Elsevier

Metabolism

Volume 62, Issue 5, May 2013, Pages 609-621
Metabolism

Review
Exercise improves cardiac autonomic function in obesity and diabetes

https://doi.org/10.1016/j.metabol.2012.09.005Get rights and content

Abstract

Physical activity is a key element in the prevention and management of obesity and diabetes. Regular physical activity efficiently supports diet-induced weight loss, improves glycemic control, and can prevent or delay type 2 diabetes diagnosis. Furthermore, physical activity positively affects lipid profile, blood pressure, reduces the rate of cardiovascular events and associated mortality, and restores the quality of life in type 2 diabetes. However, recent studies have documented that a high percentage of the cardiovascular benefits of exercise cannot be attributed solely to enhanced cardiovascular risk factor modulation. Obesity in concert with diabetes is characterized by sympathetic overactivity and the progressive loss of cardiac parasympathetic influx. These are manifested via different pathogenetic mechanisms, including hyperinsulinemia, visceral obesity, subclinical inflammation and increased thrombosis. Cardiac autonomic neuropathy is an underestimated risk factor for the increased cardiovascular morbidity and mortality associated with obesity and diabetes. The same is true for the role of physical exercise in the restoration of the heart cardioprotective autonomic modulation in these individuals. This review addresses the interplay of cardiac autonomic function in obesity and diabetes, and focuses on the importance of exercise in improving cardiac autonomic dysfunction.

Introduction

Diabetes affects more than 366 million worldwide and is accompanied with a large human and economic burden, due mainly by increased cardiovascular risk and premature mortality (www.who.int/diabetes). Physical activity is a cornerstone in diabetes management [1], [2], as well as being an independent cardiovascular and atherosclerotic risk factor [3]. Sedentary lifestyle is estimated to be responsible for approximately one third of deaths due to coronary heart disease, colon cancer, and diabetes [4]. Furthermore, low cardiopulmonary fitness is a strong and independent predictor of all-cause mortality in obesity and diabetes [5]. Less physically active people demonstrate twice the rate of coronary artery disease of those who are physically active [6], whereas the relative risk of being physically unfit exceeds that associated with smoking, hypertension, hypercholesterolemia and obesity [7]. Therefore, physical inactivity is a key factor in the etiology and progression of chronic cardiovascular and metabolic conditions, which are common, and devastating in our modern society.

Diabetic autonomic neuropathy is a common and serious complication with variable multiple organ involvement, principally of the cardiovascular system, but also of the gastrointestinal and urogenital tracts [8]. Cardiac autonomic neuropathy (CAN) is defined as the impairment of autonomic control of the cardiovascular system in the setting of diabetes after exclusion of other causes [9], [10]. Cardiac autonomic neuropathy (CAN) results from damage to the autonomic nerve fibers that innervate the heart and blood vessels, increased baroreceptor intima–media thickness, reduced vascular distensibility, and endothelial dysfunction [11], [12]. CAN causes alterations in heart-rate and modulation of vascular dynamics, which result in resting tachycardia, abnormal myocardial blood-flow regulation, and impaired cardiac function [11], [12]. CAN is associated with poorer prognosis, with increased mortality and incidence of both silent myocardial ischemia and infarction [11], [12]. Development of diabetic cardiomyopathy is traditionally attributed to CAN [13], [14], and the independent association of CAN with non-ischemic diabetic cardiomyopathy was also recently established [15].

Obesity is a very common chronic disease worldwide, resulting principally from a disturbance in energy balance [16]. Of importance, the rate of severe obesity (BMI ≥ 40 kg/m [2]) is rising exponentially in the industrialized world [16]. Metabolic syndrome (MetS) is also a cluster of abnormalities with basic characteristics being insulin-resistance and visceral obesity, which is the clinical reflection of “at risk obesity” [17], [18]. Obesity and MetS are characterized by sympathetic nervous system (SNS) predominance in the basal state and reduced SNS responsiveness after various sympathetic stimuli, such as cold exposure, postural changes, mental effort, caffeine, alcohol and nicotine intake, and hypoglycemia [18], [19]. Weight loss and exercise are the first line therapy for obesity and MetS [20], and also reduce related SNS overactivity [21]. Recent analyses have documented that the impact of exercise on conventional cardiovascular risk factors is substantially less than that achieved by pharmacological therapies, but notably also much less than that required to explain the cardiovascular morbidity and mortality benefits associated with exercise and fitness per se [21]. This suggests that a high percentage (~ 50%) of the cardiovascular benefits of exercise cannot be solely attributed to positive cardiovascular risk factor modulation. In this review, we examine evidence supporting the direct positive effect of exercise on the autonomic nervous system (ANS) function and its role in reducing cardiovascular risk in obesity and diabetes.

For this purpose, an electronic search of Medline (via PubMed) and ScienceDirect databases without date limitations was conducted. Combinations of the following keywords were used: “exercise”, “physical”, “activity”, “diabetes”, “cardiomyopathy”, “obesity”, “cardiac”, “autonomic”, “neuropathy”, “function”, “sympathetic”, “parasympathetic”, “variability”, “baroreflex”, “chemoreflex”, “catecholamines”, and “norepinephrine” to retrieve available data. Publications in English were studied in full. Studies published in other languages were considered in abstract form. We retrieved 92 studies by hand-searching meeting the criteria of sufficient evidence-based information to draw conclusions applicable to adaptation into routine clinical care. The last search was run on 18 August 2012.

Section snippets

Measurements of autonomic function

Heart rate variability (HRV) is a noninvasive, practical and reproducible measure of cardiac autonomic nervous system function. Variability in the instantaneous beat-to-beat heart-rate intervals reflects sympathetic and parasympathetic activity which modulates cardiac functional response to the body's level of metabolic activity [22]. In normal individuals, heart-rhythm has a high degree of HRV which fluctuates with respiration; heart-rate increasing with inspiration and decreasing with

Autonomic function in obesity

SNS activity is associated with both energy balance and MetS. Reciprocal associations exist between SNS activity and food-intake. Sympathetic activation via the hypothalamic regulatory feedback reduces food-intake, inhibits leptin production and secretion [18]. Leptin furthermore inhibits ectopic fat accumulation, prevents β-cell dysfunction and protects the β-cell from cytokine- and fatty acid-induced apoptosis [29]. Recent studies suggest that exercise training has differing effects on leptin

Autonomic function in diabetes

CAN is a common chronic complication of diabetes and confers high morbidity and mortality in this subset of diabetic patients [8], [9], [10], [11], [25], [26], [27], [36], [37]. Recent population based studies, found that ~ 40% of diabetic patients present features of CAN [37]. In diabetes, CAN is ultimately the result of various interactions among glycemic control, diabetes duration, age-related neuronal attrition, and blood pressure [8], [9], [10], [11], [36], [37], [38], [39]. Hyperglycemia

Autonomic response to aerobic exercise training

The central nervous system regulates cardiovascular autonomic function in a reciprocal fashion, and increased vagal modulation is usually associated with decreased SNS activity. Recent studies have reported marked changes in heart rate during aerobic exercise and after training interventions, which are primarily due to alterations in the ANS activity. In respect, during acute exercise, heart rate accelerates via reduced cardiac vagal modulation and increased SNS activity. As the workload

Metabolic, hormonal and autonomic modulation of exercise in diabetes

During acute exercise, the body relies on greater peripheral use of glucose and this is further enhanced by hyperinsulinemia, which inhibits lipolysis [68]. During prolonged exercise, the decrement in plasma insulin levels further stimulates lipolysis and allows plasma free fatty acids to provide the major substrate for energy [69], [70]. The function of carnitine in energy metabolism is impaired in diabetes and is also associated with increased lipolysis and the mobilization of free fatty

The beneficial impact of exercise in diabetes

Although physical activity is a key element in the prevention and management of T2DM, many patients do not become or remain regularly active [82]. Participation in regular physical activity improves glycemic control and can prevent or delay chronic diabetic complications, along with positively influencing dyslipidemia, hypertension, cardiovascular events, all-cause mortality, and quality of life [83]. Moreover, regular physical activity helps patients with diabetes to reduce the need for

Conclusions

The rate of obesity and diabetes is rising logarithmically and is associated with significant cardiovascular morbidity and mortality. Obesity, together with diabetes is characterized by SNS overactivity and the progressive loss of cardioprotective parasympathetic heart influx. It has long been recognised that cardiac autonomic neuropathy increases morbidity and mortality in obesity and diabetes and has greater predictive power than traditional risk factors for cardiovascular events [8], [30].

Messages to the reader

  • Physical activity is a cornerstone in the management of obesity and diabetes, whereas physical inactivity is an independent cardiovascular and atherosclerotic risk factor

  • Cardiac autonomic neuropathy increases morbidity and mortality in obesity and diabetes and has greater predictive power than traditional risk factors for cardiovascular events

  • ANS dysfunction and poor physical fitness during young adulthood are associated with a 3.4-fold increased risk of incident diabetes in middle-age

  • Endurance

Conflict of interest

None to declare.

References (102)

  • A.J. Hautala et al.

    Individual responses to aerobic exercise: the role of the autonomic nervous system

    Neurosci Biobehav Rev

    (2009)
  • C.P. Earnest et al.

    Autonomic function and change in insulin for exercising postmenopausal women

    Maturitas

    (2010)
  • S. Goulopoulou et al.

    Exercise training improves cardiovascular autonomic modulation in response to glucose ingestion in obese adults with and without type 2 diabetes mellitus

    Metabolism

    (2010)
  • P. Brassard et al.

    Impact of diabetes, chronic heart failure, congenital heart disease and chronic obstructive pulmonary disease on acute and chronic exercise responses

    Can J Cardiol

    (2007)
  • P. Brassard et al.

    Influence of glycemic control on pulmonary function and heart rate in response to exercise in subjects with type 2 diabetes mellitus

    Metabolism

    (2006)
  • S.R. Chen et al.

    Impact of glycemic control, disease duration, and exercise on heart rate variability in children with type 1 diabetes mellitus

    J Formos Med Assoc

    (2007)
  • M.J. LaMonte et al.

    Physical activity and diabetes prevention

    J Appl Physiol

    (2005)
  • S.N. Blair et al.

    Changes in physical fitness and all-cause mortality. A prospective study of healthy and unhealthy men

    JAMA

    (1995)
  • K.E. Powell et al.

    The public health burdens of sedentary living habits: theoretical but realistic estimates

    Med Sci Sports Exerc

    (1994)
  • J. Myers et al.

    Exercise capacity and mortality among men referred for exercise testing

    N Engl J Med

    (2002)
  • P.D. Thompson et al.

    American Heart Association Council on Clinical Cardiology Subcommittee on Exercise, Rehabilitation, and Prevention; American Heart Association Council on Nutrition, Physical Activity, and Metabolism Subcommittee on Physical Activity. Exercise and physical activity in the prevention and treatment of atherosclerotic cardiovascular disease: a statement from the Council on Clinical Cardiology (Subcommittee on Exercise, Rehabilitation, and Prevention) and the Council on Nutrition, Physical Activity, and Metabolism (Subcommittee on Physical Activity)

    Circulation

    (2003)
  • C.I. Ardern et al.

    Revised Adult Treatment Panel III guidelines and cardiovascular disease mortality in men attending a preventive medical clinic

    Circulation

    (2005)
  • S. Tesfaye et al.

    Diabetic neuropathies: update on definitions, diagnostic criteria, estimation of severity, and treatments

    Diabetes Care

    (2010)
  • A.J. Boulton et al.

    The diabetic neuropathies: reports from the Diabetic Neuropathy Expert Panel Meeting on Neuropathy, Toronto, October 2009: introduction

    Diabetes Metab Res Rev

    (2011)
  • V. Spallone et al.

    Cardiovascular autonomic neuropathy in diabetes: clinical impact, assessment, diagnosis, and management

    Diabetes Metab Res Rev

    (2011)
  • A.I. Vinik et al.

    Diabetic cardiovascular autonomic neuropathy

    Circulation

    (2007)
  • J.D. Lefrandt et al.

    Autonomic dysfunction in diabetes: a consequence of cardiovascular damage

    Curr Diabetes Rev

    (2010)
  • C. Voulgari et al.

    The association between the spatial QRS-T angle with cardiac autonomic neuropathy in subjects with type 2 diabetes mellitus

    Diabet Med

    (2010)
  • P. Poirier et al.

    on behalf of the American Heart Association Obesity Committee of the Council on Nutrition; Physical Activity, and Metabolism. Bariatric Surgery and Cardiovascular Risk Factors: a scientific statement from the American Heart Association

    Circulation

    (2011)
  • N. Tentolouris et al.

    Sympathetic system activity in obesity and metabolic syndrome

    Ann N Y Acad Sci

    (2006)
  • S. Mora et al.

    Physical activity and reduced risk of cardiovascular events: potential mediating mechanisms

    Circulation

    (2007)
  • Heart rate variability: standards of measurement, physiological interpretation and clinical use. Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology

    Circulation

    (1996)
  • M. Baumert et al.

    Short-term heart rate variability and cardiac norepinephrine spillover in patients with depression and panic disorder

    Am J Physiol Heart Circ Physiol

    (2009)
  • H. Tsuji et al.

    Impact of reduced heart rate variability on risk for cardiac events. The Framingham Heart Study.

    Circulation

    (1996)
  • R.E. Maser et al.

    The association between cardiovascular autonomic neuropathy and mortality in individuals with diabetes: a meta-analysis

    Diabetes Care

    (2003)
  • F. Iellamo et al.

    Effects of residential exercise training on baroreflex sensitivity and heart rate variability in patients with coronary artery disease: a randomized, controlled study

    Circulation

    (2000)
  • L.H. Opie et al.

    Blood pressure and peripheral circulation

  • I. Skrapari et al.

    Baroreflex function: determinants in healthy subjects and disturbances in diabetes, obesity and metabolic syndrome

    Curr Diabetes Rev

    (2006)
  • E. Lambert et al.

    Single-unit sympathetic discharge pattern in pathological conditions associated with elevated cardiovascular risk

    Clin Exp Pharmacol Physiol

    (2008)
  • M. Rosenbaum et al.

    Adaptive thermogenesis in humans

    Int J Obes (Lond)

    (2010)
  • P. Poirier

    Obesity, adiposity indices, and blood pressure; ethnicity does matter

    Am J Hypertens

    (2008)
  • J. Galgani et al.

    Energy metabolism, fuel selection and body weight regulation

    Int J Obes (Lond)

    (2008)
  • Vinik AI, Maser RE, Ziegler D. Autonomic imbalance: prophet of doom or scope for hope? Diabet Med....
  • K. Kitsios et al.

    Glycemia and cardiovascular risk: challenging evidence based medicine

    Hippokratia

    (2011)
  • N. Papanas et al.

    Neuropathy in prediabetes: does the clock start ticking early?

    Nat Rev Endocrinol

    (2011)
  • C. Voulgari et al.

    Diabetic cardiomyopathy: from the pathophysiology of the cardiac myocytes to current diagnosis and management strategies

    Vasc Health Risk Manag

    (2010)
  • S.R. Colberg et al.

    American College of Sports Medicine; American Diabetes Association. Exercise and type 2 diabetes: the American College of Sports Medicine and the American Diabetes Association: joint position statement

    Diabetes Care

    (2010)
  • R.L. Verrier et al.

    Autonomic aspects of arrhythmogenesis: the enduring and the new

    Curr Opin Cardiol

    (2004)
  • M.N. Hawkins et al.

    The effects of aerobic fitness and beta1-adrenergic receptor blockade on cardiac work during dynamic exercise

    J Appl Physiol

    (2009)
  • G.E. Billman et al.

    Effect of endurance exercise training on heart rate onset and heart rate recovery responses to submaximal exercise in animals susceptible to ventricular fibrillation

    J Appl Physiol

    (2007)
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