High Blood Sugar, Even for a Short Period, Causes Atherosclerosis

This article is about how a single episode of high blood sugar can cause atherosclerosis. Two landmark studies validate that reasonable blood sugar control in people with diabetes prevents vascular problems.

In some people with diabetes, their HbA1C may always be normal, yet they still develop atherosclerosis. That can be frustrating to the patient, especially if they know that they worked hard to keep their sugars acceptable.

Glycosylated hemoglobin (HbA1C) is a measure of blood sugar from the past three months.

Transient high glucose causes persistent genetic changes and altered gene expression during subsequent normoglycemia investigated this phenomenon. The research was done using human cells. The result showed that transient rises in the blood sugar cause changes in the neural factor kappa beta (nf-Κβ). The epigenetic changes eventually lead to atherosclerosis formation even when the blood sugar becomes normal again.  Epigenetics are non-genetic influences on genes. Similar to an “on” and “off” switch. Here is a quote from the study.

In summary, the observations reported here show that transient hyperglycemia causes persistent atherogenic effects during subsequent normoglycemia by inducing long-lasting changes in chromatin remodeling, recruitment of the histone  methyltransferase Set7, and increased H3K4 monomethylation in the proximal NF-B promoter, leading to increased  expression of p65, MCP-1, and VCAM-1. Together, these results provide a molecular basis for understanding some of the variation in risk for diabetic complications that is not explained by HbA1c.

Nucleosome_1KX5_2.png
DNA associates with histone from chromatin

The Diabetes Control and Complications Trial

The findings above are consistent with the results of the landmark DCCT and EDIC trials. In the Diabetes Control and Complications Trial (DCCT), a study group of Type 1 diabetic patients (juvenile-onset diabetes) had intensive control of the blood sugar with insulin therapy. A lower HbA1C reflected the lower blood sugar. The other group, which is the control,  received the standard of care (less aggressive), and their HbA1C is higher than the study group.

After 6.5 years, the intensive group had lesser diabetic vascular complications in the eyes, kidneys, nerves, and cardiovascular system compared to the control group. These significant findings led to changes in the standard of care for all patients with Type 1 diabetes.

The Epidemiology of Diabetes Interventions and Complications Study

Twenty years later, both DCCT trial groups were reevaluated as part of the Epidemiology of Diabetes Interventions and Complications Study (EDIC).

The intensive group in the DCCT studies continued to lower diabetic complications and cardiovascular deaths. It is noteworthy that after the initial DCCT research, both study and control groups went back to their doctors, and their HbA1C levels had similar levels.

This long-term benefit of intensive blood sugar control in Type 1 diabetics is termed “metabolic memory.” High blood sugar on atherosclerosis formation also applies even to non-diabetics, pre-diabetics, and Type 2 diabetics.

Next time, when you look at that pile of leftover Halloween candies, try to recall this article.

Related Reading:

  1. I’m only Pre-Diabetic, So I’m Still OK, right?
  2. The Magical Endothelium
  3. Diabetes Destroy Arteries

  4. Are You Skipping Breakfast?
  5. The Difference between Intermittent Fasting and Starvation
  6. The Two Minute Warning
  7. The Metabolic Syndrome
  8. Diseases Associated with the Metabolic Syndrome
  9. The Deadliest Diseases Associated with Metabolic Syndrome
  10. The Story of KAATSU. The Incredible Technique for Muscle Toning and Hypertrophy

References:

  1. El-Osta et al., Transient high glucose causes persistent epigenetic changes and altered gene expression during subsequent normoglycemia. J Exp Med. 2008 Sep 29;205(10):2409-17. doi: 10.1084/jem.20081188. Epub 2008 Sep 22.
  2. Nathan DM; DCCT/EDIC Research Group. The diabetes control and complications trial/epidemiology of diabetes interventions and complications study at 30 years: an overview. Diabetes Care. 2014;37(1):9–16. doi:10.2337/dc13-2112

Image Credit:

Histone By Zephyris at the English language Wikipedia, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=6998210

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