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Quick Summary tl;dr
A study of 28,024 followed for over 20 years showed the diabetes and insulin resistance are far stronger risk factors for coronary heart disease than LDL cholesterol.
Diabetes was associated with a 10.71-fold increased risk of coronary heart disease in women <55, and a 10.92 increased risk of coronary heart disease in women <65.
The risk associated with diabetes and insulin resistance even without diabetes was 4 – 8 times greater than the risk associated with LDL cholesterol.
When the researchers looked more closely at LDL-associated risk, they noticed no risk was associated with having more large fluffy LDL. The risk was due to small LDL. Those with insulin resistance have less large fluffy and more small LDL.
Just a few months ago, in January 2021, an important study was published in the journal JAMA Cardiology that demonstrated insulin resistance is the strongest risk factor for coronary heart disease (CHD). (Sagar B. Dugani, 2021)
Study Design
This study followed 28,024 women for a median time period of 21.4 years. During this time, 1,548 (5.5%) of the women developed CHD. The researcher collected data on over 50 clinical factors and biomarkers, so were able to determine what the strongest risk factors were for heart disease. The risk associated with each variable was reported as a Hazards Ratio (HR), which is the fold increase in risk associated with the presence of that variable as compared to when it is absent. For example, if women with high triglycerides were twice as likely to have CHD as women with lower triglycerides, the HR would be 2.
Diabetes and Insulin Resistance
Of the clinical parameters, diabetes was associated with the highest risk of CHD by far. For women <55, the HR of diabetes was 10.71. For women 55 - 65, the HR of diabetes was 10.92. In other words, having diabetes increased coronary heart disease risk by over 1000%!
Unsurprisingly, metabolic syndrome had the second strongest association with CHD. Metabolic syndrome is defined by the presence of at least three of the following: low HDL, high triglycerides, high blood pressure, large waist circumference, high fasting glucose or insulin. I said “unsurprisingly” because metabolic syndrome is a disease that itself is associated with insulin resistance and diabetes. For women <55, the HR of metabolic syndrome was 6.09.
Consistent with the clinical associations, a blood marker of insulin resistance - lipoprotein insulin resistance (LIPR) - was the strongest risk factor among the biomarkers for CHD. The HR associated with LIPR was 6.4 among women <55. And the associated remained even when the researchers adjusted for diabetes.
These data show that if you want to reduce your risk of heart disease, focus on improving insulin resistance. Probably the best way to do this is to eat a clean low-carb diet. Sleep and exercise as also important lifestyle factors.
Having diabetes increases coronary heart disease risk by over 1000%!
Cholesterol
Also unsurprisingly, HDL was negatively associated with CHD and triglycerides were positively associated with CHD. Simply put, you want high HDL and low triglycerides. Importantly, HDL and triglycerides were both stronger risk factors than LDL cholesterol, the so called “bad cholesterol.”
Here is a list of just some clinical variables and markers that were associated with a greater risk of heart disease than LDL: Being overweight or obese, smoking, diabetes, metabolic syndrome, high blood pressure, sedentary lifestyle, high triglycerides, low HDL, and any of four markers of inflammation (CRP, fibrinogen, ICAM-1, GlycA). In fact, the HR associated LDL cholesterol was just 1.38, about 1/8th the risk associated with diabetes.
What’s more, when the researchers examined the risk associated with the different LDL particle sizes, there was no association between big fluffy LDL particles and CHD. By contrast, small LDL particles were associated with CHD risk, HR = 2.25. This is an extremely important detail because when low-carb diets increase LDL, they do so specifically by increasing large LDL ( Norwitz et al, 2020), while often decreasing small LDL. Thus, even if overall LDL goes up on a low-carb diet you risk may not increase.
Having diabetes increases your risk of heart disease 8-times more than having high LDL.
Conclusion
There is a lot of debate about what “causes” heart disease and what we should treat to reduce cardiovascular risk. Conventional care for heart health focuses on lowering LDL cholesterol, while largely turning a blind eye towards insulin resistance. In America, a primary care physician is far more likely to order and LDL than a fasting insulin, not to mention a Kraft test, 2-hour insulin, HOMA-IR, or LIPR (other measures of insulin resistance).
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But these data show us insulin resistance is a far stronger risk factor for heart disease than LDL. What’s more, statins, the most common drug used to lower LDL cholesterol, can increase insulin resistance and diabetes risk. Take a moment for that to sink in... And, while a low-carb diet can increase LDL, it tends to specifically increase large LDL, which is not associated with increased risk.
These data, collected in 28,024 women over the course of decades, suggest the way we go about preventing coronary heart disease in this country is wrong. The medical algorithm is if LDL is greater than 190 mg/dL, go on a statin. Is that 190 mg/dL of big LDL? Small LDL? The question is rarely asked and the most effective means to improve insulin resistance, a low-carb diet, is often cast aside because as few as 20-30% of people who choose that lifestyle experience a rise in large LDL, increasing their total LDL.
It’s a radical idea, but what if we were to focus on the 10.71-fold increased risk associated with diabetes, rather than on the 1.38-fold increased risk associated with LDL (which is misguided anyway because it lacks the nuance of distinguishing among LDL particle sizes)? Just a thought.
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