Effect of high-intensity interval training on cardiometabolic component risks in persons with paraplegia: Results of a randomized controlled trial.

The aim of this work is to determine the effect of upper-body high intensity interval training (HIIT) on cardiometabolic risks in individuals with chronic paraplegia. Twenty-seven individuals (14 females, 13 males, mean ± SD age: 46 ± 9 years) with chronic paraplegia (spinal cord injury between T2 and L5 >1-year post-injury) took part in a randomized controlled trial and were included in the final analysis. Participants in the HIIT group (n = 18) performed ∼30 min of arm crank exercise (60 s intervals at 80%-90% peak heart rate) four times per week, for 6 weeks. Participants in the control (CON) group (n = 9) were asked to maintain their habitual diet and physical activity patterns over the study period. Outcome measures were taken at baseline and follow-up. The primary outcome measures were fasting insulin, peak power output (PPO) and peak aerobic capacity ( V ̇ O 2 peak ${{\dot{V}}_{{{{\mathrm{O}}}_{\mathrm{2}}}{\mathrm{peak}}}}$ ). Secondary outcome measures included body composition, postprandial glycaemic control, fasting blood lipids, inflammatory biomarkers and resting blood pressure. Differences between groups were assessed by ANCOVA, using baseline values as a covariate. PPO was higher in the HIIT (101 W, 97-106) compared to the CON (90 W, 83-96) group at follow-up (P = 0.006). There were no differences in fasting insulin (P = 0.415) or relative V ̇ O 2 peak ${{\dot{V}}_{{{{\mathrm{O}}}_{\mathrm{2}}}{\mathrm{peak}}}}$ (P = 0.417). Postprandial Matsuda insulin sensitivity index (ISIMatsuda) was higher in the HIIT (5.42, 4.69-6.15) compared to the CON (3.75, 2.46-5.04) group at follow-up (P = 0.036). Six weeks of upper-body HIIT increased PPO and ISIMatsuda, with no other beneficial effect on cardiometabolic component risks in persons with chronic paraplegia. HIGHLIGHTS: What is the central question of this study? What is the effect of upper-body high intensity interval training (HIIT) on cardiometabolic component risks in individuals with chronic paraplegia? What is the main finding and its importance? Six weeks of upper-body HIIT increased PPO and improved insulin sensitivity, but had no beneficial effect on other cardiometabolic component risks in persons with chronic paraplegia. The large effect size observed for insulin sensitivity may be important in terms of reducing the risk of type-2 diabetes in this population.

Extent and prevalence of post-exercise and nocturnal hypoglycemia following peri-exercise bolus insulin adjustments in individuals with type 1 diabetes.

AIM: To detail the extent and prevalence of post-exercise and nocturnal hypoglycemia following peri-exercise bolus insulin dose adjustments in individuals with type 1 diabetes (T1D) using multiple daily injections of insulins aspart (IAsp) and degludec (IDeg). METHODS AND RESULTS: Sixteen individuals with T1D, completed a single-centred, randomised, four-period crossover trial consisting of 23-h inpatient phases. Participants administered either a regular (100%) or reduced (50%) dose (100%; 5.1 ± 2.4, 50%; 2.6 ± 1.2 IU, p < 0.001) of individualised IAsp 1 h before and after 45-min of evening exercise at 60 ± 6% V̇O2max. An unaltered dose of IDeg was administered in the morning. Metabolic, physiological and hormonal responses during exercise, recovery and nocturnal periods were characterised. The primary outcome was the number of trial day occurrences of hypoglycemia (venous blood glucose ≤ 3.9 mmol L -1). Inclusion of a 50% IAsp dose reduction strategy prior to evening exercise reduced the occurrence of in-exercise hypoglycemia (p = 0.023). Mimicking this reductive strategy in the post-exercise period decreased risk of nocturnal hypoglycemia (p = 0.045). Combining this strategy to reflect reductions either side of exercise resulted in higher glucose concentrations in the acute post-exercise (p = 0.034), nocturnal (p = 0.001), and overall (p < 0.001) periods. Depth of hypoglycemia (p = 0.302), as well as ketonic and counter-regulatory hormonal profiles were similar. CONCLUSIONS: These findings demonstrate the glycemic safety of peri-exercise bolus dose reduction strategies in minimising the prevalence of acute and nocturnal hypoglycemia following evening exercise in people with T1D on MDI. Use of newer background insulins with current bolus insulins demonstrates efficacy and advances current recommendations for safe performance of exercise. CLINICAL TRIALS REGISTER: DRKS00013509.

Performance of the Freestyle Libre flash glucose monitoring (flash GM) system in individuals with type 1 diabetes: A secondary outcome analysis of a randomized crossover trial.

AIMS: The efficacy of flash glucose monitoring (flash GM) systems has been demonstrated by improvements in glycaemia; however, during high rates of glucose flux, the performance of continuous glucose monitoring systems was impaired, as detailed in previous studies. This study aimed to determine the performance of the flash GM system during daily-life glycaemic challenges such as carbohydrate-rich meals, bolus insulin-induced glycaemic disturbances and acute physical exercise in individuals with type 1 diabetes. MATERIALS AND METHODS: This study comprised four randomized trial visits with alternating pre- and post-exercise bolus insulin doses. Throughout the four 14-hour inpatient phases, 19 participants received three carbohydrate-rich meals and performed moderate-intensity exercise. Venous blood glucose and capillary blood glucose during exercise was compared to interstitial glucose concentrations. Flash GM accuracy was assessed by median absolute relative difference (MARD) (interquartile range [IQR]) using the Bland-Altman method and Clark error grid, as well as according to guidelines for integrated CGM approvals (Class II-510(K)). RESULTS: The overall MARD (IQR) during inpatient phases was 14.3% (6.9%-22.8%), during hypoglycaemia (≤3.9 mmol/L) was 31.6% (16.2%-46.8%), during euglycaemia (4.0 mmol/L - 9.9 mmol/L) was 16.0% (8.5%-24.0%) and during hyperglycaemia (≥10 mmol/L) was 9.4% (5.1%-15.7%). Overall Bland-Altman analysis showed a bias (95% LoA) of 1.26 mmol/L (-1.67 to 4.19 mmol/L). The overall MARD during acute exercise was 29.8% (17.5%-39.8%), during hypoglycaemia was 45.1% (35.2%-51.1%), during euglycaemia was 30.7% (18.7%-39.2%) and during hyperglycaemia was 16.3% (10.0%-22.8%). CONCLUSION: Flash GM interstitial glucose readings were not sufficiently accurate within the hypoglycaemic range and during acute exercise and require confirmatory blood glucose measurements.

MulTI-domain self-management in older People wiTh OstEoarthritis and multi-morbidities: protocol for the TIPTOE randomised controlled trial.

BACKGROUND: Four out of five people living with osteoarthritis (OA) also suffer with at least one other long-term health condition. The complex interaction between OA and multiple long-term conditions (MLTCs) can result in difficulties with self-care, restricted mobility, pain, anxiety, depression and reduced quality of life. The aim of the MulTI-domain Self-management in Older People wiTh OstEoarthritis and Multi-Morbidities (TIPTOE) trial is to evaluate the clinical and cost-effectiveness of the Living Well self-management support intervention, co-designed with people living with OA, integrated into usual care, in comparison to usual care alone. METHODS: TIPTOE is a multi-centre, two-arm, individually randomised controlled trial where 824 individuals over 65 years old with knee and/or hip joint pain from their OA affected joint and at least one other long-term health condition will be randomised to receive either the Living Well Self-Management support intervention or usual care. Eligible participants can self-refer onto the trial via a website or be referred via NHS services across Wales and England. Those randomised to receive the Living Well support intervention will be offered up to six one-to-one coaching sessions with a TIPTOE-trained healthcare practitioner and a co-designed book. Participants will be encouraged to nominate a support person to assist them throughout the study. All participants will complete a series of self-reported outcome measures at baseline and 6- and 12-month follow-up. The primary outcome is symptoms and quality of life as assessed by the Musculoskeletal Health Questionnaire (MSK-HQ). Routine data will be used to evaluate health resource use. A mixed methods process evaluation will be conducted alongside the trial to inform future implementation should the TIPTOE intervention be found both clinically and cost-effective. An embedded 'Study Within A Project' (SWAP) will explore and address barriers to the inclusion of under-served patient groups (e.g. oldest old, low socioeconomic groups, ethnic groups). DISCUSSION: TIPTOE will evaluate the clinical and cost-effectiveness of a co-designed, living well personalised self-management support intervention for older individuals with knee and/or hip OA and MLTCs. The trial has been designed to maximise inclusivity and access. TRIAL REGISTRATION: ISRCTN 16024745 . Registered on October 16, 2023.

The effects of upper- vs. lower-body aerobic exercise on perceived pain in individuals with chronic knee pain: a randomised crossover trial.

Background and objectives: Some patients with chronic knee pain experience an increase in knee pain following a single bout of exercise involving their knee joint, which can negatively affect exercise adherence and thus result in reduced overall health and lack of disease management. We want to determine whether a single bout of upper-body (UB) aerobic arm-ergometry exercise is effective in reducing the experience of pain in those with chronic knee pain compared with lower-body (LB) aerobic leg ergometry exercise. Methods: A total of 19 individuals (women = 11, men = 8; age = 63 ± 8 years; body mass index = 24 ± 3 kg/m2) who suffered from chronic knee pain for ≥3 months took part in this study. Arm-ergometry and cycle-ergometry exercises were performed for 30 min at a moderate intensity, separated by 7 days. Pain intensity was assessed by means of a visual analogue scale (VAS) pre- and post-exercise and for 7 days post-exercise. Pressure pain threshold (PPT) and mechanical detection threshold (MDT) were measured pre- and post-exercise at both local and distal anatomical sites. Data are presented as mean ± SD. Results: VAS pain was significantly reduced (p = 0.035) at 1 day post-exercise following the UB exercise trial (-1.4 ± 0.8) when compared with the LB exercise trial (+0.1 ± 2.1). Both UB and LB exercises were effective in reducing local and distal PPT. MDT responses were heterogeneous, and no differences between the UB and LB exercise conditions were noted. Conclusion: An acute bout of upper-body aerobic arm-ergometry exercise evoked a significant decrease in the affected knee joint pain in individuals with chronic knee pain of up to 24 h/1 day post-exercise compared with lower-body aerobic exercise. While the exact mechanisms remain unclear, upper-body exercise may offer a viable, novel therapeutic treatment for patients with chronic knee pain.

Improved Nocturnal Glycaemia and Reduced Insulin Use Following Clinical Exercise Trial Participation in Individuals With Type 1 Diabetes.

Aim: To explore the influence of clinical exercise trial participation on glycaemia and insulin therapy use in adults with type 1 diabetes (T1D). Research Design and Methods: This study involved a secondary analysis of data collected from 16 individuals with T1D who completed a randomized clinical trial consisting of 23-h in-patient phases with a 45-min evening bout of moderate intensity continuous exercise. Participants were switched from their usual basal-bolus therapy to ultra-long acting insulin degludec and rapid-acting insulin aspart as well as provided with unblinded interstitial flash-glucose monitoring systems. To assess the impact of clinical trial participation, weekly data obtained at the screening visit (pre-study involvement) were compared against those collated on the last experimental visit (post-study involvement). Interstitial glucose [iG] data were split into distinct glycaemic ranges and stratified into day (06:00-23:59) and night (00:00-05:59) time periods. A p-value of ≤ 0.05 was accepted for significance. Results: Following study completion, there were significant decreases in both the mean nocturnal iG concentration (Δ-0.9 ± 4.5 mmol.L-1, p < 0.001) and the time spent in severe hyperglycaemia (Δ-7.2 ± 9.8%, p = 0.028) during the night-time period. The total daily (Δ-7.3 ± 8.4 IU, p = 0.003) and basal only (Δ-2.3 ± 3.8 IU, p = 0.033) insulin dose requirements were reduced over the course of study involvement. Conclusions: Participation in clinical research may foster improved nocturnal glycaemia and reduced insulin therapy use in people with T1D. Recognition of these outcomes may help encourage volunteers to partake in clinical research opportunities for improved diabetes-related health outcomes. Clinical Trial Registration: DRKS.de; DRKS00013509.

Metabolomic, hormonal and physiological responses to hypoglycemia versus euglycemia during exercise in adults with type 1 diabetes.

INTRODUCTION: This study sought to compare the metabolomic, hormonal and physiological responses to hypoglycemia versus euglycemia during exercise in adults with type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS: Thirteen individuals with T1D (hemoglobin; 7.0%±1.3% (52.6±13.9 mmol/mol), age; 36±15 years, duration diabetes; 15±12 years) performed a maximum of 45 min submaximal exercise (60%±6% V̇O2max). Retrospectively identified exercise sessions that ended in hypoglycemia ((HypoEx) blood glucose (BG)≤3.9 mmol/L) were compared against a participant-matched euglycemic condition ((EuEx) BG≥4.0, BG≤10.0 mmol/L). Samples were compared for detailed physiological and hormonal parameters as well as metabolically profiled via large scale targeted ultra-high-performance liquid chromatography coupled to tandem mass spectrometry. Data were assessed using univariate and multivariate analysis techniques with false discovery rate adjustment. Significant results were considered at p≤0.05. RESULTS: Cardiorespiratory and counterregulatory hormone responses, whole-body fuel use and perception of fatigue during exercise were similar under conditions of hypoglycemia and euglycemia (BG 3.5±0.3 vs 5.8±1.1 mmol/L, respectively p<0.001). HypoEx was associated with greater adenosine salvage pathway activity (5'-methylthioadenosine, p=0.023 and higher cysteine and methionine metabolism), increased utilization of glucogenic amino acids (glutamine, p=0.021, alanine, aspartate and glutamate metabolism and homoserine/threonine, p=0.045) and evidence of enhanced ß-oxidation (lower carnitine p<0.001, higher long-chain acylcarnitines). CONCLUSIONS: Exposure to acute hypoglycemia during exercise potentiates alterations in subclinical indices of metabolic stress at the level of the metabolome. However, the physiological responses induced by dynamic physical exercise may mask the symptomatic recognition of mild hypoglycemia during exercise in people with T1D, a potential clinical safety concern that reinforces the need for diligent glucose management. TRIAL REGISTRATION NUMBER: DRKS00013509.

Resistance Isn't Futile: The Physiological Basis of the Health Effects of Resistance Exercise in Individuals With Type 1 Diabetes.

The importance of regular exercise for glucose management in individuals with type 1 diabetes is magnified by its acknowledgment as a key adjunct to insulin therapy by several governmental, charitable, and healthcare organisations. However, although actively encouraged, exercise participation rates remain low, with glycaemic disturbances and poor cardiorespiratory fitness cited as barriers to long-term involvement. These fears are perhaps exacerbated by uncertainty in how different forms of exercise can considerably alter several acute and chronic physiological outcomes in those with type 1 diabetes. Thus, understanding the bodily responses to specific forms of exercise is important for the provision of practical guidelines that aim to overcome these exercise barriers. Currently, the majority of existing exercise research in type 1 diabetes has focused on moderate intensity continuous protocols with less work exploring predominately non-oxidative exercise modalities like resistance exercise. This is surprising, considering the known neuro-muscular, osteopathic, metabolic, and vascular benefits associated with resistance exercise in the wider population. Considering that individuals with type 1 diabetes have an elevated susceptibility for complications within these physiological systems, the wider health benefits associated with resistance exercise may help alleviate the prevalence and/or magnitude of pathological manifestation in this population group. This review outlines the health benefits of resistance exercise with reference to evidence in aiding some of the common complications associated with individuals with type 1 diabetes.

Heart rate dynamics during cardio-pulmonary exercise testing are associated with glycemic control in individuals with type 1 diabetes.

INTRODUCTION: This study investigated the degree and direction (kHR) of the heart rate to performance curve (HRPC) during cardio-pulmonary exercise (CPX) testing and explored the relationship with diabetes markers, anthropometry and exercise physiological markers in type 1 diabetes (T1DM). MATERIAL AND METHODS: Sixty-four people with T1DM (13 females; age: 34 ± 8 years; HbA1c: 7.8 ± 1% (62 ± 13 mmol.mol-1) performed a CPX test until maximum exhaustion. kHR was calculated by a second-degree polynomial representation between post-warm up and maximum power output. Adjusted stepwise linear regression analysis was performed to investigate kHR and its associations. Receiver operating characteristic (ROC) curve was performed based on kHR for groups kHR < 0.20 vs. > 0.20 in relation to HbA1c. RESULTS: We found significant relationships between kHR and HbA1c (ß = -0.70, P < 0.0001), age (ß = -0.23, P = 0.03) and duration of diabetes (ß = 0.20, P = 0.04). Stepwise linear regression resulted in an overall adjusted R2 of 0.57 (R = 0.79, P < 0.0001). Our data revealed also significant associations between kHR and percentage of heart rate at heart rate turn point from maximum heart rate (ß = 0.43, P < 0.0001) and maximum power output relativized to bodyweight (ß = 0.44, P = 0.001) (overall adjusted R2 of 0.44 (R = 0.53, P < 0.0001)). ROC curve analysis based on kHR resulted in a HbA1c threshold of 7.9% (62 mmol.mol-1). CONCLUSION: Our data demonstrate atypical HRPC during CPX testing that were mainly related to glycemic control in people with T1DM.

Poor glycaemic control is associated with reduced exercise performance and oxygen economy during cardio-pulmonary exercise testing in people with type 1 diabetes.

BACKGROUND: To explore the impact of glycaemic control (HbA1c) on functional capacity during cardio-pulmonary exercise testing in people with type 1 diabetes. METHODS: Sixty-four individuals with type 1 diabetes (age: 34 ± 8 years; 13 females, HbA1c: 7.8 ± 1% (62 ± 13 mmol/mol), duration of diabetes: 17 ± 9 years) performed a cardio-pulmonary cycle ergometer exercise test until volitional exhaustion. Stepwise linear regression was used to explore relationships between HbA1c and cardio-respiratory data with p ≤ 0.05. Furthermore, participants were divided into quartiles based on HbA1c levels and cardio-respiratory data were analysed by one-way ANOVA. Multiple regression analysis was performed to explore the relationships between changes in time to exhaustion and cardio-respiratory data. Data were adjusted for confounder. RESULTS: HbA1c was related to time to exhaustion and oxygen consumption at the power output elicited at the sub-maximal threshold of the heart rate turn point (r = 0.47, R2 = 0.22, p = 0.03). Significant differences were found at time to exhaustion between QI vs. QIV and at oxygen consumption at the power output elicited at the heart rate turn point between QI vs. QII and QI vs. QIV (p < 0.05). Changes in oxygen uptake, power output and in oxygen consumption at the power output elicited at the heart rate turn point and at maximum power output explained 55% of the variance in time to exhaustion (r = 0.74, R2 = 0.55, p < 0.01). CONCLUSIONS: Poor glycaemic control is related to less economical use of oxygen at sub-maximal work rates and an earlier time to exhaustion during cardio-pulmonary exercise testing. However, exercise training could have the same potential to counteract the influence of poor glycaemic control on functional capacity. Trial registration NCT01704417. Date of registration: October 11, 2012.