Impaired muscle oxygenation despite normal pulmonary function in type 2 diabetes without complications.

Long-term hyperglycemia in individuals with type 2 diabetes (T2D) can detrimentally impact pulmonary function and muscle oxygenation. As a result, these factors can impede the body's adaptation to physical exertion. We aimed to evaluate the oxygen pathway during maximal exercise among overweight/obese individuals with type 2 diabetes free from complications, in comparison with a group of matched overweight/obese individuals without diabetes, specifically concentrating on the effects on pulmonary function and muscle oxygenation. Fifteen overweight/obese adults with type 2 diabetes [glycated hemoglobin (HbA1c) = 8.3 ± 1.2%] and 15 matched overweight/obese adults without diabetes underwent pre- and post exercise lung function assessment. A maximal incremental exercise test was conducted, monitoring muscle oxygenation using near-infrared spectroscopy and collecting arterial blood gas samples. Both groups exhibited normal lung volumes at rest and after exercise. Spirometric lung function did not significantly differ pre- and post exercise in either group. During maximal exercise, the type 2 diabetes group showed significantly lower augmentation in total hemoglobin and deoxygenated hemoglobin compared with the control group. Despite comparable usual physical activity levels and comparable heart rates at exhaustion, the type 2 diabetes group had a lower peak oxygen consumption than controls. No significant differences were found in arterial blood gas analyses ([Formula: see text], [Formula: see text], [Formula: see text], and [Formula: see text]) between the groups. Individuals with type 2 diabetes free from complications displayed normal pulmonary function at rest and post exercise. However, impaired skeletal muscle oxygenation during exercise, resulting from reduced limb blood volume and altered muscle deoxygenation, may contribute to the lower V̇o2peak observed in this population.NEW & NOTEWORTHY Individuals with type 2 diabetes free from micro- and macrovascular complications have normal resting pulmonary function, but their V̇o2peak is impaired due to poor skeletal muscle oxygenation during exercise. Tailoring exercise regimes for this population should prioritize interventions aimed at enhancing muscle oxygenation and blood flow improvement.

Association between low-carbohydrate-diet score, glycemia and cardiovascular risk factors in adults with type 1 diabetes.

BACKGROUND AND AIMS: Low-carbohydrate-diets (LCDs) are gaining popularity in individuals with type 1 diabetes (T1D). However, the impact of such diets on glycemia and cardiovascular risk factors is debated. This study aims to evaluate associations between low-carbohydrate intakes using LCD score with glycemia and cardiovascular risk factors (lipid profile) in adults with T1D or LADA in Québec, Canada. METHODS AND RESULTS: This is a cross-sectional study using data collected in the BETTER registry (02/2019 and 04/2021) including self-reported 24-h dietary recalls to calculate LCD scores, waist circumference, level-2 and level-3 hypoglycemic episodes and measured biochemical data (HbA1c, LDL-cholesterol and non-HDL-cholesterol). Participants were divided into quartiles (Q) based on LCD scores. Two hundred eighty-five adults (aged 48.2 ± 15.0 years; T1D duration 25.9 ± 16.2 years) were included. Categorical variables underwent Chi-squared/Fisher's Exact tests, while continuous variables underwent ANOVA tests. Mean carbohydrate intake ranged from 31.2 ± 6.9% (Q1) to 56.5 ± 6.8% (Q4) of total daily energy. Compared to Q4, more people in Q1 reported HbA1c ≤ 7% [≤53.0 mmol/mol] (Q1: 53.4% vs. Q4: 29.4%; P = 0.011). The same results were found in the models adjusted for age, sex and T1D duration. A greater proportion of participants in Q1 never experienced level-3 hypoglycemia compared to Q3 (Q1: 60.0% vs. Q3: 31.0%; P = 0.004). There were no differences across quartiles for frequency of level-2 hypoglycemia events and lipid profile (LDL-cholesterol and non-HDL-cholesterol). CONCLUSIONS: Low-carbohydrate intakes are associated with higher probabilities of reaching HbA1c target and of never having experienced level-3 hypoglycemia. No associations with level-2 hypoglycemia frequency, nor cardiovascular risk factors were observed.

Association between cystic fibrosis transmembrane regulator genotype and clinical outcomes, glucose homeostasis indices and CF-related diabetes risk in adults with CF.

People living with cystic fibrosis (pwCF) homozygous for F508del present more severe phenotypes. PwCF with compound heterozygous genotypes F508del /A455E and F508del /L206W may have milder cystic fibrosis (CF) phenotypes. We compared F508del homozygotes and common compound heterozygotes (F508del and a second pathogenic variant) in adult patients. Nutritional, pulmonary function and glucose homeostasis indices data were collected from the prospective Montreal CF cohort. Two-hundred and three adults with CF having at least one F508del variant were included. Individuals were divided into subgroups: homozygous F508del/F508del (n=149); F508del/621+1G>T (n=17); F508del/711+1G>T (n=11); F508del/A455E (n=12); and F508del/L206W (n=14). Subgroups with the F508del/L206W and F508del/A455E had a lower proportion with pancreatic exocrine insufficiency (p<0.0001), a higher fat mass (p<0.0001), and lower glucose area under the curve (AUC) (p=0.027). The F508del/L206W subgroup had significantly higher insulin secretion (AUC; p=0.027) and body mass index (p<0.001). Pulmonary function (FEV1) was significantly higher for the F508del/L206W subgroup (p<0.0001). Over a median of 7.37 years, the risk of developing CFRD in 141 patients was similar between groups. PwCF with heterozygous F508del/L206W and F508del/A455E tended to have pancreatic exocrine sufficiency, better nutritional status, improved pulmonary function and better diabetogenic indices, but this does not translate into lower risk of CF-related Diabetes.

Respiratory function in uncomplicated type 1 diabetes: Blunted during exercise even though normal at rest!

AIMS: Type 1 diabetes is associated with a substantially increased risk of impaired lung function, which may impair aerobic fitness. We therefore aimed to examine the ventilatory response during maximal exercise and the pulmonary diffusion capacity function at rest in individuals with uncomplicated type 1 diabetes. METHODS: In all, 17 adults with type 1 diabetes free from micro-macrovascular complications (glycated haemoglobin: 8.0 ± 1.3%), and 17 non-diabetic adults, carefully matched to the type 1 diabetes group according to gender, age, level of physical activity and body composition, participated in our study. Lung function was assessed by spirometry and measurements of the combined diffusing capacity for nitric oxide (DLNO) and carbon monoxide (DLCO) at rest. Subjects performed a maximal exercise test during which the respiratory parameters were measured. RESULTS: At rest, DLCO (30.4 ± 6.1 ml min-1  mmHg-1 vs. 31.4 ± 5.7 ml min-1 mmHg-1 , respectively, p = 0.2), its determinants Dm (membrane diffusion capacity) and Vc (pulmonary capillary volume) were comparable among type 1 diabetes and control groups, respectively. Nevertheless, spirometry parameters (forced vital capacity = 4.9 ± 1.0 L vs. 5.5 ± 1.0 L, p < 0.05; forced expiratory volume 1 = 4.0 ± 0.7 L vs. 4.3 ± 0.7 L, p < 0.05) were lower in individuals with type 1 diabetes, although in the predicted normal range. During exercise, ventilatory response to exercise was different between the two groups: tidal volume was lower in type 1 diabetes vs. individuals without diabetes (p < 0.05). Type 1 diabetes showed a reduced VO2max (34.7 ± 6.8 vs. 37.9 ± 6.3, respectively, p = 0.04) in comparison to healthy subjects. CONCLUSIONS: Individuals with uncomplicated type 1 diabetes display normal alveolar-capillary diffusion capacity and at rest, while their forced vital capacity, tidal volumes and VO2 are reduced during maximal exercise.

Cystic Fibrosis-Related Diabetes: Clinical approach and knowledge gaps.

Cystic Fibrosis-Related Diabetes (CFRD) is a unique type of diabetes mellitus that shares some features with both type 1 and type 2 diabetes. Yet, its distinguishing feature of acute pulmonary complications associated with hyperglycemia and the catabolic metabolism associated with a relative insulin deficiency poses challenges to the application of traditional definitions and treatments for diabetes mellitus. People with CF (pwCF) undergo rigorous annual screening starting at age 10, a process that is challenging for patients and limited by sensitivity, specificity, and reproducibility. As pwCF continue to live longer, over 50% are expected to develop CFRD over their lifetime, including up to 20% of adolescents. Increasing numbers of people with CFRD will make this disease increasingly relevant to diabetes practitioners. Evidence-guided practice in CFRD care is limited by small and short studies. Our current understanding of CFRD may change significantly with the recent introduction of CF Transmembrane Regulator (CFTR) modulator medications. This review will explore current challenges in the diagnosis and management of CFRD, specifically highlighting knowledge gaps in the pathophysiology of CFRD, optimal screening methods, priorities for research and provide guidance with regards to screening, diagnosis, and treatment.

Impact of glycemic variability on cognitive impairment, disordered eating behaviors and self-management skills in patients with type 1 diabetes: study protocol for a cross-sectional online study, the Sugar Swing study.

BACKGROUND: People living with type 1 diabetes (PWT1D) are at increased risk for impairments in brain function, which may impact on daily life. Cognitive impairments in PWT1D might contribute to increasing eating disorders, reducing self-management skills, and deteriorating glycemic control. Glycemic variability may be a key determinant of disordered eating behaviors, as well as of cognitive impairments. The main objective of this study is to better understand the impact of glycemic variability in disordered eating behaviors and cognitive impairment, and its consequences on self-management skills in PWT1D. METHOD: We aim to recruit 150 PWT1D with 50% of men and women in this cross-sectional study. Participants will record their glycemic variability over a 10-day period using a continuous glucose monitoring system (CGMS) and track their dietary intakes using image-assisted food tracking mobile application (2 days). Over four online visits, eating behaviors, diabetes self-management's skills, anxiety disorders, depression disorder, diabetes literacy and numeracy skills, cognitive flexibility, attention deficit, level of interoception, and impulsivity behaviors will be assessed using self-reported questionnaires. Cognitive functions (i.e., attention, executive functions, impulsivity, inhibition and temporal discounting), will be measured. Finally, medical, biological and sociodemographic data will be collected. To further our understanding of the PWT1D experience and factors impacting glycemic self-management, 50 PWT1D will also participate in the qualitative phase of the protocol which consist of individual in-depth face-to-face (virtual) interviews, led by a trained investigator using a semi-structured interview. DISCUSSION: This study will contribute to highlighting the consequences of blood sugar fluctuations (i.e., "sugar swings"), in daily life, especially how they disrupt eating behaviors and brain functioning. A better understanding of the mechanisms involved could eventually allow for early detection and management of these problems. Our study will also seek to understand the patients' point of view, which will allow the design of appropriate and meaningful recommendations. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05487534. Registered 4 August 2022.

Peak glucose during an oral glucose tolerance test is associated with future diabetes risk in adults with cystic fibrosis.

AIMS/HYPOTHESIS: Cystic fibrosis-related diabetes (CFRD) affects up to 50% of adults with cystic fibrosis (CF) and its presence is associated with adverse effects on nutritional status and pulmonary function. Early diagnosis could minimise CFRD morbidity, yet current methods of an OGTT at 0 and 2 h yield unreliable results. Our aim was to determine which indices from a 2 h OGTT with sampling every 30 min might improve prediction of CFRD. METHODS: Cross-sectional analysis at baseline (n = 293) and observational prospective analysis (n = 185; mean follow-up of 7.5 ± 4.2 years) of the Montreal Cystic Fibrosis Cohort were performed. Blood glucose and insulinaemia OGTT variables were studied in relation to lung function (forced expiratory volume in 1 s [FEV1]), BMI and risk of developing CFRD. RESULTS: At baseline, maximum OGTT glucose (Gmax) was negatively associated with FEV1 (p = 0.003). Other OGTT values, including classical 2 h glucose, were not. A higher Gmax was associated with lower insulin secretory capacity, delayed insulin peak timing and greater pancreatic insufficiency (p < 0.01). Gmax was positively associated with the risk of developing CFRD (p = 0.0029); no individual with a Gmax < 8 mmol/l developed CFRD over the following decade. No OGTT variable correlated to the rate of change in BMI or FEV1. CONCLUSIONS/INTERPRETATION: In adults with CF, Gmax is strongly associated with the risk of developing CFRD; Gmax < 8 mmol/l could identify those at very low risk of future CFRD. Gmax is higher in individuals with pancreatic insufficiency and is associated with poorer insulin secretory capacity and pulmonary function.

The promising future of insulin therapy in diabetes mellitus.

The first therapeutic use of insulin by Frederick Banting and Charles Best in 1921 revolutionized the management of type 1 diabetes and considerably changed the lives of many patients with other types of diabetes. In the past 100 years, significant pharmacological advances took place in the field of insulin therapy, bringing closer the goal of optimal glycemic control along with decreased diabetes-related complications. Despite these developments, several challenges remain, such as increasing treatment flexibility, reducing iatrogenic hypoglycemia, and optimizing patient quality of life. Ongoing innovations in insulin therapy (e.g., new insulin analogs, alternative routes of insulin administration, and closed-loop technology) endeavor to overcome these hurdles and change the landscape of diabetes mellitus management. This report highlights recent advances made in the field of insulin therapy and discusses future perspectives.

Use of once-weekly semaglutide in patients with type 2 diabetes in routine clinical practice: Results from the SURE Canada multicentre, prospective, observational study.

AIM: To investigate once-weekly (OW) semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA), in patients with type 2 diabetes (T2D) in routine clinical practice. METHODS: The SURE Canada study was a multicenter, prospective, observational study. Adults with T2D and one or more documented HbA1c values 12 weeks or less before semaglutide initiation were enrolled. The primary endpoint was change in HbA1c from baseline to end of study (EOS; ~30 weeks). Secondary endpoints included change in body weight (BW), waist circumference and patient-reported outcomes (PROs) and the proportion of patients achieving HbA1c of less than 7.0%, weight loss (WL) of 5% or higher, and a composite of HbA1c reduction of 1% or higher and WL of 3% or higher at EOS. Data were analysed and presented for patients on semaglutide at EOS overall and for the following baseline medication subgroups: oral antihyperglycaemic drugs (OADs) only; GLP-1RA experienced; insulin ± OADs without GLP-1RA. RESULTS: In total, 452 patients initiated semaglutide and 356 completed the study on treatment. For the 452 patients, mean baseline HbA1c was 8.1%; 86 (19.0%) patients had HbA1c of less than 7.0%. Mean dose of semaglutide at EOS was 0.76 ± 0.31 mg. Mean HbA1c was reduced by 0.9%-point (95% confidence interval [CI]: 0.97; 0.78). Mean BW was reduced by 4.3 kg (95% CI: 4.79; 3.76). At EOS, 46.9% of patients achieved HbA1c of less than 7.0%, 40.9% achieved WL of 5% or higher and 24.1% achieved the composite endpoint. PROs improved from baseline to EOS. No new safety concerns were reported. CONCLUSIONS: In SURE Canada, patients treated with OW semaglutide in routine clinical practice experienced clinically significant improvements in HbA1c, BW and other outcomes, supporting semaglutide use in routine clinical practice.

Perceptions and expectations of adults with type 1 diabetes for the use of artificial pancreas systems with and without glucagon addition: Results of an online survey.

BACKGROUND AND AIMS: The first hybrid artificial pancreas (AP) systems with insulin only (mono-hormonal) have recently reached the market while next generations systems are under development including those with glucagon addition (bi-hormonal). Understanding the expectations and impressions of future potential users about AP systems is important for optimal use of this clinically effective emerging technology. METHODS AND RESULTS: An online survey about AP systems which consisted of 50 questions was addressed to people with type 1 diabetes in the province of Quebec, Canada. Surveys were completed by 123 respondents with type 1 diabetes (54% women, mean (SD) age 40.2 (14.4) y.o., diabetes duration 23.7 (14.1) years, 58% insulin pump users and 43% glucose sensor users). Of the respondents, 91% understood how AP systems work, 79% trusted them with correct insulin dosing, 73% were willing to replace their current treatment with AP and 80% expected improvement in quality of life. Anxiety about letting an algorithm control their glucose levels was expressed by 18% while the option of ignoring or modifying AP instructions was favoured by 88%. As for bi-hormonal AP systems, 83% of respondents thought they would be useful to further reduce hypoglycemic risks. CONCLUSIONS: Overall, respondents expressed positive views about AP systems use and high expectations for a better quality of life, glycemic control and hypoglycemia reduction. Data from this survey could be useful to health care professionals and developers of AP systems.

Abnormal glucose tolerance in a pediatric cystic fibrosis cohort: Trends in clinical outcomes and associated factors in the preceding years.

BACKGROUND AND AIMS: Deterioration of anthropometric and lung function parameters was shown to precede the onset of cystic fibrosis-related diabetes (CFRD) in adults. In children, studies have been conducted in small cohorts with relatively short observation period. Study objectives were to document the longitudinal trends of anthropometric, pulmonary, nutritional and metabolic parameters from cystic fibrosis (CF) diagnosis to the ascertainment of abnormal glucose tolerance and identify parameters associated with the incidence of such abnormalities in a pediatric CF cohort. METHODS AND RESULTS: Retrospective cohort study of 281 children with CF. Longitudinal trends of anthropometric, lung function, nutritional and metabolic data were generated from CF diagnosis to the ascertainment of abnormal glucose tolerance defined as the presence of either impaired glucose tolerance (IGT), unconfirmed CFRD or CFRD. Cox models and Kaplan-Meier curves were used to identify factors associated with developing abnormal glucose tolerance. Forty-five percent of cohort had normal glucose tolerance (NGT), 27% IGT, 10% unconfirmed CFRD and 18% CFRD. Children who developed CFRD displayed lower height z-scores from a very early age. Conversely, HbA1c levels began to rise closer to CFRD ascertainment. Height z-scores (HR: 0.45; CI 95% [0.29-0.69]) and HbA1c (HR: 2.43; CI 95% [1.86-3.18]) in years preceding ascertainment were associated with the risk of developing CFRD. CONCLUSION: Children who developed CFRD display distinctive trends for height z-scores from a very early age, whereas HbA1c appears as a marker of established glucose metabolism derangements.

Effect of caloric restriction with or without physical activity on body composition and epicardial fat in type 2 diabetic patients: A pilot randomized controlled trial.

BACKGROUND AND AIMS: There is debate over the independent and combined effects of caloric restriction (CR) and physical activity (PA) on reduction in fat mass and in epicardial fat thickness. We compared the impact of a similar energy deficit prescription by CR or by CR combined with PA on total fat mass, epicardial fat thickness, and cardiometabolic profile in individuals with type 2 diabetes. METHODS AND RESULTS: In this 16-week randomized controlled study, 73 individuals were randomly enrolled to receive: 1) a monthly motivational phone call (Control), 2) a caloric deficit of -700 kilocalories/day (CR), or 3) a caloric deficit of -500 kilocalories/day combined with a PA program of -200 kilocalories/day (CR&PA). Total fat mass, epicardial fat, and cardiometabolic profile were measured at baseline and after 16 weeks. While comparable weight loss occurred in both intervention groups (-3.9 ± 3.5 kg [CR], -5.1 ± 4.7 kg [CR&PA], -0.2 ± 2.9 kg [Control]), changes in total fat mass were significantly different between all groups (-2.4 ± 2.9 kg [CR], -4.5 ± 3.4 kg [CR&PA], +0.1 ± 2.1 kg [Control]; p < 0.05) as well as epicardial fat thickness (-0.4 ± 1.6 mm [CR], -1.4 ± 1.4 mm [CR&PA], +1.1 ± 1.3 mm [Control]; p < 0.05). There were no significant differences in trends for cardiometabolic parameters improvement between groups. CONCLUSIONS: For a similar energy deficit prescription and comparable weight loss, the combination of CR&PA provides a greater reduction in fat mass and epicardial fat thickness than CR alone in individuals with comparable weight loss and with a similar energy deficit prescription. These results, however, do not translate into significant improvements in cardiometabolic profiles. CLINICALTRIALS. GOV IDENTIFIER: NCT01186952.

Comparison of two carbohydrate intake strategies to improve glucose control during exercise in adolescents and adults with type 1 diabetes.

BACKGROUND AND AIMS: During aerobic physical activity (PA), hypoglycemia is common in people with type 1 diabetes (T1D). Few studies have compared the effectiveness of different carbohydrate (CHO) intake strategies to prevent PA-induced hypoglycemia. Our objective was to compare the efficacy of two CHO intake strategies, same total amount but different CHO intake timing, to maintain glucose levels in the target range (4.0-10.0 mmol/L) during PA in people with T1D. METHODS AND RESULTS: An open-label, randomized, crossover study in 33 participants (21 adults; 12 adolescents). Participants practiced 60 min PA sessions (ergocyle) at 60% VO2peak 3.5 h after lunch comparing an intake of 0.5 g of CHO per kg of body weight applied in a pre-PA single CHO intake (SCI) or in a distributed CHO intake (DCI) before and during PA. The percentage of time spent in glucose level target range during PA was not different between the two strategies (SCI: 75 ± 35%; DCI: 87 ± 26%; P = 0.12). Hypoglycemia (<4.0 mmol/L) occurred in 4 participants (12%) with SCI compared to 6 participants (18%) with DCI (P = 0.42). The SCI strategy led to a higher increase (P = 0.01) and variability of glucose levels (P = 0.04) compared with DCI. CONCLUSIONS: In people living with T1D, for a 60 min moderate aerobic PA in the post-absorptive condition, a 0.5 g/kg CHO intake helped most participants maintain acceptable glycemic control with both strategies. No clinically significant difference was observed between the SCI and DCI strategies. ClinicalTrials.gov Identifier: NCT03214107 (July 11, 2017).

Individuals with self-determined motivation for eating have better overall diet quality: Results from the PREDISE study.

The study aimed at documenting motivational orientations for the regulation of eating as defined by self-determination theory and their association with sociodemographic characteristics and overall diet quality. As part of the PREDISE study, French-speaking women (n = 550) and men (n = 547), aged 18-65 years, living in the Province of Québec, Canada, completed online validated questionnaires. The Regulation of Eating Behavior Scale, based on the self-determination theory, assessed self-determined and non-self-determined motivation to regulate one's eating behavior. Three web-based 24-h food recalls were completed and used to compute the Canadian Healthy Eating Index 2007 (C-HEI), an indicator of the overall adherence to Canadian guidelines for healthy eating. Multiple linear regressions were performed to assess how regulation styles are associated with the C-HEI. Model 1 included no covariate, model 2 included sociodemographic covariates, and fully adjusted model 3 included as covariates sociodemographic variables as well as variables that were previously associated with diet quality, namely nutrition knowledge and social support for healthy eating. Women (p < 0.0001), older individuals (p = 0.0002), those with a higher education level (p < 0.0001), and non-smokers (p < 0.0001) reported higher self-determined motivation score than their counterparts. Self-determined motivation was positively (model 1: B = 4.67, p < 0.0001; model 2: B = 3.82, p < 0.0001; model 3: B = 3.61, p < 0.0001) and non-self-determined motivation was negatively (model 1: B = -1.62, p = 0.0009; model 2: B = -1.63, p = 0.0006; model 2: B = -1.49, p = 0.0022) associated with C-HEI. The present study suggests that some subgroups of the general adult population show more self-determined motivation for eating, which is associated with a better diet quality independently of individual characteristics and other individual and social determinants of healthy eating. Strategies to help individuals internalize the regulation of eating should be further investigated.

A single-blind, randomised, crossover study to reduce hypoglycaemia risk during postprandial exercise with closed-loop insulin delivery in adults with type 1 diabetes: announced (with or without bolus reduction) vs unannounced exercise strategies.

AIMS/HYPOTHESIS: For individuals living with type 1 diabetes, closed-loop insulin delivery improves glycaemic control. Nonetheless, maintenance of glycaemic control during exercise while a prandial insulin bolus remains active is a challenge even to closed-loop systems. We investigated the effect of exercise announcement on the efficacy of a closed-loop system, to reduce hypoglycaemia during postprandial exercise. METHODS: A single-blind randomised, crossover open-label trial was carried out to compare three strategies applied to a closed-loop system at mealtime in preparation for exercise taken 90 min after eating at a research testing centre: (1) announced exercise to the closed-loop system (increases target glucose levels) in addition to a 33% reduction in meal bolus (A-RB); (2) announced exercise to the closed-loop system and a full meal bolus (A-FB); (3) unannounced exercise and a full meal bolus (U-FB). Participants performed 60 min of exercise at 60% [Formula: see text] 90 min after eating breakfast. The investigators were not blinded to the interventions. However, the participants were blinded to the sensor glucose readings and to the insulin infusion rates throughout the intervention visits. RESULTS: The trial was completed by 37 adults with type 1 diabetes, all using insulin pumps: mean±SD, 40.0 ± 15.0 years of age, HbA1c 57.1 ± 10.8 mmol/mol (7.3 ± 1.0%). Reported results were based on plasma glucose values. During exercise and the following 1 h recovery period, time spent in hypoglycaemia (<3.9 mmol/l; primary outcome) was reduced with A-RB (mean ± SD; 2.0 ± 6.2%) and A-FB (7.0 ± 12.6%) vs U-FB (13.0 ± 19.0%; p < 0.0001 and p = 0.005, respectively). During exercise, A-RB had the least drop in plasma glucose levels: A-RB -0.3 ± 2.8 mmol/l, A-FB -2.6 ± 2.9 mmol/l vs U-FB -2.4 ± 2.7 mmol/l (p < 0.0001 and p = 0.5, respectively). Comparison of A-RB vs U-FB revealed a decrease in the time spent in target (3.9-10 mmol/l) by 12.7% (p = 0.05) and an increase in the time spent in hyperglycaemia (>10 mmol/l) by 21% (p = 0.001). No side effects were reported during the applied strategies. CONCLUSIONS/INTERPRETATION: Combining postprandial exercise announcement, which increases closed-loop system glucose target levels, with a 33% meal bolus reduction significantly reduced time spent in hypoglycaemia compared with the other two strategies, yet at the expense of more time spent in hyperglycaemia. TRIAL REGISTRATION: ClinicalTrials.gov NCT0285530 FUNDING: JDRF (2-SRA-2016-210-A-N), the Canadian Institutes of Health Research (354024) and the Fondation J.-A. DeSève chair held by RR-L.

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 (i.e. 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. Graphical abstract.

Measurement of bioactive osteocalcin in humans using a novel immunoassay reveals association with glucose metabolism and ß-cell function.

Osteocalcin (OCN) is a bone-derived hormone involved in the regulation of glucose metabolism. In serum, OCN exists in carboxylated and uncarboxylated forms (ucOCN), and studies in rodents suggest that ucOCN is the bioactive form of this hormone. Whether this is also the case in humans is unclear, because a reliable assay to measure ucOCN is not available. Here, we established and validated a new immunoassay (ELISA) measuring human ucOCN and used it to determine the level of bioactive OCN in two cohorts of overweight or obese subjects, with or without type 2 diabetes (T2D). The ELISA could specifically detect ucOCN concentrations ranging from 0.037 to 1.8 ng/mL. In a first cohort of overweight or obese postmenopausal women without diabetes (n = 132), ucOCN correlated negatively with fasting glucose (r = -0.18, P = 0.042) and insulin resistance assessed by the homeostatic model assessment of insulin resistance (r = -0.18, P = 0.038) and positively with insulin sensitivity assessed by a hyperinsulinemic-euglycemic clamp (r = 0.18, P = 0.043) or insulin sensitivity index derived from an oral glucose tolerance test (r = 0.26, P = 0.003). In a second cohort of subjects with severe obesity (n = 16), ucOCN was found to be lower in subjects with T2D compared with those without T2D (2.76 ± 0.38 versus 4.52 ± 0.06 ng/mL, P = 0.009) and to negatively correlate with fasting glucose (r = -0.50, P = 0.046) and glycated hemoglobin (r = -0.57, P = 0.021). Moreover, the subjects with ucOCN levels below 3 ng/mL had a reduced insulin secretion rate during a hyperglycemic clamp (P = 0.03). In conclusion, ucOCN measured with this novel and specific assay is inversely associated with insulin resistance and ß-cell dysfunction in humans.

Assessment of Risks and Benefits of Beta Cell Replacement Versus Automated Insulin Delivery Systems for Type 1 Diabetes.

PURPOSE OF REVIEW: Current approaches to insulin replacement in type 1 diabetes are unable to achieve optimal levels of glycemic control without substantial risk of hypoglycemia and substantial burden of self-management. Advances in biology and technology present beta cell replacement and automated insulin delivery as two alternative approaches. Here we discuss current and future prospects for the relative risks and benefits for biological and psychosocial outcomes from the perspective of researchers, clinicians, and persons living with diabetes. RECENT FINDINGS: Beta cell replacement using pancreas or islet transplant can achieve insulin independence but requires immunosuppression. Although insulin independence may not be sustained, time in range of 80-90%, minimal glycemic variability and abolition of hypoglycemia is routine after islet transplantation. Clinical trials of potentially unlimited supply of stem cell-derived beta cells are showing promise. Automated insulin delivery (AID) systems can achieve 70-75% time in range, with reduced glycemic variability. Impatient with the pace of commercially available AID, users have developed their own algorithms which appear to be at least equivalent to systems developed within conventional regulatory frameworks. The importance of psychosocial factors and the preferences and values of persons living with diabetes are emerging as key elements on which therapies should be evaluated beyond their impact of biological outcomes. Biology or technology to deliver glucose dependent insulin secretion is associated with substantial improvements in glycemia and prevention of hypoglycemia while relieving much of the substantial burden of diabetes. Automated insulin delivery, currently, represents a more accessible bridge to a biologic cure that we expect future cellular therapies to deliver.

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.