Article at a Glance
- HbA1c, or Hemoglobin A1c, measures the average blood sugar levels in the body over a period of 2-3 months.
- Sugar binds to hemoglobin, the protein in red blood cells, through a process known as glycation. HbA1c looks at how much sugar has bound to red blood cells.
- The body stores excess sugar as glycogen, however, once glycogen stores are full, glucose is converted by the body to triglyceride fats. It is for this reason that those with elevated blood sugar also often have elevated triglycerides.
- As it can be an indicator of increased risk for several diseases, HbA1c is recognized as an important blood test in the medical community.
- Elevated HbA1c is a marker of insulin resistance, a condition in which the body can no longer use glucose as energy efficiently. Insulin resistance is the doorway to type 2 diabetes.
- The immune system is activated by chronically elevated blood sugar which leads to inflammation.
- Genetics play a big role in how our bodies process sugars, with genes like ADIPOQ and FTO emerging as influential on insulin pathways.
- When creating a regimen for controlling blood sugar, it’s important to manage both long term blood sugar levels, as well as blood sugar in the hours after a meal.
This is a post about my blood sugar numbers, including HbA1c (a metric that measures average blood sugar levels over the past 3 months), why they’re low and strategies we can all use to keep our blood sugar in check. Plus, at the end of the post, Aaron gives a full genetic breakdown, explaining why I am genetically unlikely to develop type 2 diabetes (“T2D”).
First, when I say my blood sugars numbers are “low,” I mean they are basically in range (anything at or above 5.7 is trouble), well outside the scope of the type 2 diabetes (“T2D”), insulin resistance world. I do not mean that I am hypoglycemic, which is a condition associated with blood sugar that is dangerously low. To the contrary, part of today’s discussion centers around people who trend hyperglycemic, meaning their blood sugar numbers are chronically elevated which places them at greater risk of developing metabolic syndrome and T2D.
As a foundational principle, let’s just come right out and say that high blood sugar is a bad thing. Some believe that elevated HbA1c and insulin resistance increase the risk for cancer and dementia, and there are studies to back them up. Don’t listen to the nutrition gurus out there who tell you all blood sugar issues are driven by animal products. They do play a role, but just as the Keto world tends to downplay the potential risks associated with dietary fat, the Vegan world downplays the dangers of sugar. Especially if you’re at a genetic disadvantage in clearing and using glucose, elevated blood sugar is a very real problem and one of the primary drivers of the chronic disease epidemic. And no matter what you may have heard from the Vegan podcast and film world, you can be diabetic as a vegetarian.1 Perhaps not as likely, but still possible.
So, bottom line: absent hard N=1 data, take Keto advice on fats with a grain of salt, and same for the Vegans on sugar. The goal is to understand what is driving spikes in your blood sugar (not someone else’s) and plan accordingly. If you haven’t had HbA1c and related markers tested lately, EverlyWell offers at home blood sugar test kits.
But I digress, back to the blog.
- Glucose – the universal fuel source
- What is HbA1c?
- Why does elevated blood sugar cause inflammation?
- Blood sugar after a meal vs. Chronically high blood sugar
- My blood sugar numbers (HbA1c, Glucose, Insulin, and More)
- Is it all in my genes? The genetics of blood sugar
- Tips for keeping blood sugar under control
- Supplements to lower blood sugar
- Closing thoughts
Glucose – the universal fuel source
Blood sugar basically means blood glucose.
When we eat carbohydrates, the body breaks down the food into glucose, a simple sugar every cell in the body can use for energy. Insulin is the hormone the body then uses to get glucose into cells, or into the “bank” as glycogen where it is stored for later use. That’s right, since glucose is vital to life, we evolved to store it for a rainy day. The glucose storage bank comes in layers, with the first storage option being the liver and muscle tissue. Glucose stored in the liver or in the muscles is banked as glycogen, which is essentially a large strand of glucose molecules bound together. When we lift weights, or go for a run, the body draws down stored glycogen in the muscles and we become more “insulin sensitive.”
In an ideal world, every one of us would be perfectly insulin sensitive and use most all of the glucose we consume.
However, in today’s high sugar world, not all of us do such a great job of effectively using the glucose we eat. In some cases, especially in people who are at a genetic disadvantage in clearing and using glucose, excess glucose is stored as fat, or it remains elevated in the blood which leads to a cycle of inflammation.2 The idea here is that the body can only store so much glucose as glycogen. When the liver and muscles are “full” of stored glycogen, a process known as “de novo lipogenesis” allows the body to convert the excess glucose to triglyceride fat and store it in fat tissue.3 The first layer glucose storage organs have limits on glycogen, but there is no limit to the fat that a person will store.
This is why people who have elevated blood sugar tend also to have high triglycerides, and why I included my historical triglyceride data alongside the more traditional diabetes metrics below.
What is HbA1c?
HbA1c, or hemoglobin A1c, tests measure your average blood sugar level over the past 2-3 months. Hemoglobin is a protein found in red blood cells. Glucose in the blood “glycates,” or binds to these hemoglobin proteins. So, the more glucose in the blood, the more red blood cells bind to the blood sugar, which then gives us the ability to measure blood sugar levels over time. The 2-3 months of blood sugar data we get from HbA1c tests correlates to the average life cycle of a red blood cell, which is about 3 months.
Startups like EverlyWell allow consumers to measure their blood glucose and HbA1c levels from the comfort of their own home.
HbA1c tests are most often used to gauge the risk of developing diabetes, but HbA1c numbers have also been linked to neurological health by neurologists like Dr. David Perlmutter of Grain Brain fame. Dr. Perlmutter has published blogs analyzing data tending to show that the size of our brains actually shrink as HbA1c levels climb. And here’s the rub: HbA1c levels thought to be “normal,” even some of the results from my old labs I share below, register in a range associated with some degree of cognitive decline.4
Dr. Perlmutter’s work has motivated me to move my HbA1c number down below where it currently sits at between 5.1 – 5.4. My target is a sub 5.0 HbA1c.
Why does elevated blood sugar cause inflammation?
Metabolically, this is an insanely complex issue, but I have come to understand it as follows: the body wants us to use glucose, it’s central to life and universally recognized at the cellular level as fuel.
However, like everything else in the body, it has its place, and that place is inside the cell. The immune system knows this and goes on alert when glucose hangs around in the blood for too long. When blood glucose levels stay high over long periods of time, the immune system is triggered, almost as if to say, “hey, you’re not supposed to be here, get out of here, get into the cell.” As a result of sensing an invader (not an antigen per se because antibodies aren’t released, but more of an immunogen), the immune system releases inflammatory cytokines in a looped cycle, that over time, cause tissue damage, leading to inflammation.5
Blood sugar and white blood cell activity
For a technical example, CD33 immune cells are a type of protective sheath for white blood cells. While the CD33 system is functioning and blood sugar levels are under control, white blood cells behave themselves. However, when glucose levels stay elevated, CD33 expression is reduced, the white blood cells go haywire, and the production of inflammatory proteins called cytokines are the result.6 Cytokines such as TNF-a cause damage to cells and increase levels of oxidative stress, which in turn damage fats, protein and even DNA.
Blood sugar, glycation and oxidative stress
Think back a minute to the glycation discussion above. The binding of sugar to the hemoglobin proteins in the blood also cause inflammation as “glycation end products” are produced. This throws off more oxidative stress, which leads to more damaged fats, proteins, etc. Glycation and the damage sugar can do when it binds to fats and proteins is one of the arguments nutrition scientists like Dr. Rhonda Patrick offer as the cause of heart disease. To simplify, sugar damages fats and those damaged fats get into lipoproteins where they wreak havoc at the artery wall. This is why meals that combine high fat and high sugar are particularly damaging, they oxidize the flood of fat making it effectively radioactive to our endothelial cells.
I’ve written previously about how oxidized phospholipids (plant fats) have been shown to bind preferentially to dangerous lipoproteins such as Lp(a), so the theory makes sense. The question is what level of glycation is damaging?
In sum, chronically elevated levels of sugar in the blood cause an inflammatory cascade in the body which is why it is worthwhile to study ways to keep our HbA1c and blood sugar spikes under control.
Blood sugar after a meal vs. Chronically high blood sugar
When is elevated blood sugars bad for us? Is it the chronically elevated numbers that are the true bad guys, or do the quick spikes after higher glycemic meals cause trouble as well?
Blood glucose levels after a meal are called postprandial levels. There is some evidence that the spikes in blood sugar after a meal may be an independent task factor for certain diseases, especially heart disease.7 This is kind of a scary proposition as most people have no idea what their post meal blood sugar data looks like. Longevity experts like Dr. Peter Attia have expressed preference for a two hour oral glucose tolerance test (OGTT) over HbA1c, presumably because of the importance of the post prandial period.
As such, the idea is to keep blood sugar under control over the course of weeks and months, but also to prevent major spikes during the day.
Ok, now on to my actual test results.
My blood sugar numbers (HbA1c, Glucose, Insulin, and More)
Ok, so let’s do a quick walk through of each metric. Of course, we have already covered HbA1c, so we will leave that out.
HOMA-IR – HOMA-IR, or the homeostasis model assessment-estimated insulin resistance, is a calculation clinicians use to measure insulin resistance. It is calculated by multiplying fasting plasma insulin by fasting plasma glucose, then dividing by the constant 22.5. When HOMA-IR is greater than 3.80, it is thought to be evidence of insulin resistance.
Glucose – This one is pretty straightforward. How much glucose is hanging around in the blood after going without food for at least 8 hours? Levels of between 70 and 100 mg/dl are considered normal, 100-125 mg/dl are believed to evidence of prediabetes.
GSP – Ok, here is where I hit a snag, and I think I have a SNP to pin it on as well. GSP stands for glycated serum protein, as the name suggests, it measures the amount of protein that has been glycated (bound to sugar) in the blood over the previous two weeks. Less than 200 umol/L is optimal, but I sit above that in the 230s.
I believe it is due to a diet that has traditionally not paid much attention to glycemic load (yes, I will main line mega doses of ice cream or cookies from time to time, at least in the past) as well as an unfavorable SNP in a gene that we see as regulating post prandial glucose levels, ADCY5. I am homozygous for the risk allele, and as a result, I may be seeing large spikes in blood sugar after meals that are quickly brought back to earth by other favorable pathways. However, as we have discussed above, the post prandial period is one in which damage can be done, so writing this post has me much more focused on my insulin sensitivity post meals.
However, I should point out that GSP as a metric is thought to be most relevant in cases of T2D, and in cases of elevated albumin, and my albumin numbers are low at 4.5.8
Insulin – again, fairly self explanatory. This test looks at the insulin in your blood, lower is better because it signifies your body doesn’t have to work as hard to get glucose in your cells. High fasting insulin is a sign of insulin resistance.
Triglycerides – call them sugar fat or energy fat, both are basically correct. For our purposes here, it’s important to reemphasize that the body converts glucose into triglyceride fat when it has stored as much glycogen as possible for a “rainy day.” Anything below 150 mg/dl is considered normal by most labs, and my TG have been as low as 66.
Is it all in my genes? The genetics of blood sugar
We touched on the ADCY5 gene, but how much of blood sugar metabolism is genetic? It is certainly top of mind when we categorize nutrition plan customers into their diet types.
For this part of the post I have brought in Aaron to run through my genetics, which definitely give us a clue as to why my blood sugar numbers generally look to be in good shape, ADCY5 SNPs notwithstanding.
Thanks John, on to the genetics of blood sugar, a topic we delve deep into in the custom nutrition plans. For starters, our scoring algorithm place John in the Mediterranean diet type category, which is marked by a higher tolerance for higher glycemic foods.
As you can imagine there are masses of proteins which modulate the glucose level in the body, and many of the genes which encode for these proteins have been shown to contain SNPs which influence T2D risk, circulating glucose and a whole host of other factors.
Simply put the answer to the first question is yes, for a whole host of key SNPs John carries no risk alleles, or is at worse a heterozygote. Let’s break that down a little and have a look at some of the individual effects.
MAP kinase-activating death domain protein (MADD) is an adaptor protein which interacts with another protein TNF-alpha receptor 1 to activate mitogen-activated protein kinase signaling within cells regulating controlled cell death. There is some interesting work which has linked a SNP in MADD with elevated blood glucose levels, by altering the conversion of pro-insulin to functional insulin. Although this effect is modulated is unknown as MADD has no known glucose related functions. The SNP is detailed in the table below along with my own genotype. As you can see, John does not carry any risk alleles so score one for him.
|rs ID||Risk allele||Non-risk allele||Risk effect||My genotype|
|rs7944584||T||A||Increased circulating glucose.||AA|
Alpha-2A adrenergic receptor (ADRA2A) has been shown to be involved in regulating circulating glucose levels and there is a proposed association with T2D (R, R), and the SNPs are detailed below. As you can see John is homozygous for the non-risk alleles. What’s interesting about this gene and the two SNPs is a complete lack of a mechanism linking the protein with changes in glucose levels, given the quite strong effects observed. There is some suggestion that the risk alleles lead to increased expression of the ADRA2A protein could increase T2D risk and that this may be something to target therapeutically, but this is the limit of current understanding. One other interesting finding is that while each SNP alone is important, carrying risk alleles for both together further increased T2D risk and levels of circulating glucose.
|rs ID||Risk allele||Non-risk allele||Risk effect||My genotype|
|rs553668||A||G||Increased risk of developing T2D||GG|
|rs10885122||T||G||Increased circulating blood glucose.||GG|
Adiponectin (AdipoQ) is a protein hormone which regulates pathways related to fat storage and metabolism. Secreted exclusively from fat cells AdipoQ modulates sugar and fat metabolism in the body by increasing insulin sensitivity and fatty acid breakdown, so as you can imagine low levels are associated with an increased T2D risk and increased circulating glucose levels. There is one SNP of interest which is detailed in the table below. But again as you can see John is homozygous for the non-risk allele so another potential reason why his blood sugar numbers are good. For this SNP the risk ‘C’ allele is associated with increased circulating glucose levels and an associated increased risk of developing T2D through alterations in AdipoQ activity (rather than expression). Importantly the authors didn’t discriminate between heterozygous and homozygous carriers of the risk allele, rather grouping everyone together.
|rs ID||Risk allele||Non-risk allele||Risk effect||My genotype|
|rs17366743||C||T||Increased circulating glucose and increased T2D risk.||TT|
Three important SNPs and for each one John sits square in the positive effect category, which goes some way to explain his good blood sugar scores. But there are some where the story isn’t quite as rosy.
Fat mass and obesity-associated protein (FTO) is probably one of the most well-known genes/proteins, as it is often termed the “obesity” gene and is widely investigated. However despite been so well known what FTO actually does to regulate body mass, and how SNPs alter this activity, remains unknown. One proposed method is that FTO regulates hunger and so SNPs may lead to increased eating even when full,9 whereas another mechanism proposes that FTO changes expression of another protein IRX3 which regulates fat metabolism, and may, therefore, impact on fat storage and glucose metabolism.10 So because of this unknown activity, we don’t place great emphasis on FTO in our analyses but show it here more because it’s so well known. There are many SNPs in FTO that are thought to impart an effect but the most well known is rs1121980 which is detailed below.
|rs ID||Risk allele||Non-risk allele||Risk effect||My genotype|
|rs1121980||A||G||Increased risk of gaining weight, and risk of associated disorders including T2D.||AG|
Looking good so far, but there is one SNP where John does have some issues. Adenylyl cyclase type 5 (ADCY5) converts ATP, the cells energy currency, into another molecule called cyclic adenosine monophosphate which in this case regulates the release of insulin from cells in the pancreas in response to elevated blood glucose. Two copies of the risk allele ‘A’ of the SNP rs11708067 detailed below are associated with a 50% reduction in expression of ADCY5 compared to heterozygotes (no data shown for non-risk homozygotes).11 This reduced expression is thought to lead to an impaired pro-insulin to insulin conversion meaning blood glucose levels remaining higher for longer.12 Together these effects have been linked with an increased risk of developing type 2 diabetes.13 So we have a mechanism and an effect what about John’s SNPs? Well as you can see in the table not quite as good for this gene. although John’s theory about ADCY5 and elevated GSP is just that a theory. There isn’t much to prove that connection as of now, hence the very low science grade.
|rs ID||Risk allele||Non-risk allele||Risk effect||My genotype|
|rs11708067||A||G||Increased circulating glucose and increased risk of developing T2D.||AA|
John’s Genetic Summary
This is an excellent case of why not to analyze your genes individually. If you look at ADCY5 alone you’d probably panic: well defined negative effects, being homozygous for the risk allele puts John in the worse possible place etc… But this isn’t borne out by his actual blood sugar numbers which are uniformly good (with the possible exception of the GSP number). But when you look at his sugar/carbohydrate-related genes as a whole you can maybe see an explanation as to why John’s blood sugars are consistently good. This can be seen in his nutrition report where he was scored into a higher carbohydrate category. This doesn’t mean he can go nuts and binge on sugar as even the best genes in the world won’t help with that, but it does mean that he can more readily deal with a higher carbohydrate intake which gives him more flexibility in other aspects of his diet.
Ok, thanks Aaron, I am now taking back the mic to go through some strategies for lowering blood sugar.
Tips for keeping blood sugar under control
Ok, so we’ve been in the weeds on the genetics of blood sugar metabolism and looked at some of my lab work. What are some practical tips for keeping blood sugar in check, both long term and immediately after a meal in the all important “post prandial” period?
Lift weights bro
You don’t have to be a meat head or a cross fit bro to benefit from training with weights. To the contrary, I have recently gotten back into lifting as a strategy for staying more insulin sensitive.
How does this work? I doubt anyone has actually read this post cover to cover, not even my Mom, but if you are one of the rare ones with the attention span to churn through the entirety of a mega post like this, I will bring your attention back to the idea of glycogen storage and de novo lipogenesis. The liver and muscle tissue are storage centers for glucose, but they can only take so much. Exercises like lifting weights cause the muscle to spend glycogen, which in turn allows the same muscle to mop up more glucose the next time you eat a meal. The process of lifting gives you the ability to get the glucose you eat into the cell where it belongs.14
Fasted run / workout prior to breakfast
Another line of studies tends to show that working out in a fasted state, prior to breakfast, increases the body’s ability to burn fat and makes us more insulin sensitive. My current pre-breakfast regimen is a few sprints on the treadmill followed by four different weights exercises isolating a body group (legs one day, chest another).
In this study, healthy young men were gorged with a high fat diet at 30% above normal caloric intake. All of the subjects became insulin resistant expect the group who worked out before breakfast.15
Another study found that as little as 7.5 – 20 minutes of high intensity interval training prior to breakfast improved blood glucose levels for as long as 3 days after the workouts.16
Generally speaking, the small intestine is the glucose absorption organ. When we eat pancakes, the refined grains are rapidly converted to sugar and the sugar gets into the blood direct from the small intestine. However, if our carbohydrate sources can make their way intact to the large intestine, as happens when we eat high fiber foods, that’s where all the magic happens. There we get fermentation and production of the short chain fatty acids that give us energy and protect the lining of the gut. Resistant starch is a type of carbohydrate that is not easily converted to glucose. As such, it survives the small intestine intact where it ferments in the large intestine. Due to the fact that they don’t easily break down into sugar, foods rich in resistant starch like green bananas, beans and oats are thought to help regulate blood sugar spikes.
We can even increase the resistant starch in foods like potatoes and white rice by allowing them to cool for several hours after cooking. Some blogs falsely claim that the process of then reheating these foods destroys the resistant starch, but this is not the case. Don’t trust me, take a look at this John’s Hopkins page on resistant starch which I found useful.
Post meal stroll
Ben Greenfield discussed a study on his blog which showed that walking, as opposed to standing, in the post prandial period lowered the rise in triglycerides seen in non diabetic men after eating. The idea is that going on a short walk after dinner improves the metabolic response, a benefit that was not seen by walking prior to the meal.17
Another study looked at blood glucose in response to exercise and found longer durations of movement after eating resulted in greater blood sugar control. One quote in particular stood out to me:
Exercise facilitates glucose transport without the presence of insulin, and more exercise contributes proportionately to a larger decrease.
Very well said. Exercise and movement helps get glucose in the cell without insulin. This is a “swing thought” I am using now whenever I eat, just a little bit of movement aids digestion and improves the glycemic response.
So, here we have a little bit of common sense – get out and take a walk after each meal, it helps regulate spikes in blood sugar in that tricky post prandial period.
Supplements to lower blood sugar
The obvious one that comes to mind for me is berberine, as it has been shown to perform just as well as the popular diabetes drug metformin in some studies. As I discuss in my blog post on micro dosing berberine, metformin has become all the rage in anti-aging circles as there is some evidence it helps stave off cancer. But many in the integrative world, Ben Greenfield being a notable voice, are concerned about diminished performance with long term use of metformin. Berberine seems to be a good alternative since it performs on par with metformin and has also shown promise in lowering LDL-C and other lipid markers.
Another supplement to look at for keeping blood sugar in check is garlic. Vegan cardiologist Joel Kahn is a fan of garlic as a heart healthy supplement and a meta analysis of studies published in 2017 found that garlic does have efficacy in lowering blood sugar in type 2 diabetics.18
In my experience, keeping blood sugar top of mind is beneficial. It blunts that voice in my head which tells me its fine to tear into a pint of ice cream or a bag of cookies. Now, of course I still get into the junk food drawer on occasion, but knowing the science of how spikes in blood sugar impact my health does help me reserve my sugar intake to the occasional treat.
I also believe there is benefit in using food preparation techniques to make foods like white rice, oats and potatoes lower on the glycemic scale and therefore healthier. As with any of the topics we touch on on the blog, the idea is not to fear glucose, but rather to learn how our bodies use it and make food choices that go with the metabolic flow, as opposed to against it.
There is a very real public health threat posed by diabetes and greater awareness of our own metabolic state, is I believe, a good thing.