Walking for subjects with type 2 diabetes: A systematic review and joint AMD/SID/SISMES evidence-based practical guideline.

AIMS: Regular exercise is considered a cornerstone in the management of type 2 diabetes mellitus (T2DM). It improves glucose control and cardiovascular risk factors, contributes to weight loss, and also improves general well-being, likely playing a role in the prevention of chronic complications of diabetes. However, compliance to exercise recommendations is generally inadequate in subjects with T2DM. Walking is the most ancestral form of physical activity in humans, easily applicable in daily life. It may represent, in many patients, a first simple step towards lifestyle changes. Nevertheless, while most diabetic patients do not engage in any weekly walking, exercise guidelines do not generally detail how to improve its use. The aims of this document are to conduct a systematic review of available literature on walking as a therapeutic tool for people with T2DM, and to provide practical, evidence-based clinical recommendations regarding its utilization in these subjects. DATA SYNTHESIS: Analysis of available RCTs proved that regular walking training, especially when supervised, improves glucose control in subjects with T2DM, with favorable effects also on cardiorespiratory fitness, body weight and blood pressure. Moreover, some recent studies have shown that even short bouts of walking, used for breaking prolonged sitting, can ameliorate glucose profiles in diabetic patients with sedentary behavior. CONCLUSIONS: There is sufficient evidence to recognize that walking is a useful therapeutic tool for people with T2DM. This document discusses theoretical and practical issues for improving its use. This article is co-published in the journals Sport Sciences for Health and Nutrition, Metabolism and Cardiovascular Diseases.

Review of general suggestions on physical activity to prevent and treat gestational and pre-existing diabetes during pregnancy and in postpartum.

The aim of this review is to provide general suggestions on physical activity (PA) in pre-gestational and gestational diabetes mellitus (GDM) and encourage women to take part in safe and effective activities throughout pregnancy, in the absence of other contraindications. PA before and during pregnancy and in postpartum has many positive effects on the mother, as it could reduce the risk of GDM, excessive weight gain and lower back pain and also prevents, in the postpartum, diabetes mellitus. It may also reduce the duration of labour and complications at childbirth, fatigue, stress, anxiety and depression, thereby leading to an improved sense of wellbeing. Clinically, it is thought to help prevent preeclampsia and premature birth even though RCTs provide conflicting evidence with regard to the prevention of GDM. The main reason for this rests on the fact that the majority of clinical trials have not been able to replicate the preventive effect of PA on the onset of GDM, such as the different adherence of the patient to PA. Herein, we survey the literature regarding exercise and PA on GDM prevention and treatment as well as on clinical outcomes in pre-GDM in pregnancy. On the basis of the current literature, we also present a series of general recommendations and suggestions on PA and exercise training in pregnancy among both diabetic patients and those at risk for GDM.

Determination of metabolic equivalents during low- and high-intensity resistance exercise in healthy young subjects and patients with type 2 diabetes.

The purpose of this study was to quantify the metabolic equivalents (METs) of resistance exercise in obese patients with type 2 diabetes (T2DM) and healthy young subjects and to evaluate whether there were differences between sessions executed at low- versus high-intensity resistance exercise. Twenty obese patients with T2DM (62.9±6.1 years) and 22 young subjects (22.6±1.9 years) performed two training sessions: one at vigorous intensity (80% of 1-repetition maximum (1RM)) and one at moderate intensity (60% of 1RM). Both groups carried out three strength exercises with a 2-day recovery between sessions. Oxygen consumption was continuously measured 15 min before, during and after each training session. Obese T2DM patients showed lower METs values compared with young healthy participants at the baseline phase (F= 2043.86; P<0.01), during training (F=1140.59; P<0.01) and in the post-exercise phase (F=1012.71; P<0.01). No effects were detected in the group x intensity analysis of covariance. In this study, at both light-moderate and vigorous resistance exercise intensities, the METs value that best represented both sessions was 3 METs for the obese elderly T2DM patients and 5 METs for young subjects.

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.

Correlates of muscle strength in diabetes: The study on the assessment of determinants of muscle and bone strength abnormalities in diabetes (SAMBA).

BACKGROUND AND AIMS: Apart from late motor nerve dysfunction, factors affecting muscle strength in diabetes are largely unknown. This study was aimed at assessing muscle strength correlates in diabetic subjects encompassing a wide range of peripheral nerve function and various degrees of micro and macrovascular complications. METHODS AND RESULTS: Four-hundred consecutive patients with type 1 and 2 diabetes (aged 46.4 ± 13.9 and 65.8 ± 10.3 years, respectively) from the Study on the Assessment of Determinants of Muscle and Bone Strength Abnormalities in Diabetes (SAMBA) were examined for upper and lower body muscle isometric maximal voluntary contraction by dynamometry. Univariate and multivariate regression analyses were applied to identify strength correlates. Isometric force at both the upper and lower limbs was significantly lower in subjects with than in those without any complication. At univariate analysis, it was strongly associated with age, diabetes duration, physical activity (PA) level, cardio-respiratory fitness, anthropometric parameters, surrogate measures of complications, and parameters of sensory and autonomic, but not motor (except amplitude) neuropathy. Multivariate analysis revealed that upper and lower body strength correlated independently with male gender and, inversely, with age, autonomic neuropathy score (or individual autonomic function abnormalities), and vibration perception threshold, but not sensory-motor neuropathy score. Diabetes duration and PA level were excluded from the model. CONCLUSIONS: Both upper and lower body muscle strength correlate with measures of diabetic complications and particularly with parameters of sensory and especially autonomic nerve function, independently of diabetes duration and PA level, thus suggesting the involvement of mechanisms other than manifest motor nerve impairment.

Relationship of exercise volume to improvements of quality of life with supervised exercise training in patients with type 2 diabetes in a randomised controlled trial: the Italian Diabetes and Exercise Study (IDES).

AIMS/HYPOTHESIS: A positive impact of exercise intervention programmes on quality of life (QoL) may be important for long-term patient compliance to exercise recommendations. We have previously shown that QoL improves significantly with supervised exercise, whereas it worsens with counselling alone, in patients with type 2 diabetes from the Italian Diabetes and Exercise Study (IDES). Here, we report data on the relationship between changes in QoL and volume of physical activity/exercise in these individuals. METHODS: This multicentre parallel randomised controlled, open-label, trial enrolled sedentary patients with type 2 diabetes (n = 606 of 691 eligible) in 22 outpatient diabetes clinics. Patients were randomised by centre, age and diabetes treatment using a permuted-block design to twice-a-week supervised aerobic and resistance training plus exercise counselling (exercise group) versus counselling alone (control group) for 12 months. Health-related QoL was assessed by the 36-Item Short Form (SF-36) Health Survey. RESULTS: In the exercise group (n = 268 of 303 randomised), there was a trend for increasing QoL with increasing exercise volume, with significant improvement of the physical component summary (PCS) measure only above 17.5 metabolic equivalents h⁻¹ week⁻¹ and a clear volume-relationship for the mental component summary (MCS) measure. A relationship with volume of physical activity also was observed in the control group (n = 260 of 303 randomised), despite overall deterioration of all scores. Independent correlates of improvements in both PCS and MCS were exercise volume, study arm and, inversely, baseline score. CONCLUSIONS/INTERPRETATION: This large trial shows a relationship between changes in physical and mental health-related QoL measures and volume of physical activity/exercise, with supervised exercise training also providing volume-independent benefits.

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-1ß, 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.

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 (HbA(1c)) 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 (VO(2max))] and resistance circuit training [at 60-80% of 1 repetition maximum (RM)]. The training significantly improved VO(2max) (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 HbA(1c), 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)-gamma after 6 months of train - ing (p=0.024); PPARalpha 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), PPARgamma coactivator 1alpha (PGC- 1alpha), 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 PPARgamma and PPARalpha in DM2 subjects with metabolic syndrome.

Physical activity/exercise training in type 2 diabetes. The role of the Italian Diabetes and Exercise Study.

Cardiorespiratory fitness is inversely related to the development of type 2 diabetes and cardiovascular morbidity and mortality. Trials in individuals with impaired glucose tolerance have highlighted the role of physical activity/exercise in the prevention of type 2 diabetes. Moreover, physical activity and exercise training have been recognized as treatment options for patients with type 2 diabetes. Both aerobic and resistance training were shown to produce beneficial effects by reducing HbA(1c), inducing weight loss and improving fat distribution, lipid profile and blood pressure in patients with type 2 diabetes. Mixed aerobic and resistance training was recently shown to be more effective than either one alone in ameliorating HbA(1c). However, further research is needed to establish the volume, intensity and type of exercise that are required to reduce cardiovascular burden and particularly to define the best strategy for promoting long-term compliance and durable lifestyle changes in individuals with type 2 diabetes. The Italian Diabetes Exercise Study (IDES) is a prospective Italian multicentre randomized controlled trial, of larger size and longer duration than previously published trials. It has been designed to assess the combined effect of structured counselling and supervised mixed (aerobic plus resistance) exercise training, as compared with counselling alone, on HbA(1c) and other cardiovascular risk factors as well as fitness parameters in individuals with type 2 diabetes and the metabolic syndrome. This study was also aimed at testing a sustainable strategy for promoting and maintaining a sufficient level of physical activity among individuals with type 2 diabetes to be implemented at the population level.

Self glucose monitoring and physical exercise in diabetes.

Cardiorespiratory fitness, which is determined mainly by the level of physical activity, is inversely related to mortality in the general population as well as in subjects with diabetes, the incidence of which is also increased by low exercise capacity. Exercise is capable of promoting glucose utilization in normal subjects as well as in insulin-deficient or insulin-resistant diabetic individuals. In diabetic subjects treated with insulin or insulin secretagogues, exercise may also result in complications, with too much insulin causing hypoglycaemia and not enough insulin leading to hyperglycaemia and possibly ketoacidosis; both complications may also occur several hours after exercise. Therefore, self-monitoring of blood glucose before, during (for exercise duration of more than 1 h) and after physical exercise is highly recommended, and also carbohydrate supplementation may be required. In the Italian Diabetes Exercise Study (IDES), measurement of blood glucose and systolic and diastolic blood pressure levels before and after supervised sessions of combined (aerobic + resistance) exercise in type 2 diabetic subjects with the metabolic syndrome showed significant reductions of these parameters, though no major hypoglycaemic or hypotensive episode was detected. The extent of reduction of blood glucose was related to baseline values but not to energy expenditure and was higher in subjects treated with insulin than in those on diet or oral hypoglycaemic agents (OHA). Thus, supervised exercise training associated with blood glucose monitoring is an effective and safe intervention to decrease blood glucose levels in type 2 diabetic subjects.

Plasma levels of adrenomedullin, a vasoactive peptide, in type 2 diabetic patients with and without retinopathy.

AIM: The aim of this study was to investigate whether adrenomedullin (AM) secretion is modified in type 2 diabetic patients with and without retinopathy. METHODS: The study was performed on 92 patients with type 2 diabetes, 65 of whom had uncomplicated diabetes, 27 had retinopathy, and 40 had mild to moderate hypertension. Patients with serum creatinine levels >1.2 mg/dL, were excluded. Circulating AM was assayed using a specific radioimmunoassay. RESULTS: AM concentrations were significantly higher in type 2 diabetic patients (25+/-2.1 pg/mL) than in the 31 normal subjects (11+/-0.8 pg/mL) (P<0.001). Type 2 diabetic patients with retinopathy had significantly greater AM levels (30.8+/-3.4 pg/mL) than both controls (P<0.001) and type 2 diabetic patients without retinopathy (25.2+/-2 pg/mL same as previous value) (P<0.001). No statistical difference was found between diabetic patients with pre-proliferative retinopathy (27.3+/-4.7 pg/mL) and proliferative retinopathy (24+/-3.1 pg/mL) (P=0.543). In type 2 diabetic patients, a significant correlation between plasma AM levels and HbA1c values (r=0.467; P<0.01) was found. CONCLUSION: Our findings indicate that circulating AM is increased in type 2 diabetic patients and that increase correlates with poor glucose metabolic control and presence of retinopathy.

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 HbA(1c), greater increase in VO(2max) 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 HbA(1c) that can be seen significant if compared with aerobic training alone and resistance training alone.