ReviewExercise improves cardiac autonomic function in obesity and diabetes
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
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Physical activity is a cornerstone in the management of obesity and diabetes, whereas physical inactivity is an independent cardiovascular and atherosclerotic risk factor
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Cardiac autonomic neuropathy increases morbidity and mortality in obesity and diabetes and has greater predictive power than traditional risk factors for cardiovascular events
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ANS dysfunction and poor physical fitness during young adulthood are associated with a 3.4-fold increased risk of incident diabetes in middle-age
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Endurance
Conflict of interest
None to declare.
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