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The Definitive Guide to Blood Sugar

What’s sweet, red, sticky, and deadly?

Blood sugar. (I’m sure there are other things that qualify, but most of them contain sugar of some sort so I’m sticking with it.)

Too little of it, and you go into hypoglycemic shock. That can kill you if left untreated.

Too much of it, and you waste away slowly. Chronic overexposure to sugar will degenerate your tissues and organs.

Yes, getting blood sugar right is extremely important. Vital, even.

Today, I’m going to explain how and why we measure blood sugar, what the numbers mean, why we need to control it, and how to maintain that control.

First, blood sugar is tightly controlled in the body. The average person has between 4-7 grams of sugar circulating throughout their body in a fasted state—that’s around a teaspoon’s worth. How does that work when the average person consumes dozens of teaspoons in a single day?

Again, it’s tightly controlled.

The majority of the sugar “in our system” is quickly whisked away for safekeeping, burning, or conversion. We store as much of it as glycogen in our liver and muscle as we can. We burn some for energy. And, if there’s any left over, we can convert it to fat in the liver.

But sometimes, sugar lingers. In diabetics, for example, blood sugar runs higher than normal. That’s actually how you identify and diagnose a person with diabetes: they have elevated blood sugar.

There are several ways to measure blood sugar.

What’s Normal?

According to the American Diabetes Association, any fasting blood sugar (FBG) under 100 mg/dl is completely normal. It’s safe. It’s fine. Don’t worry, just keep eating your regular diet, and did you get a chance to try the donuts in the waiting room? They only start to worry at 110-125 (pre-diabetic) and above 125 (diabetic).

This may be unwise. Healthy people subjected to continuous glucose monitoring have much lower average blood glucose—89 mg/dl [2]. A 2008 study [3] found that people with a FBG of 95-99—still “normal”—were 2.33 times more likely to develop diabetes in the future than people on the low-normal end of the scale.

As for postprandial blood glucose, the ADA likes anything under 140 mg/dl.

How about HbA1c? A “normal” HbA1c is anything under 5.7. And 6.0 is diabetic. That’s what the reference ranges, which mostly focuses on diabetes. What does the research say? In this study [4], under 5 was best for heart disease. In this study [4], anything over 4.6 was associated with an increased risk of heart disease.

That 5.7 HbA1c isn’t looking so great.

What’s “normal” also depends on your baseline state.

Healthy FBG depends on your BMI. At higher FBG levels, higher BMIs are protective. A recent study [5] showed that optimal fasting blood glucose for mortality gradually increased with bodyweight. Low-normal BMIs had the lowest mortality at normal FBG (under 100), moderately overweight BMIs had the lowest mortality at somewhat impaired FBG (100-125), and the highest BMIs had the lowest mortality at diabetic FBG levels (over 125).

If you’re very low-carb, postprandial blood glucose will be elevated after a meal containing carbs. This is because very low-carb, high-fat diets produce physiological insulin resistance [6] to preserve what little glucose you have for the tissues that depend on it, like certain parts of the brain. The more resistant you are to insulin, the higher your blood glucose response to dietary glucose.

HbA1c depends on a static red blood cell lifespan. A1c seeks to establish the average level of blood sugar [1] circulating through your body over the red blood cell’s life cycle, rather than track blood sugar numbers that rapidly fluctuate through the day, week, and month. If we know how long a red blood cell lives, we have an accurate measurement of chronic blood sugar levels. The clinical consensus assumes the lifespan is three months. Is it?

Not always. The life cycle of an actual red blood cell differs between and even within individuals [7], and it’s enough to throw off the results by as much as 15 mg/dl [8].

Ironically, people with healthy blood sugar levels might have inflated HbA1c levels. One study [9] found that folks with normal blood sugar had red blood cells that lived up to 146 days, and RBCs in folks with high blood sugar had life cycles as low as 81 days. For every 1% rise in blood sugar, red blood cell lifespan fell by 6.9 days. In those with better blood sugar control, RBCs lived longer and thus had more time to accumulate sugar and give a bad HbA1c reading. In people with poorer blood sugar control, red blood cells live shorter lives and have less time to accumulate sugar, potentially giving them “better” HbA1c numbers.

Anemia can inflate HbA1c. Anemia depresses the production of red blood cells. If you have fewer red blood cells in circulation, the ones you do have accumulate more sugar since there are fewer cells “competing” for it. Anemia isn’t anything to sniff at, but it does throw off HbA1c.

Hyperglycemia and Health

Okay, is hyperglycemia actually a problem? I’ve heard some suggest that hyperglycemia is a marker of poor metabolic health, but it’s not actually causing anything bad itself. I agree with the first part—hyperglycemia indicates poor metabolic health and is a risk factor for things like heart disease and early mortality [1]—but not the last. Indeed, hyperglycemia is both an effect and direct cause of multiple health issues.

Most cell types, when faced with systemic hyperglycemia [10], have mechanisms in place to regulate the passage of glucose through their membranes. They can avoid hyperglycemic toxicity by keeping excess sugar out. Other cell types, namely pancreatic beta-cells, neurons, and the cells lining the blood and lymphatic vessels, do not have these mechanisms. In the presence of high blood sugar, they’re unable to keep excess sugar out. It’s to these three types of cells that hyperglycemia is especially dangerous.

Unfortunately, these are all pretty important cells.

What happens when too much glucose makes it into one of these cells?

Reactive oxygen species [11] (ROS) generation is a normal byproduct of glucose metabolism by the cell’s mitochondria. If the stream of glucose into the cell is unregulated, bad things begin to happen: excessive ROS, a mediator of increased oxidative stress; depletion of glutathione, the prime antioxidant in our bodies; advanced glycation endproduct (AGE) formation; and activation of protein kinase C, a family of enzymes involved in many diabetes-related complications [12]. It’s messy stuff.

How does this play out in the specific cell types that are susceptible, and what does it mean for you?

Pancreatic beta-cells: These cells are responsible for secreting insulin in response to blood glucose. They essentially are the first line of defense against hyperglycemia. If maintained for too long or too often, hyperglycemia inhibits the ability of pancreatic beta-cells to do their job. For instance, type 2 diabetics have reduced pancreatic beta-cell mass [13]; smaller cells have lower functionality. Mitochondrial ROS (often caused by hyperglycemia) also reduce the insulin secreted by the cells [14], thereby reducing their ability to deal with the hyperglycemia and compounding the initial problem.

Neurons: The brain’s unique affinity for glucose makes its glucose receptor-laden neuronal cells susceptible to hyperglycemia. It simply soaks up glucose, and if there’s excessive amounts floating around, problems arise. Hyperglycemia is consistently linked to cognitive impairment [15], causes the shrinking of neurons and the inducement of spatial memory loss [16], and induces neuronal oxidative stress [17]. It also impairs the production of nitric oxide [18], which is involved in the hippocampus’ regulation of food intake.

Endothelial cells: Flow mediated dilation (FMD) is the measure of a blood vessels’ ability to dilate [19] in response to increased flow demands. Under normal conditions, the endothelial cells release nitric oxide, a vasodilator, in response to increased shear stress. Under hyperglycemic conditions [20], nitric oxide release is inhibited and FMD reduced. A decreased FMD means your endothelial function is compromised and may cause atherosclerosis (PDF [21]).

Electrolyte depletion: Persistent hyperglycemia can cause the body to shed glucose by urinating it out. In doing so, you also end up shedding electrolytes.

Okay, okay. Controlling your blood sugar is important. Avoiding hyperglycemia is one of the most important things you can do for your health and longevity. How do I do it?

How to Improve Blood Sugar

When I take a bird’s eye view of all this, the best glucose-lowering exercise is the one you’ll do on a regular basis. It’s all good.

If you’re low-carb or keto and need to pass a glucose tolerance test, eat 150-250 grams of carbs per day in the week leading up to the test. This will give you a chance to shift back into sugar-burning mode.

Long Term Blood Glucose Control?

Consistency is everything. Consistently doing all the little tips and hacks we just went over that lower blood sugar in the moment will lead to long term blood sugar control. If you take vinegar before and walk after every single meal for the rest of your life, you will control postprandial blood sugar. If you avoid excess carbohydrates, you will exert long-term control over blood sugar levels. If you exercise 3-4 times a week and get plenty of low-level activity, you’ll be much less likely to have hyperglycemia.

Thus concludes the Definitive Guide to Blood Sugar. If you have any questions or comments, drop them in down below. Thanks for reading!

References:

Adams RJ, Appleton SL, Hill CL, et al. Independent association of HbA(1c) and incident cardiovascular disease in people without diabetes [4]. Obesity (Silver Spring). 2009;17(3):559-63.

Lee EY, Lee YH, Yi SW, Shin SA, Yi JJ. BMI and All-Cause Mortality in Normoglycemia, Impaired Fasting Glucose, Newly Diagnosed Diabetes, and Prevalent Diabetes: A Cohort Study [5]. Diabetes Care. 2017;40(8):1026-1033.

Virtue MA, Furne JK, Nuttall FQ, Levitt MD. Relationship between GHb concentration and erythrocyte survival determined from breath carbon monoxide concentration [31]. Diabetes Care. 2004;27(4):931-5.

Das evcimen N, King GL. The role of protein kinase C activation and the vascular complications of diabetes [12]. Pharmacol Res. 2007;55(6):498-510.

Guillausseau PJ, Meas T, Virally M, Laloi-michelin M, Médeau V, Kevorkian JP. Abnormalities in insulin secretion in type 2 diabetes mellitus [13]. Diabetes Metab. 2008;34 Suppl 2:S43-8.

Sakai K, Matsumoto K, Nishikawa T, et al. Mitochondrial reactive oxygen species reduce insulin secretion by pancreatic beta-cells [14]. Biochem Biophys Res Commun. 2003;300(1):216-22.

Malone JI, Hanna S, Saporta S, et al. Hyperglycemia not hypoglycemia alters neuronal dendrites and impairs spatial memory [16]. Pediatr Diabetes. 2008;9(6):531-9.

Kawano H, Motoyama T, Hirashima O, et al. Hyperglycemia rapidly suppresses flow-mediated endothelium-dependent vasodilation of brachial artery [20]. J Am Coll Cardiol. 1999;34(1):146-54.

Winding KM, Munch GW, Iepsen UW, Van hall G, Pedersen BK, Mortensen SP. The effect on glycaemic control of low-volume high-intensity interval training versus endurance training in individuals with type 2 diabetes [23]. Diabetes Obes Metab. 2018;20(5):1131-1139.

Rafiei H, Robinson E, Barry J, Jung ME, Little JP. Short-term exercise training reduces glycaemic variability and lowers circulating endothelial microparticles in overweight and obese women at elevated risk of type 2 diabetes [24]. Eur J Sport Sci. 2019;19(8):1140-1149.

Mcdonald JD, Chitchumroonchokchai C, Li J, et al. Replacing carbohydrate during a glucose challenge with the egg white portion or whole eggs protects against postprandial impairments in vascular endothelial function in prediabetic men by limiting increases in glycaemia and lipid peroxidation [25]. Br J Nutr. 2018;119(3):259-270.

Daza EJ, Wac K, Oppezzo M. Effects of Sleep Deprivation on Blood Glucose, Food Cravings, and Affect in a Non-Diabetic: An N-of-1 Randomized Pilot Study [26]. Healthcare (Basel). 2019;8(1)

Watanabe D, Kuranuki S, Sunto A, Matsumoto N, Nakamura T. Daily Yogurt Consumption Improves Glucose Metabolism and Insulin Sensitivity in Young Nondiabetic Japanese Subjects with Type-2 Diabetes Risk Alleles [28]. Nutrients. 2018;10(12)

Comerford KB, Pasin G. Emerging Evidence for the Importance of Dietary Protein Source on Glucoregulatory Markers and Type 2 Diabetes: Different Effects of Dairy, Meat, Fish, Egg, and Plant Protein Foods [29]. Nutrients. 2016;8(8)

Thondre PS. Food-based ingredients to modulate blood glucose [30]. Adv Food Nutr Res. 2013;70:181-227.