Chronotropic Incompetence During Exercise in Type 2 Diabetes: Aetiology, Assessment Methodology, Prognostic Impact and Therapy

Abstract

During incremental exercise tests, chronotropic incompetence (CI), which is the inability of the heart rate (HR) to rise in proportion to an increase in metabolic demand, is often observed in patients with type 2 diabetes mellitus (T2DM). Despite the fact that CI is associated with exercise intolerance and elevated risks of development of cardiovascular disease and premature death, this clinical anomaly is often ignored or overlooked by clinicians and physiologists. CI is, however, a significant clinical abnormality that deserves further attention, examination and treatment. The aetiology of CI in T2DM remains poorly understood and is complex. Certain T2DM-related co-morbidities or physiological anomalies may contribute to development of CI, such as altered blood catecholamine and/or potassium levels during exercise, structural myocardial abnormalities, ventricular and/or arterial stiffness, impaired baroreflex sensitivity and cardiovascular autonomic neuropathy. Clinicians should thus be aware of the potential presence of yet undetected anomalies or diseases in T2DM patients who experience CI during exercise testing. However, an effective treatment for CI in T2DM is yet to be developed. Exercise training programmes seem to be the only potentially effective and feasible interventions for partial restoration of the chronotropic response in T2DM, but it remains poorly understood how these interventions lead to restoration of the chronotropic response. Studies are thus warranted to elucidate the aetiology of CI and develop an effective treatment for CI in T2DM. In particular, the impact of (different) exercise interventions on CI in T2DM deserves greater attention in future studies.

Impact of blood glucose control on sympathetic and vagus nerve functional status in patients with type 2 diabetes mellitus

“…The prevalence of type 2 diabetes mellitus (DM) is increasing constantly worldwide [1]. It is known that abnormal glucose metabolism could damage major body organs such as heart, blood vessels, kidneys and nerves.…”

Heart Rate During an Exercise Test and Acute High-intensity Interval Training in Type 2 Diabetes

“…With respect to this lower ∆HR INT in the T2D group, it has previously been reported that T2D subjects are unable to increase their HR proportionally to the increase in muscle activity or metabolic demand. This phenomenon is known as chronotropic incompetence; and it is measured mainly by tests with increasing exercise intensities [8,9]. However, we presume that in the present study, this adaptation may be most likely due to the older age of the T2D group, since it is known that there is a marked and inevitable ageing-related reduction in maximum HR in response to exercise [25,26].…”

“…Exercise training is a cornerstone for the prevention [1][2][3] and treatment of metabolic disorders and associated cardiometabolic complications such as type 2 diabetes mellitus (T2D) and hypertension [4][5][6][7]. Nevertheless, individuals with disturbed glycaemic profile have shown abnormal cardiovascular responses to exercise, for instance T2D subjects exhibit blunted heart rate (HR) increments in proportion to the exercise-induced metabolic demand [8,9]. However, it has been shown improvements on HR responses upon regular exercise training in T2D individuals during recognized time-ef-ficient exercise modalities [10].…”

“…However, it has been shown improvements on HR responses upon regular exercise training in T2D individuals during recognized time-ef-ficient exercise modalities [10]. The underlying mechanisms related to this disturbed HR response to exercise are not fully understood, but T2D pathology is associated with various co-morbidities that could contribute to this altered response, such as abnormal blood catecholamine levels during exercise, structural myocardial alterations, ventricular and or arterial stiffness, impaired baroreflex sensitivity and cardiovascular autonomic neuropathy [9].…”

Effect of Beta-Blocker Therapy, Maximal Heart Rate, and Exercise Capacity During Stress Testing on Long-Term Survival (from The Henry Ford Exercise Testing Project)

“…9–14 Nevertheless, despite its prognostic utility, chronotropic incompetence remains underappreciated in clinical practice, 1,9 in part from the potential confounding effects of beta blocker therapy (BBT), and the multitude of heart rate thresholds and equations derived for this patient population. 1,7,11–13,15 Notably, exercise capacity is also a powerful predictor of survival, 16–20 however, the combined effect of exercise capacity and BBT on the prognostic value of peak exertional heart rate remains unexplored.…”