Temporal tracking of cysteine 34 oxidation of plasma albumin as a biomarker of muscle damage following a bout of eccentric exercise.

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.

The Effect of Exercise Intensity on Carbohydrate Sparing Postexercise: Implications for Postexercise Hypoglycemia.

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.

High intensity interval training as a novel treatment for impaired awareness of hypoglycaemia in people with type 1 diabetes (HIT4HYPOS): a randomised parallel-group study.

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 HbA1c 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.

Effect of Neck-Deep Immersion in Cool or Thermoneutral Water on Blood Glucose Levels in Individuals With Type 1 Diabetes.

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.

Protein Ingestion in Reducing the Risk of Late-Onset Post-Exercise Hypoglycemia: A Pilot Study in Adolescents and Youth with Type 1 Diabetes.

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.

Reproducibility of plasma glucose responses to moderate-intensity exercise in individuals with type 1 diabetes.

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% V̇O2 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.

Effects of Simulated High Altitude on Blood Glucose Levels During Exercise in Individuals With Type 1 Diabetes.

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.

A Novel Mobile Health App to Educate and Empower Young People With Type 1 Diabetes to Exercise Safely: Prospective Single-Arm Mixed Methods Pilot Study.

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 HbA1c, 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.

Nausea after Repeated Sprints: Is Lactic Acidosis Really the Culprit?

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.

Antidiuretic hormone and the activation of glucose production during high intensity aerobic exercise.

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 % V̇O2peak for up to 40 min or until exhaustion. During and after exercise, the participants were subjected to a morning euglycaemic/euinsulinaemic clamp while [6,6-2H2]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.

Acute hyperglycaemia does not have a consistent adverse effect on exercise performance in recreationally active young people with type 1 diabetes: a randomised crossover in-clinic study.

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 HbA1c ≤ 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 [m2 BSA]-1 min-1 insulin (where BSA is body surface area) (Eu20); hyperglycaemia (17 mmol/l) with 20 mU [m2 BSA]-1 min-1 insulin (Hyper20); and hyperglycaemia (17 mmol/l) with 5 mU [m2 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, HbA1c 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.

A 1-week diet break improves muscle endurance during an intermittent dieting regime in adult athletes: A pre-specified secondary analysis of the ICECAP trial.

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.

Continuous versus Intermittent Dieting for Fat Loss and Fat-Free Mass Retention in Resistance-trained Adults: The ICECAP Trial.

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.

Effect of Exercise Intensity on Exogenous Glucose Requirements to Maintain Stable Glycemia At High Insulin Levels in Type 1 Diabetes.

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 ±â€…SD age, 22.6 ±â€…4.7 years; glycated hemoglobin, 61 ±â€…14 mmol/mol; body mass index, 24.0 ±â€…3.3 kg/m2, V̇O2 peak, 36.6 ±â€…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 (±â€…SEM) to maintain euglycemia was 4.4 ±â€…0.4 mg·kg-1 min-1 prior to exercise, and increased significantly by 1.8 ±â€…0.4, 3.0 ±â€…0.4, 4.2 ±â€…0.7, and 3.5 ±â€…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 competitive athlete with type 1 diabetes.

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.

A randomised controlled study of high intensity exercise as a dishabituating stimulus to improve hypoglycaemia awareness in people with type 1 diabetes: a proof-of-concept study.

AIMS/HYPOTHESIS: Approximately 25% of people with type 1 diabetes have suppressed counterregulatory hormonal and symptomatic responses to insulin-induced hypoglycaemia, which renders them at increased risk of severe, disabling hypoglycaemia. This is called impaired awareness of hypoglycaemia (IAH), the cause of which is unknown. We recently proposed that IAH develops through habituation, a form of adaptive memory to preceding hypoglycaemia. Consistent with this hypothesis, we demonstrated restoration of defective counterregulatory hormonal responses to hypoglycaemia (referred to as dishabituation) in a rodent model of IAH following introduction of a novel stress stimulus (high intensity training [HIT]). In this proof-of-concept study we sought to further test this hypothesis by examining whether a single episode of HIT would amplify counterregulatory responses to subsequent hypoglycaemia in people with type 1 diabetes who had IAH (assessed by Gold score ≥4, modified Clarke score ≥4 or Dose Adjustment For Normal Eating (DAFNE) hypoglycaemia awareness rating 2 or 3). The primary outcome was the difference in adrenaline response to hypoglycaemia following both a single episode of HIT and rest. METHODS: In this randomised, crossover study 12 participants aged between 18 and 55 years with type 1 diabetes for ≥5 years and an HbA1c <75 mmol/mol (9%) were recruited. Individuals were randomised using computer generated block randomisation to start with one episode of HIT (4 × 30 s cycle sprints [2 min recovery] at 150% of maximum wattage achieved during [Formula: see text] assessment) or rest (control). The following day they underwent a 90 min hyperinsulinaemic-hypoglycaemic clamp study at 2.5 mmol/l with measurement of hormonal counterregulatory response, symptom scores and cognitive testing (four-choice reaction time and digit symbol substitution test). Each intervention and subsequent clamp study was separated by at least 2 weeks. The participants and investigators were not blinded to the intervention or measurements during the study. The investigators were blinded to the primary outcome and blood analysis results. RESULTS: All participants (six male and six female, age 19-54 years, median [IQR] duration of type 1 diabetes 24.5 [17.3-29.0] years, mean [SEM] HbA1c 56 [3.67] mmol/mol; 7.3% [0.34%]) completed the study (both interventions and two clamps). In comparison with the rest study, a single episode of HIT led to a 29% increase in the adrenaline (epinephrine) response (mean [SEM]) (2286.5 [343.1] vs 2953.8 [384.9] pmol/l); a significant increase in total symptom scores (Edinburgh Hypoglycaemia Symptom Scale: 24.25 [2.960 vs 27.5 [3.9]; p<0.05), and a significant prolongation of four-choice reaction time (591.8 [22.5] vs 659.9 [39.86] ms; p<0.01] during equivalent hypoglycaemia induced the following day. CONCLUSIONS/INTERPRETATION: These findings are consistent with the hypothesis that IAH develops in people with type 1 diabetes as a habituated response and that introduction of a novel stressor can restore, at least partially, the adapted counterregulatory hormonal, symptomatic and cognitive responses to hypoglycaemia. TRIAL REGISTRATION: ISRCTN15236211.

Oxidation of cysteine 34 of plasma albumin as a biomarker of oxidative stress.

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 (-SO2, -SO3) 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.

Role of lactic acidosis as a mediator of sprint-mediated nausea.

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, pCO2 , 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 pCO2 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 NPrrm > 0.595, p < .0001) and H+ concentrations (VAS and NPrrm > 0.689, p < .0001), but an inconsistent relationship with pCO2 (VAS rrm  = 0.250, p = .040; NP rrm  = 0.144, p = .248) and bicarbonate levels (VAS rrm  = -0.252, p = .095; NP rrm  = -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.

Exercise Management for Young People With Type 1 Diabetes: A Structured Approach to the Exercise Consultation.

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.