Diabetes mellitus type 2 is one of the most common diseases in industrialized countries and is one of the main risk factors for the development of micro- and macrovascular diseases. Vascular complications are causes of death in up to 80% of these patients and 75% of deaths are due to coro- nary artery disease.1,2
Although exercise training should be part of the treatment regimen in patients with diabetes according to national and international guide- lines, it is only integrated into the daily routine by a minority of patients. This ought to change, since only a multifactorial risk intervention which includes exercise training has the potential to treat the underlying causes of both diabetes and coro- nary artery disease (Figure 18-1).3
Physical Exercise
The incidence of diabetes mellitus correlates inversely with the degree of physical activity.4 Regular aerobic exercise of 30 min/day at a mod- erate intensity can cut the risk for impaired glucose tolerance by half and the diabetes risk by up to three-quarters.5–7
Although there is no direct proof that endothe- lial dysfunction leads to atherosclerosis, it has been shown that endothelial dysfunction is asso- ciated with increased cardiovascular mortality.8 Endothelial dysfunction is found when the
endothelium has been damaged. This occurs as a result of smoking, hyperglycemia, hyperlipidemia, and hypertension. It can be improved by intensive physical exercise not only in normoglycemic patients but also in patients with diabetes melli- tus and coronary artery disease.6,9 In diabetics, however, this effect is not yet found after 4 weeks but only after a prolonged training period of 6 months. This delayed improvement in diabetic patients, as compared to normoglycemic patients, may be due to the rather diffuse atherosclerotic process that occurs in diabetes throughout the coronary tree with little normally functioning endothelium left to release nitric oxide (NO) and to react with a vasodilatory stimulus such as acetylcholine (Figure 18-2).
A meta-analysis showed that normoglycemic patients with coronary artery disease10benefited from endurance training as part of a rehabilita- tion program, with a reduction in mortality of 31%. This prognostic effect of physical exercise, especially for diabetic patients, has been demon- strated in several studies4,11 (see Table 18-1) and includes a marked reduction in both the risk of developing coronary artery disease and the rate of cardiac mortality.12 To obtain these benefits, energy consumption due to physical exercise training should ideally be between 1000 and 2000 kcal/week, which corresponds to 3–5 hours of submaximal endurance training per week.13
18
Exercise Training in Diabetes Mellitus:
An Efficient but Underused Therapeutic Option in the Prevention and Treatment of Coronary Artery Disease
Josef Niebauer
138
18. Exercise Training in Diabetes Mellitus 139
Smoking - Smoking sessation
Obesity
Dyslipidemia Hypertension Physical inactivity - Physical exercise
- Diet
- Statins - Physical exercise - Diet
- Blood pressure control - Physical exercise - Diet
- Blood-glucose control - Physical exercise - Diet
- Physical exercise Hyperglycemia
Atherosclerosis
FIGURE18-1. Multifactorial risk factor intervention: Modifiable risk factors associated with atherosclerosis and their respective treatment options.
Paradoxical vasoconstriction
saline acetylcholine
FIGURE18-2. The left panel shows the left coronary artery without focal stenoses. When acetylcholine is infused into the vessel as shown in the right panel, in healthy vessels vasodilatation would occur, whereas in diabetes paradoxical vasoconstriction occurs due to exten- sive damage to the endothelium.
Exercise Training Combined with Blood Glucose Control
The importance of early diagnosis and sub- sequent therapy of diabetes has been highlighted by the United Kingdom Prospective Diabetes Study (UKPDS). The results showed that it is nec- essary to keep HbA1c levels <6.0mmol/L in order to reduce the incidence of cardiovascular events.14 These data were confirmed by a study of Hu et al.
in 84,941 nurses where it could be demonstrated in a subgroup with a low-risk profile (body mass index <25, healthy diet, >30 minutes of physical exercise per day, non-smokers, less than half a unit of alcohol drink per day) that the incidence of dia- betes mellitus type 2 was significantly lower than for the rest of the nurses.13It was also shown that 91% of the cases of newly developed diabetes could have been prevented by a lifestyle similar to that of the subgroup of nurses with a low-risk profile.
140 J. Niebauer
Tuomilehto et al.15 studied 522 overweight patients with impaired glucose tolerance to assess the impact of dietary counseling and the recom- mendation to exercise regularly on the incidence of type 2 diabetes mellitus. After 4 years the inci- dence of newly developed diabetes was significantly lower in the intervention group (11%) than in the control group (23%).
Another study compared the effect of a healthy lifestyle on the occurrence of diabetes with that of metformin.16After an average of 2.8 years it was shown that a healthy lifestyle could prevent dia- betes mellitus type 2 more effectively (58%) than metformin (31%).
The STENO-2 study investigated the influence of standard care with an intensified treatment approach that included behavioral changes which aimed at weight reduction, increased physical activity, and intensified pharmacological therapy on type 2 diabetic patients with micro-albumin- uria.17After an average study period of 7.8 years intensified therapy was able to reduce cardiovascu- lar and microvascular events by 50% (Table 18.1).17 In the studies mentioned, physical training was only recommended but not conducted under close supervision.17Future studies must show whether increased exercise compliance due to group exer- cise sessions or supervision of home exercise with the help of telemedicine can urther augment these beneficial effects. Our own data show that not only in-hospital but also ambulatory group training in addition to daily home exercise can further improve the risk factor profile.18
Although it is beyond the scope of this chapter, it ought to be mentioned how important lipid control
is and that statin therapy has to be part of the regimen, regardless of patients’ cholesterol levels, due to its pleiotropic effects, which are associated with a mortality benefit. Although risk factors for normoglycemic patients with coronary artery disease such as dyslipoproteinemia, hypertension, and obesity can be treated successfully with intensified physical exercise and an individually adapted diet, only lipid control has been convinc- ingly shown to reduce cardiovascular mortality.19,20
Conclusion
For patients with stable coronary artery disease an intensive multifactorial risk factor intervention is a feasible intervention strategy. It increases exercise performance, improves the cardiovascular risk factor profile, myocardial perfusion, and endothe- lial function and has been shown to be associated with improved morbidity and mortality in epi- demiologic studies. Although exercise training is inexpensive, ubiquitously available, and extremely effective, it remains underused and under- prescribed. Awareness of physicians and patients has to increase to help include this effective “drug”
into the daily life of as many patients as possible.
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TABLE18-1. Therapeutic strategies and their effects on diabetes mellitus
Author/study Treatment Result
Turner et al.14 Blood glucose control Reduction of cardiovascular complication rate
UKPDS 3821 Blood glucose control Reduction of risk for micro- and macrovascular complications Gaede et al.17 Multifactorial 50% reduction of cardiovascular complications
Hu et al.5 Diet, physical activity Prevention of diabetes through a healthier lifestyle Hu et al.13 Physical activity Risk reduction for developing diabetes (50%) Tanasescu et al.12 Physical activity Risk reduction for CAD (33%) and mortality (40%)
Wei et al.7 Physical fitness Risk reduction for developing diabetes by 25%
Hu et al.13 Physical activity Risk reduction for CV events inversely proportional to increasing physical activity Batty et al.11 Physical activity Risk reduction for CV events depending on running speed and leisure-time activity Wei et al.23 Physical activity Reduction of mortality through exercise by 50%
HPS24 Statins Reduction of cardiovascular disease by 33%
4-S25 Statins Risk reduction for CV events and mortality
CARE26 Statins Reduction of cardiovascular events by 5.2%
CAD = coronary heart disease; CV = cardiovascular.
18. Exercise Training in Diabetes Mellitus 141
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