Exercise: the brittle cornerstone of type 2 diabetes treatment

Van Noorden and Isaak identified regular exercise, along with diet and insulin, as one of the three components of good therapy as early as 1927 (for references, see [1]). From a physiological perspective, structured exercise interventions have been shown to be at least as efficacious as the pharmaceutical agents currently available for improving glycaemic control [2, 3] and cardiovascular risk profile [4]. Despite the growing body of evidence showing the health benefits of exercise in type 2 diabetes, a recently published large-scale US survey shows that the majority of patients with diabetes do not engage in regular physical activity [5], and there is currently no reason to believe that this is any different across the rest of the world. Although physician advice has been shown to be a strong predictor of attempts to change lifestyle habits, health professionals may not take the time or provide enough specific information to help patients successfully change their physical activity behaviour [6]. Apparently, most physicians and diabetes nurses around the world find it difficult to prescribe structured exercise routines for individual patients, and the high costs, lack of reimbursement, low compliance and/or absence of proper infrastructure may be responsible for this [7]. Not so long ago, cardiac patients and their doctors experienced similar problems; however, exercise-based cardiac rehabilitation programmes have been shown to be effective and feasible if available evidence-based guidelines are supported by a motivated and knowledgeable staff and applied in a patient-tailored way [8]. Although the long-term outcome of such an approach is currently being investigated in a large-scale prospective study on intensive lifestyle interventions, the preliminary results look promising [9]. Thus, cardiac rehabilitation programmes could serve as a model for future ‘pre-cardiac diabetes rehabilitation’ programmes.

Current guidelines from the American Diabetes Association recognise the therapeutic strength of exercise intervention [10] and prescribe an exercise frequency of at least three times per week with no more than two consecutive days without physical activity. However, these clinical guidelines need to be considered as a minimum prescription and, therefore, as a less than optimum situation. Recent guidelines on physical activity and public health in older adults from the American College of Sports Medicine and American Heart Association also recommend muscle-strengthening and balance exercise as an integrated part of physical activity intervention in older adults [11]. Older adults with chronic conditions, including coronary artery disease, osteoarthritis and type 2 diabetes, should develop an activity plan in consultation with a healthcare provider, taking into account therapeutic and risk management issues [11]. Long-standing insulin-treated type 2 diabetic patients form an expanding subpopulation and require a more individualised approach. These type 2 diabetic patients generally suffer from severe exercise intolerance as a result of low oxidative capacity, neuropathy-related muscle weakness, sarcopenia and/or micro- and macrovascular disease [12]. As generic exercise intervention programmes are too demanding for most of these patients, intermediate programmes are needed to bring the patient to a level at which they are able to participate in such programmes. The intermediate programmes should involve bouts of relatively high-intensity exercise, applied in an intermittent fashion, to augment muscle strength and functional performance. The greater amount of work performed and lower cardiorespiratory load achieved with intermittent exercise [13, 14] not only allows for a greater metabolic adaptative response in healthy individuals [15], but has also proved to be more effective than endurance exercise training in patients experiencing pulmonary limitations [14]. Although these so-called ‘in-and-out’ exercises have been proved safe in both cardiac [13] and high-risk insulin-treated type 2 diabetic patients [16], the long-term efficacy of such intermediate programmes in type 2 diabetes patients remains to be established.

Most lifestyle intervention programmes generally focus on the implementation of endurance exercise. Historically, this type of exercise has been associated with efficacy in reducing body fat mass and improving aerobic fitness and whole-body insulin sensitivity. An endurance exercise programme should involve energy expenditure equivalent to ∼↭1.7–2.1 MJ (≈400–500 kcal) per exercise bout on 3, but preferably 5 days per week [17, 18]. More vigorous exercise in uncomplicated insulin-resistant states will further improve glycaemic control and enhance cardiorespiratory fitness and microvascular function. Recently diagnosed obese type 2 diabetic patients would benefit most from a programme mainly consisting of moderate-intensity endurance exercise, aiming for a minimum energy expenditure of at least 5 MJ (≈1,200 kcal) [18], but preferably more than 8.5 MJ (≈2,000 kcal), per week [19]. In the obese type 2 diabetic patient such an endurance intervention programme should be combined with dietary restriction to maximise fat mass loss. Given the concomitant risk of losing muscle mass, at least one resistance exercise session should be included per week [20]. However, it remains difficult to translate laboratory results to community settings [21], and long-term outcomes may be disappointing. Therefore, adequate intensity, progression and adherence are required, or benefits will not accrue or persist.

Both endurance and resistance exercise have been shown to improve whole-body insulin sensitivity and/or glucose tolerance [3, 22]. It was recently shown that both endurance and resistance exercise have equal therapeutic strength in insulin-resistant states [3, 22]. The combined application of endurance and resistance exercise training might be of even greater clinical benefit in patients with uncomplicated type 2 diabetes [3]. However, the combined exercise benefits seen in the Diabetes Aerobic and Resistance Exercise (DARE) trial may, at least in part, be explained by a higher weekly energy expenditure. Nevertheless, for several other reasons, resistance exercise represents an attractive exercise mode to prescribe and implement in therapeutic intervention programmes. Unlike the DARE study population with uncomplicated type 2 diabetes, the majority of type 2 diabetic patients suffer from some form of muscle weakness, osteoarthritis, mobility impairments, peripheral and/or cardiovascular disease, not only resulting in reduced exercise tolerance [23], but also in a potentially high risk of overload injuries [3, Praet et al., unpublished results]. In line with this, it has proved difficult to get type 2 diabetic patients to adhere to strict endurance exercise intervention routines [7]. Alternatively, moderate intensity endurance exercise combined with resistance (i.e. intermittent intensity) exercise represents a lower cardiovascular and cardiorespiratory challenge and improves functional performance to a similar extent [13, 14]. Although we have recently shown that long-term adherence in such a primary healthcare-based exercise intervention is ∼↭40% (Praet et al., unpublished results), the combination of endurance and resistance type exercise is preferred as it makes the programme more varied and, as such, increases the adherence and compliance rates.

A similar approach with even greater emphasis on resistance exercise should be particularly useful in the vastly expanding subgroup of elderly (>70 years) type 2 diabetic patients [24]. Loss of skeletal muscle mass represents one of the main factors responsible for the increase in the incidence of type 2 diabetes with age [25]. The loss of muscle mass is proportionally related to the reduction in blood glucose disposal capacity and the decline in muscle strength [24, 26]. The latter prevents many elderly diabetic patients from participating in lifestyle intervention programmes [24]. Therefore, effective exercise intervention programmes targeting insulin resistance in elderly type 2 diabetes patients should focus on increasing skeletal muscle mass and strength—therapeutic advice that has been well summarised by the slogan, ‘Bring on the heavy weights’ [24]. They should consist mainly of resistance exercise, with exercise volume and intensity being progressively increased towards three sets of between eight and ten repetitions, with intensities ranging from 50–80% of one repetition maximum (1-RM) for between seven and ten exercises and/or muscle groups [22]. Adequate nutritional support might further improve the benefits of resistance type exercise training in elderly patients [27].

When prescribing exercise intervention for type 2 diabetes patients it should be noted that long-term adherence to an exercise intervention programme may vary with the presence of comorbidities, deconditioning and/or orthopaedic limitations [26]. Before exposing type 2 diabetes patients to more vigorous exercise programmes, silent myocardial ischaemia should be excluded if their cardiac risk over 10 years exceeds 10% [10]. However, patients with higher anxiety and/or depression scores also perceive more barriers to exercise [28]. Therefore, a multidisciplinary team should not only consider the level of impairment to exercise tolerance, but also appraise psychosocial stress factors. Such an individually tailored exercise intervention programme may reduce the risk of dropout and empower the patient to adhere to such lifestyle changes [29].

Clinical implementation of exercise in the treatment of type 2 diabetes is important for the primary and secondary prevention of type 2 diabetes, but is still far from being standard practice. To enhance its clinical application, lessons may be learned from the experience with exercise-based cardiac rehabilitation programmes. Moreover, current guidelines should include more detailed information on the preferred type and intensity of exercise for specific patient subgroups. Before choosing the most appropriate exercise modalities, the patient’s disease stage should be well characterised and exercise stress testing should be considered. Based on baseline aerobic fitness, level of comorbidity and appendicular skeletal muscle mass and strength, patients should be provided with a fitting exercise intervention programme to optimise its therapeutic value. Most type 2 diabetes patients find it difficult to adhere to a structured exercise intervention regimen, and compliance can be enhanced by proper multidisciplinary care and continued exercise training under strict personal supervision. More clinical research is warranted to establish the efficacy of a more differentiated approach for type 2 diabetes subpopulations at different stages of the disease and with different levels of comorbidity.