Digging Deeper: How Hyperglycemia Works

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One of the areas of the body most affected by hyperglycemia are the blood vessels within the eye. This image was taken with the Joslin Vision Network.

Educators tell their patients that hyperglycemia or high blood glucose wreaks havoc with just about every organ and tissue in the body as a way of explaining why keeping A1C close to target is so important. But we rarely go into depth about why this happens. Today’s blog pulls back the curtain a bit to discuss one of the causes of hyperglycemic-induced cellular damage.

Vascular dysfunction is one of the precursors of cardiac disease as well as being responsible for loss of lower limb functionality. Persistent, long-duration hyperglycemia changes the structure (producing inflammation and enlargement) of the cells that deliver oxygen and nutrients to the body. It can affect proteins, lipids and cellular DNA and RNA. DNA and RNA are responsible for cell reproduction and damage to their structure can affect future cell generations. One of the causes of this diabetes-induced vascular decay is excessive amounts of reactive oxygen species (ROS) generated by hyperglycemia.

Reactive oxygen species (ROS) are oxygen containing, unstable molecules. Due to their highly volatile form, they are prone to interact with other unstable molecules. Most ROS are produced during normal cellular metabolism in the mitochondria, the hard-driving engine of the cell. ROS have an important role to play in cellular metabolism: they regulate how easy it is to compress the blood vessels. And the body has reserves of antioxidants that interact with them to render them harmless. However, the body’s ability to metabolize ROS is diminished when too many of them are released.

Hyperglycemia in diabetes increases ROS production in a number of ways. It fosters the binding of glucose to protein molecules, a reaction which also generates ROS.

ROS is also produced by the electron-transport chain in the mitochondria, part of the body’s energy-creation process. Elevated glucose levels activate the chain, increasing the quantity of ROS.

In addition, hyperglycemia stimulates production of NADPH oxidase, one of the non-protein components of the enzymes involved in cellular metabolism. Higher amounts of NADPH oxidase are associated with a higher ROS concentration.

So excessive ROS is bad news. But there may be some hope on the horizon. Researchers are looking at an antidepressant drug called Paroxetine® as a possible treatment for vascular damage caused by diabetes. In addition to its antidepressant effects, recent studies have found that arteries in rats with diabetes were spared the consequences of hyperglycemia while taking the drug.

But whether Paroxetine® turns out to be a wonder drug or not, keeping your glucose level in good control will also go a long way towards reducing ROS.

2 Responses to Digging Deeper: How Hyperglycemia Works

  1. This is an interesting article describing how high sugar leads to diabetes complications. Is there any data on how high the sugars need to be before this starts and if the degree of occurrence is related to either the height or duration of the sugars. Many people with Diabetes who are trying to balance the benefits of tight control against the risk of hypoglycemia are wondering how low should they go. To what lengths should they avoid postprandial hyperglycemia and what peaks are acceptable? Is checking sugar 2 hours after eating adequate if their sugar peaks earlier and is the peak related to complications?

    • From what we know, the higher the A1C the greater the risk of complications. A1C is composed of both the duration and the degree of glucose excursion, so both of these elements are important is determining risk of complications. Hypoglycemia is problematic from both a health and societal perspective, therefore keeping blood glucose above at minimum 70mg/dl is important.

      The American Diabetes Association and Joslin recommend that post-prandial numbers not exceed 180mg/dl at 2 hours in general. Patients who are pregnant should be checking at 1 hour postprandially. To answer your question about when to check, 2 hours is usual, unless you take mealtime insulin or eat high fat meals. With high fat meals peak blood glucose rise is often three to four hours later.

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