A patient with type 2 diabetes managed with diet and exercise who takes metoprolol

Acute glycaemic management before, during and after exercise for cardiac rehabilitation participants with diabetes mellitus: a joint statement of the British and Canadian Associations of Cardiovascular Prevention and Rehabilitation, the International Council for Cardiovascular Prevention and Rehabilitation and the British Association of Sport and Exercise Sciences

1. //orcid.org/0000-0001-6235-3395John P Buckley1,2,
2. Michael Riddell3,4,
3. Duane Mellor5,6,
4. Richard M Bracken6,
5. Marie-Kristelle Ross7,
6. //orcid.org/0000-0002-3906-3784Andre LaGerche8,9,
7. Paul Poirier10

1. 1 Shrewsbury Centre for Active Living, University of Chester Faculty of Medicine and Life Sciences, Chester, Cheshire West and Chester, UK
2. 2 Institute of Sport Exercise and Health, University College London, London, UK
3. 3 School of Kinesiology and Health Science, York University, Toronto, Ontario, Canada
4. 4 LMC Healthcare, Diabetes and Endocrinology, Toronto, Ontario, Canada
5. 5 Aston Medical School, Aston University, Birmingham, West Midlands, UK
6. 6 Sport and Exercise Science, Swansea University College of Engineering, Swansea, Wales, UK
7. 7 Hotel-Dieu de Levis, Laval University Faculty of Medicine, Quebec city, Quebec, Canada
8. 8 Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia
9. 9 St Vincent's Hospital Melbourne Pty Ltd, Fitzroy, Victoria, Australia
10. 10 Cardiology, Institut universitaire de cardiologie et de pneumologie de Québec, Quebec City, Quebec, Canada

1. Correspondence to Professor John P Buckley, Shrewsbury Centre for Active Living, University of Chester Faculty of Medicine Dentistry and Life Sciences, Chester CH1 4BJ, UK; j.buckley{at}chester.ac.uk

Abstract

Type 1 [T1] and type 2 [T2] diabetes mellitus [DM] are significant precursors and comorbidities to cardiovascular disease and prevalence of both types is still rising globally. Currently,~25% of participants [and rising] attending cardiac rehabilitation in Europe, North America and Australia have been reported to have DM [>90% have T2DM]. While there is some debate over whether improving glycaemic control in those with heart disease can independently improve future cardiovascular health-related outcomes, for the individual patient whose blood glucose is well controlled, it can aid the exercise programme in being more efficacious. Good glycaemic management not only helps to mitigate the risk of acute glycaemic events during exercising, it also aids in achieving the requisite physiological and psycho-social aims of the exercise component of cardiac rehabilitation [CR]. These benefits are strongly associated with effective behaviour change, including increased enjoyment, adherence and self-efficacy. It is known that CR participants with DM have lower uptake and adherence rates compared with those without DM. This expert statement provides CR practitioners with nine recommendations aimed to aid in the participant’s improved blood glucose control before, during and after exercise so as to prevent the risk of glycaemic events that could mitigate their beneficial participation.

• cardiovascular
• diabetes
• exercise rehabilitation
• heart disease
• nutrition

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• cardiovascular
• diabetes
• exercise rehabilitation
• heart disease
• nutrition

Introduction and aims

This guidance statement is aimed at helping front-line practitioners better manage the growing number of cardiac rehabilitation [CR] participants who have diabetes.1 It has been developed and written by a group of practitioner–academics with a special interest in how diabetes management interacts with their practices in cardiology [three authors], dietetics [one author], rehabilitation therapy [one author] or exercise science applied to metabolic care [two authors]. All of the authors have previous experience in contributing to national and international practice guidelines/standards in either CR and/or diabetes. They have been brought together to combine their expertise to represent the multi-professional CR associations of the UK and Canada, who are partnered with 38 other countries that make up the International Council of Cardiovascular Prevention and Rehabilitation [ICCPR]. This means that the statement has also been reviewed and endorsed by doctors, nurses, physiotherapists, exercise physiologists, dietitians and psychologists representing health professionals and groups from around the world. The statement is laid out in two parts; Part 1 is a summary table [table 1] of nine key recommendations on managing glycaemic control in and around exercise, and Part 2 provides the evidence-based consensus that underpins these recommendations.

Table 1

A summary of nine key statements for managing glycaemic control in cardiac rehabilitation participants before, during and after exercise

Table 2

Acute exercise interactions with diabetes medications [adapted from Nagi and Gallen;18 Eckstein et al]19

Part 1

The summary guidance statements in table 1 include scores [+sign in brackets] from the GRADE* system2 for evidence quality, which was used in the development of the recent Diabetes UK Nutritional Guidelines.3 4

Part 2

Background

Evidence search and review

The search and review strategy involved using health and medicine databases [CINAHL, PubMed, MEDLINE, Embase and TRIP]. Initial searches commenced by reviewing existing key position statements and guidelines from other national and international associations that combined the topics of exercise, cardiovascular health/rehabilitation, diabetes and glycaemic management. The only statement which was most closely allied to this same focus was the 2012 position statement of the American Association of Cardiovascular and Pulmonary Rehabilitation [AACVPR].5 6 More recently [2019], the European Association of Preventive Cardiology [EAPC]7 produced guidelines but these focussed on principles of exercise prescription and outcomes in type 2 diabetes mellitus [T2DM], as opposed to our focus on mitigating acute risks from exercise of glycaemic events in CR8 participants with either type 1 diabetes mellitus [T1DM] and T2DM. Following this, we searched and reviewed landmark review and consensus statements reporting on acute glycaemic management during exercise in people with diabetes from the past 10 years.9–21 In noting the dates of the cited evidence in these statements, our final search involved the reference lists of the cited evidence and then searching and reviewing individual studies beyond the last date where guidelines did not yet exist. Our review and consensus not only included the efforts of the authors but also a second level checking by the council members of the multi-professional societies of the British and Canadian Associations of Cardiovascular Prevention and Rehabilitation, the British Association of Sport and Exercise Sciences and the ICCPR. In considering evidence quality, the authors wish to emphasise that this consensus statement focusses on pragmatic acute matters of safety and behavioural efficacy of completing individual exercise sessions. The systematically reviewed guidance on following appropriate risk stratification published by one of our authors on exercise safety in T1DM and T2DM22 provides a key example of our underpinning rationale in translating applications into the arena of CR. Furthermore each of the Guidance notes in table 1 have been scored with the GRADE system for evidence quality2 as applied in recent Diabetes UK guidelines led by another one of our authors.3 If the guidance in this new statement can aid practitioners in reassuring CR participants with DM that they are safe to exercise and this positively influences their participation behaviour, then it has fulfilled its aims. As a result, it has been realised that much future research is required to evaluate the efficacy of these recommendations in terms of participant behaviour and education efficacy. As always, the largest challenge to outcomes in physical activity and exercise, whether in public health or rehabilitation/secondary prevention, is not simply biomedical or physiological, they are the complex behavioural interactions influenced by society, psychology, genetics and lifestyle impositions.

Identifying the need

T1DM and T2DM are significant precursors and comorbidities to cardiovascular disease and the prevalence of both types is still rising globally.23–25 Pan-European data show that over 25% of people with established coronary heart disease have a history of DM, where >90% have T2DM.7 26–28 Compared with T2DM, T1DM has a greater overall cardiovascular disease risk.29 Risk factor analyses have also identified specific DM associations for heart failure, stroke and peripheral vascular disease.30 31 Therefore, modern programmes of CR need to have their staff able to manage additional exercise considerations for DM. A recent Position Paper from the EAPC provides guidance on exercise prescription for people with T2DM participating in cardiovascular disease [CVD] prevention and rehabilitation programmes.7 The prevalence of T1DM is also increasing globally32 33 and a majority of this population also develop macrovascular disease at rates similar to what is observed in T2DM.34 Although the glycaemic control of individuals with T1DM35 and T2DM36 remains a major challenge in both developed and developing countries, considerable evidence supports the concept that regular physical activity and exercise programming benefits both T1DM and T2DM groups in the prevention of microvascular and macrovascular disease progression.10 11 13

Rationale, aims and framework of this statement

Although the debate continues on whether improved glucose control in those with CVD actually helps to prevent further DM progression,37 it is clear that poor glycaemic management will mitigate the performance of optimally safe, effective and enjoyable physical activity for the CR participant.38 As noted earlier, key statements on the guidance and numerous health benefits that exercise confers in individuals with diabetes already exist from a number of international authorities from Canada, Europe and the USA.6 7 9 10 13 15 39 This current Statement neither aims to review the physiological and long-term health benefits of increased physical activity in people with cardiovascular and metabolic disease nor to supersede these other published guidelines. This current consensus statement specifically aims to focus on guidance for managing the acute glycaemic needs before, during and after an exercise session in CR participants with diabetes. The objectives for meeting the aims of this statement include the following elements:

• Factors influencing physical activity behaviour influenced by concerns around blood glucose management,

• Preventing incidences and/or managing hypoglycaemic or hyperglycaemic events,

• Preventing accidents, injury or symptoms from neuropathies leading to sensorimotor deficiencies, and

• Considering interactions between exercise and medications for the CR participant with diabetes.

The above elements will be covered in three main sections:

1. Overarching considerations for all participants with DM [Sections 3 to 5];

2. Specific glycaemic risk and management in T1DM [Section 6];

3. Specific glycaemic risk and management in T2DM [Section 7].

Section 8, provides some brief notes regarding exercise intensity interactions with obesity and Section 9 the conclusion.

Overarching considerations; behaviour, screening and activity intensity

Behavioural considerations

Globally, it is estimated that the behaviour of physical inactivity is a cardiovascular disease risk factor found in up to ~45% of individuals, for whom many have cardiovascular disease, T2DM or cancer [breast and colon]; in some western higher-income countries the prevalence of inactivity rises to 70%.40 41 It is therefore likely that many people entering a CR programme, including participants with diabetes, will have a history of physical inactivity and naturally requiring a staged approach of targeted lifestyle behavioural-change strategies. It is a large enough challenge to get CR participants more physically active to any degree, let alone achieving the minimum targets recommended for an exercise-based rehabilitation programme [ie, >60 min per week at an intensity ≥2.5 metabolic equivalents].42–44 One of the key challenges to CR participation is the perceived health risk to participation.45 46 This fear is further compounded in those with DM, especially those with T1DM, where there is an added fear of hypoglycaemia and its consequences.13 47 48 Even if CR participants with diabetes take up participation in CR, their physical activity goal attainment is poorer compared with participants without diabetes.1 7 49 Hypoglycaemia is also a barrier for engagement in exercise for those individuals with T2DM who are on insulin therapy or sulphonylureas.50 In some settings, high intensity exercise may promote a rise in glucose resulting in hyperglycaemia in patients with T1DM and some with T2DM,51 52 and this may also be perceived as a barrier to participate. For example, if a CR participant arrives to join an exercise group whose blood glucose is at a relatively contraindicated level for exercise of too high or too low a level [ie, >15 mmol/L or 8.0 mmol/L], then milder intensity aerobic exercise could be initiated first, while if glucose levels were on the lower end [ie, 1.5 mmol/L before exercise onset in individuals with T1DM] which requires urgent medical attention/intervention.13 Though not common in T2DM, ketoacidosis can occur, and the same urgent attention should be given for blood ketones levels >1.5 mmol/L.72

Sensorimotor considerations

Sensory and motor disturbances in diabetes are common and may increase the risk for falls and injury.74 Care should be taken to maximise safety and minimise foot injuries associated with increased levels of physical activity in these patients, including balance assessment and regular foot exams.75 While not directly related to acute glycaemic management, many complications of diabetes can compound the problems associated with hypoglycaemia or hyperglycaemia, which thus limit the ability of participants performing physical activity. These include: renal disease, where raised urea level is known to lead to fatigue;76 retinopathy with concerns over activities that increase intraocular pressure; peripheral neuropathy linked with hand/foot ulcers and loss of motor sensation; autonomic neuropathy that affects recognising symptoms of angina and hypoglycaemia; reducing the ability of the heart rate to increase and reduced thermoregulation.14 If a CR participant with diabetes has known complications or appears to have symptoms suggesting loss of neuro or motor function, it is vital that immediate advice from specialists is sought. It is important to note however, that patients with advanced disease can still exercise if certain precautions are made including the supervision of exercise sessions by a qualified exercise specialist and a modified training programme.77 78

Diabetes interactions with cardiovascular medications

Beta blockers, heart rate and oxygen-uptake kinetics

Beta-blocker medication, commonly taken by most CR participants, attenuates heart rate response and oxygen uptake kinetics during exercise.79 Diabetes also reduces the responsiveness of the heart rate to increased work demands [and similarly for oxygen uptake responses] when either exercise commences or when exercise intensity is increased.80 The potential mechanisms for this have been reported to be, but not yet fully agreed, either neuro-chronotropic80 and/or a result of lower activity/fitness levels linked with lowered left ventricular function.81 82 Until the evidence is clearer on the combined effect of diabetes and beta-blockade, it would seem prudent for CR participants with diabetes on beta-blockers to expect a further reduction in heart rate responsiveness to any given change in exercise intensity compared with beta-blocked CR participants without diabetes.

In individuals who manage their glycaemia with insulin administration [basal and/or bolus insulin] as well as considering any adjustments to doses with their diabetes specialist team; the site of injection should also be considered.13 It is thought that the increased blood flow associated with exercise in the legs or arms may increase the rate of uptake of insulin as compared with other insulin administration locations [abdomen, upper buttock]. This could increase the risk of hypoglycaemia with exercise. It is generally advised that insulin administration should be limited to the abdomen or upper buttock if an exercise session is to be initiated post-insulin administration.83 However, this may not fully protect against exercise-associated hypoglycaemia and other preventative actions may be required [ie, insulin dose reduction, carbohydrate snacking].52 84–87

Statins, traditional thiazides and some beta blockers can reduce glycaemic control in diabetes88–92 and in some patients metformin can reduce the benefits of atorvastatin.93 In relation to the interactions between medications, exercise and diabetes, there is much literature on beta-blockers either affecting liver glucose output, insulin release, muscle glucose uptake and reductions in hypoglycaemic symptom sensations [eg, tachycardia blunted].92 94 95 Non-vasodilating beta-blockers [metoprolol, bisoprolol, atenolol and bucindolol] can negatively impact on glucose control but vasodilating beta-blockers [carvedilol and nebivolol] are reported to have little deleterious effect on glucose control.96 It is therefore important to check which beta-blocker the CR participant is taking, and to enquire with the medical team of the potential benefits of using a vasodilating beta-blocker.

It has also been reported that there are two negative effects of the blood glucose lowering medications from the sulphonylurea glibenclamide on normal exercise responses, which are important to CR participants:

1. The benefit of ‘the warm-up’ to prevent subsequent ischaemia during moderate to higher intensity exercise is impaired in those with stable angina,97 98 thus increasing the chances of exertion-related angina during a typical exercise session, and

2. The normal effect that exercise has on acutely reducing blood insulin during higher intensity exercise is significantly impaired,99 which means that higher intensity exercise could contribute to hypoglycaemia in those treated with gliclazide and other sulphonylureas.

Table 2 provides a summary of the interactions between common medications used in diabetes management and exercise.

Euglycaemic ketoacidosis with SGLT-2 Inhibitors

Sodium-glucose cotransporter-2 [SGLT-2] inhibitors are mainly prescribed in T2DM, but can also be used in T1DM under very specific circumstances.100–102 They are principally seen as an add-on therapy when biguanides [eg, metformin] alone are not sufficient to reach the glycaemic targets. The SGLT-2 inhibitors have shown benefits in patients with cardiovascular disease,103 making it an interesting choice in that population. However, ketoacidosis, even in the absence of hyperglycaemia, has been reported in patients taking SGLT-2 inhibitors.5 Although rare, this euglycaemic ketoacidosis is serious and could potentially be fatal if not recognised.100 102 In light of this evidence, any patients on SGLT-2 inhibitors should be asked to report if and when they have experienced symptoms of nausea, vomiting or malaise, and also other typical symptoms of ketoacidosis [increased urination frequency, thirst, abdominal pain, confusion, ‘pear-drop breath’, flushed face, fatigue, rapid breathing, dry mouth and skin]. A concomitant decline in exercise performance would be a key sign of any of these symptoms of ketoacidosis and exercise would sensibly be contraindicated for a number of reasons in these instances anyway. The effects of SGLT2 antagonism on hypoglycaemia risk associated with exercise are unknown, but these medications typically result in lower glucose concentrations in general and more vigilant glucose and ketone monitoring [using portable ketone metres] around exercise seems prudent.

Time of day of exercise influences

In addition to the effects of the timing of eating around exercise on glycaemic control, the time of day [circadian effects] of exercise also influence glycaemic regulation in both T1DM and T2DM.20 104–106 In those patients to whom it is of concern to reduce the risk of post-exercise hypoglycaemic events, morning exercise is recommended and for those more prone to hyperglycaemia, afternoon and evening exercise [including HIIT in T2DM] have been demonstrated as preferable.104 106–109 In these noted studies of morning exercise before breakfast [~0700 hours], the post-breakfast glucose levels were actually more normal compared with having breakfast before exercise, with fewer hypos’ in the subsequent 15 to 24 hours. However, fasted morning HIIT may promote a significant rise in glucose concentration in both T1DM and T2DM.106 110 It is also important to note that post-exercise hypoglycaemic events can be delayed up to 15 hours,71 111 so it is important to inform CR participants to monitor their blood glucose levels more carefully in this period.

Specific considerations for type 1 diabetes

A general rule is that those with T1DM are at higher risk of an exertion-related glycaemic event compared with those with T2DM.12 Managing blood glucose levels in and around exercise in people with T1DM is therefore more challenging and crucial than in T2DM. The guidance on glucose management summarised in table 1 is of most pertinence to this group of CR participants. While more evidence is required on efficacy, it would seem prudent for CR practitioners to now be skilled in using and include glucose and ketone monitoring devices as part of their standard equipment, in a similar way to having blood pressure, heart rate and ECG monitors.

Aerobic endurance type exercises [walking, jogging, light-to-moderate cycling] are likely to contribute to hypoglycaemia, whereas activities involving short bursts of higher intensity activity [sprints, weight training and circuit training] can contribute to hyperglycaemia.13 Unlike T2DM, where glycaemic control can be improved over time with increased levels of physical activity, in T1DM such improvements do not usually ensue.11 112 Risk of severe hypoglycaemia increases markedly with age and disease duration in this population.113 In light of such a benefit paradox for T1DM, it is important to reinforce with CR participants that their main gain from the exercise is significant improvements in cardiovascular health and fitness.114 115 Specific to diabetes, the CR participant can be informed that increasing levels of physical activity and improved fitness can help in reducing the risk of retinopathy and moderately increased albuminuria.13 116 For those people with T1DM and poorer glycaemic control, there is an increased chance of an atypically accelerated heart rate response at higher exercise intensities [>75% maximal heart rate] and it is important to observe the intensity of exercise at this point to determine if the participant is over-exerting themself.117 Poor glucose control is also associated with a greater risk for diabetic ketoacidosis in T1DM.113

While the recent advances in glucose management with continuous subcutaneous insulin infusion [pump] or closed-loop insulin pumps have reduced some of the burden of diabetes self-care, through allowing freer independent care and freer living, the individualised nature of T1DM remains a challenge.118 119 This is especially true when setting individual insulin delivery levels in and around exercise, sports participation and nutrition. A tripartite team approach between the individual patient, the diabetes specialist [physician and/or nurse] and the exercise practitioner thus continues to remain an important factor in achieving quality, safe and effective care for the individual participant. Insulin treatment is essential as part of the management of T1DM, therefore when planning physical activity, the type and amount of insulin [affected by time of last injection and dose] as well as the time of the last carbohydrate containing meal [including quality and quantity] needs to be considered. The overarching considerations are whether the exercise is planned or unplanned, and the intensity and duration of the exercise.13 In general, lowering insulin pump basal rates needs to be made in advance of aerobic exercise by approximately 60 to 90 min, if possible, to be effective in limiting hypoglycaemia.86 Insulin pumps can be beneficial for improving glucose control after exercise as compared with multiple daily injections,120 because they likely allow for temporary basal rate reductions to prevent post-exercise hypoglycaemia and bolus or basal rate corrections for post-exercise hyperglycaemia.13

Contraindications for T1DM hypoglycaemia and hyperglycaemia levels and related management

A comprehensive consensus statement by a group of international sport and exercise and diabetes experts13 provides initial guidance on encouraging the participation in physical activity. The guidance takes a proactive approach to mitigating, where possible, potential contraindications with the aim ‘to do all that is possible’ to increase physical activity and exercise participation in patients with T1DM. They state that the target blood glucose zone during exercise should be between 7 to 10 mmol/L [126 to 180 mg/dL] and to quote the guidance directly from this consensus statement,13 the following systematic steps should be employed:

Blood glucose concentrations before exercise commencement and recommended glucose management strategies

• The carbohydrate intakes shown here aim to stabilise glycaemia at the start of exercise. Blood glucose at the start of exercise must also be viewed within a wider context. Factors to consider include directional trends in glucose and insulin concentrations, patient safety and individual patient preferences based on experience. Carbohydrate intake will need to be higher if circulating insulin concentrations are high at the onset of exercise.

Starting glycaemia below target [< 5 mmol/L; < 90 mg/dL]

• Ingest 15 to 30 g of glucose before starting exercise.

• Delay exercise until blood glucose is ≥5 mmol/L [≥90 mg/dL] and monitor closely for hypoglycaemia.

Starting glycaemia near target [5.0 to 6.9 mmol/L; 90 to 124 mg/dL]

• Ingest 10 g of glucose before starting aerobic exercise.

• Anaerobic exercise and high intensity interval training sessions can be started.

Starting glycaemia at target levels [7 to 10 mmol/L; 126 to 180 mg/dL]

• Aerobic exercise can be started.

• Anaerobic exercise and high intensity interval training sessions can be started, but glucose concentrations could rise.

Starting glycaemia slightly above target [10.1 to 15.0 mmol/L; 182 to 270 mg/dL]

• Aerobic exercise can be started.

• Anaerobic exercise can be started, but glucose concentrations could rise.

Starting glycaemia above target [> 15 mmol/L; > 270 mg/dL]

• If the hyperglycaemia is unexplained [not associated with a recent meal], check blood ketones levels. If blood ketones levels are modestly elevated [up to 1·4 mmol/L], exercise should be restricted to a light intensity for only a brief duration [