Aim This systematic review aimed to determine the effect of aerobic exercise interventions, including high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT), on liver fat in adults. A secondary aim was to investigate the interaction between total weekly exercise volume and exercise-related energy expenditure and change in liver fat. Methods Relevant databases were searched to December 2020 for randomised trials, comparing HIIT to control, MICT to control, or HIIT to MICT. Studies were excluded if they did not implement ≥2 weeks intervention or assess liver fat using magnetic resonance-based techniques. Weighted mean differences and 95% confidence intervals (CI) were calculated. Regression analyses were undertaken to determine the interaction between weekly exercise volume in minutes and kcal with change in liver fat %. Results The search returned 28,262 studies of which 19 were included involving 745 participants. Both HIIT and MICT elicited moderate reductions in liver fat % when compared to control (HIIT:-2.85%, 95%CI:-4.86 to -0.84, p=0.005, I²=0%, n=114, low certainty evidence; MICT:-3.14%, 95%CI:-4.45 to -1.82, p<0.001, I²=5.2%, n=533, moderate certainty evidence). There was no difference between HIIT or MICT (-0.34%, 95%CI:-2.20 to 1.52, p=0.721, I²=0%, n=177, moderate certainty evidence). Neither total exercise volume in minutes (β=0.0002, SE=0.0017, Z=0.13, p=0.89) nor exercise-related energy expenditure in kcal (β=0.0001, SE=0.0002, Z=-0.63, p=0.52) were related to changes in liver fat %. Conclusion HIIT elicits comparable improvements in liver fat to MICT despite often requiring less energy and time commitment. Further studies should be undertaken to assess the relative importance of aerobic exercise prescription variables, such as intensity, on liver fat.

OBJECTIVE: We aimed to examine the effects of a 5:2 diet (2 days per week of energy restriction by formula diet) or an exercise (2 days per week of high-intensity interval training and resistance training) intervention compared with routine lifestyle education (control) on glycemic control and cardiometabolic health among adults with overweight/obesity and type 2 diabetes. RESEARCH DESIGN AND METHODS: This two-center, open-label, three-arm, parallel-group, randomized controlled trial recruited 326 participants with overweight/obesity and type 2 diabetes and randomized them into 12 weeks of diet intervention (n = 109), exercise intervention (n = 108), or lifestyle education (control) (n = 109). The primary outcome was the change of glycemic control measured as glycated hemoglobin (HbA1c) between the diet or exercise intervention groups and the control group after the 12-week intervention. RESULTS: The diet intervention significantly reduced HbA1c level (%) after the 12-week intervention (−0.72, 95% CI −0.95 to −0.48) compared with the control group (−0.37, 95% CI −0.60 to −0.15) (diet vs. control −0.34, 95% CI −0.58 to −0.11, P = 0.007). The reduction in HbA1c level in the exercise intervention group (−0.46, 95% CI −0.70 to −0.23) did not significantly differ from the control group (exercise vs. control −0.09, 95% CI −0.32 to 0.15, P = 0.47). The exercise intervention group was superior in maintaining lean body mass. Both diet and exercise interventions induced improvements in adiposity and hepatic steatosis. CONCLUSIONS: These findings suggest that the medically supervised 5:2 energy-restricted diet could provide an alternative strategy for improving glycemic control and that the exercise regimen could improve body composition, although it inadequately improved glycemic control.

Regular physical activity is a key, patient-centred therapy for people with diabetes to manage their glycaemia. The International Working Group on the Diabetic Foot (IWGDF) recommends optimisation of glycaemic control for people with/at risk of diabetes-related foot ulcer (DFU), however people with DFU are commonly instructed by clinicians to avoid physical activity so as not to worsen the ulcer. The effects of exercise on glycaemia, fitness, and wound healing in people with active DFU are not clear. To examine the effects of regular exercise (training) on glycaemia, cardiorespiratory fitness, and muscular strength, metabolic health, and ulcer healing in adults with diabetes and an active foot ulcer. Online databases and reference lists of included studies were searched from earliest records to December 2023. Studies involving adult populations with DFU and incorporating interventions of exercise training were included. Data were extracted independently by two reviewers. Of the 5,592 studies screened eight studies were included with a total of 213 participants. Exercise interventions involved foot range of movement exercises and/or aerobic and/or resistance type exercise. No studies reported on cardiorespiratory fitness or anthropometry and limited data were available for glycaemic and muscular strength outcomes. Interpretation of data on safety, wound healing, and adherence to exercise were limited due to inconsistent reporting. Despite some data that exercise may have a positive impact on wound healing, evidence regarding its benefits and safety is significantly lacking, despite metabolic (particularly glycaemic) and fitness outcomes being core to the rationale for exercise therapy in diabetes. Given the importance of exercise in current management guidelines for diabetes, and the plausibility of positive health effects of exercise training for people with DFU, there is a need for research to move from foot focused to person-centred outcomes to better inform the implementation of exercise therapy for people with DFU.

Objectives: This study aimed to evaluate the effects of a novel, low-volume combined high-intensity interval training (HIIT) and progressive resistance training (PRT) in overweight/obese adults.Methods: This randomised control trial compared the effect of regular supervised HIIT combined with PRT (Exercise) with an unsupervised stretching intervention (Control), in previously inactive adults with either normal glucose (NG), pre-diabetes or type 2 diabetes (T2DM) with body mass index of >25 kg/m². Participants were randomly allocated (1:1) to receive low-volume exercise or control by an online randomisation tool. The primary outcome was the difference in change of hepatic steatosis between Exercise and Control. A prespecified sensitivity analysis was undertaken for weight stable participants (<5% change in bodyweight from baseline). Secondary outcomes were change in hepatic steatosis within the glucose groups, glycaemic control, cardiorespiratory fitness, muscle strength and body composition.Results: Between June 2018 and May 2021, 162 participants were randomly assigned (NG: 76, pre-diabetes: 60, T2DM: 26) and 144 were included in the final analysis. Mean absolute change in hepatic steatosis was −1.4% (4.9) in Exercise (n=73) and −0.1% (7.2) in Control (n=71)(p=0.25). By preplanned sensitivity analysis, the mean change in hepatic steatosis with Exercise (n=70) was −1.5% (5) compared with 0.7% (4.6) with Control (n=61) (p=0.017). Subgroup analysis within the glucose groups showed that exercise reduced hepatic steatosis in those with pre-diabetes but not NG or T2DM (pre-diabetes: −1.2% (4.4) in Exercise and 1.75% (5.7) in Control, p=0.019).Conclusion: These findings show that low-volume HIIT with PRT yields improvements in muscle strength and cardiorespiratory fitness and may have a small effect on hepatic steatosis.Trial registration number: The trial was prospectively registered with the ANZCTR (ACTRN12617000552381).

Background: Chronic wounds, such as diabetes-related foot ulcers, arise from delayed wound healing and create significant health and economic burdens. Macrophages regulate healing by shifting between pro- and anti-inflammatory phenotypes, known as macrophage polarization. Sex and diabetes can impair wound healing, but their influence on macrophage phenotype in skin tissue during wound healing remains unclear, which was investigated in this study using a novel two-sex diabetic mouse model. Methods: Diabetes was induced in male and female C57BL/6J mice using low-dose streptozotocin injections and high-fat diet feeding, with chow-fed mice as controls. After 18 weeks, each mouse received four circular full-thickness dorsal skin wounds. The macrophage phenotypes in wounded skin tissues at Day 0 and Day 10 post-wounding were analyzed using mass cytometry with manual gating and automated computational clustering. Results: Male diabetic mice exhibited more severe hyperglycemia and insulin resistance compared to females. Although diabetic mice did not display delayed wound healing, male mice had a greater proportion of total macrophages than females, especially a higher proportion of pro-inflammatory matrix metalloproteinase-9 (MMP-9)+ macrophages and a lower proportion of anti-inflammatory adiponectin receptor 1 (AdipoR1)+ macrophages in male diabetic mice compared to females, indicating an imbalanced polarization towards a pro-inflammatory phenotype that could result in poorer wound healing. Interestingly, computational clustering identified a new pro-inflammatory, pro-healing phenotype (Ly6C+AdipoR1+CD163–CD206–) more abundant in females than males, suggesting this phenotype may play a role in the transition from the inflammatory to the proliferative stage of wound healing. Conclusions: This study demonstrated a significant sex-based difference in macrophage populations, with male diabetic mice showing a pro-inflammatory bias that may impair wound healing, while a unique pro-inflammatory, pro-healing macrophage population more abundant in females could facilitate recovery. Further research is needed to investigate the role of these newly identified phenotypes in regulating impaired wound healing.

In prediabetes (PD), circulating inflammatory biomarkers are associated with increased CVD¹ risk. Exercise (Ex) has a positive effect on cardiovascular fitness and metabolic outcomes in PD but Ex effects on inflammation markers in PD are not fully known and were investigated in this study. Adults with PD (n=34) and normal fasting glucose (NG) (n=34) were randomised into one of four groups: NG control (NGC, n=16), NG Ex (NGE, n=18), PD control (PC, n=16) and PD Ex (PE, n=18). NGE/PE completed 12 weeks of supervised HIIT and progressive resistance training (PRT) 2 times/week, and NGC/PC unsupervised stretching 3 times/week. Baseline, age and weight were similar in PD and NG. Compared with NG, FPG and HbA1c were higher and VO₂peak was significantly lower in PD (29±7 vs. 33±8 mL/kg/min, p=0.03). Comparing NG and PD at baseline, serum IL-1β was higher in NG (11.4±9.0 vs. 7.9±2.8 pg/mL, p=0.04), IL-12p70 and IL-22 were higher in PD (respectively, 5.7±3.6 vs. 4.4±2.2 pg/mL; 164.6±90.3 vs. 122.2±83.2 pg/mL, both p<0.05) and IL-1α, IL-6, IL-8, IL-15, M-CSF and TNFα were similar. At follow-up, HbA1c was reduced by -0.07±0.11% in NGE and -0.09±0.17% in PC (both p80% adherence revealed that IL-1α, IL-1β, IL-8 and IL-15 were reduced in NGE, however no change was seen in PE despite a reduction in HbA1c of -0.14±0.17% (p=0.02). PD is associated with reduced cardiorespiratory fitness and increased IL-12p70 and IL-22. Ex reduced IL-12p70 and M-CSF in those with NG but not PD, even after stratifying by adherence and despite improvements in clinical markers. This study indicates low volume HIIT with PRT may not be adequate to reduce serum inflammatory biomarkers in prediabetes. Disclosure C. J. Baker: None. D. Min: None. J. Gerofi: None. X. Wang: None. S. L. Hocking: Advisory Panel; Self; Eli Lilly and Company, Inova, Novo Nordisk, Pfizer Inc. S. Colagiuri: None. N. A. Johnson: None. S. M. Twigg: Advisory Panel; Self; Abbott Diabetes, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Sanofi-Aventis, Consultant; Self; Aktivo Labs, Sanofi-Aventis, Research Support; Self; Abbott Diabetes, Speaker’s Bureau; Self; Abbott Diabetes, AstraZeneca. Funding National Health and Medical Research Council (APP1113612)