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

Division of Metabolism, Endocrinology and Diabetes, University of Michigan, Ann Arbor, Michigan. Electronic address: .
Journal of the American College of Cardiology (Impact Factor: 16.5). 12/2012; 61(4). DOI: 10.1016/j.jacc.2012.10.028
Source: PubMed


OBJECTIVES: The goal of these studies was to determine the association between cardiovascular autonomic neuropathy (CAN) and indices of left ventricle (LV) structure and function in patients with type 1 diabetes (T1DM) in the Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) study. BACKGROUND: The pathophysiology of LV dysfunction in T1DM remains unclear, especially when the LV ejection fraction (EF) is preserved. Whether CAN is associated with LV dysfunction is unclear. METHODS: Indices of LV structure and function were obtained by cardiac magnetic resonance imaging (CMRI). CAN was assessed by cardiovascular reflex testing (R-R response to paced breathing, Valsalva ratio, and blood pressure response to standing). Analyses were performed in 966 DCCT/EDIC participants with valid CMRI and CAN data (mean age 51 years, 52% men, mean diabetes duration 29 years, and mean glycosylated hemoglobin 7.9%). RESULTS: Systolic function (EF, end-systolic and end-diastolic volumes, stroke volumes) was not different in 371 subjects with CAN compared with 595 subjects without CAN. In multiple-adjusted analyses, participants with either abnormal R-R variation or a composite of abnormal R-R variation, abnormal Valsalva ratio, and postural blood pressure changes had significantly higher LV mass, mass-to-volume-ratio, and cardiac output compared with those with normal tests (p < 0.0001 for all). After further adjustment for traditional cardiovascular risk factors, subjects with abnormal R-R variation had higher LV mass and cardiac output compared with those with a normal R-R variation (p < 0.05). CONCLUSIONS: In this large cohort of patients with T1DM, CAN is associated with increased LV mass and concentric remodeling as assessed by CMRI independent of age, sex, and other factors. (Diabetes Control and Complications Trial [DCCT]; NCT00360815) (Epidemiology of Diabetes Interventions and Complications [EDIC]; NCT00360893).

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    • "For example, Chung et al. reported that complications such as retinopathy and nephropathy occurred more often in type 2 DM patients with DSPN, a sensory neuropathy [3]. There is also evidence that co-occurrence of DSPN and cardiac autonomic neuropathy is associated with changes in ventricular structure and function [4,5]. Others have found that cardiac autonomic neuropathy is an independent predictor of cardiovascular disease mortality [6]. "
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    ABSTRACT: Cardiomyopathy and distal symmetrical polyneuropathy (DSPN), including sensory and autonomic dysfunction, often co-occur in diabetic mellitus (DM) patients. However, the temporal relationship and progression between these two complications has not been investigated. Using a streptozotocin DM animal model that develops insensate neuropathy, our aim was to examine in parallel the development of DSPN and DM-associated changes in cardiac structure and function as well as potential mechanisms, such as autonomic dysfunction, evaluated by changes in urinary and myocardial norepinephrine content and myocardial neuronal markers. Sensory neuropathy was measured by behavioral tests using Von Frey filaments and Hargreaves methods. Echocardiography was used to evaluate myocardial structural and function. Autonomic function was evaluated by measuring urinary and myocardial norepinephrine (NE) levels by enzyme-linked immunosorbent assay and high-performance liquid chromatography/mass spectrometry. Quantitative immunohistochemistry was used to measure the myocardial neuronal markers, calcitonin gene-related peptide (CGRP) and general neuronal protein gene product 9.5 (PGP 9.5). The DM group developed tactile and thermal insensate neuropathy 4-5 weeks after DM onset. Cardiovascular changes were found between 4 and 12 weeks after DM onset and included bradycardia, diastolic and systolic dysfunction and cardiac dilation. There was a 2.5-fold reduction in myocardial NE levels and a 5-fold increase in urinary NE levels in the DM group. Finally, there was a 2.3-fold increase in myocardial CGRP levels in the DM group and no change in PGP9.5 levels. Cardiovascular structural and functional changes developed early in the course of DM and in combination with insensate neuropathy. In parallel, signs of cardiac autonomic dysfunction were also found and included decreased myocardial NE levels and altered CGRP levels. These results may indicate the need for early cardiovascular evaluation in DM patients with insensate neuropathy.
    Cardiovascular Diabetology 01/2014; 13(1):11. DOI:10.1186/1475-2840-13-11 · 4.02 Impact Factor
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    • "T2DM is one of the most important risk factors for cardiovascular disease [12]. The various factors involved in the development of cardiovascular complications of T2DM include hypertension, hyperglycemia, hyperlipidemia and smoking which can eventually lead to cardiomyopathy , heart failure, heart attack, and stroke [13]. "
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    Diabetes research and clinical practice 05/2013; 101(1). DOI:10.1016/j.diabres.2013.04.005 · 2.54 Impact Factor
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    ABSTRACT: Prevention of long-term complications remains the main challenge in the treatment of diabetes. A strong relationship between glucose control and development of complications is apparent in all epidemiologic studies. Yet, intervention trials have yielded questionable results, particularly when intensive treatment was introduced in patients with long-standing diabetes. It has been postulated that in these subjects, prior exposure to chronic hyperglycemia may have generated a negative "metabolic memory," preventing full exertion of the beneficial effects of any subsequent improvement of glucose control. This phenomenon has been replicated in animal models and it recognizes a molecular basis in the role of oxidative stress, advanced glycation processes, and epigenetic mechanisms accounting for self-perpetuating modifications of gene expression. Conversely, early intervention in both type 1 and type 2 diabetes has proven that good glycemic control reduces the risk of development and progression of complications with a beneficial effect that extends well beyond the duration of near-normoglycemia. This has brought up the concept of "metabolic legacy," an advantage handed down by early and effective implementation of treatments designed to reduce blood glucose levels as safely as possible along with multifactorial intervention of all cardiovascular risk factors. The evidence, nature, and clinical implication of these concepts are reviewed.
    Current Diabetes Reports 03/2013; 13(3). DOI:10.1007/s11892-013-0371-2 · 3.08 Impact Factor
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