dietary journey I had normal blood glucose, but had borderline high blood pressure (140/85), I was 40 lbs heavier, I had numerous areas of joint pain and tendinitis, my energy was poor and I was seeing sign of hyperinsulinemia via skin changes in the way of axillary skin tags.  In short I had metabolic syndrome and normoglycemic hyperinsulinemia.  Fast forward 5 years and my blood pressure is completely normal, my gums that the dentist used to complain about have completely normalized, my libido and capacity for erections are equal to what they were in my twenties, all joint and tendon pain is gone, my exercise capacity is at an all time lifetime best, fine wrinkles in my skin have faded, all previous skin tags have completely disappeared, my resting heart rate has dropped by about 10 points (62-52 bpm) and my max heart rate increased from 180-190. I easily maintain a lean and very muscular physique with a waist to height ratio being a very favorable 0.47.   Despite all this my fasting blood glucose has elevated (like an Inuit).   As I mentioned above, when I eat my normal diet I have never seen a blood glucose above 135, so I’m definitely not seeing the extreme fluctuations so often associated with diabetic pathophysiology, and in fact the only time I’ve seen anything higher was a 172 1hr after ingesting 100gms of sugar in order to perform a home oral glucose tolerance test. Couple this with the fact that my fasting insulin is a very low 2.6 which gives me an extremely low calculated HOMA-IR score of 0.8 and indicates very good insulin sensitivity.  Other methods of calculating insulin sensitivity like the trygleride-glucose index (8.1) and LP-IR score all show excellent insulin sensitivity.  These things coupled with my current clinical history certainly point away from on going diabetic pathology to include some of the hybrid types such as MODY (maturity onset diabetes of youth).  

 
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For those of you reading this don’t think for a second you should dismiss or blow off a high blood glucose number as it most likely is a problem.  If however you are clinically doing great and you are on a low carb or carnivorous diet, it will be very helpful to obtain much more information to at least include insulin.  It is important to understand the difference between clinically associated markers of disease, such as cholesterol, C Reactive Protein (and I’ll submit even glucose) and the actual disease itself. Going forward I will certainly keep an eye on things but more importantly it will be far more important to pay attention to actual measures of tissue (rather than blood) indices. Things like CIMT and CAC studies as well as possible tissue AGE scores.

 

Links

 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5094325/

https://www.nejm.org/doi/full/10.1056/NEJMoa0802743

https://www.nejm.org/doi/full/10.1056/NEJMoa0802743

https://academic.oup.com/jn/article/128/9/1442/4722474

https://www.ncbi.nlm.nih.gov/m/pubmed/28096127/

https://www.ncbi.nlm.nih.gov/m/pubmed/17179517/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3008226/

https://febs.onlinelibrary.wiley.com/doi/pdf/10.1016/j.febslet.2007.01.082

https://link.springer.com/chapter/10.1007/978-3-319-40458-5_19

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3335257/

https://www.ncbi.nlm.nih.gov/m/pubmed/3132203/

http://m.jbc.org/content/271/17/9982.full

https://www.ncbi.nlm.nih.gov/m/pubmed/9134052/

https://onlinelibrary.wiley.com/doi/full/10.1111/jdi.12449

https://www.ncbi.nlm.nih.gov/m/pubmed/24430320/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3847661/

Shawn Baker