Matthew D. Hordern

Exercise Training for Type 2 Diabetes Mellitus Impact on Cardiovascular Risk: A Scientific Statement From the American Heart Association

1. Introduction …3244 2. Beneficial Effects of Exercise in T2DM…3245 3. Cardiac Risks of Exercise Training in T2DM…3249 4. Noncardiac Risks of Exercise Training in T2DM…3251 5. Exercise Training Guidelines…3252 6. Approaches to Adherence…3254 7. Special/Minority Groups…3255 8. Conclusions…3256 9. References…3257 The increasing prevalence of overweight and obesity has led to an unprecedented epidemic of type 2 diabetes mellitus (T2DM)1–4 and is likely to be followed by an epidemic of patients with complications of T2DM.5 Given the observed increases in the prevalence of T2DM in adults over the past few decades in developed countries,1,2,6 population-based efforts to reduce the cardiovascular complications of T2DM are as critical as the measures to prevent the problem.4,7 T2DM is the sixth-leading cause of death,8 with most deaths attributed to cardiovascular disease (CVD; nearly 70%) and with ischemic heart disease being responsible for nearly 50% of these deaths.9 The economic cost of T2DM has been estimated to be

Exercise-induced muscle damage, plasma cytokines, and markers of neutrophil activation

172 billion in 2007 in the United States alone3 (up from

Exercise prescription for patients with type 2 diabetes and pre-diabetes: A position statement from Exercise and Sport Science Australia

132 billion in 2002)10 and is likely to be greater when the other indirect costs of its associated complications are included.11 These complications are due to atherosclerotic vascular disease4 but also reflect a susceptibility of patients with T2DM to heart failure,12,13 perhaps mediated by direct effects on the myocardium.14,15 Pharmaceutical intervention for glycemic control has shown beneficial results for microvascular complications in patients with T2DM; however, whether this therapy has beneficial effects on macrovascular complications and …

Effects of exercise intervention on myocardial function in type 2 diabetes

INTRODUCTION Unaccustomed eccentric exercise often results in muscle damage and neutrophil activation. We examined changes in plasma cytokines stress hormones, creatine kinase activity and myoglobin concentration, neutrophil surface receptor expression, degranulation, and the capacity of neutrophils to generate reactive oxygen species in response to in vitro stimulation after downhill running. METHODS Ten well-trained male runners ran downhill on a treadmill at a gradient of -10% for 45 min at 60% VO2max. Blood was sampled immediately before (PRE) and after (POST), 1 h (1 h POST), and 24 h (24 h POST) after exercise. RESULTS At POST, there were significant increases (P < 0.01) in neutrophil count (32%), plasma interleukin (IL)-6 concentration (460%), myoglobin (Mb) concentration (1100%), and creatine kinase (CK) activity (40%). At 1 h POST, there were further increases above preexercise values for neutrophil count (85%), plasma Mb levels (1800%), and CK activity (56%), and plasma IL-6 concentration remained above preexercise values (410%) (P < 0.01). At 24 h POST, neutrophil counts and plasma IL-6 levels had returned to baseline, whereas plasma Mb concentration (100%) and CK activity (420%) were elevated above preexercise values (P < 0.01). There were no significant changes in neutrophil receptor expression, degranulation and respiratory burst activity, and plasma IL-8 and granulocyte-colony stimulating factor concentrations at any time after exercise. Neutrophil count correlated with plasma Mb concentration at POST (r = 0.64, P < 0.05), and with plasma CK activity at POST (r = 0.83, P < 0.01) and 1 h POST (r = 0.78, P < 0.01). CONCLUSION Neutrophil activation remains unchanged after downhill running in well-trained runners, despite increases in plasma markers of muscle damage.

Subclinical LV dysfunction and 10-year outcomes in type 2 diabetes mellitus

Type 2 diabetes mellitus (T2DM) and pre-diabetic conditions such as impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) are rapidly increasing in prevalence. There is compelling evidence that T2DM is more likely to develop in individuals who are insufficiently active. Exercise training, often in combination with other lifestyle strategies, has beneficial effects on preventing the onset of T2DM and improving glycaemic control in those with pre-diabetes. In addition, exercise training improves cardiovascular risk profile, body composition and cardiorespiratory fitness, all strongly related to better health outcomes. Based on the evidence, it is recommended that patients with T2DM or pre-diabetes accumulate a minimum of 210 min per week of moderate-intensity exercise or 125 min per week of vigorous intensity exercise with no more than two consecutive days without training. Vigorous intensity exercise is more time efficient and may also result in greater benefits in appropriate individuals with consideration of complications and contraindications. It is further recommended that two or more resistance training sessions per week (2-4 sets of 8-10 repetitions) should be included in the total 210 or 125 min of moderate or vigorous exercise, respectively. It is also recommended that, due to the high prevalence and incidence of comorbid conditions in patients with T2DM, exercise training programs should be written and delivered by individuals with appropriate qualifications and experience to recognise and accommodate comorbidities and complications.

DETERMINANTS OF CHANGES IN BLOOD GLUCOSE RESPONSE TO SHORT-TERM EXERCISE TRAINING IN PATIENTS WITH TYPE 2 DIABETES

Objective: To identify the effects of a 1-year exercise intervention on myocardial dysfunction in patients with type 2 diabetes mellitus (T2DM). Design: Randomised controlled trial, the Diabetes Lifestyle Intervention Study. Setting: University hospital. Patients: 223 T2DM patients without occult coronary artery disease, aged 18–75 were randomised to an exercise training group (n = 111) or a usual care group (n = 112). Complete follow-up data were available in 176 (88 exercise, 88 usual care). Interventions: Exercise training consisted of gym, followed by telephone-monitored home-based exercise training. Main outcome measures: Tissue Doppler-derived myocardial velocities, strain-rate and strain, body composition, glycated haemoglobin (HbA1c), maximum oxygen consumption (VO2max) and physical activity. Results: Overall changes in myocardial function were not different between groups despite improvements in waist circumference, fat mass, blood glucose, HbA1c, insulin sensitivity, VO2max and 6-minute walk distance in the intervention group (p<0.05). The latter also spent significantly more time in vigorous activity (p<0.05). A post-hoc analysis revealed that intervention patients who spent more time in both moderate and vigorous activity showed a significant improvement in myocardial tissue velocity (p<0.01), HbA1c (p = 0.03) and VO2max (p = 0.03) compared to controls. Myocardial strain rate (p = 0.03) and HbA1c improved in intervention patients with the greatest increase in moderate activity (p = 0.03). Conclusions: In patients with T2DM, current exercise recommendations led to an improvement in metabolic function, but failed to improve myocardial function in the overall group. Patients with greater increases in both moderate and vigorous activity showed improvements in myocardial function, glycaemic control and cardiorespiratory fitness. Trial registration number: ACTRN12607000060448.

Application of an Exercise Intervention on the Evolution of Diastolic Dysfunction in Patients with Diabetes Mellitus: Efficacy and Effectiveness

Objective New imaging techniques have permitted the detection of subclinical LV dysfunction (LVD) in up to half of patients with type 2 diabetes mellitus (DM) with a normal EF. However, the connection between early LVD and prognosis is unclear. This study aimed to define the long-term outcome of LVD associated with type 2 DM. Methods In this prospective cohort study, 230 asymptomatic patients with type 2 DM underwent measurement of global longitudinal 2D strain (GLS) for detection of LVD and were followed for up to 10 years. All subjects had normal EF (≥50%) and no evidence of coronary artery disease at recruitment. Outcome data were obtained through centralised state-wide death and hospital admission registries. The primary endpoint was all-cause mortality and hospitalisation. Results On study entry, almost half (45%) of the cohort had evidence of LVD as detected by GLS. Over a median follow-up of 7.4±2.6 years (range 0.6–9.7 years), 68 patients (30%) met the primary endpoint (LVD: 37%; normal LV function: 24%). GLS was independently associated with the primary endpoint (HR=1.10; p=0.04), as was systolic blood pressure (HR=1.02; p<0.001) and levels of glycosylated haemoglobin (HR=1.28; p=0.011). Patients with LVD had significantly worse outcome than those without (χ2=4.73; p=0.030). Conclusions Subclinical LVD is common in asymptomatic patients with type 2 DM, is readily detectable by GLS imaging and is independently associated with adverse outcome. Trial registration number Australian and New Zealand Clinical Trials Registry (ACTRN12612001178831).

Lifestyle change diminishes a hypertensive response to exercise in type 2 diabetes

The aim of the present study was to determine the effects of a 4-week exercise training intervention on blood glucose, insulin sensitivity, BMI (body mass index) and cardiorespiratory fitness in patients with Type 2 diabetes, and to identify and establish criteria for patients who are more likely to improve their blood glucose from short-term exercise training. A randomized, controlled trial of exercise training, comprising two supervised and one non-supervised sessions of individualized cardiorespiratory and resistance exercise per week, was performed in 132 healthy patients with Type 2 diabetes (exercise training group, n=68), with the aim of accumulating a minimum of 150 min of moderate-intensity exercise for 4 weeks. BMI, waist circumference, blood pressure, blood lipid profile, blood glucose, insulin, insulin sensitivity [calculated by HOMA(IR) (homoeostasis model assessment of insulin resistance) and QUICKI (quantitative insulin check index)], beta-cell function (calculated by HOMA(beta-Cell)), HbA(1c) (glycated haemoglobin) and VO(2max) (maximal oxygen consumption) were measured at baseline and at 4 weeks. The exercise training group had significant improvements in VO(2max), BMI and triacylglycerols (triglycerides). There were no significant changes in blood glucose, HOMA(IR), QUICKI or HOMA(beta-Cell). Decreases in blood glucose were significantly predicted by baseline blood glucose and HbA(1c), with these variables accounting for 15.9% of the change in blood glucose (P<0.001). ROC (receiver operator characteristic) curve analysis revealed that patients with a blood glucose >8.85 mmol/l (sensitivity=73%, specificity=78%) and HbA(1c) >7.15% (sensitivity=79%, specificity=60%) were more likely to achieve a clinically significant decrease in blood glucose. In conclusion, in apparently healthy patients with Type 2 diabetes, a 4-week exercise intervention improved cardiorespiratory fitness, BMI and triacylglycerols. Elevated blood glucose and HbA(1c) predicted improvements in blood glucose.

Application of an Exercise Intervention on the Evolution of Diastolic Dysfunction in Patients With Diabetes MellitusClinical Perspective

Background—Diastolic dysfunction (DD) is associated with adverse cardiovascular outcomes. We studied the impact of an exercise-based lifestyle intervention on the evolution of DD in patients with type 2 diabetes mellitus (T2DM) and prospectively investigated the clinical correlates of DD progression. Methods and Results—A total of 223 outpatients with T2DM were randomized to supervised exercise-based lifestyle intervention (initial gym-based program and lifestyle and diet advice followed by telephone-guided supervision) or usual care. Patients underwent echocardiographic assessment of diastolic function and metabolic and clinical evaluation at baseline and 3 years. Changes in prevalence and evolution of DD were assessed and correlations sought with clinical and metabolic variables. DD was present in 50% of patients at baseline and 54% at 3 years, with no difference between the usual care and intervention groups (60% versus 48%, P=0.10). Abnormal DD at the final visit was independently associated with older age and a decrease in peak oxygen consumption over time (P<0.05). There was no impact on glycemic control or exercise capacity. In a subanalysis restricted to patients who finished the full 3-year follow-up, control subjects were independently associated with DD at 3 years (&bgr;=0.90; odds ratio, 2.46; P=0.034), with the only other independent correlate being older age (&bgr;=0.05; odds ratio, 1.06; P=0.019). Conclusions—Despite being efficacious in the subgroup who completed 3 years of exercise-based lifestyle intervention, randomization to this program was not effective in reducing progression of subclinical DD in patients with T2DM, which may reflect the recognized difficulty of adherence to prolonged exercise intervention. Clinical Trial Registration—URL: http://www.anzctr.org.au. Unique identifier: ACTRN12607000060448.

Acute response of blood glucose to short-term exercise training in patients with type 2 diabetes.

PURPOSE A hypertensive response to exercise (HRE) is common in patients with type 2 diabetes and is associated with increased left ventricular (LV) mass and mortality. This study aimed to determine whether lifestyle modification would improve exercise blood pressure (BP) and reduce LV mass in patients with type 2 diabetes. METHODS One hundred and eighty-five patients with type 2 diabetes were randomized to 1 yr of lifestyle intervention (n=97, mean ± SD age=54.7 ± 11.3 yr, 51% men) or usual care (control; n=88, age=53.8 ± 8.1 yr, 61% men). Brachial BP was measured at rest and during a graded maximal exercise test at baseline and 1 yr. Patients also underwent two-dimensional echocardiography to determine LV dimensions. A subgroup of 61 patients had resting and exercise central BP estimated from radial tonometry. An HRE was defined as a maximal exercise systolic BP of ≥210 mm Hg for men and ≥190 mm Hg for women. RESULTS At study entry, there were 101 patients (55%) with an HRE (n=51 controls). Compared with controls, lifestyle intervention significantly reduced the propensity to develop an HRE in those participants who did not have HRE at baseline (29.8% vs 59.5%, P=0.006). However, absolute values of exercise and resting (brachial and central) BP and LV mass were not significantly changed (all P values >0.05). There were significant (all P values <0.05) improvements in V˙O2max, body mass index, plasma glucose, insulin resistance, and HDL cholesterol after lifestyle intervention compared with control. CONCLUSIONS Lifestyle intervention significantly attenuates the development of an HRE but does not reduce cardiac size after 1 yr in patients with type 2 diabetes.