HDL Cholesterol Relates to Insulin Resistance, and That's the Heart Disease Engine

April 24, 2022

HDL Cholesterol Relates to Insulin Resistance, and THAT's the Heart Disease Engine

We have known since 1977 that it's low HDLs that are the real risk of coronary artery disease. What we didn't realize back in the 1970-90's was the dimension of insulin resistance overlaid on HDLs. For folks with insulin sensitivity, higher LDLs have virtually no risk at all. It's the binding of LDLs to the vessel wall, their subsequent oxidation that then drives them to be gobbled up by macrophages that deposit the lipid pool in the artery. And that process is driven by insulin resistance.

Each of us has about 1000 LDL particles per cell in our body. Per cell. There are a lot of LDLs. Their job is to deliver cholesterol from the liver to cells to help make membranes. HDLs are much smaller, and there are 10 of them for every LDL, but they never get sticky. Their job is to take leftover cholesterol individual cells don't need and take it back to the liver. They don't have the APOB molecule on their surface, so they can't stick to the vessel wall. It's sticky LDLs that stick to the vessel wall. How do they get sticky?

Ah! That's the issue we need to understand. Stickiness comes about because of insulin resistance and subsequently higher blood glucose. Any given LDL particle becomes more likely to be bound to proteoglycans in the intimal space when it is enriched with the apolipoprotein ApoC III—a process that occurs during states of insulin resistance.

Then there is the added dimension of ceramides, the waxy fats that make our internal organelle membranes much more rigid. We develop with when we eat too much sugar and saturated fat. With too many ceramides in our membranes, they get too stiff and can't export HDLs. Ceramides also point straight at fructose.

And how many of us are insulin resistant? That's the million-dollar question. If you take the most recent guidelines about waist circumference, A1c, BMI etc, you will find that only 12% of Americans are metabolically healthy. The rest have some degree of insulin resistance. And they are making arterial plaque. Using the most recent guidelines, metabolic health was defined as having optimal levels of waist circumference (WC <40/34.5  in for men/women), glucose (fasting glucose <100 mg/dL and hemoglobin A1c <5.7%), blood pressure (systolic <120 and diastolic <80 mmHg), triglycerides (<150 mg/dL), and high-density lipoprotein cholesterol (≥40/50 mg/dL for men/women), and not taking any related medication.

Obsessing about total cholesterol misses the point, almost completely. Our guidelines for administering statins are off the mark badly. What we want is healthy arteries. And the proper guideline is Insulin < 5, HDL, 40/50 (men/women), BP below 120/80.

And that brings up back to our HDLs. HDLs are the garbage trucks of our bodies, carrying leftover cholesterol back from cells that don't need it. Healthy cells have healthy peroxisomes and healthy levels of plasmalogens in their internal membranes. If you eat too much fructose, your make more ceramides, the waxy fats that make membranes more rigid. Your mitochondria and peroxisomes get damaged and you have trouble exporting HDLs, proportionately to your falling HDLs and rising ceramides. Low HDLs mean metabolically damaged cells with insulin resistance. High ceramides mean lower plasmalogens. So, if you think there is a correlation between insulin resistance and Alzheimer's, you got it right.


You can reverse all that. Sugar is such a powerful engine to drive trouble, first and foremost, you must get sugar consumption down. Your waist to hip ratio, your HDL, your insulin, and your blood pressure will all reveal to you your metabolic health. Key to all your efforts is losing weight. There you have it. It's not total cholesterol, it's insulin resistance. Weight loss and control of body size is our metabolic story.

www.What will Work for me. I've been on a three-month streak of wearing a continuous glucose monitor. I'm humbled by what I have learned. Yesterday, in the middle of a 16-mile bike ride without having eaten any lunch, I felt a bit washed out and tired. There was a Clif Bar, chocolate, in my bike bag, leftover from last fall. 6 months old. Frozen in our garage all winter. Wow, it looked good. 250 calories, 17 grams added sugars. My glucose by my monitor was 77. Down went the Clif Bar. 15 minutes later, glucose 145. Whew. It dropped back down pretty fast because we were biking. But for half an hour there, I was glycating my LDLs. That's what is happening to all of us. No more Clif bars for me.

References: JAHA, Am J of Med, NLM, ATVB, Metabolic Syndrome and Related Disorders,

Pop Quiz

1. What is the job of your HDLs?                                  Answer: Picking up excess cholesterol and take it back to the liver.   (That means your cells are healthy, have enough cholesterol and the internal membranes are robust and replete with plasmalogens, low on ceramides.)

2. A healthy cell with healthy membranes can be demonstrated by what?                               Answer: the ability to "efflux", export, cholesterol, so HDLs have to go up.

3. Insulin resistance can be measured and defined by insulin level. T or F.                                Answer: True. You want a level below 5. Average American is 12. "Normal range", or what is seen in the population is 2-29.

4. What percentage of Americans are metabolically healthy?                                   Answer: 12%

5. Slender women with a total cholesterol of 230 and an HDL of 70 should be on statins. T or F.                      Answer: False. That's why our cholesterol guidelines are broken.

Column Written by Dr John Whitcomb, MD, Brookfield Longevity, Brookfield, WI www.LiveLongMD.com. 262-784-5300