Cardiovascular Determinants of Aerobic Exercise Capacity in Adults With Type 2 Diabetes

Abstract

To assess the relationship between subclinical cardiac dysfunction and aerobic exercise capacity (peak VO 2) in adults with type 2 diabetes (T2D), a group at high risk of developing heart failure. RESEARCH DESIGN AND METHODS Cross-sectional study. We prospectively enrolled a multiethnic cohort of asymptomatic adults with T2D and no history, signs, or symptoms of cardiovascular disease. Age-, sex-, and ethnicity-matched control subjects were recruited for comparison. Participants underwent bioanthropometric profiling, cardiopulmonary exercise testing, and cardiovascular magnetic resonance with adenosine stress perfusion imaging. Multivariable linear regression analysis was undertaken to identify independent associations between measures of cardiovascular structure and function and peak VO 2. RESULTS A total of 247 adults with T2D (aged 51.8 6 11.9 years, 55% males, 37% black or south Asian ethnicity, HbA 1c 7.4 6 1.1% [57 6 12 mmol/mol], and duration of diabetes 61 [32-120] months) and 78 control subjects were included. Subjects with T2D had increased concentric left ventricular remodeling, reduced myocardial perfusion reserve (MPR), and markedly lower aerobic exercise capacity (peak VO 2 18.0 6 6.6 vs. 27.8 6 9.0 mL/kg/min; P < 0.001) compared with control subjects. In a multivariable linear regression model containing age, sex, ethnicity, smoking status, and systolic blood pressure, only MPR (b 5 0.822; P 5 0.006) and left ventricular diastolic filling pressure (E/e9) (b 5 20.388; P 5 0.001) were independently associated with peak VO 2 in subjects with T2D. CONCLUSIONS In a multiethnic cohort of asymptomatic people with T2D, MPR and diastolic function are key determinants of aerobic exercise capacity, independent of age, sex, ethnicity, smoking status, or blood pressure. Heart failure (HF) has emerged as one of the commonest and deadliest complications of type 2 diabetes (T2D) (1). Even in asymptomatic individuals with T2D, there is a high prevalence of left ventricular (LV) systolic and diastolic dysfunction and/or cardiac remodeling (2,3). The American Heart Association has classified such individuals as having stage B HF (4), and this group is at high risk of developing clinical symptoms. Earlier identification of the cardiovascular manifestations of stage B HF may permit earlier diagnosis and treatment of those patients most at risk (5).

Mechanisms of reduced peak oxygen consumption in subjects with uncomplicated type 2 diabetes

“…Our findings confirm most previous reports (although not all [ 39 ]) describing reduced S’ velocity of the mitral annulus measured through tissue Doppler in patients with T2D during exercise [ 40 – 42 ], an observation that was also related to myocardial fibrosis as measured though cardiac magnetic resonance [ 43 ]. Given the large prevalence of diastolic dysfunction in T2D subjects [ 38 ] and the results of a recent report by Gulsin et al [ 44 ], we were surprised not to see alteration in E/e’ in our population with effort intolerance, neither at rest nor during exercise. In the work of Gulsin and coll., however, diastolic indices were not measured during exercise, and the association was essentially driven by a minority of subjects with a baseline E/e’ > of 12.5, and in the whole population the effect size was small with + 1 units of E/e’ justifying -0.3 ml/kg/min of VO 2peak .…”

Clinical associations with stage B heart failure in adults with type 2 diabetes

“…Indeed, we have recently shown that MPR is associated with aerobic exercise capacity in asymptomatic adults with T2D, independent of age, sex, ethnicity, smoking status, glycaemia and diastolic function. 5 This suggests a central role for microvascular dysfunction in SBHF in people with T2D.…”

“…This is especially significant given the vast majority of people with T2D develop heart failure with preserved ejection (HFpEF), a condition that has no proven effective treatments. 4 We have recently demonstrated that subclinical concentric LV remodelling, arterial stiffening, abnormalities in diastolic and systolic function, and reduced myocardial perfusion are present in T2D, 5 , 6 and these features are increasingly recognised as pathognomic features of SBHF and precursors to the onset of clinical heart failure. 4 , 5 The clinical factors contributing to early cardiovascular dysfunction in people with T2D, however, are poorly understood.…”

“… 4 We have recently demonstrated that subclinical concentric LV remodelling, arterial stiffening, abnormalities in diastolic and systolic function, and reduced myocardial perfusion are present in T2D, 5 , 6 and these features are increasingly recognised as pathognomic features of SBHF and precursors to the onset of clinical heart failure. 4 , 5 The clinical factors contributing to early cardiovascular dysfunction in people with T2D, however, are poorly understood. Previous imaging studies have been hindered by variations in methods of assessing cardiac structure and function, as well as small sample sizes (seldom greater than 100 subjects) and incomplete datasets with significant risk of overfitting the regression models.…”

Subclinical Cardiac Dysfunction is Associated with Reduced Cardiorespiratory Fitness and Cardiometabolic Risk Factors in Firefighters

“…Coronary microvascular dysfunction is associated with a higher BMI, is linked to increased microvascular resistance and provides independent prognostic information for cardiovascular risk in obese patients 34,35 . Asymptomatic diabetic patients undergoing cardiac MRI have also been shown to have decreased myocardial blood flow from microvascular dysfunction, a finding that was linked to reduced peak VO 2 36 . Thus, inducible myocardial dysfunction may be the result of endothelial dysfunction and coronary microvascular dysfunction.…”