Glucose management for exercise using continuous glucose monitoring (CGM) and intermittently scanned CGM (isCGM) systems in type 1 diabetes: position statement of the European Association for the Study of Diabetes (EASD) and of the International Society for Pediatric and Adolescent Diabetes (ISPAD) endorsed by JDRF and supported by the American Diabetes Association (ADA)

Physical exercise is an important component in the management of type 1 diabetes across the lifespan. Yet, acute exercise increases the risk of dysglycaemia, and the direction of glycaemic excursions depends, to some extent, on the intensity and duration of the type of exercise. Understandably, fear of hypoglycaemia is one of the strongest barriers to incorporating exercise into daily life. Risk of hypoglycaemia during and after exercise can be lowered when insulin‐dose adjustments are made and/or additional carbohydrates are consumed. Glycaemic management during exercise has been made easier with continuous glucose monitoring (CGM) and intermittently scanned continuous glucose monitoring (isCGM) systems; however, because of the complexity of CGM and isCGM systems, both individuals with type 1 diabetes and their healthcare professionals may struggle with the interpretation of given information to maximise the technological potential for effective use around exercise (ie, before, during and after). This position statement highlights the recent advancements in CGM and isCGM technology, with a focus on the evidence base for their efficacy to sense glucose around exercise and adaptations in the use of these emerging tools, and updates the guidance for exercise in adults, children and adolescents with type 1 diabetes

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Development platform for artificial pancreas algorithms.

Background and aimsAssessing algorithms of artificial pancreas systems is critical in developing automated and fault-tolerant solutions that work outside clinical settings. The development and evaluation of algorithms can be facilitated with a platform that conducts virtual clinical trials. We present in this paper a clinically validated cloud-based distributed platform that supports the development and comprehensive testing of single and dual-hormone algorithms for type 1 diabetes mellitus (T1DM).MethodsThe platform is built on principles of object-oriented design and runs user algorithms in real-time virtual clinical trials utilizing a multi-threaded environment enabled by concurrent execution over a cloud infrastructure. The platform architecture isolates user algorithms located on personal machines from proprietary patient data running on the cloud. Users import a plugin into their algorithms (Matlab, Python, or Java) to connect to the platform. Once connected, users interact with a graphical interface to design experimental protocols for their trials. Protocols include trial duration in days, mealtimes and amounts, variability in mealtimes and amounts, carbohydrate counting errors, snacks, and onboard insulin levels.ResultsThe platform facilitates development by solving the ODE model in the cloud on large CPU-optimized machines, providing a 62% improvement in memory, speed and CPU utilization. Users can easily debug & modify code, test multiple strategies, and generate detailed clinical performance reports. We validated and integrated into the platform a glucoregulatory system of ordinary differential equations (ODEs) parameterized with clinical data to mimic the inter and intra-day variability of glucose responses of 15 T1DM patients.ConclusionThe platform utilizes the validated patient model to conduct virtual clinical trials for the rapid development and testing of closed-loop algorithms for T1DM

Serum Metabolomics of Activity Energy Expenditure and its Relation to Metabolic Syndrome and Obesity

Modifiable lifestyle factors, including exercise and activity energy expenditure (AEE), may attenuate the unfavorable health effects of obesity, such as risk factors of metabolic syndrome (MetS). However, the underlying mechanisms are not clear. In this study we sought to investigate whether the metabolite profiles of MetS and adiposity assessed by body mass index (BMI) and central obesity are inversely correlated with AEE and physical activity. We studied 35 men and 47 women, aged 30–60 years, using doubly labeled water to derive AEE and the Sedentary Time and Activity Reporting Questionnaire (STAR-Q) to determine the time spent in moderate and vigorous physical activity. Proton nuclear magnetic resonance spectroscopy was used for serum metabolomics analysis. Serine and glycine were found in lower concentrations in participants with more MetS risk factors and greater adiposity. However, serine and glycine concentrations were higher with increasing activity measures. Metabolic pathway analysis and recent literature suggests that the lower serine and glycine concentrations in the overweight/obese state could be a consequence of serine entering de novo sphingolipid synthesis. Taken together, higher levels of AEE and physical activity may play a crucial part in improving metabolic health in men and women with and without MetS risk factors

Native low-density lipoproteins are priming signals of the NLRP3 inflammasome/interleukin-1β pathway in human adipose tissue and macrophages

Abstract Elevated plasma numbers of atherogenic apoB-lipoproteins (apoB), mostly as low-density lipoproteins (LDL), predict diabetes risk by unclear mechanisms. Upregulation of the NLRP3 inflammasome/interleukin-1 beta (IL-1β) system in white adipose tissue (WAT) is implicated in type 2 diabetes (T2D); however, metabolic signals that stimulate it remain unexplored. We hypothesized that (1) subjects with high-apoB have higher WAT IL-1β-secretion than subjects with low-apoB, (2) WAT IL-1β-secretion is associated with T2D risk factors, and (3) LDL prime and/or activate the WAT NLRP3 inflammasome. Forty non-diabetic subjects were assessed for T2D risk factors related to systemic and WAT glucose and fat metabolism. Regulation of the NLRP3 inflammasome was explored using LDL without/with the inflammasome’s priming and activation controls (LPS and ATP). LDL induced IL1B-expression and IL-1β-secretion in the presence of ATP in WAT and macrophages. Subjects with high-apoB had higher WAT IL-1β-secretion independently of covariates. The direction of association of LDL-induced WAT IL-1β-secretion to T2D risk factors was consistently pathological in high-apoB subjects only. Adjustment for IL-1β-secretion eliminated the association of plasma apoB with T2D risk factors. In conclusion, subjects with high-apoB have higher WAT IL-1β-secretion that may explain their risk for T2D and may be related to LDL-induced priming of the NLRP3 inflammasome. ClinicalTrials.gov (NCT04496154): Omega-3 to Reduce Diabetes Risk in Subjects With High Number of Particles That Carry "Bad Cholesterol" in the Blood—Full Text View—ClinicalTrials.gov

CFTR silencing in pancreatic β-cells reveals a functional impact on glucose-stimulated insulin secretion and oxidative stress response

Cystic fibrosis (CF)-related diabetes (CFRD) has become a critical complication that seriously affects the clinical outcomes of CF patients. Although CFRD has emerged as the most common nonpulmonary complication of CF, little is known about its etiopathogenesis. Additionally, whether oxidative stress (OxS), a common feature of CF and diabetes, influences CFRD pathophysiology requires clarification. Aim: The objective of this study is to shed light on the role of CFTR in combination with OxS in insulin secretion from pancreatic β-cells. Methods: CFTR silencing was accomplished in MIN6 cells by stable expression of small hairpin RNAs and glucose-induced insulin secretion was evaluated in the presence/absence of the pro-oxidant system iron/ascorbate (Fe/Asc) along with or without the antioxidant Trolox. Results: insulin output from CFTR-silenced MIN6 cells was significantly reduced at basal and at different glucose concentrations compared with control Mock cells. Furthermore, CFTR silencing rendered MIN6 cells more sensitive to OxS as evidenced by both increased lipid peroxides and weakened antioxidant defense, especially following incubation with Fe/Asc. The decreased insulin secretion in CFTR-silenced MIN6 cells was associated with high levels of NF-κB (the major participant in inflammatory responses), raised apoptosis and diminished ATP production in response to the Fe/Asc challenge. These defects were alleviated by the addition of Trolox, thereby pointing out the role of OxS in aggravating the effects of CFTR deficiency. Conclusions: Our findings indicate that CFTR deficiency with OxS may contribute to endocrine cell dysfunction and insulin secretion, which at least in part may explain the development of CFRD

Impact d’un entraînement en visioconférence chez l'adolescent en situation d’obésité sur l’aptitude aérobie et la composition corporelle : Résultats préliminaires

International audienceContexte : Les jeunes en situation d’obésité ont un niveau d’activité physique (AP) plus faible que les jeunes normo-pondérés (1). La pratique d’AP en visioconférence pourrait permettre de limiter les barrières à l’AP (transport, temps, motivation) et d’autonomiser les adolescents tout en gardant une pratique collective, encadrée et sécuritaire (2). L’objectif de notre étude est de comparer l’efficacité d’un programme d’activité physique supervisé réalisé en visioconférence versus en présentiel. Méthodologie : Trente jeunes (9-17 ans) en situation d’obésité, divisés en 3 groupes (n=10), ont participé à notre étude : entraînement en visioconférence (Ent_V), entraînement en présentiel (Ent_P) et sans programme d’entraînement (S_Ent). Les adolescents des groupes entraînements ont suivi un programme d’AP composé de 2 séances d’une heure d’AP par semaine pendant 4 mois. Avant (T0) et après la période de quatre mois (T4), les adolescents ont effectué un test sous-maximal d’effort (PWC170) afin d’estimer l’aptitude aérobie. La composition corporelle a été mesurée par une balance impédancemètre. Résultats : Chez le groupe Ent_V, la puissance relative à la masse corporelle développée à 170 Bpm a augmenté à T4 (p=0,007). Aucune différence significative n’a été révélée pour les groupes Ent_P et S_Ent. Concernant l’analyse de la composition corporelle, nous avons noté une stabilisation pour les groupes entraînements. En revanche, la masse corporelle et le pourcentage de masse grasse corporelle ont augmenté significativement entre T0 et T4 pour le groupe S_Ent (respectivement, p = 0,003 et p = 0,006). Conclusion : Un programme d’activité physique de quatre mois réalisés en visioconférence permet de stabiliser le poids corporel et d’améliorer l’aptitude aérobie chez des adolescents en situation d’obésité. Ces résultats préliminaires restent à confirmer avec un nombre plus important de participants

Acyl-CoA synthetase long-chain 5 genotype is associated with body composition changes in response to lifestyle interventions in postmenopausal women with overweight and obesity: a genetic association study on cohorts Montréal-Ottawa New Emerging Team, and Complications Associated with Obesity

Abstract Background Genetic studies on Acyl-CoA Synthetase Long-Chain 5 (ACSL5) demonstrate an association between rs2419621 genotype and rate of weight loss in women with obesity in response to caloric restriction. Our objectives were to (1) confirm results in two different populations of women with overweight and obesity (2) study rs2419621’s influence on body composition parameters of women with overweight and obesity following lifestyle interventions. Methods rs2419621 genotype was determined in women with overweight and obesity who participated in the Montréal-Ottawa New Emerging Team (MONET n = 137) and Complications Associated with Obesity (CAO n = 37) studies. Genotyping was done using TaqMan MGB probe-based assay. Multiple linear regression analyses were used to test for associations. Results When studying women with overweight and obesity, rs2419621 [T] allele carriers had a significantly greater decrease in visceral fat, absolute and percent fat mass and a greater increase in percent lean mass in response to lifestyle intervention in comparison to non-carriers. Studying only individuals with obesity showed similar results with rs2419621 [T] allele carriers also displaying a significantly greater decrease in body mass index following the lifestyle intervention in comparison to non-carriers. Conclusion Women with overweight and obesity carrying the ACSL5 rs2419621 [T] allele are more responsive to lifestyle interventions in comparison to non-carriers. Conducting such genetic association studies can aid in individualized treatments/interventions catered towards an individual’s genotype

La peur de l’hypoglycémie et du déséquilibre du diabète : des freins à l’activité physique chez les enfants et adultes vivant avec un diabète de type 1. Quels liens réels avec les excursions glycémiques dans la vie quotidienne ? RESULTATS PRELIMINAIRES

International audienceLa peur de l’hypoglycémie et du déséquilibre du diabète : des freins à l’activité physique chez les enfants et adultes vivant avec un diabète de type 1. Quels liens réels avec les excursions glycémiques dans la vie quotidienne ? RESULTATS PRELIMINAIRESParent C, Lespagnol E, Berthoin S, Tagougui S, Coquart A, Stuckens C, Gueorguieva I, Balestra C, Tonoli C, Kozon B, Weill J, Fontaine P, Rabasa-Lhoret R, Heyman E. Contexte – Alors que l’activité physique (AP) est recommandée dans la prise en charge du diabète de type 1 (DT1), les enfants et adultes DT1 présentent souvent des freins à la pratique d’une AP comme la crainte des excursions glycémiques extrêmes induites par l’exercice [1,2]. Néanmoins, aucune étude n’a vérifié si les personnes déclarant avoir des freins relatifs à la peur de l’hypoglycémie, de l’hyperglycémie ou à la perte de contrôle du diabète, sont réellement davantage sujettes à ces déséquilibres glycémiques au quotidien. Méthodes – Soixante-cinq enfants/adolescents et 69 adultes DT1 ont complété le questionnaire BAPAD-1 et porté un capteur de glucose en continu sur une semaine mesurant objectivement les excursions glycémiques. Les participants reportaient le nombre d’hypoglycémies sévères, d’hyperglycémies acido-cétosiques de la dernière année et le niveau de reconnaissance des hypoglycémies. Résultats préliminaires (sur 121 participants) – Quel que soit le sous-groupe, la barrière principale est la peur de l’hypoglycémie (3,65±1,9). La perte de contrôle du diabète apparaît également importante chez les enfants/adolescents (2,84±1,9) et leurs parents (2,94±1,7). Néanmoins, dans tous les sous-groupes, les 2 sous-items «risques hypo et hyperglycémique» ne sont pas corrélés au temps passé en hypo ou hyperglycémie. Étonnamment, les adultes déclarant un score élevé de perte de contrôle du diabète sont sujets à une moindre variabilité glycémique (SD) (r=-0,42, P<0,05). Conclusion – Il semble que les adultes les plus préoccupés par la perte de contrôle du diabète à l’exercice, soient ceux qui réussissent à maintenir une moindre variabilité glycémique. De plus, la peur de l’hypoglycémie, qui reste le premier frein à la pratique d’AP, n’est pas associée à une plus grande propension à faire des hypoglycémies dans la vie quotidienne. La suite des analyses permettra d’examiner le lien avec les variations glycémiques propres aux périodes d’activité physique et à la récupération précoce et tardive (e.g. nocturne) qui s’en suit