What Really Happens with Chronic Hyperglycemia?

Savannah Helm Uncategorized

Reports show that only about 30% of people with Type 2 Diabetes (T2DM) achieve good blood glucose control.1 Despite the number of therapies available for T2DM, including:

  • exogenous insulin, and
  • medications that decrease glucose release from the liver,
  • increased use of glucose by skeletal muscles, or
  • delays in the absorption of glucose from food.

The micro and macro vascular complications remain a challenge. It is now known that these complications are a result of chronic high levels of blood sugar that result in long term oxidative stress, chronic inflammation, non-enzymatic glycation of proteins, and epigenetic changes. Overproduction of free radicals from oxidative stress appears to be the link that unites hyperglycemia and the multiple biochemical forces that result in diabetes complications.

Glucose is the main fuel for the body. However, three major metabolic flaws can prove harmful to a person with T2DM:

  • increased hepatic glucose production,
  • impaired pancreatic insulin secretion, and
  • peripheral tissue insulin resistance.

One or a combination of these flaws leads to chronic hyperglycemia that in turn affect life span, morbidity, and mortality. According the American Diabetes Association, A1C measures the average blood glucose for 60 to 90 days with a value of 5.7%-6.4% indicating prediabetes, and 6.5% or greater being positive for diabetes.1 Fasting blood glucose levels are normal if less than 100 mg/dl, prediabetic if 100 mg/dl-125 mg/dl, and diabetic at 126 mg/dl or higher. 1

Nitric Oxide Production and Reactive Oxidative Stress

The endothelium of the blood vessels is the main organ involved in the development of cardiovascular disease in T2DM, including atherosclerosis and hypertension. The endothelium carries out the important role of forming the gas, Nitric Oxide (NO), that triggers the relaxation of blood vessels and increases the blood flow to organs from the brain to the heart. Hyperglycemia interferes with NO production by causing systemic inflammation and dysfunction of the endothelial lining through the production of excess reactive oxidative stress (ROS) free radicals that the body’s antioxidant system is unable to remove.2 Newer therapies, discussed in the next blog, are being tested to delay or reverse these problems.

Metabolic Memory Theory

Numerous studies have pointed to the theory of “metabolic memory” demonstrating that those individuals who underwent intensive diabetes treatment had fewer adverse clinical complications than those who underwent standard treatment, despite having similar HbA1c values in the long term.3 Early initiation of intensive treatment is an important factor because those who began treatment earlier had fewer complications. Those who did not have good glycemic control were less able to reverse the damage, if poor control extended over a longer period. However, this “metabolic memory” may help explain why intensive glucose control did not stop cardiovascular disease and why vascular dysfunction continues even after glucose is normalized. Once diagnosed with T2DM, the condition has more than likely become chronic. As a result of “metabolic memory,” even in those who underwent intensive treatment, endothelial damage may continue as a result of past high glucose levels, oxidative damage, epigenetic changes, chronic inflammation, and non-enzymatic glycation of protein. 2-3

Earlier Diagnosis and Earlier Onset of Complications

As we know, T2DM is not just for adults any longer. With the increase in obesity and inactivity, there is an ever-increasing number of children under the age of 18 diagnosed with the disease. From 2002 to 2012 the diagnosis of T2DM in children 10 to 19 years of age increased at a rate of 4.8% per year. Earlier diagnosis of diabetes means earlier onset of cardiovascular disease and its complications. Current studies have pointed to extensive development of renal, cardiovascular, pregnancy-related, eye, and nerve conditions in young adults diagnosed with T2DM. 4

Knowing that current approaches to diabetes treatment have not been as effective as they could or should be, it appears to be time to look at other approaches.

By Sarah Laidlaw, MS, RDN, CDE 


  1. Diagnosing Diabetes and Learning About Prediabetes. Available at: http://www.diabetes.org/diabetes-basics/diagnosis/
  2. Fried R, Carlton RM. Type 2 Diabetes: Cardiovascular and related complications and evidence-based complementary treatments. Boca Raton: CRC Press, 2018.
  3. Testa R, Bonfigli AR, Prattichizzo F, et al. The “Metabolic Memory” Theory and the Early Treatment of Hyperglycemia in Prevention of Diabetic Complications. 2017:9(5).pii:E437. Doi:10.3390/nu9050437
  4. National Institutes of Health: NIH Research Matters. Diabetes increasing in youths.https://www.nih.gov/news-events/news-releases/rates-new-diagnosed-cases-type-1-type-2-diabetes-rise-among-children-teens

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