Association Between Cardiovascular Autonomic Neuropathy and Left Ventricular Dysfunction in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT-EDIC) Study

Study Questions:

Is there an association between cardiac autonomic neuropathy (CAN) and left ventricular (LV) dysfunction in patients with type 1 diabetes (T1DM)?


This was a secondary analysis from the DCCT/EDIC study. Consenting patients with T1DM underwent CAN testing and cardiac magnetic resonance imaging (cMRI) to measure LV end-diastolic volume (LVEDV) and end-systolic volume (LVESV) function. A positive CAN test was defined as: 1) an R-R variation of <15 to paced breathing, or 2) an R-R variation <20 with Valvalva ratio <1.5 or a >10 mm Hg drop in diastolic blood pressure upon standing. The primary measure of interest was the change in unit LV function in patients with and without CAN.


Of the 1,441 patients enrolled into the original study, 944 had cMRI and CAN testing. The cohort’s mean age was 51 ± 7 years, and 64% of patients had hypertension. There were 371 (38%) patients with CAN. Patients with CAN were older, had longer duration of diabetes, worse renal function, and higher glycated hemoglobin than those without CAN. There were no differences in ejection fraction (mean 61%), LVEDV, or LVESV between groups (both p > 0.70). Patients with CAN had greater LV mass (142 ± 1.5 g) than those without (135 ± 1.0 g, p < 0.001), and higher cardiac output (6.2 ± 0.1 vs. 5.7 ± 0.1 L/min, p < 0.0001), respectively. After adjusting for multiple correlates, CAN remained significantly associated with LV mass and cardiac output.


In T1DM patients enrolled into this study, the presence of CAN was associated with increased LV mass and adverse remodeling.


Cardiomyopathy is common in patients with diabetes. In this analysis, type 1 diabetics with CAN demonstrated greater LV mass and cardiac output than diabetics without CAN. These cMRI abnormalities are suggestive of underlying abnormalities in LV diastolic function. The authors hypothesize that hypertrophy may be related to excessive sympathetic activation (with loss of vagal baroreflex) in those with CAN. This raises the question of whether aggressive beta-blocker therapy may assist in reducing the complications of sympathetic nervous system excess. The next studies should focus on confirming diastolic abnormalities (with catheterization measures of hemodynamics) and catecholamine excess.

Clinical Topics: Heart Failure and Cardiomyopathies, Noninvasive Imaging, Prevention, Magnetic Resonance Imaging, Hypertension

Keywords: Ventricular Dysfunction, Left, Diabetes Mellitus, Type 1, Magnetic Resonance Imaging, Hypertension

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