How Does Hyperglycemia Cause Damage And What Can We Do To Avoid It?

I have read many research papers since my diagnosis seventeen years ago but until very recently I had never seen a research paper specifically addressing in detail the subject of how and why high blood glucose levels cause harm to our bodies. It seems to me that understanding that is basic to finding better ways to maintain long term diabetes health.

This report was published in the Warwick UK University News last month: New study sheds light on how blood vessel damage from high glucose concentrations unfolds. The underlying research study can be found here: Activation of the unfolded protein response in high glucose treated endothelialcells is mediated by methylglyoxal. 

The scientists were interested in discovering the effects of hyperglycemia on endothelial cells and how that contributed to the development of vascular complications of diabetes. They were also looking for methods to reduce those effects.

As I am not a biochemist I found the Warwick report analysis of the paper more understandable. This is the section I found particularly interesting:

Hyperglycemia is the condition in which an individual’s blood glucose is abnormally high and is commonly caused by diabetes.

The researchers confirmed that glucose metabolism in endothelial cells is increased in high concentrations of glucose. They showed for the first time that this occurs because an enzyme that metabolises glucose in these cells, called hexokinase-2 (HK2), degrades more slowly in high glucose concentration and thereby metabolises more glucose than normal. Increased glucose metabolism is the driver of metabolic dysfunction of endothelial cells in model hyperglycemia.

They were able to correct this effect using a novel dietary supplement previously developed by the research team called a glyoxalase 1 inducer or Glo1 inducer.

They also found that the HK2 effect was the major mechanism increasing formation of a reactive glucose-derived substance called methylglyoxal (MG), known to be increased in diabetes and linked to damage to blood cells, kidneys, retina and nerves in arms and legs in diabetes – so-called vascular complication of diabetes.

MG binds and modifies proteins, causing them to become misfolded. In this study the researchers identified 222 proteins susceptible to MG modification and this activates a protein quality surveillance system called the unfolded protein response, which removes damaged proteins. When the unfolded protein response is overworked with a high level of misfolded protein substrate it causes an inflammatory response and there is an increased risk of blood clot formation. These processes contribute to blood vessel damage involved in the development of vascular complication of diabetes.

My focus is slightly different. The scientists found a dietary supplement may help; to me that might be useful some time in the future but is much less important than this: “When the unfolded protein response is overworked with a high level of misfolded protein substrate it causes an inflammatory response and there is an increased risk of blood clot formation. These processes contribute to blood vessel damage involved in the development of vascular complication of diabetes.”

Over the years since I first began using Jennifer’s Test, Test, Test method to modify my menu I have slowly formed the opinion that maintaining peak post-prandial blood glucose levels as close to non-diabetic as I reasonably can is much more important than other tests such as A1c or fasting blood glucose.

I believe this research adds support to my ideas but I emphasise the following is purely my personal opinion as a long term type 2 diabetic.

• Our bodies have a natural ability to heal most wounds or damage with time.
• Short term blood glucose spikes above high normal (~8 mmol/l or 140 mg/dl) cause immediate damage. The higher the spike, or the longer it is maintained, the worse the damage. 
• I believe that damage can be repaired by our body given sufficient time but repeated frequent hyperglycemia can have a cumulative effect if the damage exceeds the body's ability to repair it in time.The body needs periods of normal blood glucose level to repair past harm. Constantly elevated blood glucose levels, even if only slightly above normal, impair the body's normal healing processes.

Put those thoughts together and I see a need to concentrate on two separate but allied blood glucose goals:

• I aim to maintain steady blood glucose levels as close as is reasonably possible to non-diabetic. 
• Avoiding brief blood glucose spikes is wise but nobody is perfect and they will happen. I aim to minimise their frequency and level.

My personal definition of a non-diabetic range is 4-8mmol/l or 70-140 mg/dl. 

In my own experience reducing post-meal spikes also improved my steady levels between meals. For that reason I have concentrated on minimising post-meal spikes as my main treatment goal. I suffer from dawn phenomenon but I do not get too concerned about fasting blood glucose provided it is not too high and peak post-prandial results are good; to me fasting blood glucose is a diagnostic indicator rather than a management tool.

Provided my levels between blood glucose spikes are good I don't get too excited when occasional spikes occur. Instead I try to learn from them and discover the cause and try not to repeat them.

I practise what I preach. My doctor's report has changed very little since I wrote this in 2015: Are Diabetes Complications Inevitable? Not necessarily...

Cheers, Alan, T2, Australia.

Everything in Moderation - Except Laughter 
There Is Nothing I Could Eat I like More Than my Eyes