Dear Mark: Why Hyperglycemia Is Bad and Those Stubborn Final Pounds

SugarToday we’ve got a fairly short one with just two questions and answers. First, I tackle a big topic: the specific effects of hyperglycemia on the body. That hyperglycemia is bad for us is implicit, but it’s important to understand why it’s so dangerous. Today, I give a brief but detailed overview of the negative effects of chronic high blood sugar. Next, Carrie gives a female reader a few thoughts on how to (and whether to) lose the last few stubborn pounds. Her unique advice involves sprinting, reframing, rethinking, and restating.

Hi Mark,

I know it’s too much to ask, but having browsed the internet and your site thoroughly about it, I just cannot get a satisfying answer to how (biochemically) high blood sugar does its damage to the body. How is it toxic? I know about AGEs and how it damages blood vessels, but even in scientific articles there’s no – again satisfying – answer as to HOW? How is coma the body’s response to too much high blood sugar? How it gives you migraines? How it reduces healing abilities? etc, etc, etc.

Maybe I’m not good at searching this or I don’t have access to the proper medical journals, but I was just wondering if you could enlighten us about this topic in a deeper way.

Thanks and regards from Colombia.


Great question.

Most cell types, when faced with systemic hyperglycemia, 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 (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. 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; smaller cells have lower functionality. Mitochondrial ROS (often caused by hyperglycemia) also reduce the insulin secreted by the cells, 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, causes the shrinking of neurons and the inducement of spatial memory loss, and induces neuronal oxidative stress. It also impairs the production of nitric oxide, 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 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, nitric oxide release is inhibited and FMD reduced. A decreased FMD strongly predicts cardiovascular events (PDF) and may cause atherosclerosis (PDF).

Thanks again for the question. While saying “Chronic hyperglycemia is bad for you” is true enough, it’s more helpful to know exactly why it’s bad.

Now, let’s hear from Carrie:

My husband and I have been eating Primal for about 6 months now and he has lost 50 pounds. Although I feel much better and have more energy, I hit a plateau after 3 months and have only lost 20 pounds. My husband has reached his ideal weight and I still would like to lose another 20 pounds. We are living a primal lifestyle and exercising regularly and I am wondering if you can offer any advice around how I can lose the last 20 pounds? Is there anything else I can do?

One of the first things I suggest to women who have hit a plateau is to incorporate sprints into their workouts: 2 times a week, running full speed in intervals or 6-10 sprints for 30 seconds with a minute of rest in between. Cycling sprints work, too. You can also run up hills instead of on flat ground. Doing it on the beach will be harder and you’ll go slower but hit your butt and thighs differently than on flat ground. Women are naturally better at burning fat in response to exercise, so sprints are an ideal, time-efficient way to do that. It wasn’t until I started incorporating sprints that I truly reached my ideal body composition.

If you are over 40 you should have your hormone levels checked to make sure you are not perimenopausal and that your hormones are balanced. Where are you carrying the excess weight? If it is around your belly, this could be a sign that you need hormonal balancing. Visit a medical professional that specializes in women’s health. I myself had the best results with low doses of hormone replacements, but more “natural” methods are also worth a shot and can be exhausted beforehand.

Once you have addressed both of these “physical” issues, ask yourself some important questions.

How can you have a healthy relationship with where your body is now? Figure out what it would take to make peace with your body. Is it holding you back from doing anything, physically, that you’d like to be doing? Does it truly reduce your quality of life in a meaningful, tangible way? Are you healthy, happy (when not thinking about your last few pounds), and generally living life in a vibrant manner? Maybe you are content and just haven’t realized it yet.

What if this is your body’s ideal weight? Remember that women naturally carry more body fat and distribute it differently than men. We make babies with our body fat, and the hips, butt, and thighs are supposed to have a bit more bounce than the rest of the body. It’s totally normal to have it there and a sign that you’re healthy!

Personally, I also like to set intentions around my goals – things and thoughts and abstractions I would like to create and make manifest. They somehow seem more real when I do this. And if they seem real enough that I start acting like they are, aren’t they real? For all intents and purposes, I’d say that they are.

Here’s an example:

“I am making healthy conscious food choices, effortlessly reaching my ideal lean(er) bodyweight, and loving my healthy, limber, strong, fit body.”

I say these things to myself with powerful intention as I’m saying them, almost like a meditation where the focus is on the breath itself. Only here, you’re focusing on the words – how they sound, what they mean, what they mean to you. This isn’t a woo-woo, mystical attempt to “create your own reality.” It’s just a powerful way to establish and ingrain resolve.

Write your intentions down. Say them out loud. Be very specific and clear. It might feel funny saying/writing these usually abstract thoughts that only play out in your head, but it makes them real and attainable. And oftentimes you’ll find that the things you thought you were worried about aren’t even worth it. That you’re happy after all!

Good luck and don’t hesitate to write back with more questions.

That’s it for this week, folks. Thanks for reading and keep the questions coming!

About the Author

Mark Sisson is the founder of Mark’s Daily Apple, godfather to the Primal food and lifestyle movement, and the New York Times bestselling author of The Keto Reset Diet. His latest book is Keto for Life, where he discusses how he combines the keto diet with a Primal lifestyle for optimal health and longevity. Mark is the author of numerous other books as well, including The Primal Blueprint, which was credited with turbocharging the growth of the primal/paleo movement back in 2009. After spending more than three decades educating folks on why food is the key component to achieving and maintaining optimal wellness, Mark launched Primal Kitchen, a real-food company that creates flavorful and delicious kitchen staples crafted with premium ingredients like avocado oil. With over 70 condiments, sauces, oils, and dressings in their lineup, Primal Kitchen makes it easy to prep mouthwatering meals that fit into your lifestyle.

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