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      Progression of cardiovascular autonomic neuropathy and cardiovascular disease in type 2 diabetes

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          Abstract

          Background

          To examine whether the progression rate of cardiovascular autonomic neuropathy (CAN) stage is an independent predictive factor for cardiovascular disease (CVD) in type 2 diabetes.

          Methods

          Standardized cardiovascular autonomic reflex tests (CARTs) using traditional Ewing method were performed at baseline. The follow-up CARTs was recommended once every two years. We estimated the primary CVD endpoint, defined as coronary artery disease and ischemic stroke. The association between the progression rate of CAN stage and CVD was examined using time-dependent Cox proportional hazard models.

          Results

          At baseline, 578 patients completed follow-up CARTs; the cohort comprised 329 women (56.9%) with a mean age of 58.3 ± 10.3 years and a mean diabetes duration of 10.1 ± 6.2 years. One hundred and seventy-six patients (30.4%) developed CAN progression between baseline and follow-up CARTs. In the multivariable Cox proportional hazards regression analysis, patients with CAN progression demonstrated a 3.32 times higher risk (95% confidence interval, CI 1.81–6.14, P < 0.001) of CVD than those without CAN progression. Patients who experienced CAN progression from the normal to definite stage had the greatest risk of CVD compared to other patients (hazard ratio 4.91, 95% CI 2.05–11.77, P for trend = 0.001).

          Conclusions

          CAN stage progression was associated with an increased risk of CVD in this type 2 diabetes cohort. Patients with rapid CAN progression had the greatest risk of CVD. Thus, regular screening and risk management of CAN progression is necessary to prevent CVD.

          Electronic supplementary material

          The online version of this article (10.1186/s12933-018-0752-6) contains supplementary material, which is available to authorized users.

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          Most cited references29

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          Diabetic Neuropathies: A statement by the American Diabetes Association

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            Intensified multifactorial intervention in patients with type 2 diabetes mellitus and microalbuminuria: the Steno type 2 randomised study.

            In type 2 diabetes mellitus the aetiology of long-term complications is multifactorial. We carried out a randomised trial of stepwise intensive treatment or standard treatment of risk factors in patients with microalbuminuria. In this open, parallel trial patients were allocated standard treatment (n=80) or intensive treatment (n=80). Standard treatment followed Danish guidelines. Intensive treatment was a stepwise implementation of behaviour modification, pharmacological therapy targeting hyperglycaemia, hypertension, dyslipidaemia, and microalbuminuria. The primary endpoint was the development of nephropathy (median albumin excretion rate >300 mg per 24 h in at least one of the two-yearly examinations). Secondary endpoints were the incidence or progression of diabetic retinopathy and neuropathy. The mean age was 55.1 years (SD 7.2) and patients were followed up for 3.8 years (0.3). Patients in the intensive group had significantly lower rates of progression to nephropathy (odds ratio 0.27 [95% CI 0-10-0.75]), progression of retinopathy (0.45 [0.21-0.95]), and progression of autonomic neuropathy (0.32 [0.12-0.78]) than those in the standard group. Intensified multifactorial intervention in patients with type 2 diabetes and microalbuminuria slows progression to nephropathy, and progression of retinopathy and autonomic neuropathy. However, further studies are needed to establish the effect of intensified multifactorial treatment on macrovascular complications and mortality.
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              Detection of silent myocardial ischemia in asymptomatic diabetic subjects: the DIAD study.

              To assess the prevalence and clinical predictors of silent myocardial ischemia in asymptomatic patients with type 2 diabetes and to test the effectiveness of current American Diabetes Association screening guidelines. In the Detection of Ischemia in Asymptomatic Diabetics (DIAD) study, 1,123 patients with type 2 diabetes, aged 50-75 years, with no known or suspected coronary artery disease, were randomly assigned to either stress testing and 5-year clinical follow-up or to follow-up only. The prevalence of ischemia in 522 patients randomized to stress testing was assessed by adenosine technetium-99m sestamibi single-photon emission-computed tomography myocardial perfusion imaging. A total of 113 patients (22%) had silent ischemia, including 83 with regional myocardial perfusion abnormalities and 30 with normal perfusion but other abnormalities (i.e., adenosine-induced ST-segment depression, ventricular dilation, or rest ventricular dysfunction). Moderate or large perfusion defects were present in 33 patients. The strongest predictors for abnormal tests were abnormal Valsalva (odds ratio [OR] 5.6), male sex (2.5), and diabetes duration (5.2). Other traditional cardiac risk factors or inflammatory and prothrombotic markers were not predictive. Ischemic adenosine-induced ST-segment depression with normal perfusion (n = 21) was associated with women (OR 3.4). Selecting only patients who met American Diabetes Association guidelines would have failed to identify 41% of patients with silent ischemia. Silent myocardial ischemia occurs in greater than one in five asymptomatic patients with type 2 diabetes. Traditional and emerging cardiac risk factors were not associated with abnormal stress tests, although cardiac autonomic dysfunction was a strong predictor of ischemia.
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                Author and article information

                Contributors
                dryun@catholic.ac.kr
                markparkjecos@gmail.com
                kakki@catholic.ac.kr
                ybahn@catholic.ac.kr
                kosh@catholic.ac.kr
                Journal
                Cardiovasc Diabetol
                Cardiovasc Diabetol
                Cardiovascular Diabetology
                BioMed Central (London )
                1475-2840
                2 August 2018
                2 August 2018
                2018
                : 17
                : 109
                Affiliations
                [1 ]ISNI 0000 0004 0470 4224, GRID grid.411947.e, Division of Endocrinology and Metabolism, Department of Internal Medicine, St. Vincent’s Hospital, College of Medicine, , The Catholic University of Korea, ; Ji-dong, Paldal-gu, Suwon, 16247 South Korea
                [2 ]ISNI 0000 0001 2297 5165, GRID grid.94365.3d, Epidemiology Branch, National Institute of Environmental Health Sciences, , National Institutes of Health, ; Research Triangle Park, Durham, NC USA
                Author information
                http://orcid.org/0000-0003-3703-1479
                Article
                752
                10.1186/s12933-018-0752-6
                6071370
                30071872
                c82e1c39-5a73-4164-9950-3c4e7e819002
                © The Author(s) 2018

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 17 May 2018
                : 26 July 2018
                Categories
                Original Investigation
                Custom metadata
                © The Author(s) 2018

                Endocrinology & Diabetes
                cardiovascular autonomic neuropathy,cardiovascular disease,type 2 diabetes

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