Association Between Cardiovascular Autonomic Neuropathy and Left Ventricular Dysfunction DCCT/EDIC Study (Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications)
ABSTRACT 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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ABSTRACT: AIMS: The aim of this study was to evaluate the effect of laparoscopic Roux-en-Y gastric bypass (RYGB) surgery compared with usual care with and without Exenatide therapy in obese people with type 2 diabetes mellitus (T2DM) and hypertension. METHODS: 108 obese T2DM with hypertension were enrolled and randomly allocated to usual care (group A), usual care plus Exenatide (group B), and RYGB surgery (group C). Demographic characteristics, metabolic parameters and cardiac structure/function along with inflammatory cytokines were measured and compared before and after 12 months. RESULTS: At 12 months, diabetes remission had occurred in no patients in groups A and B versus 90% in group C, and there was a significant decrease in requirement of antihypertensive drugs in group C compared with groups A and B (P<0.05). Other parameters (body mass index, hemoglobin A1c, homeostasis model assessment of insulin resistance, lipids), inflammation index (high sensitivity C-reactive protein, tumor necrosis factor-α, high molecular weight adiponectin) and cardiac structure (left ventricular mass index) were significantly improved in groups B and C, but patients in group C had the greatest degree of improvement (P<0.05). CONCLUSION: RYGB surgery improves a number of parameters including cardiovascular function in obese hypertensive people with T2DM. This is likely to be due to, at least in part, an improvement in the abnormal metabolic panel and to reduced inflammation.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; DOI:10.1007/s11892-013-0371-2 · 3.38 Impact Factor
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ABSTRACT: Autonomic cardiac neurons have a common origin in the neural crest but undergo distinct developmental differentiation as they mature toward their adult phenotype. Progenitor cells respond to repulsive cues during migration, followed by differentiation cues from paracrine sources that promote neurochemistry and differentiation. When autonomic axons start to innervate cardiac tissue, neurotrophic factors from vascular tissue are essential for maintenance of neurons before they reach their targets, upon which target-derived trophic factors take over final maturation, synaptic strength and postnatal survival. Although target-derived neurotrophins have a central role to play in development, alternative sources of neurotrophins may also modulate innervation. Both developing and adult sympathetic neurons express proNGF, and adult parasympathetic cardiac ganglion neurons also synthesize and release NGF. The physiological function of these “non-classical” cardiac sources of neurotrophins remains to be determined, especially in relation to autocrine/paracrine sustenance during development.Organogenesis 05/2013; 9(3). DOI:10.4161/org.24892 · 2.60 Impact Factor