Effect of a Behavioural Intervention for Adoption and Maintenance of a Physically Active Lifestyle on Psychological Well-Being and Quality of Life in Patients with Type 2 Diabetes: The IDES_2 Randomized Clinical Trial.

BACKGROUND: Psychological well-being and quality of life (QoL) are important outcomes of lifestyle interventions, as a positive impact may favour long-term maintenance of behaviour change. OBJECTIVE: This study investigated the effect of a behavioural intervention for adopting and maintaining an active lifestyle on psychological well-being and health-related QoL in individuals with type 2 diabetes. METHODS: Three hundred physically inactive and sedentary patients were randomized 1:1 to receive 1 month's theoretical and practical counselling once a year (intervention group, INT) or standard care (control group, CON) for 3 years. Psychological well-being and QoL, assessed using the World Health Organization (WHO)-5 and the 36-Item Short Form (SF-36) questionnaire, respectively, were pre-specified secondary endpoints. The primary endpoint was sustained behaviour change, as assessed by accelerometer-based measurement of physical activity (PA) and sedentary time. RESULTS: WHO-5 and SF-36 physical and mental component summary (PCS and MCS) scores increased progressively in the INT group and decreased in the CON group, resulting in significant between-group differences (WHO-5: mean difference 7.35 (95% confidence interval (CI) 3.15-11.55), P = 0.0007; PCS 4.20 (95% CI 2.25-6.15), P < 0.0001; MCS 3.04 (95% CI 1.09-4.99), P = 0.0025). Percentage of participants with likely depression decreased in the INT group and increased in the CON group. PA volume changes were independently associated with WHO-5 changes, which were significantly higher in participants who accumulated > 150 min·wk-1 of moderate-to-vigorous intensity PA versus those who did not (13.06 (95% CI 7.51-18.61), P < 0.0001), whereas no relationship was detected for QoL. CONCLUSION: A counselling intervention that was effective in promoting a sustained change in PA and sedentary behaviour significantly improved psychological well-being and QoL. TRIAL REGISTRATION: ClinicalTrials.gov; NCT01600937; 10 October 2012.

Livestock-Associated Methicillin-Resistant Staphylococcus aureus and Related Risk Factors in Holdings of Veal Calves in Northwest Italy.

Livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) have emerged worldwide as zoonotic pathogens. Data on LA-MRSA in veal calf production in Italy are lacking; the aim of this survey was to fill current knowledge gaps in its prevalence and characteristics. Between February 2012 and January 2013 nasal swabs were taken from 1650 three- to six-month-old veal calves on 55 farms in Piedmont (northwest Italy), including gathering-related epidemiological data. S. aureus were screened for methicillin resistance by phenotypic and molecular (mecA gene detection) methods. MRSA were further genotyped by multilocus sequence typing. About 30% of the herds tested positive for MRSA: three different clonal complexes (CC398, CC97, and CC1) and staphylococcal cassette chromosome mec types (IVa, IVb, and V) were detected. Multilevel logistic regression model indicated poor cleaning, importation from Austria, and animal age as risk factors and coagulase-negative staphylococci colonization as a predictive factor for the occurrence of MRSA. The detection of CCs circulating in pigs and dairy cattle in Italy underscores the ability of the LA-MRSA clones to spread among animal production systems. In addition to maintaining preventive control measures for human health, better cleaning procedures need to be implemented, especially after new calves have been introduced into the herd.

Hazard perception and possibility of simplifying food safety management systems in small businesses in Piedmont region, Italy.

Small food businesses, because of their limited resources, are hard pressed to comply with the requirements of a conventional food safety management system (FSMS). To overcome it, the European legislation provides some flexibility in the application of FSMS. With this study, we evaluated the change in the perception and awareness of hazards in food production and in the attitudes of food business operators (FBOs) after a regional regulation was introduced to allow flexibility and a campaign of training activities on the FSMS simplification opportunities. Training activities targeting various stakeholders have been carried out in Piedmont region since 2014. A total of 283 FBOs from the dairy and the meat supply chains were recruited for a two-round survey. Overall, the majority of the FBOs believed that application of an FSMS helps to overcome official controls, to produce healthy foods, to better manage the production process, and for staff training; its usefulness for enhancing customer trust was judged of limited value. FBO knowledge on the possibility of simplifying the FSMS activities increased significantly between surveys, suggesting the success of the information campaigns. Over time, simplification increased in the meat but not in the dairy supply chain, where it involved nearly 70% of FBOs. The cost of FSMS (mainly due to microbiological analysis) and the time it takes were the main reasons for FBO resistance to its application. Simplification of FSMS procedures were welcomed by the vast majority (>90%) of FBOs. The perception of hazards was low and generic, suggesting the need for targeted training activities.

Muscle fatigability in patients with type 2 diabetes: relation with long-term complications.

AIMS: It is unclear whether long-term complications play a role in muscle fatigue characteristic of patients with type 2 diabetes mellitus (T2DM). The purpose of this study was to investigate the association between muscle fatigability and microvascular and macrovascular complications in patients with T2DM. METHODS: One-hundred forty-six patients with T2DM (80 males, 66 females, aged 66.9 ± 7.9 years) were recruited. Maximal voluntary contraction (MCV) and endurance time (ET, 50% of the MVC) were assessed at the knee extensor muscles with an isometric dynamometer. Univariate and multivariate correlations of ET values with diabetic complications, a wide range of surrogate measures of these sequelae, and cardiovascular risk factors were examined. RESULTS: A higher muscle fatigability was detected in patients with diabetic peripheral neuropathy (DPN, ET: -32.4%), cardiovascular disease (CVD, ET: -32.1%), retinopathy (ET: -35.8%), and nephropathy (ET: -30.4%). At univariate analysis, muscle fatigability was associated with age, physical activity level, diabetes duration, HbA1c , systolic blood pressure, albuminuria, eGFR, and several parameters of nervous and vascular function. Multivariate analysis showed that, after adjusting for covariates, ET was independently associated with sensory nerve conduction velocity, vibration perception threshold at malleolus, and ankle-brachial index. In addition, ET values were independently associated with the presence of DPN, CVD, and retinopathy. CONCLUSIONS: In T2DM, muscle fatigability is associated with presence of DPN, CVD, and retinopathy. Such defect appears to be mediated predominantly by sensory nerve and peripheral vascular dysfunction.

Study to Weigh the Effect of Exercise Training on BONE quality and strength (SWEET BONE) in type 2 diabetes: study protocol for a randomised clinical trial.

INTRODUCTION: Type 2 diabetes (T2D) is associated with an increased fracture risk despite normal-to-increased bone mineral density, suggesting reduced bone quality. Exercise may be effective in reducing fracture risk by ameliorating muscle dysfunction and reducing risk of fall, though it is unclear whether it can improve bone quality. METHODS AND ANALYSIS: The 'Study to Weigh the Effect of Exercise Training on BONE quality and strength (SWEET BONE) in T2D' is an open-label, assessor-blinded, randomised clinical trial comparing an exercise training programme of 2-year duration, specifically designed for improving bone quality and strength, with standard care in T2D individuals. Two hundred T2D patients aged 65-75 years will be randomised 1:1 to supervised exercise training or standard care, stratified by gender, age ≤ or >70 years and non-insulin or insulin treatment. The intervention consists of two weekly supervised sessions, each starting with 5 min of warm-up, followed by 20 min of aerobic training, 30 min of resistance training and 20 min of core stability, balance and flexibility training. Participants will wear weighted vests during aerobic and resistance training. The primary endpoint is baseline to end-of-study change in trabecular bone score, a parameter of bone quality consistently shown to be reduced in T2D. Secondary endpoints include changes in other potential measures of bone quality, as assessed by quantitative ultrasound and peripheral quantitative CT; bone mass; markers of bone turnover; muscle strength, mass and power; balance and gait. Falls and asymptomatic and symptomatic fractures will be evaluated over 7 years, including a 5-year post-trial follow-up. The superiority of the intervention will be assessed by comparing between-groups baseline to end-of-study changes. ETHICS AND DISSEMINATION: This study was approved by the institutional ethics committee. Written informed consent will be obtained from all participants. The study results will be submitted for peer-reviewed publication. TRIAL REGISTRATION NUMBER: NCT02421393; Pre-results.

Effect of a Behavioral Intervention Strategy on Sustained Change in Physical Activity and Sedentary Behavior in Patients With Type 2 Diabetes: The IDES_2 Randomized Clinical Trial.

Importance: There is no definitive evidence that changes in physical activity/sedentary behavior can be maintained long term in individuals with type 2 diabetes. Objective: To investigate whether a behavioral intervention strategy can produce a sustained increase in physical activity and reduction in sedentary time among individuals with type 2 diabetes. Design, Setting, and Participants: The Italian Diabetes and Exercise Study 2 was an open-label, assessor-blinded, randomized clinical superiority trial, with recruitment from October 2012 to February 2014 and follow-up until February 2017. In 3 outpatient diabetes clinics in Rome, 300 physically inactive and sedentary patients with type 2 diabetes were randomized 1:1 (stratified by center, age, and diabetes treatment) to receive a behavioral intervention or standard care for 3 years. Interventions: All participants received usual care targeted to meet American Diabetes Association guideline recommendations. Participants in the behavioral intervention group (n = 150) received 1 individual theoretical counseling session and 8 individual biweekly theoretical and practical counseling sessions each year. Participants in the standard care group (n = 150) received only general physician recommendations. Main Outcomes and Measures: Co-primary end points were sustained change in physical activity volume, time spent in light-intensity and moderate- to vigorous-intensity physical activity, and sedentary time, measured by an accelerometer. Results: Of the 300 randomized participants (mean [SD] age, 61.6 [8.5] years; 116 women [38.7%]), 267 completed the study (133 in the behavioral intervention group and 134 in the standard care group). Median follow-up was 3.0 years. Participants in the behavioral intervention and standard care groups accumulated, respectively, 13.8 vs 10.5 metabolic equivalent-h/wk of physical activity volume (difference, 3.3 [95% CI, 2.2-4.4]; P < .001), 18.9 vs 12.5 min/dof moderate- to vigorous-intensity physical activity (difference, 6.4 [95% CI, 5.0-7.8]; P < .001), 4.6 vs 3.8 h/d of light-intensity physical activity (difference, 0.8 [95% CI, 0.5-1.1]; P < .001), and 10.9 vs 11.7 h/d of sedentary time (difference, -0.8 [95% CI, -1.0 to -0.5]; P < .001). Significant between-group differences were maintained throughout the study, but the between-group difference in moderate- to vigorous-intensity physical activity decreased during the third year from 6.5 to 3.6 min/d. There were 41 adverse events in the behavioral intervention group and 59 in the standard care group outside of the sessions; participants in the behavioral intervention group experienced 30 adverse events during the sessions (most commonly musculoskeletal injury/discomfort and mild hypoglycemia). Conclusions and Relevance: Among patients with type 2 diabetes at 3 diabetes clinics in Rome who were followed up for 3 years, a behavioral intervention strategy compared with standard care resulted in a sustained increase in physical activity and decrease in sedentary time. Further research is needed to assess the generalizability of these findings. Trial Registration: ClinicalTrials.gov Identifier: NCT01600937.

Evaluation of the efficacy of a training course in food safety addressed to food charity volunteers.

In Italy, the Banco Alimentare Onlus manages a network of 8,000 charitable organizations that distribute 67,000 tons of foodstuffs to 1.6 million needy persons. To provide their volunteers with the required food safety knowledge, the Banco Alimentare del Piemonte Onlus commissioned the Istituto Zooprofilattico Sperimentale del Piemonte, Liguria e Valle d'Aosta to hold training courses in food safety. Before and after each session, the participants completed a questionnaire to evaluate their knowledge on the topic of food safety. The responses were entered in a dedicated database and analyzed using STATA ver. 15.1. Comparison of the scores for each participant before and after training revealed a considerable discordance [ICC 0.06, 95% confidence interval (CI) 0.00-0.18]. Analysis of the post-training questionnaires showed that the number of questions left unanswered decreased and the number of correct answers increased. The difference between the percentage of correct and incorrect responses before and after the training course was statistically significant (P<0.001). Comparison of responses to the pre- and post-training questionnaires provided the data for statistical evaluation of the efficacy of the training course.

Outbreak of febrile gastroenteritis caused by Listeria monocytogenes 1/2a in sliced cold beef ham, Italy, May 2016.

In May 2016, two separate clusters of febrile gastroenteritis caused by Listeria monocytogenes were detected by the local health authority in Piedmont, in northern Italy. We carried out epidemiological, microbiological and traceback investigations to identify the source. The people affected were students and staff members from two different schools in two different villages located in the Province of Turin; five of them were hospitalised. The epidemiological investigation identified a cooked beef ham served at the school canteens as the source of the food-borne outbreak. L. monocytogenes was isolated from the food, the stools of the hospitalised pupils and the environment of the factory producing the cooked beef ham. All isolates except one were serotype 1/2a, shared an indistinguishable PFGE pattern and were 100% identical by whole genome sequencing (WGS). By combining a classical epidemiological approach with both molecular subtyping and WGS techniques, we were able to identify and confirm a Listeria gastroenteritis outbreak associated with consumption of sliced cold beef ham.

Correlates of Calcaneal Quantitative Ultrasound Parameters in Patients with Diabetes: The Study on the Assessment of Determinants of Muscle and Bone Strength Abnormalities in Diabetes.

OBJECTIVE: Quantitative ultrasound (QUS) provides an estimate of bone mineral density (BMD) and also evaluates bone quality, which has been related to increased fracture risk in people with diabetes. This study aimed at assessing the correlates of calcaneal QUS parameters in diabetic subjects encompassing various degrees of micro and macrovascular complications and a wide-range of peripheral nerve function. METHODS: Four hundred consecutive diabetic patients were examined by QUS to obtain values of broadband ultrasound attenuation (BUA), the speed of sound (SOS), quantitative ultrasound index (QUI), and BMD. RESULTS: Among surrogate measures of complications, sensory and motor nerve amplitude and heart rate response to cough test and standing correlated with QUS parameters at univariate analysis, together with age, body mass index (BMI), waist circumference, lipid profile, and renal function. Multivariate analysis revealed that BUA, SOS, QUI, and BMD were independently associated with age, male gender, hemoglobin A1c, BMI (or fat, but not fat-free mass), and somatic and autonomic nerve function parameters. CONCLUSIONS: These data indicate that peripheral nerve dysfunction is associated with worse QUS parameters, possibly contributing to increased fracture risk in diabetes. The positive relation of QUS measures with adiposity needs further investigation. This trial is registered with ClinicalTrials.gov (NCT01600924).

Effect of a Behavioral Intervention Strategy for Adoption and Maintenance of a Physically Active Lifestyle: The Italian Diabetes and Exercise Study 2 (IDES_2): A Randomized Controlled Trial.

OBJECTIVE: Adherence to physical activity (PA) recommendations is hampered by the lack of effective strategies to promote behavior change. The Italian Diabetes and Exercise Study 2 (IDES_2) is a randomized controlled trial evaluating a novel behavioral intervention strategy for increasing PA and decreasing sedentary time (SED-time) in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: The study randomized 300 physically inactive and sedentary patients with type 2 diabetes 1:1 to receive theoretical and practical counseling once yearly for 3 years (intervention group [INT]) or standard care (control group [CON]). Here, we report the 4-month effects on objectively (accelerometer) measured daily light-intensity PA (LPA), moderate-to-vigorous-intensity PA (MVPA), and SED-time, and cardiovascular risk factors. RESULTS: LPA and MVPA both increased, and SED-time decreased in both groups, although changes were significantly more marked in INT participants (approximately twofold for LPA and SED-time and approximately sixfold for MVPA). A significant reduction in HbA1c was observed only in INT subjects. An increase in LPA >0.92 h · day-1 and in MVPA >7.33 min · day-1 and a decrease in SED-time >1.05 h · day-1 were associated with an average decrease in HbA1c of ∼1% and also with significant improvements in fasting glucose, body weight, waist circumference, and hs-CRP. Changes in PA and SED-time were independent predictors of improvements in HbA1c. CONCLUSIONS: This behavioral intervention is effective in the short term for increasing LPA and MVPA and reducing SED-time. Significant improvements in cardiometabolic risk profiles were observed in subjects experiencing the most pronounced changes in PA and SED-time, even if below the recommended level.

Level and correlates of physical activity and sedentary behavior in patients with type 2 diabetes: A cross-sectional analysis of the Italian Diabetes and Exercise Study_2.

OBJECTIVE: Patients with type 2 diabetes usually show reduced physical activity (PA) and increased sedentary (SED)-time, though to a varying extent, especially for low-intensity PA (LPA), a major determinant of daily energy expenditure that is not accurately captured by questionnaires. This study assessed the level and correlates of PA and SED-time in patients from the Italian Diabetes and Exercise Study_2 (IDES_2). METHODS: Three-hundred physically inactive and sedentary patients with type 2 diabetes were enrolled in the IDES_2 to be randomized to an intervention group, receiving theoretical and practical exercise counseling, and a control group, receiving standard care. At baseline, LPA, moderate-to-vigorous-intensity PA (MVPA), and SED-time were measured by accelerometer. Physical fitness and cardiovascular risk factors and scores were also assessed. RESULTS: LPA was 3.93±1.35 hours∙day-1, MVPA was 12.4±4.6 min∙day-1, and SED-time was 11.6±1.2 hours∙day-1, with a large range of values (0.89-7.11 hours∙day-1, 0.6-21.0 min∙day-1, and 9.14-15.28 hours∙day-1, respectively). At bivariate analysis, LPA and MVPA correlated with better cardiovascular risk profile and fitness parameters, whereas the opposite was observed for SED-time. Likewise, values of LPA, MVPA, and SED-time falling in the best tertile were associated with optimal or acceptable levels of cardiovascular risk factors and scores. At multivariate analysis, age, female gender, HbA1c, BMI or waist circumference, and high-sensitivity C reactive protein (for LPA and SED-time only) were negatively associated with LPA and MPA and positively associated with SED-time in an independent manner. CONCLUSIONS: Physically inactive and sedentary patients with type 2 diabetes from the IDES_2 show a low level of PA, though values of LPA, MVPA, and SED-time vary largely. Furthermore, there is a strong correlation of these measures with glycemic control, adiposity and inflammation, thus suggesting that even small improvements in LPA, MVPA, and SED-time might be associated with significant improvement in cardiovascular risk profile. TRIAL REGISTRATION: ClinicalTrials.gov NCT01600937.

The Italian Diabetes and Exercise Study 2 (IDES-2): a long-term behavioral intervention for adoption and maintenance of a physically active lifestyle.

BACKGROUND: Physical activity (PA)/exercise have become an integral part of the management of type 2 diabetes mellitus (T2DM). However, current guidelines are difficult to put into action in this population due to a number of barriers, especially the lack of acceptable, feasible, and validated behavioral intervention strategies. The present manuscript reports the rationale, study design and methods, and design considerations of the Italian Diabetes and Exercise Study (IDES)-2, a randomized controlled trial testing the efficacy of a behavior change strategy in increasing total daily PA and reducing sedentary time (SED-time) in patients with T2DM. METHODS/DESIGN: Starting 7 January 2014, the IDES_2 began enrolling 300 patients with known T2DM of at least 1-year duration in three tertiary referral outpatient Diabetes Clinics in Rome. Additional requirements are age 40 to 80 years, body mass index 27 to 40 kg/m(2), sedentary lifestyle, and physically inactive for at least 6 months, ability to walk 1.6 km without assistance, and eligibility after cardiovascular evaluation. Patients are randomized by center and within each center, by age and type of diabetes treatment to either the intervention or the control group. Patients in the intervention (INT) group (n = 150) receive theoretical and practical exercise counseling consisting of aggregated behavior change techniques (one individual theoretical counseling session plus eight twice-a-week individual theoretical and practical exercise counseling sessions) once a year for 3 years. Patients in the control (CON) group (n = 150), receive standard care, including general physician recommendations for daily PA. The primary outcomes are total daily PA and SED-time, as measured objectively by the use of an accelerometer. Secondary outcomes include physical fitness, modifiable cardiovascular risk factors, musculoskeletal disturbances, well-being/depression, and health-related quality of life. DISCUSSION: The behavioral intervention strategy tested in the IDES_2 is based on solid theoretical grounds and uses several behavioral change techniques, two factors which were found to improve effectiveness of behavioral intervention. In addition, physicians and exercise specialists have been specifically trained for counselling/prescribing and supervising PA/exercise, respectively, in subjects suffering from metabolic disorders. Finally, the large sample size, the long study duration, and the objective measurement of PA allow statistically significant and scientifically robust conclusions to be drawn on the feasibility and efficacy of this intervention in T2DM patients. TRIAL REGISTRATION: ClinicalTrials.gov; NCT01600937 ; 10 October 2012.

Volume-dependent effect of supervised exercise training on fatty liver and visceral adiposity index in subjects with type 2 diabetes The Italian Diabetes Exercise Study (IDES).

AIMS: This study evaluated the effect of supervised exercise training on liver enzymes and two surrogate measures of non-alcoholic fatty liver disease (NAFLD) in subjects with type 2 diabetes. METHODS: Sedentary patients from 22 outpatient diabetes clinics were randomized by center, age and treatment to twice-a-week supervised aerobic and resistance training plus structured exercise counseling (exercise group, EXE; n=303) versus counseling alone (control group, CON; n=303) for 12 months. EXE participants were further randomized to low-to-moderate (n=142) or moderate-to-high (n=161) intensity training of equal energy cost. Baseline and end-of-study levels of liver enzymes, fatty liver index (FLI) and visceral adiposity index (VAI) were obtained. RESULTS: Enzyme levels did not change, whereas FLI and VAI decreased significantly in EXE, but not CON participants. Physical activity (PA) volume was an independent predictor of both FLI and VAI reductions, the extent of which increased from the 1st to the 4th quintile of PA volume and baseline to end-of-study changes in fitness parameters. Differences in the effect of LI versus HI training were negligible. CONCLUSIONS: Data from this large cohort of subjects with type 2 diabetes indicate that FLI and VAI decrease with supervised training in a volume-dependent manner.

Aujeszky's disease in red fox (Vulpes vulpes): phylogenetic analysis unravels an unexpected epidemiologic link.

We describe Aujeszky's disease in a female of red fox (Vulpes vulpes). Although wild boar (Sus scrofa) would be the expected source of infection, phylogenetic analysis suggested a domestic rather than a wild source of virus, underscoring the importance of biosecurity measures in pig farms to prevent contact with wild animals.

Effect of supervised exercise training on musculoskeletal symptoms and function in patients with type 2 diabetes: the Italian Diabetes Exercise Study (IDES).

Musculoskeletal disorders are common in subjects with type 2 diabetes mellitus (T2DM) and may represent a barrier to physical activity (PA). In the Italian Diabetes and Exercise Study, we assessed whether a strategy aimed at minimizing the risk of injury and worsening of musculoskeletal symptoms favors participation in exercise training and results in improvements in joint-specific functional scores, along with amelioration of metabolic profile. Sedentary patients with T2DM (n = 606) from 22 outpatient diabetes clinics were randomized to twice-a-week supervised aerobic and resistance training plus exercise counseling (EXE) versus counseling alone (CON) for 12 months. Musculoskeletal symptoms were evaluated at baseline in the entire cohort by the use of a self-reported questionnaire in order to design tailored exercise programs with exclusion of painful segments, and validated joint-specific scores were calculated at the end of study in a subgroup of CON (n = 65) and EXE subjects (n = 62). Musculoskeletal symptoms were present in more than ¾ of EXE and CON subjects. Yet, volumes of non-supervised PA were high, whereas dropout rates and adverse events were low in both groups. Moreover, in the EXE group, no difference was observed between patients with and without symptoms in session attendance and PA/exercise volume. Scores for symptoms and functional status of limbs and spine were significantly better in EXE than in CON subjects and correlated with PA/exercise volume and improvements in fitness parameters. Preliminary evaluation of musculoskeletal symptoms is useful in favoring compliance with supervised training programs and obtaining significant benefits to the functional status of the involved joints.

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.