Longitudinal assessment of physical function in adults with X-linked hypophosphatemia following initiation of burosumab therapy.

We assessed multiple components of muscle function in ten adults with X-linked hypophosphatemia (XLH) receiving burosumab treatment. Lower limb power (+ 9%), short physical performance battery (SPPB) score (+ 1.2 points), and physical activity (+ 65%) increased following 6 months of treatment, and hand grip increased (+ 10%) between 6 and 12 months of treatment. PURPOSE: X-linked hypophosphatemia (XLH) is a rare genetic disorder of phosphate metabolism. Burosumab is a monoclonal antibody treatment shown to improve phosphate homeostasis and improve symptoms as well as fracture healing when used as a therapy for XLH in adults. However, little is known about its effects on the large deficits in multiple components of physical function previously reported in XLH. METHODS: Ten adults (6 females, age 41.1 ± 15.7 y) were recruited from specialist centres in London and Bristol. During clinical visits for initial burosumab treatment and at 6-month and 12-month follow-up, physical function, and physical activity (PA) assessments were performed. In detail, lower limb power was assessed by mechanography via a countermovement jump, mobility by short physical performance battery (SPPB), functional capacity by 6-min walk test (6MWT), upper limb strength by hand grip dynamometry, and PA via an International Physical Activity Questionnaire (IPAQ). Differences between baseline and 6-month follow-up, and in a subset of 5 patients between 6- and 12-month follow-up, were assessed. RESULTS: Lower limb power increased by 9% (P = 0.049) from baseline to 6 months, as did SPPB score (+ 1.2 points, P = 0.033) and total PA (+ 65%, P = 0.046) although hand grip and 6MWT did not differ. Only for hand grip was a significant improvement (+ 10%, P = 0.023) seen between 6 and 12 months. CONCLUSIONS: Burosumab treatment is associated with improved lower limb function and mobility at 6 months, with improvement in hand grip strength at 12 months. Future studies should explore the underlying mechanisms and describe on function and other patient outcomes.

Effect of sustained decreases in sedentary time and increases in physical activity on liver enzymes and indices in type 2 diabetes.

Background: Current guidelines for nonalcoholic fatty liver disease (NAFLD) recommend high volumes and/or intensities of physical activity (PA), the achievement of which generally requires participation in supervised exercise training programs that however are difficult to implement in routine clinical practice. Conversely, counselling interventions may be more suitable, but result in only modest increases in moderate-to-vigorous-intensity PA (MVPA). This study assessed whether a counseling intervention for increasing PA and decreasing sedentary time (SED-time) is effective in improving NAFLD markers in people with type 2 diabetes. Methods: Three-hundred physically inactive and sedentary patients were randomized 1:1 to receive one-month theoretical and practical counseling once-a-year (intervention group) or standard care (control group) for 3 years. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and γ-glutamyltranspeptidase (γGT) levels were measured and fatty liver index (FLI), hepatic steatosis index (HSI), and visceral adiposity index (VAI) were calculated. Total PA volume, light-intensity PA (LPA), moderate-to-vigorous-intensity PA (MVPA), and SED-time were objectively measured by an accelerometer. Results: Throughout the 3-year period, NAFLD markers did not change in the control group, whereas ALT, γGT, FLI, and HSI decreased in the intervention group, with significant between-group differences, despite modest MVPA increases, which however were associated with larger decrements in SED-time and reciprocal increments in LPA. Mean changes in NAFLD markers varied according to quartiles of (and correlated with) changes in MVPA (all markers) and SED-time, LPA, and PA volume (ALT, γGT, and HSI). Mean changes in MVPA or PA volume were independent predictors of changes in NAFLD markers. When included in the models, change in cardiorespiratory fitness and lower body muscle strength were independently associated with some NAFLD markers. Conclusion: A behavior change involving all domains of PA lifestyle, even if insufficient to achieve the recommended MVPA target, may provide beneficial effects on NAFLD markers in people with type 2 diabetes.

Acute Effects of Vibrating Insoles on Dynamic Balance and Gait Quality in Individuals With Diabetic Peripheral Neuropathy: A Randomized Crossover Study.

OBJECTIVE: This study investigated the effects of vibrating insoles on dynamic balance and gait quality during level and stair walking and explored the influence of vibration type and frequency in individuals with diabetic peripheral neuropathy (DPN). RESEARCH DESIGN AND METHODS: Twenty-two men with DPN were assessed for gait quality and postural and dynamic balance during walking and stair negotiation using a motion capture system and force plates across seven vibratory insole conditions (Vcs) versus a control (Ctrl) condition (insole without vibration). Vibration was applied during standing and walking tasks, and 15-min rest-stop periods without vibration were interposed between conditions. Repeated measures test conditions were randomized. The primary outcomes were gait speed and dynamic balance. RESULTS: Gait speed during walking significantly improved in all Vcs compared with Ctrl (P < 0.005), with Vc2, Vc4, and Vc6 identified as the most effective. Gait speed increased (reflecting faster walking) during stair ascent and descent in Vc2 (Ctrl vs. Vc2 for ascent 0.447 ± 0.180 vs. 0.517 ± 0.127 m/s; P = 0.037 and descent 0.394 ± 0.170 vs. 0.487 ± 0.125 m/s; P = 0.016), Vc4 (Ctrl vs. Vc4 for ascent 0.447 ± 0.180 vs. 0.482 ± 0.197 m/s; P = 0.047 and descent 0.394 ± 0.170 vs. 0.438 ± 0.181 m/s; P = 0.017), and Vc6 (Ctrl vs. Vc6 for ascent 0.447 ± 0.180 vs. 0.506 ± 0.179 m/s; P = 0.043 and descent 0.394 ± 0.170 vs. 0.463 ± 0.159 m/s; P = 0.026). Postural balance improved during quiet standing with eyes closed in Vc2, Vc4, Vc6, and Vc7 (P < 0.005). CONCLUSIONS: Vibrating insoles are an effective acute strategy for improving postural balance and gait quality during level walking and stair descent in individuals with DPN. These benefits are particularly evident when the entire plantar foot surface is stimulated.

Muscular Adaptations to Concurrent Resistance Training and High-Intensity Interval Training in Adults with Type 2 Diabetes: A Pilot Study.

This pilot study aimed to compare the effects of eight weeks of concurrent resistance training (RT) and high-intensity interval training (HIIT) vs. RT alone on muscle performance, mass and quality in adults with type 2 diabetes (T2DM). Twelve T2DM adults were randomly allocated to the RT + HIIT (n = 5) or RT (n = 7) group. Before and after training, maximal oxygen uptake (VO2max), muscle strength and power were evaluated by calorimetry, dynamometry and one-repetition maximum (1RM) test. Quadriceps muscle volume was determined by MRI, and muscle quality was estimated. After RT, VO2max (+12%), knee muscle power (+20%), quadriceps muscle volume (+5.9%) and quality (leg extension, +65.4%; leg step-up, +223%) and 1RM at leg extension (+66.4%), leg step-up (+267%), lat pulldown (+60.9%) and chest press (+61.2%) significantly increased. The RT + HIIT group improved on VO2max (+27%), muscle volume (+6%), muscle power (+9%) and 1RM at lat pulldown (+47%). No other differences were detected. Among groups, changes in muscle quality at leg step-up and leg extension and VO2max were significantly different. The combination of RT and HIIT effectively improves muscle function and size and increases cardiorespiratory fitness in adults with T2DM. However, HIIT combined with RT may interfere with the development of muscle quality.

Sustained increase in physical fitness independently predicts improvements in cardiometabolic risk profile in type 2 diabetes.

AIMS: To investigate the relationship between changes in physical fitness and cardiovascular risk factors and scores in patients with type 2 diabetes receiving either a behavioural counselling intervention to increase moderate-to-vigorous-intensity physical activity (MVPA) and decrease sedentary-time (SED-time) or standard care. MATERIALS AND METHODS: This is a pre-specified ancillary analysis of the Italian Diabetes and Exercise Study_2, a 3-year randomized clinical trial in which 300 physically inactive and sedentary patients were randomized 1:1 to receive either a one-month theoretical and practical counselling each year or standard care. Mean changes from baseline throughout the 3-year period in MVPA, SED-time, cardiorespiratory fitness (VO2max ), muscle strength, flexibility, cardiovascular risk factors and scores were calculated for study completers (n = 267) and considered irrespective of study arm. RESULTS: Haemoglobin (Hb) A1c and coronary heart disease (CHD) risk scores decreased with quartiles of VO2max and lower body muscle strength changes. Multivariable linear regression analysis showed that increases in VO2max independently predicted decreases in HbA1c , blood glucose, diastolic blood pressure (BP), CHD and total stroke 10-year risk and increases in HDL cholesterol, whereas increases in lower body muscle strength independently predicted decreases in body mass index (BMI), waist circumference, triglycerides, systolic BP, CHD and fatal stroke 10-year risk. These associations remained after including changes in BMI, waist circumference, fat mass and fat-free mass, or MVPA and SED-time as covariates. CONCLUSIONS: Improvement in physical fitness predicts favourable changes in cardiometabolic risk profile, independent of changes not only in (central) adiposity or body composition but also in MVPA and SED-time. TRIAL REGISTRATION: ClinicalTrials.gov; NCT01600937; URL https://clinicaltrials.gov/ct2/show/NCT01600937.

Sustained decreases in sedentary time and increases in physical activity are associated with preservation of estimated ß-cell function in individuals with type 2 diabetes.

AIMS: In the Italian Diabetes and Exercise Study_2, a counselling intervention produced modest but sustained increments in moderate-to vigorous-intensity physical activity (MVPA), with reallocation of sedentary-time (SED-time) to light-intensity physical activity (LPA). This post hoc analysis evaluated the impact of intervention on estimated ß-cell function and insulin sensitivity. METHODS: Patients with type 2 diabetes were randomized to one-month counselling once-a-year or standard care for 3 years. The HOmeostatic Model Assessment-2 (HOMA-2) method was used for estimating indices of ß-cell function (HOMA-B%), insulin sensitivity (HOMA-S%), and insulin resistance (HOMA-IR); the disposition index (DI) was estimated as HOMA-ß%/HOMA-IR; MVPA, LPA, and SED-time were objectively measured by accelerometer. RESULTS: HOMA-B% and DI decreased in control group, whereas HOMA-B% remained stable and DI increased in intervention group. Between-group differences were significant for almost all insulin secretion and sensitivity indices. Changes in HOMA-B% and DI correlated with SED-time, MVPA and LPA. Changes in HOMA-B%, DI, and all indices were independently predicted by changes in SED-time (or LPA), MVPA, and BMI (or waist circumference), respectively. CONCLUSIONS: In individuals with type 2 diabetes, increasing MVPA, even without achieving the recommended target, is effective in maintaining estimated ß-cell function if sufficient amounts of SED-time are reallocated to LPA.

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.

Relationships of Changes in Physical Activity and Sedentary Behavior With Changes in Physical Fitness and Cardiometabolic Risk Profile in Individuals With Type 2 Diabetes: The Italian Diabetes and Exercise Study 2 (IDES_2).

OBJECTIVE: In the Italian Diabetes and Exercise Study_2 (IDES_2), behavioral counseling promoted a sustained increase in physical activity (PA) volume (+3.3 MET h ⋅ week-1), moderate- to vigorous-intensity PA (MVPA) (+6.4 min ⋅ day-1), and light-intensity PA (LPA) (+0.8 h ⋅ day-1) and decrease in sedentary time (SED-time) (-0.8 h ⋅ day-1). Here, we investigated the relationships of changes in PA/SED-time with changes in physical fitness and cardiometabolic risk profile in individuals with type 2 diabetes. RESEARCH DESIGN AND METHODS: In this 3-year randomized clinical trial, 300 physically inactive and sedentary patients were randomized 1:1 to receive 1-month theoretical and practical counseling once a year or standard care. Changes in physical fitness and cardiovascular risk factors/scores according to quartiles of accelerometer-measured changes in PA/SED-time were assessed, together with univariate and multivariable associations between these parameters, in the whole cohort and by study arm. RESULTS: Physical fitness increased and HbA1c and coronary heart disease 10-year risk scores decreased with quartiles of MVPA and SED-time change. In quartile IV of MVPA increase and SED-time decrease, cardiorespiratory fitness increased by 5.23 and 4.49 mL ⋅ min-1 ⋅ kg-1 and HbA1c decreased by 0.73 and 0.85%, respectively. Univariate correlations confirmed these relationships, and mean changes in both MPVA and SED-time predicted changes in physical fitness and cardiovascular risk factors/scores independently of one another and of other confounders. Similar findings were observed with LPA and PA volume and in each group separately. CONCLUSIONS: Even modest increments in MVPA may have a clinically meaningful impact, and reallocating SED-time to LPA may also contribute to improved outcomes, possibly by increasing total energy expenditure.

Neuromuscular dysfunction and exercise training in people with diabetic peripheral neuropathy: A narrative review.

Diabetic peripheral neuropathy (DPN) is a common condition that is associated with neuromuscular dysfunction and peripheral sensory impairment. These deficits predispose patients to sensory and motor system limitations, foot ulcers and a high risk of falls. Exercise training has been proposed as an effective tool to alleviate neural deficits and improve whole-body function. Here we review the effects of DPN on neuromuscular function, the mechanisms underlying this impairment, and the neural and muscular adaptations to exercise training. Muscle dysfunction is an early hallmark of DPN. Deficits in muscle strength, power, mass and a greater fatigability are particularly severe in the lower extremity muscles. Non-enzymatic glycation of motor proteins, impaired excitation-contraction coupling and loss of motor units have been indicated as the main factors underlying muscular dysfunction. Among the exercise-based solutions, aerobic training improves neural structure and function and ameliorates neuropathic signs and symptoms. Resistance training induces marked improvement of muscle performance and may alleviate neuropathic pain. A combination of aerobic and resistance training (i.e., combined training) restores small sensory nerve damage, reduces symptoms, and improves muscle function. The evidence so far suggests that exercise training is highly beneficial and should be included in the standard care for DPN patients.

Patient and Provider Perspective of Smart Wearable Technology in Diabetic Foot Ulcer Prevention: A Systematic Review.

Background and Objectives: Smart wearable devices are effective in diabetic foot ulcer (DFU) prevention. However, factors determining their acceptance are poorly understood. This systematic review aims to examine the literature on patient and provider perspectives of smart wearable devices in DFU prevention. Materials and Methods: PubMed, Scopus, and Web of Science were systematically searched up to October 2021. The selected articles were assessed for methodological quality using the quality assessment tool for studies with diverse designs. Results: A total of five articles were identified and described. The methodological quality of the studies ranged from low to moderate. Two studies employed a quantitative study design and focused on the patient perspective, whereas three studies included a mixed, quantitative/qualitative design and explored patient or provider (podiatrist) perspectives. Four studies focused on an insole system and one included a smart sock device. The quantitative studies demonstrated that devices were comfortable, well designed and useful in preventing DFU. One mixed design study reported that patients did not intend to adopt an insole device in its current design because of malfunctions, a lack of comfort. and alert intrusiveness, despite the general perception that the device was a useful tool for foot risk monitoring. Two mixed design studies found that performance expectancy was a predictor of a podiatrist's behavioural intention to recommend an insole device in clinical practice. Disappointing participant experiences negatively impacted the podiatrists' intention to adopt a smart device. The need for additional refinements of the device was indicated by patients and providers before its use in this population. Conclusions: The current evidence about patient and provider perspectives on smart wearable technology is limited by scarce methodological quality and conflicting results. It is, thus, not possible to draw definitive conclusions regarding acceptability of these devices for the prevention of DFU in people with diabetes.

Sensory-Motor Mechanisms Increasing Falls Risk in Diabetic Peripheral Neuropathy.

Diabetic peripheral neuropathy (DPN) is associated with peripheral sensory and motor nerve damage that affects up to half of diabetes patients and is an independent risk factor for falls. Clinical implications of DPN-related falls include injury, psychological distress and physical activity curtailment. This review describes how the sensory and motor deficits associated with DPN underpin biomechanical alterations to the pattern of walking (gait), which contribute to balance impairments underpinning falls. Changes to gait with diabetes occur even before the onset of measurable DPN, but changes become much more marked with DPN. Gait impairments with diabetes and DPN include alterations to walking speed, step length, step width and joint ranges of motion. These alterations also impact the rotational forces around joints known as joint moments, which are reduced as part of a natural strategy to lower the muscular demands of gait to compensate for lower strength capacities due to diabetes and DPN. Muscle weakness and atrophy are most striking in patients with DPN, but also present in non-neuropathic diabetes patients, affecting not only distal muscles of the foot and ankle, but also proximal thigh muscles. Insensate feet with DPN cause a delayed neuromuscular response immediately following foot-ground contact during gait and this is a major factor contributing to increased falls risk. Pronounced balance impairments measured in the gait laboratory are only seen in DPN patients and not non-neuropathic diabetes patients. Self-perception of unsteadiness matches gait laboratory measures and can distinguish between patients with and without DPN. Diabetic foot ulcers and their associated risk factors including insensate feet with DPN and offloading devices further increase falls risk. Falls prevention strategies based on sensory and motor mechanisms should target those most at risk of falls with DPN, with further research needed to optimise interventions.

Sedentary behaviour is an independent predictor of diabetic foot ulcer development: An 8-year prospective study.

AIMS: To prospectively explore the association between sedentary time (SED-time) and the development of diabetic foot ulcer (DFU) in people with diabetic peripheral neuropathy (DPN). METHODS: 175 DPN individuals who attended the annual evaluation for the SAMBA Study (2012-2019) were included. Main outcome measure was the first diagnosis of DFU. SED-time was measured by the PAS 2.1 questionnaire. Nerve function was evaluated by nerve conduction studies. Vascular function was assessed by Ankle-brachial index (ABI) and pedal pulses. Foot deformity and skin dryness were examined by visual inspection. RESULTS: 62 participants (35.5%) developed a DFU during the study. SED-time was significantly higher in people who developed DFUs (12.8 ± 3.0 vs 9.4 ± 3.1 h/day). Logistic regression showed that among several nervous (motor amplitude, OR 0.33, 95% CI, 0.18-0.60; sensory amplitude, 0.85, 0.77-0.94) and vascular parameters (ABI, 0.23, 0.1-0.61; pedal pulses, 2.81, 0.12-0.63) and foot characteristics (deformity, 2.63, 1.30-5.32; skin dryness, 2.04, 0.95-4.37), SED-time was one of the strongest variables contributing to the development of DFUs (2.95, 1.45-6.44). CONCLUSIONS: SED-time is an independent predictor of the risk of DFU in people with DPN. The monitoring of SED-time with strategies aimed at reducing it should be included in the standard care of diabetic patients.

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.

Whole body vibration of different frequencies inhibits H-reflex but does not affect voluntary activation.

This study aimed to investigate the effects of whole-body vibration (WBV) at a frequency spectrum from 20 to 50 Hz on the Hoffmann (H) reflex and the voluntary motor output of ankle plantar-flexor muscles. A single-group (n: 8), repeated measures design was adopted with four conditions: standing (no vibration), 20, 35 and 50 Hz, each lasting one minute. H-reflex of the soleus muscle, maximal voluntary contraction (MVC) and central activation ratio (CAR) of the plantar-flexors were evaluated before, 1 and 5 min after each frequency condition. H-reflex decreased by 36.7% at 20 Hz, by 28% at 35 Hz, and by 34.8% at 50 Hz after one minute from WBV compared to baseline. Neither MVC nor CAR changed after WBV at all frequency conditions. The short-term, acute inhibition of the H-reflex after WBV at 20, 35 and 50 Hz suggested that decreased excitability of spinal motoneurons is not frequency dependent. On the other hand, the lack of vibration induced effects on MVC and CAR indicated that a 1-min WBV stimulus is not sufficient to affect the voluntary motor output.

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.

Exercise in type 2 diabetes: genetic, metabolic and neuromuscular adaptations. A review of the evidence.

The biological responses to exercise training are complex, as almost all organs and systems are involved in interactions that result in a plethora of adaptations at the genetic, metabolic and neuromuscular levels.To provide the general practitioner and the sports medicine professionals with a basic understanding of the genetic, metabolic and neuromuscular adaptations at a cellular level that occur with aerobic and resistance exercise in subjects with type 2 diabetes.For each of the three domains (genetic, metabolic and neuromuscular), the results of the major systematic reviews and original research published in relevant journals, indexed in PubMed, were selected. Owing to limitations of space, we focused primarily on the role of skeletal muscle, given its pivotal role in mediating adaptations at all levels.Generally, training-induced adaptations in skeletal muscle are seen as changes in contractile proteins, mitochondrial function, metabolic regulation, intracellular signalling, transcriptional responses and neuromuscular modifications. The main adaptation with clinical relevance would include an improved oxidative capacity derived from aerobic training, in addition to neuromuscular remodelling derived from resistance training. Both training modalities improve insulin sensitivity and reduce cardiovascular risk.Taken together, the modifications that occur at the genetic, metabolic and neuromuscular levels, work correlatively to optimise substrate delivery, mitochondrial respiratory capacity and contractile function during exercise.

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 impact of type 1 diabetes and diabetic polyneuropathy on muscle strength and fatigability.

AIMS: Although it is widely accepted that diabetic polyneuropathy (DPN) is linked to a marked decline in neuromuscular performance, information on the possible impact of type 1 diabetes (T1D) on muscle strength and fatigue remains unclear. The purpose of this study was to investigate the effects of T1D and DPN on strength and fatigability in knee extensor muscles. METHODS: Thirty-one T1D patients (T1D), 22 T1D patients with DPN (DPN) and 23 matched healthy control participants (C) were enrolled. Maximal voluntary contraction (MVC) and endurance time at an intensity level of 50% of the MVC were assessed at the knee extensor muscles with an isometric dynamometer. Clinical characteristics of diabetic patients were assessed by considering a wide range of vascular and neurological parameters. RESULTS: DPN group had lower knee extensor muscles strength than T1D (-19%) and the C group (-37.5%). T1D group was 22% weaker when compared to the C group. Lower body muscle fatigability of DPN group was 22 and 45.5% higher than T1D and C group, respectively. T1D group possessed a higher fatigability (29.4%) compared to C group. A correlation was found between motor and sensory nerve conduction velocity and muscle strength and fatigability. CONCLUSIONS: Patients with T1D are characterised by both a higher fatigability and a lower muscle strength, which are aggravated by DPN. Our data suggest that factors other than nervous damage play a role in the pathogenesis of such defect.