Intensive Glucose, Blood Pressure Control Reduces Risk of Cardiovascular Autonomic Neuropathy

Rodica Pop Busui, MD, PhD, MPH

A new study from investigators at the Joslin Diabetes Center and the University of Michigan is underlining the impact of intensive blood pressure and intensive blood glucose control on managing a diabetic patient’s risk of developing cardiovascular autonomic neuropathy (CAN).

An analysis of data from more than 10,000 patients within the ACCORD trial, results indicate intensive glycemic control reduced CAN risk by 17% and intensive blood pressure control reduced risk by 22%, but also provided information on nuances in treatment.

"These findings have high clinical care relevance, as we have previously demonstrated that CAN, even in earlier stages, independently predicts cardiovascular and all-cause mortality in type 2 diabetes, and major cardiovascular events and heart failure in type 1 diabetes,” said study author Rodica Pop Busui, MD, PhD, MPH, professor of medicine at the University of Michigan, in a statement from the Joslin Diabetes Center.

With CAN representing an underdiagnosed but serious complication of diabetes, investigators sought to assess how intensive treatment of individual risk factors might influence risk of developing CAN. Using the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, investigators identified a cohort of more than 10,000 patients with diabetes treated between 2001-2010.

Of the 10,251 original ACCORD participants, investigators identified 7275 (71%) with data related to a CAN evaluation at study entry and at least 1 after randomization. For the purpose of the investigators’ analyses, CAN was defined as heart rate variability indices below the fifth percentile of normal distribution. Investigators designed their study with the intent of assessing the effects of intensive interventions, including intensive blood pressure control, intensive blood glucose control, and treatment with fenofibrate, on CAN using generalized linear mixed models.

Investigators pointed out that because the ACCORD trial ran from 2001-2010, newer therapies were not included in the study. Specifically, investigators noted none of the study patients received SGLT2 inhibitors and only a handful of participants were prescribed GLP-1 receptor agonists in the latter half of the study.

Upon analysis, results suggested intensive treatment aimed at reducing HbA1c resulted in a 17% (OR, 0.83; 95% CI, 0.74-0.93; P=.002) reduction in risk for CAN compared to standard therapy after adjustment for traditional and cardiovascular disease risk factors. Investigators also uncovered a similar trend when assessing the impact of intensive blood pressure treatment. Investigators found intensive treatment of increased blood pressure resulted in a 22% (OR, 0.78; 95% CI, 0.65-0.92; P=.004) reduction in risk for CAN compared to standard treatment approaches.

When assessing the impact of fenofibrate and statin compared to placebo, a statin was not as successful but investigators noted there was no significant difference between the interventions. Further analysis of study results indicated intensive glucose control was more effective in patients without cardiovascular disease at baseline (OR 0.73, 95% CI 0.63–0.85, P < 0.0001) than those without cardiovascular disease. For blood pressure control, an intensive approach was most effective at reducing CAN risk in patients 65 years of age or older (OR, 0.66; 95% CI, 0.49-0.88; P=.005).

"Based on previous smaller studies, we thought that intensive glycemic and blood pressure control would probably work, but these results provide us with definitive proof that these treatments can be used to prevent this serious complication of diabetes,” said study author Allesandro Doria, MD, PhD, MPH, co-director of Advanced Genomic and Genetics Core at the Joslin Diabetes Center, in the aforementioned statement.

This study, “Intensive Risk Factor Management and Cardiovascular Autonomic Neuropathy in Type 2 Diabetes: The ACCORD Trial,” was published in Diabetes Care.