Impact of whole-body resistance exercise timing on mitigating hyperglycaemia-induced vascular dysfunction.

NEW FINDINGS: What is the central question of this study? Is the estrous cycle affected during disuse atrophies and if so, how do estrous cycle changes relate to musculoskeletal outcomes? What is the main finding and its importance? Rodent estrous cycles are altered during disuse atrophy, which corresponds to musculoskeletal outcomes. However, the estrous cycle does not appear changed in Lewis Lung Carcinoma, which corresponded to no differences in muscle size compared to healthy controls. These findings suggest a relationship between estrous cycle and muscle size during atrophic pathologies. ABSTRACT: Hyperglycemia can cause disruptions in vascular function, whereas exercise has been shown to restore vascular function. The primary aim of this study is to investigate the effect of performing whole-body resistance exercise, 30-min before, immediately following, or 30- or 60-min after a high carbohydrate meal, on endothelial function, measured by flow-mediated dilation (FMD). Healthy adults will be recruited to this randomized crossover trial to compare the postprandial glycaemic and vascular responses to four different exercise timing conditions and a control: i) C- control, high carbohydrate meal/no exercise, ii) 30Pre- 30 min of resistance exercises (~30% of 1RM [Repetition Maximum]), 30 min before a high carbohydrate meal, iii) IP- 30 min of resistance exercises (~30% of 1RM), immediately following a high carbohydrate meal, iv) 30Post- 30 min of resistance exercises, 30 min after a high carbohydrate meal and v) 60Post- 30 min of resistance exercises, 60 min after a high carbohydrate meal. Measures of metabolic and vascular function will be assessed at baseline and for two hours following the carbohydrate-based breakfast meal.

Using Continuous Glucose Monitoring to Prescribe a Time to Exercise for Individuals with Type 2 Diabetes.

This study examines the potential utility of using continuous glucose monitoring (CGM) to prescribe an exercise time to target peak hyperglycaemia in people with type 2 diabetes (T2D). The main aim is to test the feasibility of prescribing an individualised daily exercise time, based on the time of CGM-derived peak glucose, for people with T2D. Thirty-five individuals with T2D (HbA1c: 7.2 ± 0.8%; age: 64 ± 7 y; BMI: 29.2 ± 5.2 kg/m2) were recruited and randomised to one of two 14 d exercise interventions: i) ExPeak (daily exercise starting 30 min before peak hyperglycaemia) or placebo active control NonPeak (daily exercise starting 90 min after peak hyperglycaemia). The time of peak hyperglycaemia was determined via a two-week baseline CGM. A CGM, accelerometer, and heart rate monitor were worn during the free-living interventions to objectively measure glycaemic control outcomes, moderate-to-vigorous intensity physical activity (MVPA), and exercise adherence for future translation in a clinical trial. Participation in MVPA increased 26% when an exercise time was prescribed compared to habitual baseline (p < 0.01), with no difference between intervention groups (p > 0.26). The total MVPA increased by 10 min/day during the intervention compared to the baseline (baseline: 23 ± 14 min/d vs. intervention: 33 ± 16 min/d, main effect of time p = 0.03, no interaction). The change in peak blood glucose (mmol/L) was similar between the ExPeak (-0.44 ± 1.6 mmol/L, d = 0.21) and the NonPeak (-0.39 ± 1.5 mmol/L, d = 0.16) intervention groups (p = 0.92). Prescribing an exercise time based on CGM may increase daily participation in physical activity in people with type 2 diabetes; however, further studies are needed to test the long-term impact of this approach.

The Effect of Exercise on Quality of Life in Type 2 Diabetes: A Systematic Review and Meta-analysis.

BACKGROUND: Exercise is a proven therapy for managing cardiometabolic risk factors in type 2 diabetes (T2D). However, its effects on patient-reported outcome measures such as quality of life (QoL) in people with T2D remain unclear. Consequently, the primary aim of this study was to determine the effect of regular exercise on QoL in adults with T2D. A secondary aim was to determine the effect of different exercise modalities on QoL. The third aim was to determine whether improvements in QoL were associated with improvements in gly'cated hemoglobin (A1C). METHODS: Relevant databases were searched to May 2022. Eligible studies included randomized trials involving ≥2 wk of aerobic and/or resistance exercise and assessed QoL using a purpose-specific tool. Mean differences and 95% confidence intervals (CI) were calculated as standardized mean difference (SMD) or weighted mean difference. A regression analysis was undertaken to examine the interaction between change in QoL with change in A1C. RESULTS: Of the 12,642 studies retrieved, 29 were included involving 2354 participants. Exercise improved QoL when compared with control (SMD, 0.384; 95% CI, 0.257 to 0.512; P < 0.001). Aerobic exercise, alone (SMD, 0.475; 95% CI, 0.295 to 0.655; P < 0.001) or in combination with resistance training (SMD, 0.363; 95% CI, 0.179 to 0.548; P < 0.001) improved QoL, whereas resistance training alone did not. Physical components of health-related QoL (HRQoL) improved with all exercise modalities, but mental components of HRQoL remained unchanged. Exercise improved A1C (mean difference, -0.509%; 95% CI, -0.806% to -0.212%; P = 0.001), and this change was associated with improvements in HRQoL ( ß = -0.305, SE = 0.140, Z = -2.18, P = 0.030). CONCLUSIONS: These results provide robust evidence that regular aerobic exercise alone or in combination with resistance training is effective for improving QoL in adults with T2D. Such improvements seem to be mediated by improvements in physical components of HRQoL and are associated with improved blood glucose control. Further studies should be undertaken to determine the relative importance of exercise duration, intensity, and frequency on patient-reported outcomes such as QoL.

Impact of a Low-Carbohydrate Compared with Low-Fat Breakfast on Blood Glucose Control in Type 2 Diabetes: A Randomized Trial.

BACKGROUND: In type 2 diabetes (T2D), consuming carbohydrates results in a rapid and large increase in blood glucose, particularly in the morning when glucose intolerance is highest. OBJECTIVES: We investigated if a low-carbohydrate (LC) breakfast (∼465 kcal: 25 g protein, 8 g carbohydrates, and 37 g fat) could improve glucose control in people with T2D when compared with a low-fat control (CTL) breakfast (∼450 kcal:20 g protein, 56 g carbohydrates, and 15 g fat). METHODS: Participants with T2D (N = 121, 53% women, mean age 64 y) completed a remote 3-month parallel-group randomized controlled trial comparing a LC with standard low-fat guideline CTL breakfast. The change in HbA1c was the prespecified primary outcome. Continuous glucose monitoring, self-reported anthropometrics, and dietary information were collected for an intention-to-treat analysis. RESULTS: HbA1c was reduced (-0.3%; 95% CI: -0.4%, -0.1%) after 12 wks of a LC breakfast, but the between-group difference in HbA1c was of borderline statistical significance (-0.2; 95% CI: -0.4, 0.0; P = 0.06). Self-reported total daily energy (-242 kcal; 95% CI: -460, -24 kcal; P = 0.03) and carbohydrate (-73 g; 95% CI: -101, -44 g; P < 0.01) intake were lower in the LC group but the significance of this difference is unclear. Mean and maximum glucose, area under the curve, glycemic variability, standard deviation, and time above range were all significantly lower, and time in the range was significantly higher, in the LC group compared with CTL (all P < 0.05). CONCLUSIONS: Advice and guidance to consume a LC breakfast appears to be a simple dietary strategy to reduce overall energy and carbohydrate intake and improve several continuous glucose monitoring variables when compared with a CTL breakfast in persons living with T2D. The trial was registered at clinicaltrials.gov as NCT04550468.

Personalising activity to target peak hyperglycaemia and improve cardiometabolic health in people with type 2 diabetes: protocol for a randomised controlled trial.

INTRODUCTION: The benefits of physical activity for glycaemic control in type 2 diabetes (T2D) are well-known. However, whether established glycaemic and cardiovascular benefits can be maximised by exercising at a certain time of day is unknown. Given postprandial glucose peaks contribute to worsening glycated haemoglobin (HbA1c) and cardiovascular risk factors, and that exercise immediately lowers blood glucose, prescribing exercise at a specific time of day to attenuate peak hyperglycaemia may improve glycaemic control and reduce the burden of cardiovascular disease in people with T2D. METHODS AND ANALYSIS: A single-centre randomised controlled trial will be conducted by the University of Wollongong, Australia. Individuals with T2D (n=70, aged 40-75 years, body mass index (BMI): 27-40 kg/m2) will be recruited and randomly allocated (1:1), stratified for sex and insulin, to one of three groups: (1) exercise at time of peak hyperglycaemia (ExPeak, personalised), (2) exercise not at time of peak hyperglycaemia (NonPeak) or (3) waitlist control (WLC, standard care). The trial will be 5 months, comprising an 8-week intervention and 3-month follow-up. Primary outcome is the change in HbA1c preintervention to postintervention. Secondary outcomes include vascular function (endothelial function and arterial stiffness), metabolic control (blood lipids and inflammation) and body composition (anthropometrics and dual-energy X-ray absorptiometry (DEXA)). Tertiary outcomes will examine adherence. ETHICS AND DISSEMINATION: The joint UOW and ISLHD Ethics Committee approved protocol (2019/ETH09856) prospectively registered at the Australian New Zealand Clinical Trials Registry. Written informed consent will be obtained from all eligible individuals prior to commencement of the trial. Study results will be published as peer-reviewed articles, presented at national/international conferences and media reports. TRIAL REGISTRATION NUMBER: ACTRN12619001049167.

Three short postmeal walks as an alternate therapy to continuous walking for women with gestational diabetes.

The purpose of this study was to determine whether postmeal walking (PMW, breaking up exercise into short bouts after meals) is an effective and feasible alternative to continuous walking for the management of gestational diabetes. Forty-one women with gestational diabetes were randomised between weeks 28-30 gestation to either standard care (30 minutes continuous exercise) or standard care with PMW (10 minutes of walking after breakfast, lunch, and dinner). Continuous glucose and activity monitors were worn to measure glycaemic control and adherence during 3 days of standard care (baseline) followed by 3 days of postmeal or continuous walking. A linear mixed model analysed the changes from baseline between postmeal and continuous walking, as an average of the 3-day periods. Thirty-two women (PMW n = 17: control n = 15, 33 ± 5 years, body mass index 25 ± 4 kg·m-2) completed the trial. Postprandial and overnight glucose concentrations were similar between PMW and control; both interventions improved from baseline. There was no difference in adherence between groups; however, PMW completed more minutes of prescribed physical activity across baseline and intervention days compared to the continuous walking standard-care group. Preliminary findings from this proof-of-concept study suggest PMW could be a promising alternative to, and work interchangeably with, traditional advice to perform continuous moderate-intensity physical activity in women with gestational diabetes. Novelty: Three 10-minute postmeal walks may be comparable to 30 minutes continuous walking for glucose control in women with gestational diabetes. Accumulating activity in short bouts after meals is a feasible alternate to continuous exercise for women with gestational diabetes.

Post-exercise Warm or Cold Water Immersion to Augment the Cardiometabolic Benefits of Exercise Training: A Proof of Concept Trial.

We investigated whether substituting the final half within 60-min bouts of exercise with passive warm or cold water immersion would provide similar or greater benefits for cardiometabolic health. Thirty healthy participants were randomized to two of three short-term training interventions in a partial crossover (12 sessions over 14-16 days, 4 week washout): (i) EXS: 60 min cycling 70% maximum heart rate (HRmax), (ii) WWI: 30 min cycling then 30 min warm water (38-40°C) immersion, and/or (iii) CWI: 30 min cycling then 30 min cold water (10-12°C) immersion. Before and after, participants completed a 20 min cycle work trial, V . O2max test, and an Oral Glucose Tolerance Test during which indirect calorimetry was used to measure substrate oxidation and metabolic flexibility (slope of fasting to post-prandial carbohydrate oxidation). Data from twenty two participants (25 ± 5 year, BMI 23 ± 3 kg/m2, Female = 11) were analyzed using a fixed-effects linear mixed model. V . O2max increased more in EXS (interaction p = 0.004) than CWI (95% CI: 1.1, 5.3 mL/kg/min, Cohen's d = 1.35), but not WWI (CI: -0.4, 3.9 mL/kg/min, d = 0.72). Work trial distance and power increased 383 ± 223 m and 20 ± 6 W, respectively, without differences between interventions (interaction both p > 0.68). WWI lowered post-prandial glucose ∼9% (CI -1.9, -0.5 mmol/L; d = 0.63), with no difference between interventions (interaction p = 0.469). Substituting the second half of exercise with WWI provides similar cardiometabolic health benefits to time matched exercise, however, substituting with CWI does not.

A low-carbohydrate protein-rich bedtime snack to control fasting and nocturnal glucose in type 2 diabetes: A randomized trial.

In type 2 diabetes, liver insulin resistance and excess hepatic glucose production results in elevated fasting glucose. A bedtime snack has been recommended to improve fasting glucose, yet there is little evidence supporting this recommendation. Moreover, the optimal composition of a bedtime snack is unknown. PURPOSE: To determine whether a low-carbohydrate protein-rich bedtime snack (Egg) could reduce fasting plasma glucose levels in people with type 2 diabetes when compared to a high-carbohydrate protein-rich bedtime snack (Yogurt) or a No Bedtime Snack condition. Secondary outcomes included glucose control assessed by continuous glucose monitoring (CGM) and fasting insulin sensitivity markers. METHODS: Using a randomized crossover design, participants with type 2 diabetes (N = 15) completed three separate isocaloric conditions: i) Egg, ii) Yogurt, and iii) No Bedtime Snack, each lasting three days. CGM was collected throughout and duplicate fasting blood samples were obtained on the morning of day 4 in each condition. RESULTS: Fasting plasma glucose (P = 0.04, d = 0.68), insulin (P = 0.04, d = 0.45), and nocturnal glucose (P = 0.02, d = 0.94) were significantly lower, and quantitative insulin sensitivity check index (QUICKI; P = 0.003) was improved, in the Egg compared to the Yogurt bedtime snack. There were no significant differences between either bedtime snack and No Bedtime Snack. CONCLUSION: In the short-term, a low-carbohydrate bedtime snack (Egg) lowered fasting glucose and improved markers of insulin sensitivity when compared to a high-carbohydrate protein-matched bedtime snack (Yogurt). However, consuming a low- or high-carbohydrate bedtime snack did not appear to lower fasting glucose compared to consuming an isocaloric diet with no bedtime snack. CLINICAL TRIAL REGISTRY: clinicaltrials.gov (NCT03207269).

Accumulating Physical Activity in Short or Brief Bouts for Glycemic Control in Adults With Prediabetes and Diabetes.

Clinical practice guidelines on physical activity and diabetes currently stipulate physical activity can be accumulated in bouts of ≥10 minutes to meet recommendations for health benefits. Individuals are also encouraged to interrupt prolonged sitting with brief activity breaks of ∼1 to 5 minutes in duration. Growing research highlights accumulating activity in shorter bouts across the day as a potential strategy to improve glycemic control and to help those who are largely sedentary meet physical activity guidelines. Research has shown favourable glycemic benefits for postprandial glucose and glycated hemoglobin with either 3 short (10 to 15 minutes) or frequent brief (1 to 5 minutes) bouts of activity spread around meals or throughout the day. To date, most studies examining accumulated activity were done with people with type 2 diabetes compared with sedentary conditions, were short term and measured various indices of glycemic control using continuous glucose monitoring. The 7 trials comparing accumulating 3 short bouts to a single bout showed comparable benefits for glycemic control (i.e. fasting glucose, 24 h mean glucose and postprandial hyperglycemia). Furthermore, timing short bouts around meals may improve postprandial glucose and hyperglycemia more than a single bout. It is unknown whether a threshold for the duration of accumulated bouts exists---that is, "how much is enough?" In this narrative review, we focus on the glycemic effects of physical activity accumulated in short or brief bouts for people with prediabetes and diabetes as compared with a single continuous bout. Given that poor adherence to physical activity recommendations and that fewer opportunities exist in modern societies for incidental (nonexercise) physical activity, accumulating activity may be a choice strategy for improving glycemic control in those with and at risk of diabetes.

Restricting carbohydrates at breakfast is sufficient to reduce 24-hour exposure to postprandial hyperglycemia and improve glycemic variability.

BACKGROUND: The breakfast meal often results in the largest postprandial hyperglycemic excursion in people with type 2 diabetes. OBJECTIVE: Our purpose was to investigate whether restricting carbohydrates at breakfast would be a simple and feasible strategy to reduce daily exposure to postprandial hyperglycemia. DESIGN: Adults with physician-diagnosed type 2 diabetes [n = 23; mean ± SD age: 59 ± 11 y; glycated hemoglobin: 6.7% ± 0.6%; body mass index (kg/m2): 31 ± 7] completed two 24-h isocaloric intervention periods in a random order. Participants consumed one of the following breakfasts: 1) a very-low-carbohydrate high-fat breakfast (LCBF; <10% of energy from carbohydrate, 85% of energy from fat, 15% of energy from protein) or 2) a breakfast with dietary guidelines-recommended nutrient profile (GLBF; 55% of energy from carbohydrate, 30% of energy from fat, 15% of energy from protein), with the same lunch and dinner provided. Continuous glucose monitoring was used to assess postprandial glucose responses over 24 h, and visual analog scales were used to assess ratings of hunger and fullness. RESULTS: The LCBF significantly reduced postprandial hyperglycemia after breakfast (P < 0.01) and did not adversely affect glycemia after lunch or dinner. As such, overall postprandial hyperglycemia (24-h incremental area under the glucose curve) and glycemic variability (mean amplitude of glycemic excursions) were reduced with the LCBF (24-h incremental area under the glucose curve: -173 ± 361 mmol/L; P = 0.03; mean amplitude of glycemic excursions: -0.4 ± 0.8 mmol/L · 24 h; P = 0.03) compared with the GLBF. Premeal hunger was lower before dinner with the LCBF than with the GLBF (P-interaction = 0.03). CONCLUSIONS: A very-low-carbohydrate high-fat breakfast lowers postbreakfast glucose excursions. The effects of this simple strategy appear to be sufficient to lower overall exposure to postprandial hyperglycemia and improve glycemic variability. Longer-term interventions are warranted. This trial was registered at clinicaltrials.gov as NCT02982330.

Minimal effect of walking before dinner on glycemic responses in type 2 diabetes: outcomes from the multi-site E-PAraDiGM study.

AIM: To examine the effect of walking before dinner on 24-h glycemic control in individuals with type 2 diabetes using the standardized multi-site Exercise-Physical Activity and Diabetes Glucose Monitoring (E-PAraDiGM) Protocol. METHODS: Eighty participants were studied under two conditions (exercise vs. non-exercise control) separated by 72 h in a randomized crossover design. Each condition lasted 2 days during which standardized meals were provided. Exercise consisted of 50 min of treadmill walking at 5.0 km/h before the evening meal, while control involved 50 min of sitting. The primary outcome measure was mean glucose during the 24-h period following exercise (or sitting) measured by continuous glucose monitoring. RESULTS: Of the 80 participants who were initially randomized, 73 completed both exercise and control. Sixty-three participants [29 males, 34 females; age = 64 ± 8 years, body mass index = 30.5 ± 6.5 kg/m2 and HbA1c = 51 ± 8 mmol/mol (6.8 ± 0.7%), mean ± SD] complied with the standardized diets and had complete continuous glucose monitoring data. Exercise did not affect mean 24-h glucose compared to control (0.03 mmol/L; 95% CI - 0.17, 0.22, P = 0.778) but individual differences between conditions ranged from - 2.8 to +1.8 mmol/L. Exercise did not affect fasting glucose, postprandial glucose or glucose variability. Glucose concentrations measured by continuous glucose monitoring were reduced during the 50 min of walking in exercise compared to sitting in control (- 1.56 mmol/L; 95% CI - 2.18, - 0.95, p < 0.001). CONCLUSION: Contrary to previous acute exercise studies, 50 min of walking before dinner in the E-PAraDiGM protocol did not affect 24-h glucose profiles. However, highly heterogeneous responses to exercise were observed. TRIAL REGISTRATION: NCT02834689.