Altered muscle mitochondrial, inflammatory and trophic markers, and reduced exercise training adaptations in type 1 diabetes.

Growing evidence of impaired skeletal muscle health in people with type 1 diabetes points toward the presence of a mild myopathy in this population. However, this myopathic condition is not yet well characterised and often overlooked, even though it might affect the whole-body glucose homeostasis and the development of comorbidities. This study aimed to compare skeletal muscle adaptations and changes in glycaemic control after 12 weeks of combined resistance and aerobic (COMB) training between people with type 1 diabetes and healthy controls, and to determine whether the impaired muscle health in type 1 diabetes can affect the exercise-induced adaptations. The COMB training intervention increased aerobic capacity and muscle strength in both healthy and type 1 diabetes sedentary participants, although these improvements were higher in the control group. Better glucose control, reduced glycaemic fluctuations and fewer hypoglycaemic events were recorded at post- compared to pre-intervention in type 1 diabetes. Analysis of muscle biopsies showed an alteration of muscle markers of mitochondrial functions, inflammation, ageing and growth/atrophy compared to the control group. These muscular molecular differences were only partially modified by the COMB training and might explain the reduced exercise adaptation observed in type 1 diabetes. In brief, type 1 diabetes impairs many aspects of skeletal muscle health and might affect the exercise-induced adaptations. Defining the magnitude of diabetic myopathy and the effect of exercise, including longer duration of the intervention, will drive the development of strategies to maximise muscle health in the type 1 diabetes population. KEY POINTS: Type 1 diabetes negatively affects skeletal muscle health; however, the effect of structured exercise training on markers of mitochondrial function, inflammation and regeneration is not known. Even though participants with type 1 diabetes and healthy control were comparable for cardiorespiratory fitness ( V̇O2max${\dot{V}_{{{\rm{O}}_{\rm{2}}}{\rm{max}}}}$ ) and muscle strength at baseline, molecular markers related to muscle health were decreased in type 1 diabetes. After training, both groups increased V̇O2max${\dot{V}_{{{\rm{O}}_{\rm{2}}}{\rm{max}}}}$ and muscle strength; however, a larger improvement was achieved by the control group. The training intervention decreased glucose fluctuations and occurrence of hypoglycaemic events in type 1 diabetes, while signs of mild myopathy found in the muscle of participants with type 1 diabetes only partially improved after training Improving muscle health by specific exercise protocols is of considerable clinical interest in therapeutic strategies for improving type 1 diabetes management and preventing or delaying long-term complications.

Delayed effect of different exercise modalities on glycaemic control in type 1 diabetes mellitus: A systematic review and meta-analysis.

BACKGROUND AND AIMS: Despite the crucial role of exercise in the prevention of comorbidities and complications in type 1 diabetes mellitus (T1DM), people living with the disease are often insufficiently physically active, mainly due to the fear of hypoglycaemia. Research using continuous glucose monitoring (CGM) devices has shown that exercise affects glycaemic control in T1DM for over 24 h. The aim of this systematic review and meta-analysis is, therefore, to investigate the delayed effects of different exercise modalities on glycaemic control in adults with T1DM. METHODS AND RESULTS: The literature search of experimental studies was conducted on PubMed, SPORTDiscus and EMBASE from January 2000 to September 2019. Twelve studies using CGM devices were included. Compared to endurance, intermittent exercise increased the time spent in hypoglycaemia (0.62, 0.07 to 1.18; standardised effect size, 95% CI) and reduced the mean interstitial glucose concentration (-0.88, -1.45 to -0.33). No differences emerged in the time spent in hyperglycaemia (-0.07, -0.58 to 0.45) or in the proportion of exercisers experiencing hypoglycaemic events (0.82, 0.45 to 1.49; proportion ratio, 95% CI) between conditions. The systematic review also found a reduced risk of hypoglycaemia if exercise is performed in the morning rather than in the afternoon, and with a 50% rapid-acting insulin reduction. It was not possible to determine the benefits of resistance exercise. CONCLUSIONS: For the first time, we systematically investigated the delayed effect of exercise in adults with T1DM, highlighted undetected effects, shortcomings in the existing literature, and provided suggestions to design future comparable studies.

Effects of acute aerobic, resistance and combined exercises on 24-h glucose variability and skeletal muscle signalling responses in type 1 diabetics.

PURPOSE: To compare the effect of high-intensity aerobic (AER), resistance (RES), and combined (COMB: RES + AER) exercise, on interstitial glucose (IG) variability and skeletal muscle signalling pathways in type 1 diabetes (T1D). METHODS: T1D participants (6 M/6F) wore a flash glucose monitoring system in four randomized sessions: one control (CONT), and one AER, RES and COMB (40 min each). Mean amplitude of glycemic excursions (MAGE), standard deviation (SD) and coefficient variation (CV) of IG were used to compare the 24 h post-exercise IG variability. Blood and muscle samples were collected to compare exercise-induced systemic and muscle signalling responses related to metabolic, growth and inflammatory adaptations. RESULTS: Both RES and COMB decreased the 24 h MAGE compared to CONT; additionally, COMB decreased the 24 h SD and CV. In the 6-12 h post-exercise, all exercise modalities reduced the IG CV while SD decreased only after COMB. Both AER and COMB stimulated the PGC-1α mRNA expression and promoted the splicing of IGF-1Ea variant, while Akt and p38MAPK phosphorylation increased only after RES and COMB. Additionally, COMB enhanced eEF2 activation and RES increased myogenin and MRF4 mRNA expression. Blood lactate and glycerol levels and muscle IL-6, TNF-α, and MCP-1 mRNAs increased after all exercise sessions, while serum CK and LDH level did not change. CONCLUSION: COMB is more effective in reducing IG fluctuations compared to single-mode AER or RES exercise. Moreover, COMB simultaneously activates muscle signalling pathways involved in substrate metabolism and anabolic adaptations, which can help to improve glycaemic control and maintain muscle health in T1D.

Comparison of time-matched aerobic, resistance, or concurrent exercise training in older adults.

A supervised 12-week intervention of time-matched aerobic vs resistance versus concurrent exercise training was employed to investigate mode- and time course-specific effects of exercise training in older adults. Community-dwelling men and women (n = 84; M/F, 45/39; 69.3 ± 3.5 years; 26.4 ± 3.8 kg m-2 ) were randomly assigned (n = 21 each) to either non-exercise control (CON), aerobic exercise only (AER), resistance exercise only (RES), or concurrent aerobic and resistance exercise (CEX). Training groups trained three times per week, each performing 72 minutes of active exercise time per week. Body composition, physical and cognitive function, and markers of metabolic health were assessed before (PRE), and after 6 (MID) and 12 (POST) weeks of exercise training. Hand-grip strength, 1RM chest press, and arm LBM were improved by both RES and CEX, but not AER. Aerobic fitness increased in AER and RES, but not CEX. Cognitive function improved in all groups, but occurred earlier (ie, at MID) in AER. CEX improved gait speed and lower limb strength and reduced trunk fat compared to either AER or RES. Leg LBM was unchanged in any group. Temporal patterns were observed as early as 6 weeks of training (gait speed, upper and lower limb strength, aerobic fitness), whereas others were unchanged until 12 weeks (hand-grip strength, timed up-and-go, sit-to-stand). Compared to either aerobic or resistance exercise training alone, concurrent exercise training is as efficacious for improving a range of health-related parameters and is more efficacious for increasing gait speed and lower limb strength, and decreasing trunk fat in older adults.