High blood glucose levels rather than insulin status (insulin deficiency versus insulin resistance) is associated with coronary artery disease in younger adults with diabetes, according to an article in the April 16th issue of the Journal of the American College of Cardiology. Researchers found that patients’ coronary arteries responded similarly to vascular function tests regardless of whether the underlying diabetes was Type 1 or Type 2.

"We noticed that the two groups were very similar in a number of different measurements we performed [with positron emission tomographic imaging] with respect to blood flow, coronary resistance and so on; so our interpretation of the data is that, because the only thing these two groups have in common is hyperglycemia, then the hyperglycemia is probably the primary culprit for the abnormalities that one sees," said Marcelo F. Di Carli, MD, lead author of the study.

The current study was designed to investigate the relative importance of insulin (Type 1 or Type 2 diabetes) and chronic hyperglycemia in the early stages of microvascular coronary disease.

"The primary purpose of the study was to look at the fundamental level of the regulation of coronary blood flow as a marker of early atherosclerosis in diabetic patients. In essence, it's a pretty simple study, we just picked two different models to account for the effects of insulin," Di Carli said.

The researchers enrolled 18 people with Type 1 diabetes, 17 people with Type 2 diabetes, and 11 healthy people as a control group. The two groups of people with diabetes were similar in age and control of blood glucose levels. Researchers observed blood flow in the hearts of participants with use of positron emission tomography and then used adenosine and cold stress to trigger different types of vessel dilation.

Evaluation of patients with both types of diabetes allowed researchers to test the importance of insulin. Significant differences between the groups would have suggested that pathogenesis of microvascular disease involved different levels of and cellular responses to insulin.

The researchers concluded that chronic hyperglycemia plays a major role in pathogenesis of vascular dysfunction because there were no differences in findings between the groups with Type 1 and Type 2 diabetes, only between the diabetic patients and the healthy controls: Differences in response to adenosine-induced hyperemia and cold pressor testing between the adults with diabetes and the control group persisted after adjustment for factors including duration of diabetes, insulin treatment, metabolic abnormalities, and autonomic neuropathy.

This study helps to close the gap between existing experimental evidence of the toxic effects of glucose on vascular endothelium and clinical studies showing that control of blood glucose levels postpones complications of diabetes such as atherosclerosis and myocardial infarction.

"We know diabetic patients have higher rates of heart attack and other problems, but the process begins much earlier in life, so that's another feature that's kind of scary, because even when patients are in their 30s you can already see these impaired coronary blood flows as an early sign of atherosclerosis. It's both an interesting and a worrisome finding," said Di Carli.

Rory Hachamovitch, MD, who was not part of the research team, said that the study findings will bring new attention to the role of glucose.

"In the medical community, there has been an increasing awareness of the importance of insulin resistance as primary driver of premature atherosclerosis in diabetes mellitus, as well as in patients with ‘prediabetic’ states. The role of hyperglycemia in the pathophysiology of macrovascular disease, on the other hand, was not felt to be significant," he said, adding that this study will help direct future research.

"The results of the study by Di Carli et al indicate that glycemic control needs to be considered along with prevention or reversal of insulin resistance in the management of patients, but the prognostic implications of these approaches need to be evaluated."