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................................................................................................................................................................ improve the lipid profile and reduce CV risk. Before embarking on high-intensity exercise, a clinical assessment should be performed including symptomatic status, and a maximal exercise stress test, functional imaging test, or CCTA may be considered in the risk assessment110 (Figure 4), particularly in individuals with familial hypercholesterolaemia. Among athletes with hypercholesterolaemia, regular exercise will rarely reduce LDL cholesterol to normal or nearnormal values; therefore, guidelines on pharmacological treatment in primary and secondary prevention should be followed strictly. Individuals with dyslipidaemia should be assessed at least every 25 years for primary prevention and annually for secondary prevention.

Pharmacological intervention, particularly with statins, is superior to exercise and lifestyle intervention alone for reducing LDL cholesterol and improving prognosis.147 Despite the minor effects of endurance exercise on serum LDL cholesterol, the clinically beneficial relationship between increased physical fitness and reduced CV events remains beyond the effects of statins.147,148 Physically active individuals with dyslipidaemia may experience muscle pain and soreness or tendinopathy accompanied by elevated muscle enzymes.149 In these cases, measures such as stopping medication temporarily followed by repeat challenge with another statin drug, with or without an alternate day regimen, or introducing other lipid-lowering agents such as ezetimibe or proprotein convertase subtilisin/kexin type 9 (PCSK-9) inhibitors should be considered.109 Individuals who develop rhabdomyolysis due to a statin should be prescribed an alternative lipid-lowering agent.

4.2.5 Diabetes mellitus Physical inactivity is a major cause of type 2 diabetes mellitus (T2DM).150 The risk of developing T2DM is 5080% higher in individuals who are physically inactive compared to their active counterparts. However, exercise does not entirely compensate for the effect of obesity.151154 Diabetes is also independently associated with an accelerated decline in muscular strength and, partly because of hyperglycaemia, may lead to reduced joint mobility.

4.2.5.1 Effect of exercise on diabetic control, risk factors and outcomes Aerobic exercise in patients with T2DM improves glycaemic control and reduces visceral fat and insulin resistance. Exercise also has beneficial effects on BP and lipid profile, and leads to modest weight loss.155,156 Both aerobic and resistance training promote prolonged adaptations in skeletal muscle, adipose tissue, and the liver associated with enhanced insulin action.157 Observational studies have shown lower mortality with exercise in both type 1 diabetes mellitus and T2DM.158 In patients with pre-diabetes or metabolic syndrome, both aerobic and resistance exercise may prevent the development of overt diabetes.159162 Intensity of exercise seems to be of greater importance than the volume of exercise; individuals who exercise at moderate or high intensity have a lower risk of developing metabolic impairment compared with those who have a similar energy expenditure at a lower intensity.160,163 The effects on muscle insulin sensitivity are observed with a relatively low volume of exercise (400 kcal/week) in previously sedentary adults, but increase with higher volumes of exercise.164 The optimal combination of duration and intensity is not well established. Highintensity interval training may be superior to moderate aerobic training in achieving metabolic effects and improvement in exercise capacity; however, whether long-term results are superior is unknown.165,166

Diabetes is a cause of coronary microvascular dysfunction (CMD), which is associated with lower exercise capacity and adverse outcomes167,168 and can be improved by exercise training.162,169171 Large randomized trials have confirmed the beneficial effect of exercise intervention on glycaemic control and risk factors, but this has not translated into a significant improvement in survival, partly because of suboptimal long-term maintenance of lifestyle changes.172 During an acute bout of exercise, glucose uptake in the muscles is increased for up to 2 h afterwards through mechanisms that are independent of insulin. The exercise-induced hypoglycaemic effect can be diminished by performing resistance training or interval training in patients with type 1 diabetes.173 There is a doseresponse relationship between intensity and volume of exercise and duration of glucose uptake by skeletal muscle that may last up to 48 h after exercise. These factors must be considered in individuals with diabetes who are undertaking intensive exercise or competitive sports in order to avoid hypoglycaemia.

4.2.5.2 Recommendations for participation in exercise in individuals with diabetes mellitus Both aerobic and resistance training are effective for glycaemic control, BP reduction, weight loss, peak exercise capacity, and dyslipidemia.174 A programme combining aerobic and resistance training has been shown to be superior in terms of glycaemic control, whereas the effect on other outcomes is unproven.174176 The ideal exercise programme to achieve the full potential of benefits in patients with diabetes is daily exercise of at least moderate intensity, e.g. brisk walking, for at least 30 min, resistance training for 15 min on most days, and lighter-intensity activities (standing, walking) every 30 min. This can be supplemented by flexibility and balance exercise, particularly in older individuals or patients with microvascular complications due to their diabetes.

4.2.5.3 Cardiac evaluation before exercise participation in individuals with diabetes mellitus Individuals with diabetes have a priori a higher likelihood of subclinical CAD; therefore, all individuals with diabetes should undergo CV assessment as outlined in Figure 4 before taking up an exercise programme of high intensity. This should be supplemented by an evaluation of glycaemic status, including risk factors for hypoglycaemia, history of hypoglycaemic episodes, presence of autonomic neuropathy, and antidiabetic treatment.177 Asymptomatic individuals with diabetes mellitus and a normal CV assessment and maximal exercise test may engage in all sports but should be warned about the potential risk of iatrogenic Downloaded from academic.oup.com/eurheartj/article/42/1/17/5898937 by guest on 07 October 2026