Search

Exercise is generally recommended for individuals with type 1 diabetes mellitus since it is associated with numerous physiological and psychological benefits. However, participation in exercise can also increase the risk of experiencing severe hypoglycaemia, a potentially life-threatening condition, both during exercise and for up to 31 hours of recovery. Fortunately, this risk of exercise-induced hypoglycaemia can be managed by adjusting the dosage of self-administered exogenous insulin and nutritional intake to maintain blood glucose levels within the normal physiological range. In order to provide evidence-based guidelines to allow individuals with type 1 diabetes to safely participate in a range of physical activities, much previous research has focused on understanding the metabolic and hormonal responses to exercise. Consequently, it is well established that moderate- and high-intensity exercise have a contrasting effect on blood glucose levels and require different management strategies to maintain euglycaemia. On the other hand, the response of blood glucose levels to a combination of moderate- and high-intensity exercise, a pattern of physical activity referred to as intermittent high-intensity exercise (IHE) has received little research attention. This is despite the fact that this type of exercise characterises the activity patterns of most team and field sports as well as spontaneous play in children.The lack of previous research into the glucoregulatory responses to IHE is reflected in existing guidelines, which either do not address IHE, or suggest similar management strategies for blood glucose levels during and after IHE as for moderate- or high-intensity exercise alone. It is important, however, to appreciate that there are fundamental differences in the metabolic responses to intermittent exercise compared with other types of exercise.Recently, a series of investigations into the glucoregulatory responses to IHE that replicates the work-to-recovery ratios observed in team and field sports have been conducted. The findings of these studies do not support the existing recommendations for managing blood glucose levels during IHE. Hence, the purpose of this article is to discuss the results of these recent studies, which provide new insight into the management of blood glucose levels during and after IHE and have implications for current guidelines aimed at minimising the risk of hypoglycaemia. These findings, along with future investigations, should provide valuable information for health professionals and individuals with type 1 diabetes on the management of blood glucose levels during and after exercise to allow for safe participation in intermittent activities along with their peers. [ABSTRACT FROM AUTHOR]

Objective: To investigate whether a short maximal sprint can provide another means to counter the rapid fall in glycemia associated with moderate-intensity exercise in individuals with type 1 diabetes and therefore decrease the risk of early postexercise hypoglycemia.Research Design and Methods: In the study, seven male subjects with type 1 diabetes injected their normal insulin dose and ate their usual breakfast. When their postprandial glycemia fell to approximately 11 mmol/l, they pedaled at 40% Vo(2peak) for 20 min on a cycle ergometer then immediately engaged in a maximal 10-s cycling sprint (sprint trial) or rested (control trial); the sprint and rest trials were administered in a counterbalanced order.Results: Moderate-intensity exercise resulted in a significant fall (P < 0.05) in glycemia in both trials (means +/- SE: 3.6 +/- 0.5 vs. 3.1 +/- 0.5 mmol/l for sprint and control, respectively). The subsequent short cycling sprint opposed a further fall in glycemia for 120 min, whereas in the absence of a sprint, glycemia decreased further (3.6 +/- 1.22 mmol/l; P < 0.05) after exercise. The stabilization of glycemia in the sprint trial was associated with elevated levels of catecholamines, growth hormone, and cortisol. In contrast, these hormones remained at stable or near-stable levels in the control trial. Changes in insulin and free fatty acid levels were similar in the sprint and control trials.Conclusions: These results suggest that after moderate-intensity exercise, it is preferable for young individuals with insulin-treated, complication-free type 1 diabetes to engage in a 10-s maximal sprint to acutely oppose a further fall in glycemia than to only rest. The addition of the sprint after moderate-intensity exercise provides another means to reduce the risk of hypoglycemia in active individuals with type 1 diabetes. [ABSTRACT FROM AUTHOR]

PURPOSE: It is common practice for the staining of muscle glycogen with periodic acid-Schiff (PAS) to thaw and dry muscle sections before staining. The goal is to investigate whether this thawing step results in a systematic error that is independent of muscle fiber type and muscle physiological state. METHODS: Muscle samples from six fasted male subjects were obtained before or after 3 min of high-intensity cycling. Each sample was sectioned; some sections were assessed for muscle fiber composition, and others were either thawed for 20 min or kept frozen before being PAS-stained for glycogen. The response to a 20-min freeze-thaw cycle was also assessed using rested and exercised rats as our experimental model, and the changes in glycogen were measured enzymatically. RESULTS: The inclusion of a 20-min thawing step resulted in a significant reduction (P < 0.05) in the weighted average of the optical density of PAS (ODPAS) staining in both the nonexercised (15 +/- 1.4%) and exercised human muscles (15 +/- 1.3%), with the absolute extent being greater in the nonexercised muscle samples (P < 0.05). Moreover, the observed decrease in ODPAS was greatest in Type IIa fibers for both the nonexercised (P < 0.05) and exercised (P < 0.05) muscle samples. The findings in rats suggest that the muscle damage associated with freeze-thawing is responsible for this stimulation of glycogenolysis. CONCLUSION: For the quantitative histochemical measurement of glycogen content in skeletal muscle, the common practice of thawing unfixed muscle sections before PAS staining should be abandoned because this causes glycogen breakdown, the extent of which varies across muscle fiber types and prior exercise history. [ABSTRACT FROM AUTHOR]

Introduction: Rheumatoid arthritis (RA) guidelines recommend methotrexate (MTX)-anchored therapy with biologic or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs); however, tolerability issues often lead to non-adherence. Canadian data on MTX tapering and/or withdrawal following b/tsDMARD initiation are minimal. This chart review assessed frequency of MTX tapering or withdrawal following b/tsDMARD initiation and the impact on disease status in Canadian adults with RA., Methods: Eligible patients had received MTX for ≥ 3 months before b/tsDMARD initiation. The b/tsDMARD was prescribed continuously for ≥ 18 months. Patients taking > 10 mg/day oral prednisone or equivalent were excluded., Results: Eight hundred eighty-nine patients (mean baseline MTX dose 19.0 mg/week) prescribed b/tsDMARDs (tumor necrosis factor inhibitor 52.1%, Janus kinase inhibitor 18.3%, interleukin-6 inhibitor [IL-6i] 11.9%, other 17.7%) were evaluated at 22 Canadian centers. Within 2 years of b/tsDMARD initiation, MTX was tapered in 123 (13.8%) patients and discontinued in 147 (16.5%), most commonly due to planned tapering (36.6%) and patient decision (27.2%), respectively, and most commonly with IL-6i use (34.9%). The MTX dose was unchanged for 582 (65.5%) patients and increased for 37 (4.2%). Missing data limit interpretations of MTX dose effects on some secondary endpoints and challenge the assertion that a disease activity measure-based treat-to-target approach is routinely used in Canadian rheumatology practice., Conclusions: Methotrexate tapering or withdrawal occurred in 30.4% of Canadians with RA within 2 years following b/tsDMARD initiation. Baseline disease activity measures were missing from many medical records. However, for patients with baseline assessments, MTX tapering or discontinuation did not worsen disease activity., (© 2024. The Author(s).)

Purpose: Exercise-induced muscle damage (EIMD) results in the generation of reactive oxygen species (ROS), but little is known about the temporal profile of change in ROS post-EIMD and how ROS levels relate to the onset of and recovery from EIMD. Our primary aim was to examine the effect of EIMD on the pattern of change in the blood level of thiol-oxidised albumin, a marker of oxidative stress., Methods: Seven male participants were subjected on separate days to eccentric muscle contraction to cause EIMD or a no-exercise condition. After each session, the participants collected daily dried blood spots to measure thiol-oxidised albumin and returned to the laboratory every 2 days for the assessment of indirect markers of EIMD, namely maximal voluntary contraction (MVC), delayed onset muscle soreness (DOMS), creatine kinase (CK), and myoglobin., Results: Eccentric exercise resulted in a significant decrease in MVC and increase in DOMS, CK, myoglobin, and thiol-oxidised albumin with the latter reaching above baseline level within 24-48 h post-exercise. All the markers of EIMD returned to baseline level within 6 days post-exercise, but not the level of thiol-oxidised albumin which remained elevated for 10 days after exercise. There was a moderate correlation between changes in thiol-oxidised albumin and DOMS, but no significant relationship between any other markers of muscle damage., Conclusion: The levels of thiol-oxidised albumin increase in response to EIMD and remain elevated for several days post-exercise. The temporal pattern of change in the level of thiol-oxidised albumin suggests that this may be a useful biomarker of muscle repair post-EIMD., (© 2024. The Author(s).)

Introduction: Upadacitinib (UPA), a selective, reversible, oral Janus kinase (JAK)-1 inhibitor, was approved in 2019 in Canada for the treatment of adults with moderately to severely active rheumatoid arthritis (RA). This phase 4 prospective study aimed to characterise the effectiveness of UPA in the real-world population of patients with RA., Methods: Adults with RA who initiated treatment with once daily UPA (15 mg) and enrolled in the Canadian Real-Life post-marketing Observational Study assessing the Effectiveness of UPadacitinib for treating rheumatoid arthritis (CLOSE-UP) and who completed a 6-month assessment as of 28 February 2023 were included. The primary endpoint of the CLOSE-UP study is the proportion of patients achieving a Disease Activity Score-28 Joint Count C-reactive protein (DAS28-CRP) < 2.6 at 6 months. Data was collected at routine visits. Data analysed and summarised descriptively for the overall interim population and for subgroups based on prior therapy included remission or low disease activity, patient-reported outcomes (PROs), and adverse events., Results: A total of 392 patients were included in the interim analysis. Overall, 63.5% (191/301) of patients achieved a DAS28-CRP score < 2.6 at month 6, with similar rates observed for all subgroups analysed according to prior therapy including those with prior JAK inhibitor exposure (range 57.4-71.0%), and in patients who received UPA monotherapy (71.6% [48/67]). Early (month 3) and sustained improvements up to 6 months were observed for all PROs. The safety profile was consistent with previous reports., Conclusion: Real-world improvements in disease activity and PROs in response to UPA treatment were consistent with clinical trial data across a range of Canadian patients with prior therapy exposure and with UPA monotherapy, with an overall favourable benefit-risk profile., Trial Registration: NCT04574492., (© 2024. The Author(s).)

Objective: Although patient outcomes in psoriatic arthritis (PsA) have improved with the advent of advanced therapies, there remains a high unmet need to treat residual disease activity. The objective of the current study was to quantify residual disease activity and burden of disease in Canadian patients with PsA., Methods: This was a multiregion, observational, retrospective analysis of patient data extracted from the Rhumadata and the International Psoriasis and Arthritis Research Team (IPART) registries, analyzing deidentified data from patients who had initiated advanced therapy for the treatment of PsA between January 2010 and December 2019. The primary endpoint was the proportion of patients failing to achieve minimal disease activity (MDA) within 6 months; secondary endpoints included clinical and patient-reported burden of disease. Descriptive statistics included summaries by region, treatment class, and number of prior advanced therapies., Results: One thousand five hundred ninety-six patients were included. The proportions of patients who failed to achieve MDA within 6 months of an advanced therapy were 64.8% in Ontario, 68.3% in Western Canada, 74.8% in Quebec, and 75% in the Atlantic/East region. Failure to achieve MDA was higher among patients receiving an IL-17i compared with a TNFi in all regions except the Atlantic/East. Between 73.2% and 78.6% of patients reported pain at 6 months, and continuing functional impairment varied from 24% in the West to 83.3% in the Atlantic/East., Conclusion: There is substantial burden and unmet need for improved therapies for Canadians with PsA. There is a wide regional variation in outcomes that requires further assessment., (Copyright © 2024 by the Journal of Rheumatology.)

Venetoclax is a first-in-class B-cell lymphoma-2 (BCL-2) inhibitor approved as continuous monotherapy and in combination with rituximab as fixed-treatment duration for relapsed and refractory chronic lymphocytic leukemia (R/R CLL). DEVOTE was a 24-week, multicenter observational study (NCT03310190) evaluating the safety, healthcare resource utilization (HCRU) and health-related quality of life (HRQoL) of patients initiating venetoclax for R/R CLL in Canada. Overall, 89 patients received 1 dose of venetoclax; 80% had prior exposure (42% resistant) to ibrutinib. Biochemical tumor lysis syndrome (TLS) occurred in five patients. We observed differences in hospitalization across Canadian provinces including in patients at low risk for TLS with no clear impact on TLS incidence. Additionally, a rapid and sustained improvement in several domains of HRQoL was observed during venetoclax initiation. Early adoption of venetoclax was mainly for R/R CLL patients with few treatment options; nonetheless, acceptable toxicity and a positive impact on HRQoL were observed.

Aims/hypothesis: Impaired awareness of hypoglycaemia (IAH) in type 1 diabetes may develop through a process referred to as habituation. Consistent with this, a single bout of high intensity interval exercise as a novel stress stimulus improves counterregulatory responses (CRR) to next-day hypoglycaemia, referred to as dishabituation. This longitudinal pilot study investigated whether 4 weeks of high intensity interval training (HIIT) has sustained effects on counterregulatory and symptom responses to hypoglycaemia in adults with type 1 diabetes and IAH., Methods: HIT4HYPOS was a single-centre, randomised, parallel-group study. Participants were identified using the Scottish Diabetes Research Network (SDRN) and from diabetes outpatient clinics in NHS Tayside, UK. The study took place at the Clinical Research Centre, Ninewells Hospital and Medical School, Dundee, UK. Participants were aged 18-55 years with type 1 diabetes of at least 5 years' duration and HbA 1c levels <75 mmol/mol (<9%). They had IAH confirmed by a Gold score ≥4, modified Clarke score ≥4 or Dose Adjustment For Normal Eating [DAFNE] hypoglycaemia awareness rating of 2 or 3, and/or evidence of recurrent hypoglycaemia on flash glucose monitoring. Participants were randomly allocated using a web-based system to either 4 weeks of real-time continuous glucose monitoring (RT-CGM) or RT-CGM+HIIT. Participants and investigators were not masked to group assignment. The HIIT programme was performed for 20 min on a stationary exercise bike three times a week. Hyperinsulinaemic-hypoglycaemic (2.5 mmol/l) clamp studies with assessment of symptoms, hormones and cognitive function were performed at baseline and after 4 weeks of the study intervention. The predefined primary outcome was the difference in hypoglycaemia-induced adrenaline (epinephrine) responses from baseline following RT-CGM or RT-CGM+HIIT., Results: Eighteen participants (nine men and nine women) with type 1 diabetes (median [IQR] duration 27 [18.75-32] years) and IAH were included, with nine participants randomised to each group. Data from all study participants were included in the analysis. During the 4 week intervention there were no significant mean (SEM) differences between RT-CGM and RT-CGM+HIIT in exposure to level 1 (28 [7] vs 22 [4] episodes, p=0.45) or level 2 (9 [3] vs 4 [1] episodes, p=0.29) hypoglycaemia. The CGM-derived mean glucose level, SD of glucose and glucose management indicator (GMI) did not differ between groups. During the hyperinsulinaemic-hypoglycaemic clamp studies, mean (SEM) change from baseline was greater for the noradrenergic responses (RT-CGM vs RT-CGM+HIIT: -988 [447] vs 514 [732] pmol/l, p=0.02) but not the adrenergic responses (-298 [687] vs 1130 [747] pmol/l, p=0.11) in those participants who had undergone RT-CGM+HIIT. There was a benefit of RT-CGM+HIIT for mean (SEM) change from baseline in the glucagon CRR to hypoglycaemia (RT-CGM vs RT-CGM+HIIT: 1 [4] vs 16 [6] ng/l, p=0.01). Consistent with the hormone response, the mean (SEM) symptomatic response to hypoglycaemia (adjusted for baseline) was greater following RT-CGM+HIIT (RT-CGM vs RT-CGM+HIIT: -4 [2] vs 0 [2], p<0.05)., Conclusions/interpretation: In this pilot clinical trial in people with type 1 diabetes and IAH, we found continuing benefits of HIIT for overall hormonal and symptomatic CRR to subsequent hypoglycaemia. Our findings also suggest that HIIT may improve the glucagon response to insulin-induced hypoglycaemia., Trial Registration: ISRCTN15373978., Funding: Sir George Alberti Fellowship from Diabetes UK (CMF) and the Juvenile Diabetes Research Foundation., (© 2023. The Author(s).)

Context: It is unclear whether immersion in cool water, typical of many beaches, increases the concentration of blood glucose in individuals with type 1 diabetes mellitus (T1DM)., Objective: To test the hypothesis in individuals with T1DM that immersion neck-deep in cool water (COOL) causes an increase in blood glucose concentration, but not exposure to thermoneutral water (THERMO) or thermoneutral air., Methods: Eight overnight-fasted participants with T1DM were exposed for 60 minutes on separate days to 3 experimental conditions: cool water (COOL, 23 °C); thermoneutral water (THERMO, 33.5 °C); or thermoneutral air (24 °C). They then recovered for 60 minutes on land at 24 °C. At time intervals, we measured: blood glucose and plasma insulin concentration, rate of carbohydrate and fat oxidation, skin and core temperature, subcutaneous blood flow, and shivering via electromyography., Results: There was no change in blood glucose concentration during the 3 experimental conditions ( P > .05). During recovery after COOL, blood glucose increased ( P < .05) but did not change in the other 2 conditions. The rate of carbohydrate oxidation during and early after COOL was higher than in the other 2 conditions ( P < .05), and COOL led to a decrease in subcutaneous blood flow and the concentration of plasma insulin ( P < .05)., Conclusion: Cool or thermoneutral neck-deep immersion in water does not cause a change in the concentration of blood glucose in people with T1DM, but on-land recovery from COOL causes an increase in blood glucose that may be due, at least in part, to the accompanying decrease in plasma insulin., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society.)

The purpose of this study was to determine the effect of exercise intensity on the proportion and rate of carbohydrate oxidation and glucoregulatory hormone responses during recovery from exercise. Six physically active participants completed 1 hr of low-intensity (LI; 50% lactate threshold) or moderate-intensity (MI; 100% lactate threshold) exercise on separate days following a randomized counterbalanced design. During exercise and for 6 hr of recovery, samples of expired air were collected to determine oxygen consumption, respiratory exchange ratio, energy expenditure, and substrate oxidation rates. Blood samples were also collected to measure glucoregulatory hormones (catecholamines, GH) and metabolites (glucose, free fatty acids, lactate, pH, and bicarbonate). During exercise, respiratory exchange ratio, energy expenditure, and the proportion and rate of carbohydrate (CHO) oxidation were higher during MI compared with LI. However, during recovery from MI, respiratory exchange ratio and the proportion and rate of CHO oxidation were lower than preexercise levels and corresponding LI. During exercise and early recovery, catecholamines and growth hormone were higher in MI than LI, and there was a trend for higher levels of free fatty acids in the early recovery from MI compared with LI. In summary, CHO oxidation during exercise increases with exercise intensity but there is a preference for CHO sparing (and fat oxidation) during recovery from MI exercise compared with LI exercise. This exercise intensity-dependent shift in substrate oxidation during recovery is explained, in part, by the pattern of change of key glucoregulatory hormones including catecholamines and growth hormone and plasma fatty acid concentrations.

Aim: To examine the within-person variability in plasma glucose responses to moderate-intensity morning exercise in young individuals with type 1 diabetes after overnight fasting and under basal insulin conditions., Methods: In this pilot study, eight participants completed 40 min of moderate-intensity exercise at 60% V̇O 2 peak on three separate days. The within-person standard deviation (SDw) in plasma glucose response was analysed both during and 1 h after exercise using the two visits per participant most closely matched by pre-exercise plasma glucose level., Results: When the two closest matched visits per individual were included for analysis, mean (±SD) change in plasma glucose level was -1.8 ± 1.1 mmoL/L during exercise and -0.6 ± 1.0 mmoL/L during recovery, with the SDw of these changes being 0.5 mmol (95% CI 0.2, 0.8) during exercise and 0.8 mmoL/L (95% CI 0.4, 1.3) during recovery. The median intra-individual difference in plasma glucose level change was 0.3 mmoL/L [IQR 0.1, 0.7] during exercise and 0.8 mmoL/L [IQR 0.4, 1.0] during recovery., Conclusion: Within-person plasma glucose responses to moderate-intensity exercise may be reproducible under fasting and basal insulin conditions and similar pre-exercise plasma glucose levels. This finding may assist the design of future studies investigating both the reproducibility of glycaemic responses to exercise and blood glucose management for individuals with type 1 diabetes., (© 2022 Diabetes UK.)

Dietary protein causes dose-dependent hyperglycemia in individuals with type 1 diabetes (T1D). This study investigated the effect of consuming 50 g of protein on overnight blood glucose levels (BGLs) following late-afternoon moderate-intensity exercise. Six participants (3M:3F) with T1D, HbA1c 7.5 ± 0.8% (58.0 ± 8.7 mmol/mol) and aged 20.2 ± 3.1 years exercised for 45 min at 1600 h and consumed a protein drink or water alone at 2000 h, on two separate days. A basal insulin euglycemic clamp was employed to measure the mean glucose infusion rates (m-GIR) required to maintain euglycemia on both nights. The m-GIR on the protein and water nights during the hypoglycemia risk period and overnight were 0.27 ± 043 vs. 1.60 ± 0.66 mg/kg/min ( p = 0.028, r = 0.63) and 0.51 ± 0.16 vs. 1.34 ± 0.71 mg/kg/min ( p = 0.028, r = 0.63), respectively. Despite ceasing intravenous glucose infusion on the protein night, the BGLs peaked at 9.6 ± 1.6 mmol/L, with a hypoglycemia risk period mean of 7.8 ± 1.5 mmol/L compared to 5.9 ± 0.4 mmol/L ( p = 0.028) on the water night. The mean plasma glucagon levels were 51.5 ± 14.1 and 27.2 ± 10.1 ng/L ( p = 0.028) on the protein and water night, respectively. This suggests that an intake of protein is effective at reducing the post-exercise hypoglycemia risk, potentially via a glucagon-mediated stimulation of glucose production. However, 50 g of protein may be excessive for maintaining euglycemia.

Acute myeloid leukemia (AML) is a hematological malignancy that predominantly affects the elderly. Prognosis declines with age. For those who cannot tolerate intensive chemotherapy, historically established treatment options have been hypomethylating agents (HMAs), low dose cytarabine (LDAC), and best supportive care (BSC). As the standard of care evolves for those unfit for intensive chemotherapy, there is a need to understand established treatment pathways, clinical outcomes and healthcare resource utilization in Canada. The CURRENT study was a retrospective chart review of AML patients not eligible for intensive chemotherapy who initiated first-line treatment between 1 January 2015 and 31 December 2018. Data were collected from 170 Canadian patients treated at six hematology centers, of whom 118 received systemic therapy and 52 received BSC as first-line treatment. Median overall survival was 8.58 months and varied from 2.96 months for BSC to 13.31 months for HMAs. Over 80% of patients had at least one outpatient visit, and 67% of patients receiving systemic therapy and 71% of those receiving BSC had at least one admission to hospital, during their first line of therapy. A total of 96 (81.4%) patients receiving first line systemic therapy and 39 (75.0%) of those receiving first line BSC had at least one red blood cell or platelet transfusion. These findings highlight the unmet need for novel therapies for patients ineligible for intensive chemotherapy.

Context: Current exercise guidelines for individuals with type 1 diabetes (T1D) do not consider the impact that high altitude may have on blood glucose levels (BGL) during exercise., Objective: To investigate the effect of acute hypoxia (simulated high altitude) on BGL and carbohydrate oxidation rates during moderate intensity exercise in individuals with T1D., Methods: Using a counterbalanced, repeated measures study design, 7 individuals with T1D completed 2 exercise sessions; normoxia and hypoxia (~4200 m simulated altitude). Participants cycled for 60 min on an ergometer at 45% of their sea-level V̇O2peak, and then recovered for 60 min. Before, during, and after exercise, blood samples were taken to measure glucose, lactate, and insulin levels. Respiratory gases were collected to measure carbohydrate oxidation rates., Results: Early during exercise (<30 min), there was no fall in BGL in either condition. After 1 h of exercise and during recovery, BGL were significantly lower under the hypoxic condition compared to both pre-exercise levels (P = 0.008) and the normoxic condition (P = 0.027). Exercise in both conditions resulted in a significant rise in carbohydrate oxidation rates, which returned to baseline levels postexercise. Before, during, and after exercise, carbohydrate oxidation rates were higher under the hypoxic compared with the normoxic condition (P < 0.001)., Conclusions: The greater decline in BGL during and after exercise performed under acute hypoxia suggests that exercise during acute exposure to high altitude may increase the risk of hypoglycemia in individuals with T1D. Future guidelines may have to consider the impact altitude has on exercise-mediated hypoglycemia., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Empowering young people with type 1 diabetes (T1D) to manage their blood glucose levels during exercise is a complex challenge faced by health care professionals due to the unpredictable nature of exercise and its effect on blood glucose levels. Mobile health (mHealth) apps would be useful as a decision-support aid to effectively contextualize a blood glucose result and take appropriate action to optimize glucose levels during and after exercise. A novel mHealth app acT1ve was recently developed, based on expert consensus exercise guidelines, to provide real-time support for young people with T1D during exercise., Objective: Our aim was to pilot acT1ve in a free-living setting to assess its acceptability and functionality, and gather feedback on the user experience before testing it in a larger clinical trial., Methods: A prospective single-arm mixed method design was used. Ten participants with T1D (mean age 17.7 years, SD 4.2 years; mean HbA 1c , 54 mmol/mol, SD 5.5 mmol/mol [7.1%, SD 0.5%]) had acT1ve installed on their phones, and were asked to use the app to guide their exercise management for 6 weeks. At the end of 6 weeks, participants completed both a semistructured interview and the user Mobile Application Rating Scale (uMARS). All semistructured interviews were transcribed. Thematic analysis was conducted whereby interview transcripts were independently analyzed by 2 researchers to uncover important and relevant themes. The uMARS was scored for 4 quality subscales (engagement, functionality, esthetics, and information), and a total quality score was obtained from the weighted average of the 4 subscales. Scores for the 4 objective subscales were determined by the mean score of each of its individual questions. The perceived impact and subjective quality of acT1ve for each participant were calculated by averaging the scores of their related questions, but were not considered in the total quality score. All scores have a maximal possible value of 5, and they are presented as medians, IQRs, and ranges., Results: The main themes arising from the interview analysis were "increased knowledge," "increased confidence to exercise," and "suitability" for people who were less engaged in exercise. The uMARS scores for acT1ve were high (out of 5) for its total quality (median 4.3, IQR 4.2-4.6), engagement (median 3.9, IQR 3.6-4.2), functionality (median 4.8, IQR 4.5-4.8), information (median 4.6, IQR 4.5-4.8), esthetics (median 4.3, IQR 4.0-4.7), subjective quality (median 4.0, IQR 3.8-4.2), and perceived impact (median 4.3, IQR 3.6-4.5)., Conclusions: The acT1ve app is functional and acceptable, with a high user satisfaction. The efficacy and safety of this app will be tested in a randomized controlled trial in the next phase of this study., Trial Registration: Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12619001414101; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=378373., (©Vinutha B Shetty, Wayne H K Soon, Alison G Roberts, Leanne Fried, Heather C Roby, Grant J Smith, Paul A Fournier, Timothy W Jones, Elizabeth A Davis. Originally published in JMIR Diabetes (https://diabetes.jmir.org), 14.10.2021.)

Introduction: Nausea caused by exhaustive sprinting is associated with high lactate ([La-]) and hydrogen ion concentrations ([H+]) and fall in blood pCO2, thus raising the issue of whether there is a causal link between nausea and these variables. For this reason, this study aimed to determine whether interspersing repeated sprints (RS) with periods of active, compared with passive, recovery results in lower levels of both nausea and changes in [La-], [H+], and pCO2., Methods: Twelve male participants completed two separate sessions comprising four 30-s sprints separated by 20 min of either active (AR; cycling at 40% V˙O2peak) or passive recovery (PR). At 6 and 18 min of each recovery period, nausea was assessed via a visual analog scale (VAS), and blood samples were collected to measure [La-], [H+], and pCO2., Results: RS significantly increased VAS score in both AR (P < 0.001) and PR (P < 0.01). After the first sprint, VAS was higher than preexercise in only AR (P < 0.01). AR was associated with lower VAS, [La-], [H+], and higher pCO2 (all P = 0.001) compared with PR after sprints 2-4. Linear mixed modeling indicated that each of the variables significantly predicts VAS scores (P < 0.0001). Repeated-measures correlation (rrm2) indicated that [La-] had the closest association with VAS (rrm2 = 0.22, P < 0.0001)., Conclusion: The lower levels of both nausea and changes in [La-], [H+], and pCO2 in response to AR suggest that nausea associated with RS may be causally related with these variables. However, the absence of a close relationship between these variables after the first sprint and the findings that [La-], [H+], and pCO2 only account for 13%-22% of the variation in VAS indicate that other mechanisms may also mediate nausea., (Copyright © 2021 by the American College of Sports Medicine.)

Aims/hypothesis: In individuals with type 1 diabetes, chronic hyperglycaemia impairs aerobic fitness. However, the effect of acute marked hyperglycaemia on aerobic fitness is unclear, and the impact of insulin level has not been examined. In this study, we explored if acute hyperglycaemia with higher or low insulin levels affects [Formula: see text] and other exercise performance indicators in individuals with type 1 diabetes., Methods: Eligible participants were aged 14 to 30 years, with complication-free, type 1 diabetes and HbA 1c  ≤ 75 mmol/mol (≤9%). Participants exercised in a clinical laboratory under three clamp (constant insulin, variable glucose infusion) conditions: euglycaemia (5 mmol/l) with 20 mU [m 2 BSA] -1  min -1 insulin (where BSA is body surface area) (Eu20); hyperglycaemia (17 mmol/l) with 20 mU [m 2 BSA] -1  min -1 insulin (Hyper20); and hyperglycaemia (17 mmol/l) with 5 mU [m 2 BSA] -1  min -1 insulin (Hyper5) on separate days. Participants and the single testing assessor were blinded to condition, with participants allocated to randomised testing condition sequences as they were consecutively recruited. Standardised testing (in order) conducted on each of the three study days included: triplicate 6 second sprint cycling, grip strength, single leg static balance, vertical jump and modified Star Excursion Balance Test, ten simple and choice reaction times and one cycle ergometer [Formula: see text] test. The difference between conditions in the aforementioned testing measures was analysed, with the primary outcome being the difference in [Formula: see text]., Results: Twelve recreationally active individuals with type 1 diabetes (8 male, mean ± SD 17.9 ± 3.9 years, HbA 1c 61 ± 11 mmol/mol [7.7 ± 1.0%], 7 ± 3 h exercise/week) were analysed. Compared with Eu20, [Formula: see text] was lower in Hyper20 (difference 0.17 l/min [95% CI 0.31, 0.04; p = 0.02] 6.6% of mean Eu20 level), but Hyper5 was not different (p = 0.39). Compared with Eu20, sprint cycling peak power was not different in Hyper20 (p = 0.20), but was higher in Hyper5 (64 W [95% CI 13, 115; p = 0.02] 13.1%). Hyper20 reaction times were not different (simple: p = 0.12) but Hyper5 reaction times were slower (simple: 11 milliseconds [95% CI 1, 22; p = 0.04] 4.7%) than Eu20. No differences between Eu20 and either hyperglycaemic condition were observed for the other testing measures (p > 0.05)., Conclusions/interpretation: Acute marked hyperglycaemia in the higher but not low insulin state impaired [Formula: see text] but to a small extent. Acute hyperglycaemia had an insulin-dependent effect on sprint cycling absolute power output and reaction time but with differing directionality (positive for sprint cycling and negative for reaction time) and no effect on the other indicators of exercise performance examined. We find that acute hyperglycaemia is not consistently adverse and does not impair overall exercise performance to an extent clinically relevant for recreationally active individuals with type 1 diabetes., Funding: This research was funded by Diabetes Research Western Australia and Australasian Paediatric Endocrine Group grants.

Introduction: Can intermittent energy restriction (IER) improve fat loss and fat-free mass retention compared with continuous energy restriction (CER) in resistance-trained adults?, Methods: Sixty-one adults (32 women) with a mean (SD) age of 28.7 (6.5) yr, body weight of 77.2 (16.1) kg, and body fat of 25.5% (6.1%) were randomized to 12 wk of 1) 4 × 3 wk of moderate (m) energy restriction interspersed with 3 × 1 wk of energy balance (mIER; n = 30; 15 wk total) or 2) 12 wk of continuous moderate energy restriction (mCER; n = 31). Analyses of all outcome measures were by intention-to-treat., Results: After accounting for baseline differences, mIER did not result in lower fat mass or body weight, or greater fat-free mass, compared with mCER after energy restriction. Mean (and 97.5% confidence interval for fat mass at the end of mIER versus mCER was 15.3 (12.5-18.0) kg versus 18.0 (14.3-21.7) kg (P = 0.321), that for fat-free mass was 56.7 (51.5-61.9) kg versus 56.7 (51.4-62.0) kg (P = 0.309), and that for body weight (with 95% confidence interval) was 72.1 (66.4-77.9) versus 74.6 (69.3-80.0) (P = 0.283). There were no differences between interventions in muscle strength or endurance or in resting energy expenditure, leptin, testosterone, insulin-like growth factor-1, free 3,3',5-triiodothyronine or active ghrelin, or in sleep, muscle dysmorphia, or eating disorder behaviors. However, participants in mIER exhibited lower hunger (P = 0.002) and desire to eat (P = 0.014) compared with those in mCER, and greater satisfaction (P = 0.016) and peptide YY (P = 0.034)., Conclusions: Similar fat loss and fat-free mass retention are achieved with mIER and mCER during 12 wk of energy restriction; however, mIER is associated with reduced appetite., (Copyright © 2021 by the American College of Sports Medicine.)

Objective: This study aimed to investigate the role that antidiuretic hormone (ADH) may play in the activation of glucose production during high intensity aerobic exercise., Materials/methods: This study was part of larger study based on a repeated measures cross-over study design and involved ten adult participants who exercised in the morning at 80 % V̇ O 2 peak for up to 40 min or until exhaustion. During and after exercise, the participants were subjected to a morning euglycaemic/euinsulinaemic clamp while [6,6- 2 H 2 ]glucose was infused and blood sampled to measure the endogenous rate of glucose appearance (Ra) and ADH levels., Results: The levels of plasma ADH were 1.8 ± 0.2 pmol/L (mean ± SEM) at rest and increased to 10.5 ± 2.1 pmol/L at the end of exercise (mean ± SEM), which lasted 8.5-40 min. In response to exercise, glucose Ra also rose significantly (p < 0.05), but there was no significant association between changes in ADH levels and glucose Ra (r = 0.49; p = 0.150)., Conclusions: Although the significant increase in glucose Ra and ADH levels during high intensity aerobic exercise suggest for the first time that these processes may be causally related, there was no significant association between these variables, maybe because of the small sample size and varying exercise durations. Hence, the importance of the causal role that ADH may play in the exercise-mediated activation of hepatic glucose production warrants further in depth investigations., Competing Interests: No conflict of interest to declare., (Crown Copyright © 2021 Published by Elsevier Inc.)

Athletes undergoing energy restriction for weight/fat reduction sometimes apply 'diet breaks' involving increased energy intake, but there is little empirical evidence of effects on outcomes. Twenty-six resistance-trained athletes (11/26 or 42% female) who had completed 12 weeks of intermittent energy restriction participated in this study. Participants had a mean (SD) age of 29.3 (6.4) years, a weight of 72.7 (15.9) kg, and a body fat percentage of 21.3 (7.5) %. During the 1-week diet break, energy intake was increased (by means of increased carbohydrate intake) to predicted weight maintenance requirements. While the 1-week diet break had no significant effect on fat mass, it led to small but significant increases in mean body weight (0.6 kg, P<0.001), fat-free mass (0.7 kg, P<0.001) and in resting energy expenditure, from a mean (and 95% confidence interval) of 7000 (6420 to 7580) kJ/day to 7200 (6620 to 7780) kJ/day (P = 0.026). Overall, muscle endurance in the legs (but not arms) improved after the diet break, including significant increases in the work completed by the quadriceps and hamstrings in a maximum-effort 25-repetition set, with values increasing from 2530 (2170 to 2890) J to 2660 (2310 to 3010) J (P = 0.018) and from 1280 (1130 to 1430) J to 1380 (1220 to 1540) J (P = 0.018) following the diet break, respectively. However, muscle strength did not change. Participants reported significantly lower sensations of hunger (P = 0.017), prospective consumption (P = 0.020) and irritability (P = 0.041) after the diet break, and significantly higher sensations of fullness (P = 0.002), satisfaction (P = 0.002), and alertness (P = 0.003). In summary, a 1-week diet break improved muscle endurance in the legs and increased mental alertness, and reduced appetite and irritability. With this considered, it may be wise for athletes to coordinate diet breaks with training sessions that require muscle endurance of the legs and/or mental focus, as well as in the latter parts of a weight loss phase when increases in appetite might threaten dietary adherence. Trial registration: Australian New Zealand Clinical Trials Registry Reference Number: ACTRN12618000638235 anzctr.org.au., Competing Interests: AS reported owning 50% of the shares in Zuman International, which receives royalties for books she has written and payments for presentations at industry conferences; receiving presentation fees and travel reimbursements from Eli Lilly and Co, the Pharmacy Guild of Australia, Novo Nordisk, the Dietitians Association of Australia, Shoalhaven Family Medical Centres, the Pharmaceutical Society of Australia, and Metagenics; and serving on the NestleÌ Health Science Optifast VLCD advisory board from 2016 to 2018. JK is employed by Weightology LLC. These affiliations do not alter our adherence to PLOS ONE policies on sharing data and materials.

Context: Under basal insulin levels, there is an inverted U relationship between exercise intensity and exogenous glucose requirements to maintain stable blood glucose levels in type 1 diabetes (T1D), with no glucose required for intense exercise (80% V̇O2 peak), implying that high-intensity exercise is not conducive to hypoglycemia., Objective: This work aimed to test the hypothesis that a similar inverted U relationship exists under hyperinsulinemic conditions, with high-intensity aerobic exercise not being conducive to hypoglycemia., Methods: Nine young adults with T1D (mean ± SD age, 22.6 ± 4.7 years; glycated hemoglobin, 61 ± 14 mmol/mol; body mass index, 24.0 ± 3.3 kg/m2, V̇O2 peak, 36.6 ± 8.0 mL·kg-1 min-1) underwent a hyperinsulinemic-euglycemic clamp to maintain stable glycemia (5-6 mmol·L-1), and exercised for 40 minutes at 4 intensities (35%, 50%, 65%, and 80% V̇O2peak) on separate days following a randomized counterbalanced study design., Main Outcome Measures: Glucose infusion rates (GIR) and glucoregulatory hormones levels were measured., Results: The GIR (± SEM) to maintain euglycemia was 4.4 ± 0.4 mg·kg-1 min-1 prior to exercise, and increased significantly by 1.8 ± 0.4, 3.0 ± 0.4, 4.2 ± 0.7, and 3.5 ± 0.7 mg·kg-1 min-1 during exercise at 35%, 50%, 65%, and 80% V̇O2 peak, respectively, with no significant differences between the 2 highest exercise intensities (P > .05), despite differences in catecholamine levels (P < .05). During the 2-hour period after exercise at 65% and 80% V̇O2 peak, GIRs did not differ from those during exercise (P > .05)., Conclusions: Under hyperinsulinemic conditions, the exogenous glucose requirements to maintain stable glycemia during and after exercise increase with exercise intensity then plateau with exercise performed at above moderate intensity ( > 65% V̇O2 peak). High-intensity exercise confers no protection against hypoglycemia., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Regular exercise is important for health, fitness and longevity in people living with type 1 diabetes, and many individuals seek to train and compete while living with the condition. Muscle, liver and glycogen metabolism can be normal in athletes with diabetes with good overall glucose management, and exercise performance can be facilitated by modifications to insulin dose and nutrition. However, maintaining normal glucose levels during training, travel and competition can be a major challenge for athletes living with type 1 diabetes. Some athletes have low-to-moderate levels of carbohydrate intake during training and rest days but tend to benefit, from both a glucose and performance perspective, from high rates of carbohydrate feeding during long-distance events. This review highlights the unique metabolic responses to various types of exercise in athletes living with type 1 diabetes. Graphical abstract.

Introduction: In order to better understand the physiological and pathophysiological roles of reactive oxygen species (ROS), multiple blood and urine biomarkers of oxidative stress have been developed. The single free thiol (Cys34) in plasma albumin is a useful biomarker of oxidative stress because thiol groups are particularly sensitive to oxidation by ROS. The primary aim of this study was to develop a gel electrophoresis-based method (mPEG assay) that would be more widely accessible than existing chromatography techniques to assay the oxidation state of albumin Cys34. Method: Blood samples were collected into a solution containing polyethylene glycol maleimide (malpeg). Plasma samples were divided into two aliquots, with a reducing agent added to one aliquot. Albumin bound to malpeg was separated from albumin by gel electrophoresis. The proportion of albumin in reduced form (-SH), disulphide form (-SSX) and irreversibly oxidised form (-SO 2 , -SO 3 ) could then be calculated. Results: Data for the mPEG assay was comparable to data from chromatographic and mass spectrometric assays. The mPEG assay was more sensitive than the albumin carbonyl assay for the detection of changes in albumin oxidation level in response to exposure to hydrogen peroxide or hypochlorous acid. This assay could also be performed on small blood samples (less than 10 µL) from fingerprick, thus facilitating longitudinal tracking of changes in albumin Cys34 oxidation level. Conclusion: The mPEG assay is a user-friendly, highly sensitive, specific, cost-effective gel electrophoresis-based method for the assay of the oxidations state of albumin Cys34 as a biomarker of oxidative stress.HighlightsProtein thiol groups are sensitive to oxidation by reactive oxygen species.Plasma albumin contains a reduced cysteine residue (Cys34) sensitive to oxidation.A novel gel electrophoresis-based method (mPEG) has been developed to measure the oxidation state of Cys34.The mPEG assay can be run on a drop of blood collected by fingerprick.

This study aims to determine whether there is a relationship between nausea level and lactic acidosis during recovery from sprinting. In all, 13 recreationally active males completed a 60 s bout of maximal intensity cycling. Prior to and for 45 min following exercise, blood pH, pCO 2 , and lactate levels were measured together with nausea. In response to sprinting, nausea, lactate, and H + concentrations increased and remained elevated for at least 10 min (p < .001), whereas pCO 2 increased only transiently (p < .001) before falling below pre-exercise levels (p < .001), with all these variables returning toward pre-exercise levels during recovery. Both measures of nausea adopted for analyses (nausea profile, NP; visual analogue scale, VAS), demonstrated significant repeated measures correlation (rmcorr) post-exercise between nausea and plasma lactate (VAS and NPr rm > 0.595, p < .0001) and H + concentrations (VAS and NPr rm > 0.689, p < .0001), but an inconsistent relationship with pCO 2 (VAS r rm  = 0.250, p = .040; NP r rm  = 0.144, p = .248) and bicarbonate levels (VAS r rm  = -0.252, p = .095; NP r rm  = -0.397, p = .008). Linear mixed modeling was used to predict the trajectory of nausea over time, with both lactate and H + concentrations found to be key predictors of nausea (p < .0001). In conclusion, this study reveals a strong positive relationship between nausea and both H + and lactate concentrations during recovery from sprinting, a finding consistent with H + and lactate being potential mediators of nausea post-sprinting. However, as the timing of the recovery of both H + and lactate was delayed, compared to that of nausea, further research is required to confirm these findings and investigate other potential mechanisms., (© 2019 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.)

Background: Running is a popular physical activity that benefits health; however, running surface characteristics may influence loading impact and injury risk. Machine learning algorithms could automatically identify running surface from wearable motion sensors to quantify running exposures, and perhaps loading and injury risk for a runner., Research Question: (1) How accurately can machine learning algorithms identify surface type from three-dimensional accelerometer sensors? (2) Does the sensor count (single or two-sensor setup) affect model accuracy?, Methods: Twenty-nine healthy adults (23.3 ± 3.6 years, 1.8 ± 0.1 m, and 63.6 ± 8.5 kg) participated in this study. Participants ran on three different surfaces (concrete, synthetic, woodchip) while fit with two three-dimensional accelerometers (lower-back and right tibia). Summary features (n = 208) were extracted from the accelerometer signals. Feature-based Gradient Boosting (GB) and signal-based deep learning Convolutional Neural Network (CNN) models were developed. Models were trained on 90% of the data and tested on the remaining 10%. The process was repeated five times, with data randomly shuffled between train-test splits, to quantify model performance variability., Results: All models and configurations achieved greater than 90% average accuracy. The highest performing models were the two-sensor GB and tibia-sensor CNN (average accuracy of 97.0 ± 0.7 and 96.1 ± 2.6%, respectively)., Significance: Machine learning algorithms trained on running data from a single- or dual-sensor accelerometer setup can accurately distinguish between surfaces types. Automatic identification of surfaces encountered during running activities could help runners and coaches better monitor training load, improve performance, and reduce injury rates., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Regular physical activity during childhood is important for optimal physical and psychological development. For individuals with Type 1 Diabetes (T1D), physical activity offers many health benefits including improved glycemic control, cardiovascular function, blood lipid profiles, and psychological well-being. Despite these benefits, many young people with T1D do not meet physical activity recommendations. Barriers to engaging in a physically active lifestyle include fear of hypoglycemia, as well as insufficient knowledge in managing diabetes around exercise in both individuals and health care professionals. Diabetes and exercise management is complex, and many factors can influence an individual's glycemic response to exercise including exercise related factors (such as type, intensity and duration of the activity) and person specific factors (amount of insulin on board, person's stress/anxiety and fitness levels). International guidelines provide recommendations for clinical practice, however a gap remains in how to apply these guidelines to a pediatric exercise consultation. Consequently, it can be challenging for health care practitioners to advise young people with T1D how to approach exercise management in a busy clinic setting. This review provides a structured approach to the child/adolescent exercise consultation, based on a framework of questions, to assist the health care professional in formulating person-specific exercise management plans for young people with T1D.

Aims: To determine whether pre-exercise ingestion of carbohydrates to maintain stable glycaemia during moderate-intensity exercise results in excessive hyperglycaemia if combined with repeated sprints in individuals with Type 1 diabetes., Methods: Eight overnight-fasted people with Type 1 diabetes completed the following four 40-min exercise sessions on separate days in a randomized counterbalanced order under basal insulinaemic conditions: continuous moderate-intensity exercise at 50% V ˙ O 2 peak; intermittent high-intensity exercise (moderate-intensity exercise interspersed with 4-s sprints every 2 min and a final 10-s sprint); continuous moderate-intensity exercise with prior carbohydrate intake (~10 g per person); and intermittent high-intensity exercise with prior carbohydrate intake. Venous blood was sampled during and 2 h after exercise to measure glucose and lactate levels., Results: The difference in marginal mean time-averaged area under the blood glucose curve between continuous moderate-intensity exercise + prior carbohydrate and intermittent high-intensity exercise + prior carbohydrate during exercise and recovery was not significant [0.2 mmol/l (95% CI -0.7, 1.1); P = 0.635], nor was the difference in peak blood glucose level after adjusting for baseline level [0.2 mmol/l (95% CI -0.7, 1.1); P = 0.695]. The difference in marginal mean time-averaged area under the blood glucose curve between continuous moderate-intensity and intermittent high-intensity exercise during exercise and recovery was also not significant [-0.2 mmol/l (95% CI -1.2, 0.8); P = 0.651]., Conclusions: When carbohydrates are ingested prior to moderate-intensity exercise, adding repeated sprints is not significantly detrimental to glycaemic management in overnight fasted people with Type 1 diabetes under basal insulin conditions., (© 2019 Diabetes UK.)

Introduction: Reducing fat mass (FM) while retaining fat free mass (FFM) is a common goal of athletes. Evidence suggests that some-but not all-forms of intermittent energy restriction (IER) may be superior to the conventional method of continuous energy restriction (CER) for people with excess body fat that are sedentary, by reducing some of the adaptive responses to ER. However, it is yet to be established whether this dietary approach is effective for athletes., Methods and Analysis: A single-blind, parallel group, randomised controlled trial with a 1:1 allocation ratio is proposed. Sixty healthy athletes aged ≥18 years will be recruited from local sporting facilities and randomised to an intervention of either moderate CER (mCER) or moderate IER (mIER). Both interventions will consist of 12 weeks of moderate ER, plus 3 weeks in energy balance (EB). The mCER intervention will entail 12 weeks of continuous moderate ER, followed by 3 weeks in EB. The mIER intervention will entail 12 weeks of moderate ER, administered as 4×3 week blocks of moderate ER, interspersed with 3×1 week blocks of EB. The co-primary outcomes are changes in FM and FFM after 12 weeks of moderate ER. Secondary outcomes will be changes in FM and FFM at 15 weeks after intervention commencement, as well as muscle performance, physical activity, sleep quality, changes in resting energy expenditure, subjective drive to eat, circulating concentrations of appetite-regulating hormones, mood states and diet acceptability., Trial Registration: ACTRN12618000638235p., Competing Interests: Competing interests: AS is the author of The Don’t Go Hungry Diet (Bantam, Australia and New Zealand, 2007) and Don’t Go Hungry For Life (Bantam, Australia and New Zealand, 2011). She has also received payment from Eli Lilly, the Pharmacy Guild of Australia, Novo Nordisk, the Dietitians Association of Australia, Shoalhaven Family Medical Centres and the Pharmaceutical Society of Australia for presentation at conferences, and has received consulting fees from Nestlé Health Science since 2016.

Aims: To determine the duration of the low hypoglycaemia risk period after the start of moderate-intensity exercise performed under basal insulinaemic conditions and whether this period is affected by the level at which glycaemia is maintained under these conditions., Methods: This was a prospective, randomized counterbalanced study. Eight participants with Type 1 diabetes (mean ± sd age 21.5 ± 4.0 years) underwent either a euglycaemic (5-6 mmol/l) or hyperglycaemic clamp (9-10 mmol/l) on separate days and were infused with insulin at basal rates and [6,6- 2 H]glucose while cycling for 40 min at 50% maximum oxygen consumption rate. The main outcome measures were the glucose infusion rates required to maintain stable glycaemia and glucoregulatory hormone levels, and rates of glucose appearance and disappearance., Results: During the first 20 min of exercise, the glucose infusion rate did not increase significantly, irrespective of the level at which glycaemia was maintained, but increased acutely between 20 and 25 min under both conditions. Maintaining higher glycaemia resulted in higher glucose infusion rate during, but not early post-exercise. With the exception of epinephrine, the glucoregulatory hormone levels and rates of glucose appearance and disappearance were similar between conditions., Conclusion: Irrespective of the levels at which glycaemia is maintained, there is a 20-min low exogenous glucose demand period during which the exogenous glucose requirements to maintain stable glycaemia do not increase during moderate exercise performed at basal insulin level., (© 2018 Diabetes UK.)

Aims: To investigate whether very-low-carbohydrate high-fat diets, typical of ketogenic diets, can improve glycaemic control without causing any ill health effects in adults with Type 1 diabetes., Methods: In this observational study, 11 adults with Type 1 diabetes (seven men, four women, mean ± sd age 36.1± 6.8 years, mean ± sd duration of diabetes 12.8 ± 10.3 years), who followed a ketogenic diet (< 55 g carbohydrate per day) for a mean ± sd of 2.6 ± 3.3 years (β-hydroxybutyrate 1.6 ± 1.3 mmol/l), underwent sampling and analysis of fasting blood, and were fitted with a blinded continuous glucose monitor for 7 days to measure glycaemic variability., Results: The mean ± sd HbA 1c levels were 35±4 mmol/mol (5.3±0.4%), and participants spent 74±20 and 3±8% of their time in the euglycaemic (4-8 mmol/l) and hyperglycaemic (>10 mmol/l) ranges, respectively, with little daily glycaemic variability (sd 1.5±0.7 mmol/l; coefficient of variation 26±8%). Blood glucose levels were <3.0 mmol/l for 3.6% of the time, and participants experienced a median (range) of 0.9 (0.0-2.0) daily episodes of hypoglycaemia. Total cholesterol, LDL cholesterol, total cholesterol/HDL cholesterol ratio, and triglycerides were above the recommended range in 82%, 82%, 64% and 27% of participants, respectively; however, HDL cholesterol levels were within the recommended range for all participants. Participants displayed no or little evidence of hepatic or renal dysfunction., Conclusion: This study provides the first evidence that, ketogenic diets in adults with Type 1 diabetes are associated with excellent HbA 1c levels and little glycaemic variability, but may also be associated with dyslipidaemia and a high number of hypoglycaemic episodes., (© 2018 Diabetes UK.)

Purpose: This study aimed to examine the effect of taurine ingestion on maximal voluntary muscle torque and power in trained male athletes with different caffeine habits., Methods: Fourteen male athletes 21.8 ± 2.5 yr old were separated into caffeine and noncaffeine consumers to control for the effect of caffeine withdrawal on muscle function. On separate occasions, participants performed four isokinetic or three maximal isometric knee extensions with and without taurine (40 mg·kg body mass) after a double-blind, counterbalanced design. Muscle contractile performances were compared between the first sets as well as between the sets where these variables scored best., Results: In response to isokinetic contraction, taurine treatment in the noncaffeine consumers resulted in a significant fall in first (-16.1%; P = 0.013) and best peak torque (-5.0%; P = 0.016) as well as in first (-17.7%; P = 0.015) and best power output (-8.0%; P = 0.008). In the caffeine consumers deprived of caffeine, taurine intake improved best power (5.2%; P = 0.045). With respect to the isometric variables, there was a significant decrease in the first (-5.1%; P = 0.002) and best peak torque (-4.3%; P = 0.032) in the noncaffeine group, but no effect in the group of caffeine consumers deprived of caffeine. Taurine ingestion increased blood taurine levels but had no effect on plasma amino acid levels., Conclusions: Taurine ingestion is detrimental to maximal voluntary muscle power and both maximal isokinetic and isometric peak torque in noncaffeine consumers, whereas taurine ingestion in caffeine-deprived caffeine consumers improves maximal voluntary muscle power but has no effect on other aspects of contractile performance.

Background: Cytokines produced by adipose and placental tissues (adipokines) have been implicated in the development of gestational diabetes mellitus (GDM). There is, however, limited research regarding the relationship between advancing pregnancy, maternal adipokine profile, insulin resistance and the development of GDM. Furthermore, no studies have investigated these parameters in women with a history of GDM who are at the highest risk of recurrence. This study examined the circulating concentrations of a number of adipokines associated with insulin resistance at two points in pregnancy, and determined whether they were altered in women who developed GDM., Methods: Non-diabetic women with a history of GDM in a previous pregnancy (n=123) had blood drawn at 14 and 28weeks of pregnancy for GDM diagnosis, together with assessment of a range of adipokine concentrations by multiplex assay (fatty acid-binding protein 4 [FABP4], leptin, chemerin, adiponectin and resistin)., Results: With advancing pregnancy, maternal adiponectin concentrations decreased, while leptin and resistin levels increased (p<0.05). In women who developed GDM at 28weeks of pregnancy (42%), fasting and postprandial glucose levels were already significantly elevated by 14weeks (p<0.05), while adiponectin concentrations were lower (p<0.05). Adiponectin remained lower at the time of GDM diagnosis (p<0.05), while the other adipokines were similar between groups at each timepoint., Conclusion: Maternal glucose and adipokine profile is altered early in pregnancy in women with a history of GDM who subsequently develop recurrent disease., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Aim: To investigate whether a 10-second (s) sprint impairs the counter-regulatory response to subsequent hypoglycaemia., Methods: Nine people (five male, four female) with Type 1 diabetes, aged 21.1 ± 4.5 years, performed a 10-s rest or a 10-s maximum-effort sprint in random order on different days, while subjected to an euinsulinaemic-euglycaemic clamp. This was followed by a hyperinsulinaemic-hypoglycaemic glucose clamp 2.5 h later to induce hypoglycaemia for 40 min. At timed intervals, the counter-regulatory hormonal responses to hypoglycaemia were measured. Blood pressure, heart rate and hypoglycaemic symptoms were also assessed., Results: During the hypoglycaemic clamp, epinephrine, norepinephrine, growth hormone and cortisol levels increased significantly from baseline, and their responses were similar after both rest and sprint conditions. In particular, plasma epinephrine rose eightfold, from 197 ± 103 pmol/l to 1582 ± 1118 pmol/l after the rest condition, and from 219 ± 119 pmol/l to 1900 ± 898 pmol/l after the sprint condition., Conclusion: A 10-s sprint is unlikely to blunt the subsequent hormonal counter-regulation to hypoglycaemia in individuals with Type 1 diabetes., (© 2017 Diabetes UK.)

Aims: The aim of the study was to evaluate the reproducibility of the plasma glucose response to moderate-intensity exercise performed on different days under controlled conditions in adolescents with Type 1 diabetes., Methods: Eight adolescents with Type 1 diabetes on continuous subcutaneous insulin infusion completed two exercise sessions, each on two separate days, under basal insulin and fasting conditions. On each day, participants cycled twice for 30 min at 55% of their peak rate of oxygen consumption, with each exercise session separated by a 30-min rest., Results: Plasma insulin levels were similar between testing days and exercise sessions. The mean absolute drop in plasma glucose from the commencement to the end of exercise was 1.6 ± 0.5 mmol/l on day 1 and 1.9 ± 0.7 mmol/l on day 2 (P = 0.3). In response to the first exercise session, plasma glucose levels relative to baseline did not change significantly (0.2 ± 0.6 and -0.2 ± 0.5 mmol/l on days 1 and 2). By contrast, the change in plasma glucose during the second exercise session was -1.1 ± 0.7 and -1.3 ± 0.7mmol/l on days 1 and 2, respectively. The mean absolute intra-individual difference in the change in plasma glucose between testing days were 0.7 ± 0.5 [95% confidence interval (CI) 0.4-1.0] and 0.7 ± 0.4 (95% CI 0.4-1.0) mmol/l, at the end of the first and second exercise sessions respectively., Conclusions: The plasma glucose response to moderate-intensity exercise under similar glycaemic and basal insulin conditions can be reproducible in adolescents with Type 1 diabetes., (© 2017 Diabetes UK.)

Type 1 diabetes is a challenging condition to manage for various physiological and behavioural reasons. Regular exercise is important, but management of different forms of physical activity is particularly difficult for both the individual with type 1 diabetes and the health-care provider. People with type 1 diabetes tend to be at least as inactive as the general population, with a large percentage of individuals not maintaining a healthy body mass nor achieving the minimum amount of moderate to vigorous aerobic activity per week. Regular exercise can improve health and wellbeing, and can help individuals to achieve their target lipid profile, body composition, and fitness and glycaemic goals. However, several additional barriers to exercise can exist for a person with diabetes, including fear of hypoglycaemia, loss of glycaemic control, and inadequate knowledge around exercise management. This Review provides an up-to-date consensus on exercise management for individuals with type 1 diabetes who exercise regularly, including glucose targets for safe and effective exercise, and nutritional and insulin dose adjustments to protect against exercise-related glucose excursions., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

It is generally acknowledged that for an orally administered ergogenic aid to enhance exercise performance it must first be absorbed by the gastrointestinal tract before exerting its effects. Recently, however, it has been reported that some ergogenic aids can affect exercise performance without prior absorption by the gastrointestinal tract. This is best illustrated by studies that have shown that rinsing the mouth with a carbohydrate (CHO) solution, without swallowing it, significantly improves exercise performance. The ergogenic effects of CHO mouth rinsing in these studies have been attributed to the activation of the brain by afferent taste signals, but the specific mechanisms by which this brain activation translates to enhanced exercise performance have not yet been elucidated. Given the benefits of CHO mouth rinsing for exercise performance, this raises the issue of whether other types of tastants, such as bitter-tasting solutions, may also improve exercise performance. Recently, we performed a series of studies investigating whether the bitter tastant quinine can improve maximal sprint performance in competitive male cyclists, and, if so, to examine some of the possible mechanisms whereby this effect may occur. These studies have shown that mouth rinsing and ingesting a bitter-tasting quinine solution can significantly improve the performance of a maximal cycling sprint. There is also evidence that the ergogenic effect of quinine is mediated, at least in part, by an increase in autonomic nervous system activation and/or corticomotor excitability. The purpose of this article is to discuss the results and implications of these recent studies and to suggest avenues for further research, which may add to the understanding of the way the brain integrates signals from the oral cavity with motor behaviour, as well as uncover novel strategies to improve exercise performance.

Objective: To investigate the effect of a supervised home-based exercise program on the recurrence and severity of gestational diabetes mellitus (GDM) together with other aspects of maternal health and obstetric and neonatal outcomes., Methods: This randomized controlled trial allocated women with a history of GDM to an exercise intervention (14-week supervised home-based stationary cycling program) or to a control group (standard care) at 13±1 weeks of gestation. The primary outcome was a diagnosis of GDM. Secondary outcomes included maternal fitness, psychological well-being, and obstetric and neonatal outcomes. A sample size of 180 (90 in each group) was required to attain 80% power to detect a 40% reduction in the incidence of GDM., Results: Between June 2011 and July 2014, 205 women provided written consent and completed baseline assessments. Of these, 33 (16%) were subsequently excluded as a result of an elevated baseline oral glucose tolerance test (OGTT), leaving 172 randomized to exercise (n=85) or control (n=87). Three women miscarried before the assessment of outcome measures (control=2; exercise=1). All remaining women completed the postintervention OGTT. The recurrence rate of GDM was similar between groups (control 40% [n=34]; exercise 40.5% [n=34]; P=.95) and the severity of GDM at diagnosis was unaffected by the exercise program with similar glucose and insulin responses to the OGTT (glucose 2 hours post-OGTT 7.7±1.5 compared with 7.6±1.6 mmol/L; P>.05). Maternal fitness was improved by the exercise program (P<.01) and psychological distress was reduced (P=.02). There were no differences in obstetric and neonatal outcomes between groups (P>.05)., Conclusion: Supervised home-based exercise started at 14 weeks of gestation did not prevent the recurrence of GDM; however, it was associated with important benefits for maternal fitness and psychological well-being., Clinical Trial Registration: ClinicalTrials.gov, https://clinicaltrials.gov, NCT01283854.

Background: Sensor-augmented pump therapy (SAPT) with a predictive algorithm to suspend insulin delivery has the potential to reduce hypoglycemia, a known obstacle in improving physical activity in patients with type 1 diabetes. The predictive low glucose management (PLGM) system employs a predictive algorithm that suspends basal insulin when hypoglycemia is predicted. The aim of this study was to determine the efficacy of this algorithm in the prevention of exercise-induced hypoglycemia under in-clinic conditions., Methods: This was a randomized, controlled cross-over study in which 25 participants performed 2 consecutive sessions of 30 min of moderate-intensity exercise while on basal continuous subcutaneous insulin infusion on 2 study days: a control day with SAPT alone and an intervention day with SAPT and PLGM. The predictive algorithm suspended basal insulin when sensor glucose was predicted to be below the preset hypoglycemic threshold in 30 min. We tested preset hypoglycemic thresholds of 70 and 80 mg/dL. The primary outcome was the requirement for hypoglycemia treatment (symptomatic hypoglycemia with plasma glucose <63 mg/dL or plasma glucose <50 mg/dL) and was compared in both control and intervention arms., Results: Results were analyzed in 19 participants. In the intervention arm with both thresholds, only 6 participants (32%) required treatment for hypoglycemia compared with 17 participants (89%) in the control arm (P = 0.003). In participants with a 2-h pump suspension on intervention days, the plasma glucose was 84 ± 12 and 99 ± 24 mg/dL at thresholds of 70 and 80 mg/dL, respectively., Conclusions: SAPT with PLGM reduced the need for hypoglycemia treatment after moderate-intensity exercise in an in-clinic setting.

Background: Current guidelines recommend that pregnant women without contraindications should engage in 30 min or more of moderate intensity exercise on most days of the week, however, many women fail to achieve this goal. This study examined the effect of adding brief higher intensity intervals to traditional continuous moderate intensity exercise on energy expenditure and the enjoyment of exercise in late pregnancy. This is important to determine given that any additional energy expenditure resulting from higher intensity intervals may be meaningless if enjoyment is compromised, since long-term adherence will likely be low., Methods: In this study, 12 healthy pregnant women at 30 ± 1 weeks gestation, aged 35 ± 6 years with a BMI of 27.1 ± 4.3 kg/m(2) performed either 30 min of continuous cycling exercise (CONT) at a steady power output equivalent to 65 % age-predicted heart rate maximum or an equivalent period of interval cycling (INTV) consisting of continuous cycling at the same power output as CONT, but with the addition of six 15-s self-paced higher intensity efforts throughout, performed at regular intervals, on separate occasions in a counterbalanced order., Results: Mean cycling power output, heart rate, oxygen consumption and energy expenditure were higher during INTV compared with CONT (P < 0.05). However, there was no difference in mean rate of perceived exertion between conditions. Enjoyment of exercise was higher with INTV (P = 0.01)., Conclusions: The addition of six 15-s higher intensity intervals to continuous moderate intensity exercise effectively increased energy expenditure by 28 %, at the same time as enhancing the enjoyment of exercise in late pregnancy. While these findings may be specific to recreationally active women, this study provides a rationale for future studies to examine the physiological and psychological responses to regular interval training during pregnancy to optimise exercise prescription., Trial Registration: Australian New Zealand Clinical Trials Registry ACTRN12616000680460 . 25 May 2016 (Registered retrospectively).

Context: No recommendations exist to inform the carbohydrate amount required to prevent hypoglycemia associated with exercise of different intensities in individuals with type 1 diabetes (T1D)., Objective: The relationship between exercise intensity and carbohydrate requirements to maintain stable euglycemia in individuals with T1D remains to be determined. It was predicted that an "inverted-U" relationship exists between exercise intensity and the amount of glucose required to prevent hypoglycemia during exercise at basal insulinemia. Our objective was to investigate this relationship and elucidate the underlying glucoregulatory mechanisms., Design, Participants, and Intervention: We subjected nine individuals (mean ± SD age, 21.5 ± 4.0 years; duration of disease, 11.4 ± 6.4 years; glycated hemoglobin, 7.9 ± 0.8% [60 mmol/mol]; body mass index, 25.4 ± 5.5 kg/m(2); VO2peak, 34.8 ± 5.1 mL·kg(-1)·min(-1); and lactate threshold, 59.9 ± 5.9% VO2peak) with T1D to a euglycemic clamp, whereby euglycemia was maintained by infusing basal insulin rates with concomitant infusion of [6,6-(2)H2]glucose for determining glucose kinetics. Glucose was infused to maintain euglycemia during and for 2 hours after exercise of different intensities (35, 50, 65, and 80% VO2peak)., Main Outcome Measures: The glucose infusion rate (GIR), levels of glucoregulatory hormones, and rates of endogenous glucose appearance and disappearance were compared between conditions., Results: The mean GIR to maintain euglycemia during exercise increased with intensity up to 50% (4.0 ± 1.6 g/h; P < .05) and 65% (4.1 ± 1.7 g/h), but no glucose was required at 80% VO2peak. Glucose rate of appearance and disappearance increased with intensity and, together with plasma catecholamines, reached higher levels at 80% VO2peak., Conclusion: Our findings support the predicted inverted-U relationship between exercise intensity and glucose requirement. However, the relationship between iv and oral glucose requirements needs to be investigated to translate these GIR data to clinical practice.

Purpose: Recently, we have shown that the combination of mouth rinsing and ingesting a bitter-tasting quinine solution immediately prior to the performance of a maximal 30-s cycling sprint significantly improves mean and peak power output. This ergogenic effect was proposed to be related to the activation of the corticomotor pathway by afferent taste signals originating from bitter taste receptors in the oral cavity. The aim of the present study was to use single-pulse transcranial magnetic stimulation to investigate whether mouth rinsing and ingestion of a bitter quinine solution increases corticomotor excitability., Methods: A series of 10 motor-evoked potentials (MEPs) were recorded from the relaxed first dorsal interosseus muscle in 16 male competitive cyclists immediately before and after they rinsed their mouth for 10 s and then ingested either a 2 mM bitter quinine solution or plain water., Results: Mean MEP amplitude was significantly increased in response to quinine administration by 16% (p < 0.05), with no evidence of a time-dependent effect over the 10 pulses. Mean MEP amplitude also increased by 10% in response to water administration (p < 0.05), though this increase was significantly smaller than the response to quinine (p < 0.05)., Conclusions: We conclude that the activation of bitter taste receptors in the oral cavity and upper gastrointestinal tract has the capacity to increase corticomotor excitability in male competitive cyclists.