It is well established that physical activity and exercise training is, as part of a multidisciplinary rehabilitation program, key to optimise health and prognosis in patients with cardiovascular disease (CVD).1 It will contribute to greater improvements in body composition, lipid profile, blood pressure, exercise capacity and muscle strength, inflammation, vascular function and even cardiac function.2 These effects may help to explain why exercise training and physical activity is independently related to enhanced survival rates and lowered risk for adverse cardiovascular events in patients with coronary artery disease, and lower hospitalisation rates in heart failure patients.3,4
However, type 2 diabetes mellitus (T2DM) is very often co-existent in CVD patients, which may clearly affect the clinical outcome (e.g. prognosis). For example, increased prevalence rates of diabetes have been reported in patients with coronary artery disease, such as in the Framingham Heart Study5 and the Multiple Risk Factor Intervention Trial6. From these studies, the prevalence of diabetes in patients with coronary artery disease varied from 14 to 26%. These prevalence rates can be even higher in heart failure patients.7 As a result, clinicians should be aware of the potential presence of T2DM in every patient with CVD at entry of a rehabilitation program, even when it is not diagnosed yet. This means that the glycaemic control should be assessed in every CVD patient to rule out the potential presence of T2DM (as defined as: either the fasting plasma glucose concentration is ≥126 mg/dL or 7.0 mmol/l, 2-h plasma glucose concentration during a 75-g oral glucose tolerance test is ≥200 mg/dl or 11.1 mmol/L, or HbA1c is ≥6.5% or 48 mmol/mol)8, and if present, clinicians should adapt their exercise prescription accordingly. The latter may be a challenge to clinicians, and is therefore the scope of this how-to-article.
Does the presence of T2DM affect my exercise prescription to a patient with CVD?
It absolutely does. Not adjusting the exercise prescription according to the presence of T2DM in a patient with CVD will lead to missed clinical benefits of exercise training, as well as increased risks for improper or medically less safe exercise training. As a result, adjustments in exercise prescription should be made in such patient to 1. Improve the clinical benefits of exercise training, and 2. Maximise the medical safety of exercise training. When both targets are then achieved, these patients may be more motivated to continue exercising on their own (after discharge from the rehabilitation unit) as they notice these clinical benefits while minimising the risks for (minor) adverse events. It must be mentioned that when deciding which exercise prescription has to be adhered to by the patient, it must be explained in detail to this patient why such prescription is preferable: this will lead to a better patient’s insight into T2DM and the role of exercise/physical activity, which can be of great benefit towards long-term adherence to physical activity guidelines (e.g. it stimulates self-efficacy).
Enhancing the clinical benefits of exercise training
The most obvious clinical benefits of exercise training, specifically in T2DM, are the enhancements of the insulin sensitivity (although short-lived (up to two days after an exercise bout)), reductions in 24-hour glycaemic variability and blood glucose excursions (also short-lived), and reductions in blood glycated haemoglobin (HbA1c, by +-0.7%). Such benefits are strongly related to improved vascular function and lowered risk for micro- and macrovascular complications and even cardiac dysfunction (e.g. lowered fibrosis). As a result, clinicians should aim to maximise the benefits of exercise training on these glycaemic control-related factors by adjusting their exercise prescription.
According to clinical guidelines, the most optimal exercise training program for T2DM patients should consist of at least 3-5 endurance exercise training sessions of at least 30 minutes per week at a moderate-to-high intensity (i.e. at least 50-70% of peak oxygen uptake (VO2peak)).9 These endurance exercises should be complemented by strength training exercises for 2-3 sessions per week involving large muscle groups at an intensity of 75-85% of 1 repetition maximum (8-10 repetitions).9 However, these exercise prescriptions very often also apply to CVD patients without T2DM, so it should be clarified into greater detail how the exercise prescription should thus be adapted according to the presence/absence of T2DM.
According to recent insights from meta-analyses, the frequency of the endurance exercise sessions seems to be predominant in order to improve the glycaemic control in T2DM patients.10 Mainly a high exercise frequency is independently related to greater enhancements of the glycaemic control in T2DM (e.g. greater reductions in HbA1c), while the session duration and exercise intensity seems less important. As a result, clinicians should address this together with the patient: how can daily physical activity become a reality and how do we achieve this? It seems that even shorter sessions may then be clinically relevant and effective (+-30 minutes). The evidence for the application of high-intensity interval training to enhance the glycaemic control is accumulating in T2DM patients: a recent meta-analysis indicated significantly greater reductions of this exercise modality on HbA1c, when compared with the more commonly used moderate-intense endurance training in T2DM patients.11 However, the medical safety of this exercise modality remains to confirmed in large cohorts of T2DM patients before being implemented in clinical practice or being advocated in clinical guidelines.
Another important adaptation in the exercise prescription to patients with T2DM is the addition of strength training on top of endurance training: this leads to significant greater improvements in the glycaemic control (e.g. greater reductions in HbA1c) in T2DM.12 However, when adding this exercise modality to endurance training, exercise volume matters the most here. It seems that significantly greater improvements in glycaemic control are noticed when a minimum of 21 strength training sets are achieved during a single exercise session.12 As such, this would translate into three sets of strength training for at least seven different muscle groups, which is considered a significant amount of exercise and, hence, time investment in this exercise modality. When selecting the types of exercise, it is also important to aim to exercise large muscle groups. The intensity of strength training does not seem to relate to changes in glycaemic control, meaning that also lower strength training intensities may be applied in certain patients.
Maximising the medical safety of exercise training
Patients with T2DM may experience (significant) co-morbidities, such as vascular disease, retinopathy, nephropathy, orthopaedic symptoms, peripheral neuropathy and/or autonomic dysfunction. Moreover, hyper- and hypoglycaemia and the intake of certain blood glucose lowering drugs may further complicate participation into exercise training programs. As a result, clinicians should be aware of how to adjust exercise prescriptions, based on the presence of these co-morbidities and reported difficulties by the patient.
Clinicians are thus advised to screen for the prevalence of potential co-morbidities, interview the patient for experienced difficulties in physical activity or sports participation, and assess the current glycaemic control at entry of a rehabilitation program, in order to adjust exercise prescription accordingly.9 Such intake screening should be executed by a multidisciplinary team, in which these clinicians adhere to established international standards.8 Based on the outcomes of this intake assessment, the following adaptations in exercise prescription should be considered9,13,14:
- Vascular disease: significant (symptomatic) peripheral arterial disease may limit walking capacity. In these patients it is therefore important to adjust the objectively determined exercise intensity (e.g. based on %VO2peak, %HRpeak of %HR reserve) when peripheral symptoms are predominant. Moreover, to some patients, prolonged exercise may not (yet) be feasible. Therefore, patients with significant peripheral arterial disease may require a rehabilitation phase in which the exercise intensity and duration is gradually increased until the desired intensity and duration is achieved. A significant proportion of T2DM patients (+-20%) may also suffer from silent myocardial ischemia. Such ischemia is detected by ECG monitoring during cardiopulmonary exercise testing: these patients are not advised to exercise above the myocardial ischemia threshold as it may provoke (unnoticed) cardiac arrhythmias. Greater exercise intensities can however be applied in fully revascularised patients.
- Retinopathy: T2DM patients with established retinopathy should not engage into sustained high-intense exercise (>75% VO2peak) or high-intensity interval training as this may facilitate the disease progression.
- Nephropathy: T2DM patients with established arterial hypertension should be treated aggressively to optimise blood pressure in order to prevent or manage nephropathy. As a result, also during exercise training, too high systolic blood pressures should be avoided (<180 mmHg) in T2Dm patients with established nephropathy, and blood pressure should be assessed regularly during exercise training.
- Orthopaedic symptoms: Patients with T2DM are more prone to experience the following orthopaedic co-morbidities: diabetic hand syndrome, Dupuytren contracture, trigger finger, frozen shoulder, Charcot foot, diffuse idiopathic skeletal hyperostosis and osteoarthritis. In addition, feet complications (e.g. abnormal colour, dryness, cracking, sweating, infection, ulceration, blistering, deformity) are more common in this population and should thus be examined as well. Exercise prescription should thus be reconsidered according to these symptoms. Most often a different exercise type should be preferred in these patients (for example: cycling) or additional physiotherapy/care of feet can be indicated.
- Peripheral neuropathy: This co-morbidity could significantly affect walking ability. Exercises (duration and speed) on a treadmill should thus be build-up gradually until the patient (with significant peripheral neuropathy) is accustomed to this exercise type.
- Autonomic dysfunction: These patients can develop dysregulations in blood pressure and/or transpiration during exercise, but also alterations in HR/workload relation during exercise. As a result, in these patients is it important to monitor blood pressure closely during exercise training and to assess the true HR/workload relation by cardiopulmonary exercise testing. Chronotropic incompetence (e.g. alterations in the HR/workload relation) is much more prevalent in T2DM patients, even without the intake of beta-blockers. It may thus occur that an exercise HR should be preferred that deviate from the known exercise intensity domains, as published in the guidelines.15
- Hypo/hyperglycaemia: A low blood glucose concentration (<4.2 mmol/l, <75 mg/d) ahead of exercise is no contra-indication to exercise training. Such patient should consume monosaccharides until a normal blood glucose concentration is achieved (>5.5 mmol/l, >100 mg/dl), after which exercise training can be started. In case of hyperglycaemia (>16.7 mmol/l, >300 mg/dl)), on the other hand, high-intense exercise (>75% VO2peak) should not be executed, as this may lead to worsening in hyperglycaemia. Certain medications can elevate the risk for hypoglycaemia during, or in the first hours after, exercise: glinides, sulfonylurea and exogenous insulin injections. For these patients, it is important to adjust medication prescription according to the planned exercise. This is of particular importance to patients undergoing exogenous insulin therapy, for which flowcharts do exist.14 All other blood glucose lowering drugs do not elevate the risk for hypoglycaemia during exercise.
Exercise training is important to CVD patients. However, when T2DM is co-prevalent significant adjustments in exercise prescriptions should be made to enhance the clinical benefits on glycaemic control and maximise the medical safety of exercise training.