Stefano Balducci

Anti-inflammatory effect of exercise training in subjects with type 2 diabetes and the metabolic syndrome is dependent on exercise modalities and independent of weight loss

BACKGROUND AND AIMS We investigated the effect of different exercise modalities on high sensitivity-C reactive protein (hs-CRP) and other inflammatory markers in patients with type 2 diabetes and the metabolic syndrome. METHODS AND RESULTS Eighty-two patients were randomized into 4 groups: sedentary control (A); receiving counseling to perform low-intensity physical activity (B); performing prescribed and supervised high-intensity aerobic (C) or aerobic+resistance (D) exercise (with the same caloric expenditure) for 12 months. Evaluation of leisure-time physical activity and assessment of physical fitness, cardiovascular risk factors and inflammatory biomarkers was performed at baseline and every 3 months. Volume of physical activity increased and HbA(1c) decreased in Groups B-D. VO(2max), HOMA-IR index, HDL-cholesterol, waist circumference and albuminuria improved in Groups C and D, whereas strength and flexibility improved only in Group D. Levels of hs-CRP decreased in all three exercising groups, but the reduction was significant only in Groups C and D, and particularly in Group D. Changes in VO(2max) and the exercise modalities were strong predictors of hs-CRP reduction, independent of body weight. Leptin, resistin and interleukin-6 decreased, whereas adiponectin increased in Groups C and D. Interleukin-1β, tumor necrosis factor-α and interferon-γ decreased, whereas anti-inflammatory interleukin-4 and 10 increased only in Group D. CONCLUSION Physical exercise in type 2 diabetic patients with the metabolic syndrome is associated with a significant reduction of hs-CRP and other inflammatory and insulin resistance biomarkers, independent of weight loss. Long-term high-intensity (preferably mixed) training, in addition to daytime physical activity, is required to obtain a significant anti-inflammatory effect.

Effect of an Intensive Exercise Intervention Strategy on Modifiable Cardiovascular Risk Factors in Subjects With Type 2 Diabetes Mellitus A Randomized Controlled Trial: The Italian Diabetes and Exercise Study (IDES)

BACKGROUND This study aimed to assess the efficacy of an intensive exercise intervention strategy in promoting physical activity (PA) and improving hemoglobin A(1c)(HbA(1c)) level and other modifiable cardiovascular risk factors in patients with type 2 diabetes mellitus (T2DM). METHODS Of 691 eligible sedentary patients with T2DM and the metabolic syndrome, 606 were enrolled in 22 outpatient diabetes clinics across Italy and randomized by center, age, and diabetes treatment to twice-a-week supervised aerobic and resistance training plus structured exercise counseling (exercise group) vs counseling alone (control group) for 12 months. End points included HbA(1c) level (primary) and other cardiovascular risk factors and coronary heart disease risk scores (secondary). RESULTS The mean (SD) volume of PA (metabolic equivalent hours per week) was significantly higher (P < .001) in the exercise (total PA [nonsupervised conditioning PA + supervised PA], 20.0 [0.9], and nonsupervised, 12.4 [7.4]) vs control (10.0 [8.7]) group. Compared with the control group, supervised exercise produced significant improvements (mean difference [95% confidence interval]) in physical fitness; HbA(1c) level (-0.30% [-0.49% to -0.10%]; P < .001); systolic (-4.2 mm Hg [-6.9 to -1.6 mm Hg]; P = .002) and diastolic (-1.7 mm Hg [-3.3 to -1.1 mm Hg]; P = .03) blood pressure; high-density lipoprotein (3.7 mg/dL [2.2 to 5.3 mg/dL]; P < .001) and low-density lipoprotein (-9.6 mg/dL [-15.9 to -3.3 mg/dL]; P = .003) cholesterol level; waist circumference (-3.6 cm [-4.4 to -2.9 cm]; P < .001); body mass index; insulin resistance; inflammation; and risk scores. These parameters improved only marginally in controls. CONCLUSIONS This exercise intervention strategy was effective in promoting PA and improving HbA(1c) and cardiovascular risk profile. Conversely, counseling alone, though successful in achieving the currently recommended amount of activity, was of limited efficacy on cardiovascular risk factors, suggesting the need for a larger volume of PA in these high-risk subjects. Trial Registration isrctn.org Identifier: ISRCTN04252749.

Exercise for the management of type 2 diabetes: a review of the evidence

The aim is to critically review the more relevant evidence on the interrelationships between exercise and metabolic outcomes. The research questions addressed in the recent specific literature with the most relevant randomized controlled trials, meta-analysis and cohort studies are presented in three domains: aerobic exercise, resistance exercise, combined aerobic and resistance exercise. From this review appear that the effects of aerobic exercise are well established, and interventions with more vigorous aerobic exercise programs resulted in greater reductions in HbA1c, greater increase in VO2max and greater increase in insulin sensitivity. Considering the available evidence, it appears that resistance training could be an effective intervention to help glycemic control, especially considering that the effects of this form of intervention are comparable with what reported with aerobic exercise. Less studies have investigated whether combined resistance and aerobic training offers a synergistic and incremental effect on glycemic control; however, from the available evidences appear that combined exercise training seems to determine additional change in HbA1c that can be seen significant if compared with aerobic training alone and resistance training alone.

Changes in insulin sensitivity in response to different modalities of exercise: a review of the evidence

Type 2 diabetes is an increasingly prevalent condition with complications including blindness and kidney failure. Evidence suggests that type 2 diabetes is associated with a sedentary lifestyle, with physical activity demonstrated to increase glucose uptake and improve glycaemic control. Proposed mechanisms for these effects include the maintenance and improvement of insulin sensitivity via increased glucose transporter type four production. The optimal mode, frequency, intensity and duration of exercise for the improvement of insulin sensitivity are however yet to be identified. We review the evidence from 34 published studies addressing the effects on glycaemic control and insulin sensitivity of aerobic exercise, resistance training and both combined. Effect sizes and confidence intervals are reported for each intervention and meta‐analysis presented. The quality of the evidence is tentatively graded, and recommendations for best practice proposed.

Effect of high- versus low-intensity supervised aerobic and resistance training on modifiable cardiovascular risk factors in type 2 diabetes; the Italian Diabetes and Exercise Study (IDES).

Background While current recommendations on exercise type and volume have strong experimental bases, there is no clear evidence from large-sized studies indicating whether increasing training intensity provides additional benefits to subjects with type 2 diabetes. Objective To compare the effects of moderate-to-high intensity (HI) versus low-to-moderate intensity (LI) training of equal energy cost, i.e. exercise volume, on modifiable cardiovascular risk factors. Design Pre-specified sub-analysis of the Italian Diabetes and Exercise Study (IDES), a randomized multicenter prospective trial comparing a supervised exercise intervention with standard care for 12 months (2005–2006). Setting Twenty-two outpatient diabetes clinics across Italy. Patients Sedentary patients with type 2 diabetes assigned to twice-a-week supervised progressive aerobic and resistance training plus exercise counseling (n = 303). Interventions Subjects were randomized by center to LI (n = 142, 136 completed) or HI (n = 161, 152 completed) progressive aerobic and resistance training, i.e. at 55% or 70% of predicted maximal oxygen consumption and at 60% or 80% of predicted 1-Repetition Maximum, respectively, of equal volume. Main Outcome Measure(s) Hemoglobin (Hb) A1c and other cardiovascular risk factors; 10-year coronary heart disease (CHD) risk scores. Results Volume of physical activity, both supervised and non-supervised, was similar in LI and HI participants. Compared with LI training, HI training produced only clinically marginal, though statistically significant, improvements in HbA1c (mean difference −0.17% [95% confidence interval −0.44,0.10], P = 0.03), triglycerides (−0.12 mmol/l [−0.34,0.10], P = 0.02) and total cholesterol (−0.24 mmol/l [−0.46, −0.01], P = 0.04), but not in other risk factors and CHD risk scores. However, intensity was not an independent predictor of reduction of any of these parameters. Adverse event rate was similar in HI and LI subjects. Conclusions Data from the large IDES cohort indicate that, in low-fitness individuals such as sedentary subjects with type 2 diabetes, increasing exercise intensity is not harmful, but does not provide additional benefits on cardiovascular risk factors. Trial Registration www.ISRCTN.org ISRCTN-04252749.

Changes in physical fitness predict improvements in modifiable cardiovascular risk factors independently of body weight loss in subjects with type 2 diabetes participating in the Italian Diabetes and Exercise Study (IDES).

OBJECTIVE Physical fitness is inversely related to mortality in the general population and in subjects with type 2 diabetes. Here, we present data concerning the relationship between changes in physical fitness and modifiable cardiovascular risk factors in subjects with type 2 diabetes from the Italian Diabetes and Exercise Study. RESEARCH DESIGN AND METHODS Sedentary patients with type 2 diabetes (n = 606) were enrolled in 22 outpatient diabetes clinics and randomized to twice-a-week supervised aerobic and resistance training plus exercise counseling versus counseling alone for 12 months. Baseline to end-of-study changes in cardiorespiratory fitness, strength, and flexibility, as assessed by Vo2max estimation, a 5–8 maximal repetition test, and a hip/trunk flexibility test, respectively, were calculated in the whole cohort, and multiple regression analyses were applied to assess the relationship with cardiovascular risk factors. RESULTS Changes in Vo2max, upper and lower body strength, and flexibility were significantly associated with the variation in the volume of physical activity, HbA1c, BMI, waist circumference, high-sensitivity C-reactive protein (hs-CRP), coronary heart disease (CHD) risk score, and inversely, HDL cholesterol. Changes in fitness predicted improvements in HbA1c, waist circumference, HDL cholesterol, hs-CRP, and CHD risk score, independent of study arm, BMI, and in case of strength, also waist circumference. CONCLUSIONS Physical activity/exercise-induced increases in fitness, particularly muscular, predict improvements in cardiovascular risk factors in subjects with type 2 diabetes independently of weight loss, thus indicating the need for targeting fitness in these individuals, particularly in subjects who struggle to lose weight.

Physical exercise as therapy for type 2 diabetes mellitus

Many studies have highlighted the importance of physical activity (PA) for health, and recent evidence now points to the positive improvements associated with exercise in type 2 diabetes mellitus (T2DM). However, few physicians are willing to prescribe exercise as a therapy for diabetic patients. In addition, there is a lack of information on how to implement exercise therapy especially in long‐term exercise regimens. The purpose of this manuscript is to summarize standards of exercise therapy for patients with T2DM, both in terms of prescribing and monitoring, according to the American College of Sports Medicine and the American Diabetes Association guidelines. We present details of the exercise therapies used in long‐term studies, describing how the parameters for exercise prescription were applied in clinical practice. These parameters are described in terms of frequency, intensity, duration, mode and rate of progression in long‐term therapeutic prescriptions. Individual responses to exercise dose are discussed, and critical issues to be considered in patients with underlying disease and in T2DM patients are highlighted. Copyright

Two weekly sessions of combined aerobic and resistance exercise are sufficient to provide beneficial effects in subjects with Type 2 diabetes mellitus and metabolic syndrome

This study was performed to establish whether only 2 sessions per week of combined aerobic and resistance exercise are enough to reduce glycated hemoglobin (HbA1c) and to induce changes in skeletal muscle gene expression in Type 2 diabetes mellitus (DM2) subjects with metabolic syndrome. Eight DM2 subjects underwent a 1-yr exercise program consisting of 2 weekly sessions of 140 min that combined aerobic [at 55–70% of maximal oxygen uptake (VO2max)] and resistance circuit training [at 60–80% of 1 repetition maximum (RM)]. The training significantly improved VO2max) (from 33.5±3.8 ml/kg/min to 38.2±3.5 ml/kg/min, p=0.0085) and muscle strength (p<0.05). Changes over baseline were significant for HbA1c, reduced by 0.45% (p=0.0084), fasting blood glucose (from 8.8±1.5 to 6.9±2.2 mmol/l, p=0.0132), waist circumference (from 98.9±4.8 to 95.9±4.6 cm, p=0.0054), body weight (from 87.5±10.7 to 85.7±10.1 kg, p=0.0375), systolic blood pressure (from 137±15 to 126±8 mmHg, p=0.0455), total cholesterol (from 220±24 to 184±13 mg/dl, p=0.0057), and LDL-cholesterol (from 150±16 to 105±15 mg/dl, p=0.0004). Mitochondrial DNA/nuclear DNA ratio at 6 and 12 months did not change. There was a significant increase of mRNA of peroxisome proliferator-activated receptor (PPAR)-γ after 6 months of training(p=0.024); PPARα mRNA levels were significantly increased at 6 (p=0.035) and 12 months (p=0.044). The mRNA quantification of other genes measured [mitochondrially encoded cytochrome c oxidase subunit II (MTCO2), cytochrome c oxidase subunit Vb (COX5b), PPARγ coactivator 1α (PGC-1α), glucose transporter 4 (GLUT 4), forkhead transcription factor BOX O1 (FOXO-1), carnitine palmitoyltransferase 1 (CPT-1), lipoprotein lipase (LPL), and insulin receptor substrate 1 (IRS-1)] did not show significant changes at 6 and 12 months. This study suggests that a twice-per-week frequency of exercise is sufficient to improve glucose control and the expression of skeletal muscle PPARγ and PPARα in DM2 subjects with metabolic syndrome.

Physical activity, a key factor to quality of life in type 2 diabetic patients

Exercise as a public health tool has largely been built around its plausible impact on physical health, including a positive impact on the prevention and management of type 2 diabetes. There is a growing interest in its potential to influence other aspects of quality of life such as mental health and general well‐being. The effects of physical activity on overall quality of life are well established in the general population and have been analyzed on various dimensions of the Health‐Related Quality of Life (HRQL) including physical and social functioning; subjective well‐being, emotion and mood; self esteem and self‐perception; cognitive performance; and sleep quality.

Neuromuscular Dysfunction in Diabetes: Role of Nerve Impairment and Training Status.

PURPOSE The purpose of this study was to investigate the effect of diabetes, motor nerve impairment, and training status on neuromuscular function by concurrent assessment of the torque-velocity relationship and muscle fiber conduction velocity (MFCV). METHODS Four groups were studied (n = 12 each): sedentary patients with diabetes in the first (lower) and fourth (higher) quartile of motor nerve conduction velocity (D1 and D4, respectively), trained diabetic (TD) patients, and nondiabetic sedentary control (C) subjects. Maximal isometric and isokinetic contractions were assessed over a wide range of angular velocities for the elbow flexors and knee extensors to evaluate the torque-velocity relationship. Simultaneously, MFCV was estimated from surface electromyography of the vastus lateralis and biceps brachii. RESULTS Isometric strength was similar among groups. The dynamic strength of elbow flexors was reduced in patients with diabetes at the higher contraction speeds. The strength of knee extensors was lower in sedentary patients with diabetes at all velocities considered, with significantly lower values in D1 than that in D4 at 60°, 90°, and 120°·s(-1), whereas it was similar between TD and C subjects, especially at low contraction velocities. At the vastus lateralis, but not the biceps brachii, MFCV was lower in D1 and D4 as compared with TD and C subjects, showing similar values. CONCLUSIONS Muscle weakness in diabetes affects also the upper limb, although to a lower extent than the lower limb, is only partly related to motor nerve impairment, and is dependent on contraction velocity. Exercise training might counteract diabetes-induced alterations in muscle fiber contractile properties and MFCV.