Timothy Fairchild

Type 2 diabetes mellitus (T2DM) is a common metabolic disorder characterized by chronic hyperglycaemia, with physical inactivity and excessive adiposity as predisposing factors. This clinical trial aimed to investigate the effects of an exercise intervention on the metabolome of T2DM participants, fasting and in response to an oral glucose tolerance test (OGTT) and an acute exercise stimulus. Thirteen people with T2DM (age 51 ± 7 years; body mass index 32.7 ± 4.9 kg/m2) completed 45 min of moderate-intensity treadmill exercise on 12 days consecutively. Blood samples were collected before and after the first and last training sessions and during a pre- and postintervention OGTT. Fasted blood samples were collected from 198 healthy control subjects and 208 people with T2DM from an independent cohort for comparison. Samples were analysed using high-resolution 1H nuclear magnetic resonance spectroscopy and liquid chromatography–mass spectrometry. The exercise intervention did not induce a shift towards a healthier fasted metabolome in people living with T2DM. In response to consumption of a glucose bolus (OGTT), glycolysis-related metabolites increased and free fatty acids decreased, with no effect of the exercise intervention. In response to acute exercise, glucose and amino acids decreased and free fatty acids increased, with similar responses on the last day of training as on the first day, indicating no effect of the intervention. The clinical trial was registered prospectively in the Australian New Zealand Clinical Trials Registry ACTRN12617000286347 on 24 February 2017.

"NmrControlsDiabetesFasted" is a quantified 1H NMR dataset of 198 healthy controls, 208 people with type 2 diabetes mellitus (T2DM) who acted as disease controls, and 13 people with T2DM who participated in a twelve-day exercise intervention. Blood samples were collected cross-sectionally for healthy controls and T2DM-controls, whereas data from two time points (i.e., pre- and post-intervention) are provided for T2DM participants of the exercise intervention. All samples in this dataset were collected in a fasted state.

"NmrLipidsDiabetes" is a dataset of 13 people with T2DM who participated in a twelve-day exercise intervention. As part of the study, participants completed an oral glucose tolerance test (OGTT) before (OGTT1) and after (OGTT2) the twelve-day intervention. Fasted blood samples were collected prior to consuming a drink containing 75g of glucose and at 30-minute intervals until reaching the two-hour mark (i.e., at 30, 60, 90, and 120 minutes post-consumption). Additionally, blood samples were collected before (Pre) and immediately after (Post) exercise training on the first (Ex1) and last day (Ex12) of the intervention. Samples around the exercise sessions were only collected for nine participants. The OGTT and exercise samples were analysed using 1H NMR and lipidomics LC-MS methods.

NMR data were collected on Bruker 600 MHz Avance III HD spectrometers equipped with a BBI probe and with integral Bruker SampleJet robots, and data were automatically processed using Bruker Topspin™ 3.6.2 and ICON NMR to enable phasing, baseline correction, and calibration to TSP (δ = 0) (Dona et al., 2014; Lodge et al., 2021; Lodge et al., 2024).

Liquid chromatography was performed by a SCIEX ExionLC (SCIEX, Concord, CA) where separation was conducted using Waters Acquity BEH C18 1.7 μm, 2.1 × 100 mm column (Waters Corp., MA, USA) at 60°C (Ryan et al., 2023). Mass detection was conducted by a SCIEX QTRAP 6500+ (SCIEX, Concord, CA) with electrospray ionisation and polarity switching (Ryan et al., 2023).

Demographics of the study population and a detailed description of sample preparation and analysis are provided in the journal article associated with this dataset. A reference to this paper will be provided upon publication.

To investigate the acute effects of hypoxia applied during discrete work and recovery phases of a perceptually regulated, high-intensity interval exercise (HIIE) on external and internal loads in inactive overweight individuals. On separate days, 18 inactive overweight (28.7 ± 3.3 kg m−2; 31 ± 8 years) men and women completed a cycling HIIE protocol (6 × 1 min intervals with 4 min active recovery, maintaining a perceived rating of exertion of 16 and 10 during work and recovery, respectively, on the 6–20 Borg scale) in randomized conditions: normoxia (NN), normobaric hypoxia (inspired O2 fraction ∼0.14) during both work and recovery (HH), hypoxia during recovery (NH) and hypoxia during work only (HN). Markers of external (relative mean power output, MPO) and internal load (blood lactate concentration, heart rate and tissue saturation index (TSI)) were measured. MPO was lower in HH compared to NN, NH and HN (all P < 0.001), with HN also being lower than NN (P < 0.001) and NH (P < 0.023). Heart rate was higher in HN than NN, HH and NH (all P < 0.001). Blood lactate response was higher in NN than HH (P = 0.003) and NH (P = 0.008). Changes in the TSI area above the curve were greater in HN relative to NN, HH and NH (all P < 0.001). Hypoxia applied intermittently during the work or recovery phases may mitigate the declines in mechanical output observed when exercise is performed in continuous hypoxia, although hypoxia implemented during the work phase resulted in elevated heart rate and lactate response. Specifically, exercise performance largely comparable to that in normoxia can be achieved when hypoxia is implemented exclusively during recovery.

Introduction/Aims
Accurate measurement of knee-extensor strength in people with inclusion body myositis (IBM) is vital to track disease progression and provide a standardized outcome for clinical trials. Isokinetic dynamometers are the current gold standard tool for measuring knee-extensor strength. A less costly, more portable tool would have more widespread clinical and research applications. Current practice is to use handheld dynamometry, but there are concerns around the accuracy of this method as it relies on precise operator technique. This study investigates whether stabilization of the handheld dynamometer with a strap (SSHD) improves agreement with the isokinetic dynamometer (IKD) for measurement of knee-extensor strength in IBM participants compared to operator-stabilized handheld dynamometry (OSHD).

Methods
Fifteen IBM participants had bilateral knee-extensor force measured using three methods of dynamometry on the same day: the isokinetic dynamometer, operator-stabilized handheld dynamometry, and strap-stabilized handheld dynamometry. A crossover design was used to account for fatigue bias.

Results
Intraclass correlations (ICC) indicated poor absolute agreement of the IKD with OSHD (Strong leg = 0.240, Weak leg = 0.328), which was better for the SSHD method. Using the SSHD reduced the bias (i.e., there was less underestimation of force) between SSHD and the IKD compared to OSHD and the IKD (p < 0.05), indicating that strap-stabilized handheld dynamometry improved agreement and intraclass correlations with the IKD compared with operator-stabilized dynamometry.

Discussion
Strap-stabilized handheld dynamometry of knee extensor strength is feasible in IBM patients and may correlate better with isokinetic dynamometry than operator-stabilized handheld dynamometry, but larger studies are needed to confirm this finding.

OBJECTIVES:
Inclusion body myositis (IBM) is a complex inflammatory muscle disease in adults over 40, with histological features of autoinflammation, cell stress and autophagic abnormalities, and marked clinically by relentless progression with no effective disease-modifying therapy. Sirolimus (rapamycin) may help maintain function by inhibiting T effector cells, preserving T regulatory cells, inducing autophagy, and improving mitochondrial function. This international trial follows a phase II pilot study.

METHODS:
This phase IIb/III double-blind, randomised, controlled trial (RCT) of sirolimus involves 140 IBM patients randomly assigned with equal allocation to sirolimus (2 mg) or matching placebo. This RCT aims to assess the efficacy of sirolimus compared to placebo in slowing or stabilising IBM progression, as measured by the mean change in patient function using the IBM Functional Rating Scale (IBM-FRS) from Baseline to Week 84. Secondary outcomes will evaluate efficacy and safety to inform future clinical trial design.

RESULTS:
Ethical approval has been granted in Australia (St Vincent’s Hospital Melbourne HREC-D 311/20) and the USA (University of Kansas Medical Center Human Research Protection Program FWA no. 00003411), with European approval pending. The protocol is version 3.0 (02-Dec-2022). Trial registration: ANZCTR: ACTRN12620001226998p, ClinicalTrials.gov: NCT04789070, UTN: U1111-1258-1354, and EU CT 2024-514575-17-00.

CONCLUSIONS:
This phase IIb/III trial builds on prior findings to assess sirolimus’s potential in slowing or halting IBM progression, preserving patient function and independence, and advancing IBM therapeutic strategies and trial design.

Exercise is recommended to improve sleep, but the role of exercise intensity is unclear. In addition, whether obesity interacts with exercise intensity to affect sleep is unknown.

PURPOSE: To investigate the effects of exercise intensity and obesity on parameters related to sleep quality (sleep efficiency [SE], sleep onset latency [SOL], wake after sleep onset [WASO], and awakenings).

METHODS: Six adults with obesity (OB; 2 M/4F; age: 35.7 ± 9.7 y; BMI: 34.4 ± 2.9; VO2peak: 21.4 ± 3.2 mL/kg/min) and seven normal weight adults (NW; 4 M/3F; age: 33.4 ± 14.5 y; BMI: 22.9 ± 1.9 kg/m2; VO2peak: 32.4 ± 5.6 mL/kg/min) completed a maximal graded cardiopulmonary peak oxygen uptake (VO2peak)/lactate threshold (LT) test on a cycle ergometer to determine exercise intensity for 3 randomized control or calorically matched exercise bouts: a) CON, no exercise; b) MOD, the power output (PO) at LT; c) HIGH, the PO associated with 75% of the difference between LT and VO2peak. Each visit occurred in the morning between 08:00-09:00 h. Sleep variables were recorded with Philips Respironics Actiwatch Spectrum Plus monitors. Participants wore the watch the day before each testing visit and through the night after the testing visit. The Cole-Kripke algorithm was used to score the actigraphy data. 2x3 mixed model ANOVAs were utilized to assess the effect of obesity status and exercise intensity on each sleep parameter using delta scores of the night before and night after each condition. Data are reported as mean ± SD.

RESULTS: NW slept an average of 7.8 ± 1.35 hrs, and OB slept an average of 7.15 ± 1.4 hrs; sleep duration was not significantly different in any group or condition (p = 0.51-0.99). Compared with CON, MOD was associated with a lower SE (-2.8 ± 5.3% vs + 3.4 ± 6.2%, p < 0.01) and higher SOL (+5.1 ± 12.2 vs -9.3 ± 20.4 minutes, p < 0.05). Sleep parameters were not different between HIGH and CON or HIGH and MOD (all;p > 0.05). Regardless of condition, SE was higher in the OB group compared with NW (+2.6 ± 6% vs -1.4 ± 5.1 %, p = 0.01).

CONCLUSION: SE and SOL may be affected by moderate intensity exercise. In addition, obesity status may impact the quality of sleep.

To investigate the role of appetite-related factors, including interleukin 6 (IL-6), irisin, interleukin 7 (IL-7), neuropeptide Y (NPY), and leptin, on appetite perception in males with obesity. Eleven males (BMI 35.3 ± 4.2 kg/m2, V̇O2peak 29 ± 3.1 mL/kg/min) participated in two experimental trials (MICE: 60 min of cycling at 60% of V̇O2peak; CTRL: 60 min of quiet resting) using a crossover design. Appetite parameters, including IL-6, IL-7, irisin, and leptin, were measured...

Context: As blood flow restriction gains popularity across different populations (eg, young and older adults) and settings (eg, clinical and sports rehabilitation), the accuracy of blood flow restricted percentage becomes crucial. We aimed to compare manually measured arterial occlusion pressure (AOP) among young adults to understand whether lower limb composition affects the pressure required to achieve AOP. The results will shed light on the adequacy of published calculations used to estimate AOP in practical and research settings.

Design: An observational cross-sectional study design was implemented to examine the relationship between lower limb composition, lower limb circumference, and measured AOP.

Methods: Twenty-two participants (12 males, 26 [4] y, 1.74 [0.07] m, 73.2 [12.5] kg) underwent a whole-body Dual-energy X-ray Absorptiometry scan before AOP (in millimeters of mercury) and lower limb circumference (in centimeters) were determined. In a supine position, a 10-cm wide cuff was manually inflated on the dominant leg to the point where a pulse could no longer be detected by a Doppler ultrasound of the posterior tibial artery to determine AOP. Lower limb composition (fat, muscle, and bone mass [in grams]) was obtained from the Dual-energy X-ray Absorptiometry scan.

Results: Lower limb muscle mass had a moderate negative relationship with AOP (r2 = .433, β = -0.004) and a moderate positive relationship with lower limb circumference (r2 = .497, β = 0.001). Lower limb circumference had the weakest relationship with AOP (r2 = .316, β = 0.050) of all measures.

Conclusions: The reported relationships between lower limb muscle mass, lower limb circumference, and AOP suggest that as muscle mass increases, lower limb circumference also increases, yet AOP decreases. This implies that limb circumference should not be used as the primary measure for calculating AOP within the sampled population. We recommend individually measuring AOP when implementing blood flow restriction in all exercise modalities.

Hyperglycaemia and high adiposity are risk factors for pain in diabetes. To clarify these links with pain, the effects of a glucose load on sensory detection, pain sensitivity, conditioned pain modulation (primary aims), and autonomic and endothelial functions (secondary aims) were examined in 64 pain-free participants: 22 with normal adiposity (determined by dual-energy X-ray absorptiometry), 29 with high adiposity, and 13 with combined high adiposity and elevated glycated haemoglobin (HbA1c; including prediabetes and type 2 diabetes). Participants ingested either 37.5-g glucose or 200-mg sucralose (taste-matched) in the first session and crossed over to the other substance in the second session one month later. At baseline, painful temple cooling (the conditioning stimulus) inhibited pressure- and heat-pain in the ipsilateral arm (the test stimuli) immediately after cooling ceased (partial η2’s >.32). Glucose ingestion weakened pressure-pain inhibition irrespective of HbA1c levels (partial η2 =.11). However, a larger reduction in pressure-pain inhibition after ingesting glucose was associated with a higher waist/hip ratio (r =.31), suggesting a role of central obesity. Heat-pain inhibition was absent at baseline in unmedicated participants with elevated HbA1c, and these participants reported more occlusion-induced pain after ingesting glucose (partial η2’s >.17). Glucose ingestion interfered with parasympathetic activity in all participants (partial η2 =.11) but did not affect endothelial function (measured by reactive hyperaemia) or alter other sensations (e.g., feet vibration detection). The disruptive effect of hyperglycaemia on conditioned pain modulation increases in line with central obesity, which might facilitate pain in diabetes.

Lay summary: Ingesting 37.5-g glucose (approximately 350-mL soft drink) interfered with pain processing in pain-free, normal-weight adults as well as those with combined overweight and high blood glucose levels. The interference was stronger alongside increasing waistline, suggesting that controlling blood glucose and body fat mass might reduce risk of chronic pain.