Institutional thickness and Liverpool exploration of a methodology

archiv

Diametrics:A User-Friendly Web Tool for Custom Analysis of Continuous Glucose Monitoring Data

Background: Continuous Glucose Monitoring (CGM) systems have revolutionized diabetes management by providing real-time blood glucose tracking. However, there is a need for openly accessible tools that can analyze CGM data in relation to specific events like meals or exercise, which often require extensive technical skills to interpret, thus restricting its broader use among researchers and clinicians. Developing user-friendly web applications to facilitate this analysis could significantly broaden accessibility and utility.Method: Diametrics was built with a focus on ease-of-use and versatility. The application’s efficacy was validated against iglu, an established R tool with a no-code web app for CGM analysis, using data from 418 participants from three studies. The unique period-specific analysis feature was demonstrated through an illustrative case study.Results: Diametrics proved effective at replicated established CGM metrics, demonstrating high concordance with iglu. The platform supports a wide range of CGM devices, accommodates data in various formats, and offers extensive customization in the analysis settings. The case study highlighted Diametrics’ ability to integrate exercise-related data with CGM readings, enabling detailed analyses of how different exercise types, intensities, and times of day impact glucose levels.Conclusions: Diametrics is a freely available, reproducible, user-friendly, and accurate web-based tool for CGM data analysis with a unique capability to analyze data over specific time periods. With its intuitive design and open-source accessibility, Diametrics provides a valuable resource in diabetes research and management, empowering users of various technical levels to perform complex analyses with ease

Polygenic mechanisms underpinning the response to exercise-induced muscle damage in humans:In vivo and in vitro evidence

We investigated whether 20 candidate single nucleotide polymorphisms (SNPs) were associated with in vivo exercise-induced muscle damage (EIMD), and with an in vitro skeletal muscle stem cell wound healing assay. Sixty-five young, untrained Caucasian adults performed 120 maximal eccentric knee-extensions on an isokinetic dynamometer to induce EIMD. Maximal voluntary isometric/isokinetic knee-extensor torque, knee joint range of motion (ROM), muscle soreness, serum creatine kinase activity and interleukin-6 concentration were assessed before, directly after and 48 h after EIMD. Muscle stem cells were cultured from vastus lateralis biopsies from a separate cohort (n = 12), and markers of repair were measured in vitro. Participants were genotyped for all 20 SNPs using real-time PCR. Seven SNPs were associated with the response to EIMD, and these were used to calculate a total genotype score, which enabled participants to be segregated into three polygenic groups: ‘preferential’ (more ‘protective’ alleles), ‘moderate’, and ‘non-preferential’. The non-preferential group was consistently weaker than the preferential group (1.93 ± 0.81 vs. 2.73 ± 0.59 N ∙ m/kg; P = 9.51 × 10−4) and demonstrated more muscle soreness (p = 0.011) and a larger decrease in knee joint ROM (p = 0.006) following EIMD. Two TTN-AS1 SNPs in linkage disequilibrium were associated with in vivo EIMD (rs3731749, p ≤ 0.005) and accelerated muscle stem cell migration into the artificial wound in vitro (rs1001238, p ≤ 0.006). Thus, we have identified a polygenic profile, linked with both muscle weakness and poorer recovery following EIMD. Moreover, we provide evidence for a novel TTN gene-cell-skeletal muscle mechanism that may help explain some of the interindividual variability in the response to EIMD.</p

The effect of different training modes on skeletal muscle microvascular density and endothelial enzymes controlling NO availability

It is becoming increasingly apparent that a high vasodilator response of the skeletal muscle microvasculature to insulin and exercise is of critical importance for adequate muscle perfusion and long-term microvascular and muscle metabolic health. Previous research has shown that a sedentary lifestyle, obesity, and ageing lead to impairments in the vasodilator response, while a physically active lifestyle keeps both microvascular density and vasodilator response high. To investigate the molecular mechanisms behind these impairments and the benefits of exercise training interventions, our laboratory has recently developed quantitative immunofluorescence microscopy methods to measure protein content of eNOS and NAD(P)Hoxidase specifically in the endothelial layer of capillaries and arterioles of human skeletal muscle. As eNOS produces NO and NAD(P)Hoxidase superoxide anions (quenching NO) we propose that the eNOS/NAD(P)Hoxidase protein ratio is a marker of vasodilator capacity. The novel methods show that endurance training (ET) and high intensity interval training (HIT) generally regarded as a time efficient alternative to ET, increase eNOS protein content and the eNOS/NADP(H) oxidase protein ratio in previously sedentary lean and obese young men. Resistance exercise training had smaller but qualitatively similar effects. Western blot data of other laboratories suggest that endurance exercise training leads to similar changes in sedentary elderly men. Future research will be required to investigate the relative importance of other sources and tissues in the balance between NO and O2- production seen by the vascular smooth muscle layer of terminal arterioles

Increased muscle blood supply and transendothelial nutrient and insulin transport induced by food intake and exercise: effect of obesity and ageing.

This review concludes that a sedentary lifestyle, obesity and ageing impair the vasodilator response of the muscle microvasculature to insulin, exercise and VEGF-A and reduce microvascular density. Both impairments contribute to the development of insulin resistance, obesity and chronic age-related diseases. A physically active lifestyle keeps both the vasodilator response and microvascular density high. Intravital microscopy has shown that microvascular units (MVUs) are the smallest functional elements to adjust blood flow in response to physiological signals and metabolic demands on muscle fibres. The luminal diameter of a common terminal arteriole (TA) controls blood flow through up to 20 capillaries belonging to a single MVU. Increases in plasma insulin and exercise/muscle contraction lead to recruitment of additional MVUs. Insulin also increases arteriolar vasomotion. Both mechanisms increase the endothelial surface area and therefore transendothelial transport of glucose, fatty acids (FAs) and insulin by specific transporters, present in high concentrations in the capillary endothelium. Future studies should quantify transporter concentration differences between healthy and at risk populations as they may limit nutrient supply and oxidation in muscle and impair glucose and lipid homeostasis. An important recent discovery is that VEGF-B produced by skeletal muscle controls the expression of FA transporter proteins in the capillary endothelium and thus links endothelial FA uptake to the oxidative capacity of skeletal muscle, potentially preventing lipotoxic FA accumulation, the dominant cause of insulin resistance in muscle fibres

Passive Heat Therapy in Sedentary Humans Increases Skeletal Muscle Capillarisation and eNOS Content but Not Mitochondrial Density or GLUT4 Content.

Passive heat therapy (PHT) has been proposed as an alternative intervention to traditional moderate intensity continous training (MICT) in individuals who are unable or unwilling to exercise. This study aimed to make the first comparison of the effect of PHT and MICT on 1) skeletal muscle capillarisation and endothelial specific eNOS content and 2) mitochondrial density, GLUT4 and IMTG content. Twenty young sedentary males (21±1years, BMI 25±1kg.m-2) were allocated to either 6 weeks of PHT (n=10; 40-50min at 40°C in a heat chamber, 3x/wk) or MICT (n=10; time matched cycling at ~65% VO2peak). Muscle biopsies were taken from the vastus lateralis muscle pre- and post-training. Immunofluorescence microscopy was used to assess changes in skeletal muscle mitochondrial density, GLUT4 and IMTG content, capillarisation and endothelial specific eNOS content. VO2peak and whole body insulin sensitivity were also assessed. PHT and MICT both increased capillary density and capillary-fibre perimeter exchange index (P<0.05), and endothelial specific eNOS content (P<0.05). However, unlike MICT (P<0.05) PHT did not increase mitochondrial density (P=0.443), GLUT4 (P=0.217) or IMTG content (P=0.957). Both intervention improved aerobic capacity and whole body insulin sensitivity (P<0.05). 6 weeks PHT in young sedentary males increases skeletal muscle capillarisation and eNOS content to a similar extent as MICT, however, unlike MICT PHT does not affect skeletal muscle mitochondrial density, GLUT4 or IMTG content