This article presents a study that showed that high blood sugar could change macrophages and cause atherosclerosis.
The study was published in the journal Circulation in Sept 2021. The authors are from Oxford, UK; the Karolinska Institute in Sweden, the Radboud University in the Netherlands; and the Life and Medical Sciences Institute (LIMES) at the University of Bonn, Germany.
In the study, macrophages, a type of white blood cell from mice, were exposed to normal levels of blood sugar (5 mmol/L, or 90 mg/dl) and high blood sugar (20 mmol/L, or 360 mg/dl) for 1, 2, 4, or 7 days.
To put into context, a blood sugar done anytime if more than 200 mg/dl indicates diabetes.
A fasting blood sugar of more than 7 mmol/L, 126mg/dl or above, is also a sign of diabetes.
High blood sugar changes RNA expression
They found that when macrophages were exposed to high blood sugar, their RNA expression was changed to become more pro-inflammatory and have a higher tendency to promote atherosclerosis.
Pro-atherosclerotic properties persisted
When they put the altered macrophages in solutions with normal blood sugar levels, the RNA expression persisted, indicating “hyperglycemia-induced trained immunity.”
The study pinpointed the transcription factor RUNX1 to cause metabolic memory.
The RNA changes caused atherosclerosis
To confirm whether the pro-atherosclerotic RNA changes in the macrophages can form atherosclerosis, they transplanted the altered macrophages in non-diabetic mice.
The result is atherosclerosis formation in the aorta of the non-diabetic mice. The aorta is the largest artery in the body and comes directly from the heart.
Significance
According to the authors, the results may explain why people with adequate diabetes control still develop cardiovascular disease later in life. It could be that during the early part of diabetes, the blood sugar may have been very high and changed the immune system to become pro-atherogenic.
In that regard, they proposed further research to target RUNX1 to prevent atherosclerosis in those with diabetes.
Comment
The concept of metabolic memory has been around and debated for years, but this research is the first to demonstrate the changes in the immune system.
I want to find out if anything can be done using lifestyle changes, either diet or physical activity, that can reverse metabolic memory. So far, I have found the use of natural products in one review article that can potentially interfere with the targets of trained immunity.
In the meantime, the best way to prevent or slow atherosclerosis is to avoid spikes in blood sugar, which can be done by regularly checking blood sugar and being compliant with diabetes medications with a healthy low-carb diet and exercise.
If a person does not have diabetes (yet), avoid after-meal sugar spikes, or post-prandial hyperglycemia can induce atherosclerosis.
After meal blood sugar spikes as a cause of vascular failure
Here are the ways to prevent after-meal hyperglycemia.
- Veggies Meat Carbohydrate Sequence Prevents After Meal Sugar Spike
- Walk After Meals to Prevent Sky High Blood Sugars
- A Healthy Lifestyle is as effective as Voglibose and Nateglinide in Lowering 10-year Cardiac Mortality
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Reference:
Edgar L et al. Hyperglycemia Induces Trained Immunity in Macrophages and Their Precursors and Promotes Atherosclerosis. Circulation. 2021 Sep 21;144(12):961-982. doi: 10.1161/CIRCULATIONAHA.120.046464. Epub 2021 Jul 13. PMID: 34255973; PMCID: PMC8448412.
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