Chronic low-grade inflammation contributes to the pathology and complications of type 2 diabetes (T2D). Interleukin-10 (IL10), an anti-inflammatory cytokine, is suggested to play a protective role in T2D. However, the impact of T2D on IL10 function has not been previously assessed. We examined the ability of IL10 to inhibit inflammation in human T2D immune cells and explored underlying mechanisms using macrophage models. IL10 was less effective at inhibiting tumour necrosis factor (TNF)-α secretion in T2D whole blood cultures, which was not explained by altered IL10 receptor surface expression. These findings were observed in macrophages exposed to high glucose, which demonstrated similar IL10 resistance or hyporesponsiveness. These findings were also not explained by changes in IL10 receptor protein or other downstream signaling proteins. High glucose was also shown to impair the ability of IL10 to activate STAT3, a downstream signaling protein of IL10. Treatment with the SHIP1 agonist, AQX-MN100, reversed IL10 hyporesponsiveness in macrophages cultured in high glucose and showed equal effectiveness at different glucose conditions. This data supports the idea that IL10 hyporesponsiveness may contribute to chronic inflammation in T2D. These novel findings suggest that strategies aimed to overcome IL10 hyporesponsiveness may hold therapeutic potential for reducing inflammation in T2D.

BackgroundExercise promotes numerous phenotypic adaptations in skeletal muscle that contribute to improved function and metabolic capacity. An emerging body of evidence suggests that skeletal muscle also releases a myriad of factors during exercise, termed “myokines”. The purpose of this study was to examine the effects of high-intensity interval training (HIIT) on the acute regulation of the mRNA expression of several myokines, including the prototypical myokine interleukin-6 (IL-6), and recently identified myokines fibronectin type III domain-containing protein 5 (FNDC5) (irisin) and meteorin-like protein (METRNL).MethodsBoth before and after a 20-day period of twice-daily high-volume HIIT, 9 healthy males (20.5 ± 1.5 years performed a standardized bout of high-intensity interval exercise (HIIE; 5 × 4 min at ~80% pretraining peak power output) with skeletal muscle biopsy samples (vastus lateralis) obtained at rest, immediately following exercise, and at 3 h recovery.ResultsBefore training, a single bout of HIIE increased IL-6 (p < 0.05) and METRNL (p < 0.05) mRNA expression measured at 3 h recovery when compared to rest. Following 20 days of HIIT, IL-6 and FNDC5 mRNA were increased at 3 h recovery from the standardized HIIE bout when compared to rest (both p < 0.05). Resting METRNL and FNDC5 mRNA expression were higher following training (p < 0.05), and there was an overall increase in FNDC5 mRNA post-training (main effect of training, p < 0.05).ConclusionIn human skeletal muscle (1) an acute bout of HIIE can induce upregulation of skeletal muscle IL-6 mRNA both before and after a period of intensified HIIT; (2) Resting and overall FNDC5 mRNA expression is increased by 20 days of HIIT; and (3) METRNL mRNA expression is responsive to both acute HIIE and short-term intense HIIT. Future studies are needed to confirm these findings at the protein and secretion level in humans.

Exercise, in the absence of weight/fat loss and without changes in circulating chemokines, has direct effects on leukocytes in obese adults with HIIT and MICT resulting in different responses. MICT may reduce monocyte migration potential through downregulation of CCR2 and CXCR2, whereas HIIT may increase potential for CCR5-mediated monocyte, neutrophil, and T-cell infiltration. The impact of different exercise protocols on leukocyte trafficking to tissues in obesity warrants further research.

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Background: Free-living adherence to high-intensity interval training (HIIT) has not been adequately tested. This randomized trial examined changes in cardiorespiratory fitness (CRF) and accelerometer-measured purposeful physical activity over 12 months of free-living HIIT versus moderate-intensity continuous training (MICT). Methods: Ninety-nine previously low-active participants with overweight/obesity were randomly assigned to HIIT (n = 47) or MICT (n = 52). Both interventions were combined with evidence-based behaviour change counselling consisting of 7 sessions over 2 weeks. Individuals in HIIT were prescribed 10 X 1-min interval-based exercise 3 times per week (totalling 75 min) whereas individuals in MICT were prescribed 150 min of steady-state exercise per week (50 mins 3 times per week). Using a maximal cycling test to exhaustion with expired gas analyses, CRF was assessed at baseline and after 6 and 12 months of free-living exercise. Moderate-to-vigorous physical activity of 10+ minutes (MVPA10+) was assessed by 7-day accelerometry at baseline, 3, 6, 9, and 12 months. Intention to treat analyses were conducted using linear mixed models. Results: CRF was improved over the 12 months relative to baseline in both HIIT (+ 0.15 l/min, 95% CI 0.08 to 0.23) and MICT (+ 0.11 l/min, 95% CI 0.05 to 0.18). Both groups improved 12-month MVPA10+ above baseline (HIIT: + 36 min/week, 95% CI 17 to 54; MICT: + 69 min/week, 95% CI 49 to 89) with the increase being greater (by 33 min, 95% CI 6 to 60) in MICT (between group difference, P = 0.018). Conclusion: Despite being prescribed twice as many minutes of exercise and accumulating significantly more purposeful exercise, CRF improvements were similar across 12 months of free-living HIIT and MICT in previously low-active individuals with overweight/obesity.

This pilot intervention was successful in increasing, and maintaining, free-living MVPA over a 24-wk period in individuals at high risk of T2D. Speculation that HIIT is inappropriate or unattainable for overweight individuals at high risk of T2D may be unfounded.

Exercise is recognized as a frontline therapy for the prevention and treatment of type 2 diabetes (T2D) but the optimal type of exercise is not yet determined. We compared the effects of high-intensity interval training (HIIT) with moderate-intensity continuous training (MICT) for improvement of continuous glucose monitoring (CGM)-derived markers of glycaemic variability, and biomarkers of endothelial cell damage (CD31+ and CD62+ endothelial microparticles (EMPs)) within a population at elevated risk of developing T2D. Fifteen inactive overweight or obese women were randomized to 2 weeks (10-sessions) of progressive HIIT (n = 8, 4-10X 1-min @ ∼90% peak heart rate, 1-min rest periods) or MICT (n = 7, 20-50 min of continuous activity at ∼65% peak heart rate). Prior and three days post-training, fasting blood samples were collected. Both HIIT and MICT improved glycaemic variability as measured by CGM standard deviation (HIIT: 0.82 ± 0.39 vs. 0.72 ± 0.33 mmol/L; MICT: 0.82 ± 0.19 vs. 0.62 ± 0.16 mmol/L, pre vs. post) and mean amplitude of glycaemic excursions (MAGE; HIIT: 1.98 ± 0.81 vs. 1.41 ± 0.90; MICT; 1.98 ± 0.43 vs. 1.65 ± 0.48, pre vs. post) with no difference between groups. CD62+ EMPs were lower following HIIT (187.7 ± 65 vs. 174.9 ± 55, pre vs. post) and MICT (170 ± 60 vs. 160.3 ± 59, pre vs. post) with no difference between groups. There was no change in 24-h mean glucose or CD31+ EMPs. Two weeks of both HIIT or MICT similarly decreased glycaemic variability and CD62+ EMPs in overweight/ obese women at elevated risk of T2D.

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