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logoIntensive insulin therapy slows heart nerve damage in type 1 diabetes patients


Cardiovascular neuropathy slowed even when glucose was not well-controlled later

ANN ARBOR (May 26, 2009) — Rodica Pop-Busui, M.D., Ph.D. (assistant professor, Division of Metabolism, Endocrinology & Diabetes, Department of Internal Medicine, University of Michigan Medical School) and colleagues have determined that intensive insulin therapy for type 1 diabetics has long-term benefits for heart nerve health, even if glucose levels are not well-controlled in the long term.

The new findings come from an analysis of the Epidemiology of Diabetes Interventions and Complications Study (EDIC), a follow-up to a landmark clinical trial called Diabetes Control and Complications Trial (DCCT), in the June 9, 2009, edition of the American Heart Association journal Circulation. The authors conclude that intensive insulin therapy protects against a type of heart damage called cardiovascular autonomic neuropathy (CAN), slowing the onset and severity of the complication even years after intensive insulin control has ended.

"I think that our results are very important, as they have significant implications for patient care," says Dr. Pop-Busui. "Problems in the autonomic nervous system, which includes the heart, strongly predict cardiovascular health in people with and without diabetes mellitus. Damage to the nerves of the heart can manifest as heart rhythm abnormalities, which increases the risk of ischemia [inadequate circulation] and cardiac death."

The original DCCT trial, begun in 1983, demonstrated that intensive insulin therapy for type 1 diabetes mellitus reduced the onset and progression of diabetic eye, kidney, and nerve damage, as well as the incidence of CAN. CAN was reduced by 53% when compared with study subjects on conventional insulin therapy.

"Intensive insulin therapy" is defined as the administration of insulin via three or more injections daily or by continuous insulin infusion (via pump), together with frequent daily blood glucose tests, in an effort to keep blood glucose levels as close to normal as possible. This is contrasted to what was considered the "conventional" care for type 1 diabetes when the DCCT study began, which generally consisted of one or two insulin injections per day, plus occasional blood or urine glucose monitoring. As a result of the DCCT findings after the trial ended in 1989, intensive insulin therapy has been adopted as the standard of care for people with type 1 diabetes.

The EDIC follow-up to the DCCT study was begun in 1993. Its goal was to examine the long-term effects of prior intensive insulin therapy on the development and progression of the complications studied in the DCCT patients. Various other analyses of the EDIC follow-up have shown the benefit to eye and kidney health that was observed in the former intensive therapy patients at the end of the DCCT has persisted and even increased over time, when compared with the former DCCT conventional treatment group. Dr. Pop-Busui and her colleagues wanted to know whether this group of patients continues to experience a lower prevalence and incidence of heart nerve damage (CAN) as well.

Dr. Pop-Busui states, "Trials such as this one that study neuropathy [nerve damage] — and, specifically, CAN — are lacking, especially compared with the wealth and quality of trials exploring other diabetes complications, such as nephropathy [kidney damage] and retinopathy [damage to the retina of the eye]."

The results suggest that, although CAN prevalence increased in both groups, the incidence was significantly lower in the group that experienced the prior intensive therapy, despite there being no differences in levels of glycemic control between the two groups of study subjects 13 to 14 years after the close of the DCCT study.

"These new data from the DCCT/EDIC follow-up provide additional support for the need to intensify glycemic control in patients with type 1 diabetes in order to reduce the total burden of diabetes complications," Dr. Pop-Busui comments. "Importantly, we demonstrated that tight glycemic control for even a few years remains of long-term benefit for CAN, an important clinical message."

The EDIC study is now entering its 16th year. The researchers plan to continue with the follow-up of CAN in these individuals.

The paper was co-authored with William H. Herman, M.D., M.P.H. and Catherine L. Martin, M.S. from the MEND Division and Eva L. Feldman, M.D., Ph.D. and James Albers, M.D., Ph.D. from the Neurology Division, along with others from the DCCT/EDIC Research Group.

A related analysis of the DCCT/EDIC results recently published by Drs. Herman and Pop-Busui et al. in Archives of Internal Medicine shows that near-normal control of glucose beginning as soon as possible after diagnosis would greatly improve the long-term prognosis of type 1 diabetes.


For more information:

Abstract ~ Full Text ~ PDF

"Effects of Prior Intensive Insulin Therapy on Cardiac Autonomic Nervous System Function in Type 1 Diabetes Mellitus: The Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study (DCCT/EDIC)"

Circulation (2009), issue 119, pp. 2886–2893

This paper also was featured as a Research Highlight in the publication Nature Reviews Cardiology (August 2009, volume 6, p. 496). [PDF]