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.

Barriers to Physical Activity in Children and Adults Living With Type 1 Diabetes: A Complex Link With Real-life Glycemic Excursions.

OBJECTIVES: Ever since the first research on barriers to physical activity (PA) highlighting fear of hypoglycemia as a major barrier, many studies have attempted to understand their demographic and behavioural determinants. However, no research has been conducted on whether these perceived barriers toward PA are based on real-life-experienced adverse glycemic effects of exercise. METHODS: Sixty-two adults and 53 children/adolescents living with type 1 diabetes, along with their parents, completed the Barriers to Physical Activity in Type 1 Diabetes-1 (BAPAD-1) questionnaire on barriers to PA. Continuous glucose-monitoring data were collected during 1 week of everyday life for 26 adults and 33 children/adolescents. Multiple linear regressions were used to explore links between BAPAD-1 scores and glycemic excursions experienced during and after everyday-life self-reported PA sessions, controlling for behavioural (accelerometry) and demographic confounders. RESULTS: In children/adolescents, the more time spent in hypoglycemia on nights after PA sessions, the more they reported hypoglycemic risk as a barrier (ß=+0.365, p=0.034). Conversely, in adults, the higher the proportion of PA sessions accompanied by a drop in blood glucose, the less hypoglycemia was a barrier (ß=-0.046, p=0.004). In parents, BAPAD-1 scores were unrelated to children/adolescents' everyday-life exercise-induced hypo/hyperglycemia. CONCLUSIONS: In children/adolescents, fear of hypoglycemia was predominant in those exposed to nocturnal hypoglycemia associated with PA sessions. In adults, fewer barriers may mean they accept a bigger drop in their glycemia during PA. This shows the importance of finding and promoting age-specific solutions to prevent exercise-induced hypoglycemia.

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.

Parental decision and intent towards COVID-19 vaccination in children with asthma: an econometric analysis.

OBJECTIVE: Vaccination will be instrumental in controlling the COVID-19 pandemic, and vaccination of children will be necessary to achieve herd immunity. Given that children with chronic health conditions may be at increased risk of COVID-19, it is crucial to understand factors influencing parental decisions about whether to have their child vaccinated. The study objectives were to measure parental intent to have their child with asthma vaccinated against COVID-19 and identify the determinants of their vaccination decision. STUDY DESIGN: This study is based on a cross-sectional exploratory observational online survey assessing parents' risk perception in the context of COVID-19. METHODS: In this study conducted in August 2020, the primary outcome was parent's answer to the question on their intention to get their child vaccinated if a vaccine against COVID-19 was available. Participants were also asked about their intention to get vaccinated themselves. Independent variables studied included sociodemographic, clinical data (e.g. presence of other chronic diseases), psychological, cognitive and risk perception related to COVID-19. Simultaneous equations models (3SLS) and seemingly unrelated regressions model (SUR) were carried out to identify factors associated with intention to have the child vaccinated and participants' intention to get vaccinated themselves against COVID-19. RESULTS: A total of 305 participants completed the survey. Overall, 19.1% of participants reported being unlikely or very unlikely to vaccinate their child against COVID-19 if a vaccine was available. Similarly, 21.0% were unlikely or very unlikely to get vaccinated themselves. The following factors were significantly associated with parents' decision to have their child vaccinated: parental level of education (p = 0.003), employment status (p < 0.001), sex of the child (p = 0.019), presence of other chronic diseases (p = 0.028), whether or not the child had been vaccinated against influenza in the past (p < 0.001), parental anxiety (p = 0.046), and consultation with a health professional since the beginning of the pandemic (p = 0.009). There was a strong relationship between likelihood of not intending to have one's child vaccinated and personal intent not to get vaccinated. CONCLUSION: These findings are essential in planning for the communication and dissemination of COVID-19 vaccination information to parents, especially for children with asthma or other chronic medical conditions.

Cleaning radiotherapy contours for radiomics studies, is it worth it? A head and neck cancer study.

A vast majority of studies in the radiomics field are based on contours originating from radiotherapy planning. This kind of delineation (e.g. Gross Tumor Volume, GTV) is often larger than the true tumoral volume, sometimes including parts of other organs (e.g. trachea in Head and Neck, H&N studies) and the impact of such over-segmentation was little investigated so far. In this paper, we propose to evaluate and compare the performance between models using two contour types: those from radiotherapy planning, and those specifically delineated for radiomics studies. For the latter, we modified the radiotherapy contours to fit the true tumoral volume. The two contour types were compared when predicting Progression-Free Survival (PFS) using Cox models based on radiomics features extracted from FluoroDeoxyGlucose-Positron Emission Tomography (FDG-PET) and CT images of 239 patients with oropharyngeal H&N cancer collected from five centers, the data from the 2020 HECKTOR challenge. Using Dedicated contours demonstrated better performance for predicting PFS, where Harell's concordance indices of 0.61 and 0.69 were achieved for Radiotherapy and Dedicated contours, respectively. Using automatically Resegmented contours based on a fixed intensity range was associated with a C-index of 0.63. These results illustrate the importance of using clean dedicated contours that are close to the true tumoral volume in radiomics studies, even when tumor contours are already available from radiotherapy treatment planning.

Sex disparities in COVID-19 outcomes of inpatients with diabetes: insights from the CORONADO study.

OBJECTIVE: Male sex is one of the determinants of severe coronavirus diseas-e-2019 (COVID-19). We aimed to characterize sex differences in severe outcomes in adults with diabetes hospitalized for COVID-19. METHODS: We performed a sex-stratified analysis of clinical and biological features and outcomes (i.e. invasive mechanical ventilation (IMV), death, intensive care unit (ICU) admission and home discharge at day 7 (D7) or day 28 (D28)) in 2380 patients with diabetes hospitalized for COVID-19 and included in the nationwide CORONADO observational study (NCT04324736). RESULTS: The study population was predominantly male (63.5%). After multiple adjustments, female sex was negatively associated with the primary outcome (IMV and/or death, OR: 0.66 (0.49-0.88)), death (OR: 0.49 (0.30-0.79)) and ICU admission (OR: 0.57 (0.43-0.77)) at D7 but only with ICU admission (OR: 0.58 (0.43-0.77)) at D28. Older age and a history of microvascular complications were predictors of death at D28 in both sexes, while chronic obstructive pulmonary disease (COPD) was predictive of death in women only. At admission, C-reactive protein (CRP), aspartate amino transferase (AST) and estimated glomerular filtration rate (eGFR), according to the CKD-EPI formula predicted death in both sexes. Lymphocytopenia was an independent predictor of death in women only, while thrombocytopenia and elevated plasma glucose concentration were predictors of death in men only. CONCLUSIONS: In patients with diabetes admitted for COVID-19, female sex was associated with lower incidence of early severe outcomes, but did not influence the overall in-hospital mortality, suggesting that diabetes mitigates the female protection from COVID-19 severity. Sex-associated biological determinants may be useful to optimize COVID-19 prevention and management in women and men.

Use of dipeptidyl peptidase-4 inhibitors and prognosis of COVID-19 in hospitalized patients with type 2 diabetes: A propensity score analysis from the CORONADO study.

AIM: To investigate the association between routine use of dipeptidyl peptidase-4 (DPP-4) inhibitors and the severity of coronavirus disease 2019 (COVID-19) infection in patient with type 2 diabetes in a large multicentric study. MATERIALS AND METHODS: This study was a secondary analysis of the CORONADO study on 2449 patients with type 2 diabetes (T2D) hospitalized for COVID-19 in 68 French centres. The composite primary endpoint combined tracheal intubation for mechanical ventilation and death within 7 days of admission. Stabilized weights were computed for patients based on propensity score (DPP-4 inhibitors users vs. non-users) and were used in multivariable logistic regression models to estimate the average treatment effect in the treated as inverse probability of treatment weighting (IPTW). RESULTS: Five hundred and ninety-six participants were under DPP-4 inhibitors before admission to hospital (24.3%). The primary outcome occurred at similar rates in users and non-users of DPP-4 inhibitors (27.7% vs. 28.6%; p = .68). In propensity analysis, the IPTW-adjusted models showed no significant association between the use of DPP-4 inhibitors and the primary outcome by Day 7 (OR [95% CI]: 0.95 [0.77-1.17]) or Day 28 (OR [95% CI]: 0.96 [0.78-1.17]). Similar neutral findings were found between use of DPP-4 inhibitors and the risk of tracheal intubation and death. CONCLUSIONS: These data support the safety of DPP-4 inhibitors for diabetes management during the COVID-19 pandemic and they should not be discontinued.

Towards a Reduced In Silico Model Predicting Biochemical Recurrence After Radiotherapy in Prostate Cancer.

OBJECTIVE: Purposes of this work were i) to develop an in silico model of tumor response to radiotherapy, ii) to perform an exhaustive sensitivity analysis in order to iii) propose a simplified version and iv) to predict biochemical recurrence with both the comprehensive and the reduced model. METHODS: A multiscale computational model of tumor response to radiotherapy was developed. It integrated the following radiobiological mechanisms: oxygenation, including hypoxic death; division of tumor cells; VEGF diffusion driving angiogenesis; division of healthy cells and oxygen-dependent response to irradiation, considering, cycle arrest and mitotic catastrophe. A thorough sensitivity analysis using the Morris screening method was performed on 21 prostate computational tissues. Tumor control probability (TCP) curves of the comprehensive model and 15 reduced versions were compared. Logistic regression was performed to predict biochemical recurrence after radiotherapy on 76 localized prostate cancer patients using an output of the comprehensive and the reduced models. RESULTS: No significant difference was found between the TCP curves of the comprehensive and a simplified version which only considered oxygenation, division of tumor cells and their response to irradiation. Biochemical recurrence predictions using the comprehensive and the reduced models improved those made from pre-treatment imaging parameters (AUC = 0.81 ± 0.02 and 0.82 ± 0.02 vs. 0.75 ± 0.03, respectively). CONCLUSION: A reduced model of tumor response to radiotherapy able to predict biochemical recurrence in prostate cancer was obtained. SIGNIFICANCE: This reduced model may be used in the future to optimize personalized fractionation schedules.

Time trends in diabetes medication prescription and factors associated with metformin discontinuation in people with newly diagnosed type 2 diabetes: A national population-based study.

OBJECTIVE: To describe, based on the French National Health Insurance (NHI) data, time trends in diabetes medications after treatment initiation in two consecutive cohorts of people newly treated for type 2 diabetes (T2D) in 2008 (1st cohort) and 2013 (2nd cohort). MATERIALS AND METHODS: People, aged 45 years and older, newly treated for T2D in 2008 and 2013 were identified in the French NHI Data System. Treatment changes were collected for each year of follow-up. Logistic regression was performed to identify factors associated with metformin discontinuation. RESULTS: Respectively, 157 940 and 160 670 beneficiaries (mean age: 63 and 64 years; men proportion: 53 and 52%) of the French NHI general scheme initiated a diabetes treatment in 2008 and 2013. Metformin was the first monotherapy and increased in use: 67% of monotherapies in 2008 versus 77% in 2013. Monotherapy percentage decreased from the second year onwards in both cohorts. A marked increase in metformin-DPP4i combination therapy was observed (14% of dual therapies in 2008 vs. 46% in 2015 in the first cohort), replacing the metformin-sulfonylureas combination as a second-line treatment. Metformin discontinuation was statistically associated with female gender, social deprivation, age and anti-diabetic polypharmacy. Discontinuation of diabetes treatment was observed after 5 years for, respectively, 10% and 13% in the first and second cohorts. CONCLUSION: Descriptive analysis of two consecutive national cohorts showed an evolution in the prescription patterns of anti-diabetic treatments over a short period. With early treatment intensification, increasing rate of metformin monotherapy, and changes in dual-therapy strategy.

Circulating biomarkers of nitric oxide bioactivity and impaired muscle vasoreactivity to exercise in adults with uncomplicated type 1 diabetes.

AIMS/HYPOTHESIS: Early compromised endothelial function challenges the ability of individuals with type 1 diabetes to perform normal physical exercise. The exact mechanisms underlying this vascular limitation remain unknown, but may involve either formation or metabolism of nitric oxide (NO), a major vasodilator, whose activity is known to be compromised by oxidative stress. METHODS: Muscle microvascular reactivity (near-infrared spectroscopy) to an incremental exhaustive bout of exercise was assessed in 22 adults with uncomplicated type 1 diabetes (HbA1c 64.5 ± 15.7 mmol/mol; 8.0 ± 1.4%) and in 21 healthy individuals (18-40 years of age). NO-related substrates/metabolites were also measured in the blood along with other vasoactive compounds and oxidative stress markers; measurements were taken at rest, at peak exercise and after 15 min of recovery. Demographic characteristics, body composition, smoking status and diet were comparable in both groups. RESULTS: Maximal oxygen uptake was impaired in individuals with type 1 diabetes compared with in healthy participants (35.6 ± 7.7 vs 39.6 ± 6.8 ml min-1 kg-1, p < 0.01) despite comparable levels of habitual physical activity (moderate to vigorous physical activity by accelerometery, 234.9 ± 160.0 vs 280.1 ± 114.9 min/week). Compared with non-diabetic participants, individuals with type 1 diabetes also displayed a blunted exercise-induced vasoreactivity (muscle blood volume at peak exercise as reflected by ∆ total haemoglobin, 2.03 ± 5.82 vs 5.33 ± 5.54 µmol/l; interaction 'exercise' × 'group', p < 0.05); this was accompanied by lower K+ concentration (p < 0.05), reduced plasma L-arginine (p < 0.05)-in particular when HbA1c was high (mean estimation: -4.0, p < 0.05)-and lower plasma urate levels (p < 0.01). Nonetheless, exhaustive exercise did not worsen lipid peroxidation or other oxidative stress biomarkers, and erythrocytic enzymatic antioxidant resources were mobilised to a comparable extent in both groups. Nitrite and total nitrosation products, which are potential alternative NO sources, were similarly unaltered. Graphical abstract CONCLUSIONS/INTERPRETATION: Participants with uncomplicated type 1 diabetes displayed reduced availability of L-arginine, the essential substrate for enzymatic nitric oxide synthesis, as well as lower levels of the major plasma antioxidant, urate. Lower urate levels may reflect a defect in the activity of xanthine oxidase, an enzyme capable of producing NO from nitrite under hypoxic conditions. Thus, both canonical and non-canonical NO production may be reduced. However, neither of these changes exacerbated exercise-induced oxidative stress. TRIAL REGISTRATION: clinicaltrials.gov NCT02051504.

The importance of feature aggregation in radiomics: a head and neck cancer study.

In standard radiomics studies the features extracted from clinical images are mostly quantified with simple statistics such as the average or variance per Region of Interest (ROI). Such approaches may smooth out any intra-region heterogeneity and thus hide some tumor aggressiveness that may hamper predictions. In this paper we study the importance of feature aggregation within the standard radiomics workflow, which allows to take into account intra-region variations. Feature aggregation methods transform a collection of voxel values from feature response maps (over a ROI) into one or several scalar values that are usable for statistical or machine learning algorithms. This important step has been little investigated within the radiomics workflows, so far. In this paper, we compare several aggregation methods with standard radiomics approaches in order to assess the improvements in prediction capabilities. We evaluate the performance using an aggregation function based on Bags of Visual Words (BoVW), which allows for the preservation of piece-wise homogeneous information within heterogeneous regions and compared with standard methods. The different models are compared on a cohort of 214 head and neck cancer patients coming from 4 medical centers. Radiomics features were extracted from manually delineated tumors in clinical PET-FDG and CT images were analyzed. We compared the performance of standard radiomics models, the volume of the ROI alone and the BoVW model for survival analysis. The average concordance index was estimated with a five fold cross-validation. The performance was significantly better using the BoVW model 0.627 (95% CI: 0.616-0.637) as compared to standard radiomics0.505 (95% CI: 0.499-0.511), mean-var. 0.543 (95% CI: 0.536-0.549), mean0.547 (95% CI: 0.541-0.554), var.0.530 (95% CI: 0.524-0.536) or volume 0.577 (95% CI: 0.571-0.582). We conclude that classical aggregation methods are not optimal in case of heterogeneous tumors. We also showed that the BoVW model is a better alternative to extract consistent features in the presence of lesions composed of heterogeneous tissue.

Comparison of feature selection in radiomics for the prediction of overall survival after radiotherapy for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the sixth more frequent cancer worldwide. This type of cancer has a poor overall survival rate mainly due to underlying cirrhosis and risk of recurrence outside the treated lesion. Quantitative imaging within a radiomics workflow may help assessing the probability of survival and potentially may allow tailoring personalized treatments. In radiomics a large amount of features can be extracted, which may be correlated across a population and very often can be surrogates of the same physiopathology. This issues are more pronounced and difficult to tackle with imbalanced data. Feature selection strategies are therefore required to extract the most informative with the increased predictive capabilities. In this paper, we compared different unsupervised and supervised strategies for feature selection in presence of imbalanced data and optimize them within a machine learning framework. Multi-parametric Magnetic Resonance Images from 81 individuals (19 deceased) treated with stereotactic body radiation therapy (SBRT) for inoperable (HCC) were analyzed. Pre-selection of a reduced set of features based on Affinity Propagation clustering (non supervised) achieved a significant improvement in AUC compared to other approaches with and without feature pre-selection. By including the synthetic minority over-sampling technique (SMOTE) for imbalanced data and Random Forest classification this workflow emerges as an appealing feature selection strategy for survival prediction within radiomics studies.

DIABEO System Combining a Mobile App Software With and Without Telemonitoring Versus Standard Care: A Randomized Controlled Trial in Diabetes Patients Poorly Controlled with a Basal-Bolus Insulin Regimen.

Background: The DIABEO® system (DS) is a telemedicine solution that combines a mobile app for patients with a web portal for health care providers. DS allows real-time monitoring of basal-bolus insulin therapy as well as therapeutic decision-making, integrating both basal and bolus dose calculation. Real-life studies have shown a very low rate of use of mobile health applications by patients. Therefore, we conducted a large randomized controlled trial study to investigate the efficacy of DS in conditions close to real life (TELESAGE study). Methods: TELESAGE was a multicenter, randomized, open study with three parallel arms: arm 1 (standard care), arm 2 (DIABEO alone), and arm 3 (DIABEO+telemonitoring by trained nurses). The primary outcome assessed the reduction in HbA1c levels after a 12-month follow-up. Results: Six hundred sixty-five patients were included in the study. Participants who used DIABEO once or more times a day (DIABEO users) showed a significant and meaningful reduction of HbA1c versus standard care after a 12-month follow-up: mean difference -0.41% for arm 2-arm 1 (P = 0.001) and -0.51% for arm 3-arm 1 (P ≤ 0.001). DIABEO users included 25.1% of participants in arm 2 and 37.6% in arm 3. In the intention-to-treat population, HbA1c changes and incidence of hypoglycemia were comparable between arms. Conclusions: A clinical and statistically significant reduction in HbA1c levels was found in those patients who used DIABEO at least once a day.

Early Endothelial Dysfunction in Type 1 Diabetes Is Accompanied by an Impairment of Vascular Smooth Muscle Function: A Meta-Analysis.

Background: A large yet heterogeneous body of literature exists suggesting that endothelial dysfunction appears early in type 1 diabetes, due to hyperglycemia-induced oxidative stress. The latter may also affect vascular smooth muscles (VSM) function, a layer albeit less frequently considered in that pathology. This meta-analysis aims at evaluating the extent, and the contributing risk factors, of early endothelial dysfunction, and of the possible concomitant VSM dysfunction, in type 1 diabetes. Methods: PubMed, Web of Sciences, Cochrane Library databases were screened from their respective inceptions until October 2019. We included studies comparing vasodilatory capacity depending or not on endothelium (i.e., endothelial function or VSM function, respectively) in patients with uncomplicated type 1 diabetes and healthy controls. Results: Fifty-eight articles studying endothelium-dependent function, among which 21 studies also assessed VSM, were included. Global analyses revealed an impairment of standardized mean difference (SMD) (Cohen's d) of endothelial function: -0.61 (95% CI: -0.79, -0.44) but also of VSM SMD: -0.32 (95% CI: -0.57, -0.07). The type of stimuli used (i.e., exercise, occlusion-reperfusion, pharmacological substances, heat) did not influence the impairment of the vasodilatory capacity. Endothelial dysfunction appeared more pronounced within macrovascular than microvascular beds. The latter was particularly altered in cases of poor glycemic control [HbA1c > 67 mmol/mol (8.3%)]. Conclusions: This meta-analysis not only corroborates the presence of an early impairment of endothelial function, even in response to physiological stimuli like exercise, but also highlights a VSM dysfunction in children and adults with type 1 diabetes. Endothelial dysfunction seems to be more pronounced in large than small vessels, fostering the debate on their relative temporal appearance.

Prognostic significance of the renal resistive index in the primary prevention of type II diabetes.

The renal resistive index has been demonstrated to predict the progression of renal disease and recurrence of major cardiac events in high-risk cardiovascular patients, in addition to other comorbidities. We aimed to assess the prognostic significance of the renal resistive index in type 2 diabetic patients for primary prevention. From 2008 to 2011, patients with type 2 diabetes underwent cardiovascular evaluation, including renal resistive index assessment by renal Doppler ultrasound. The incidence of all-cause death, cardiovascular events, dialysis requirement or a twofold increase in creatinine was recorded. Survival curves were estimated by the Kaplan-Meier method. Two hundred sixty-six patients were included; 50% of the patients were men, an HbA1C level of 8.1 ± 1.7% (65 ± 13.6 mmol/mol) and a serum creatinine level of 8 [7-9] mg/L. The mean 24-hour systolic blood pressure, 24-hour diastolic blood pressure, and 24-hour pulse pressure were 133.4 ± 16.7, 76.5 ± 9.4, and 56.9 ± 12.4 mm Hg, respectively. The median renal resistive index was 0.7 [0.6-0.7] with a threshold of 0.7 predictive of monitored events. After adjustment of the 24-hour pulse pressure, age and 24-hour heart rate, a renal resistive index ≥0.70 remained associated with all-cause death (hazard ratio: 3.23 (1.16-8.98); P = .025) and the composite endpoint of major clinical events (hazard ratio: 2.37 (1.34-4.18); P = .003). An elevated renal resistive index with a threshold of 0.7 is an independent predictor of a first cardiovascular or renal event in type 2 diabetic patients. This simple index should be implemented in the multiparametric staging of diabetes.

Muscle Oxygen Supply and Use in Type 1 Diabetes, From Ambient Air to the Mitochondrial Respiratory Chain: Is There a Limiting Step?

OBJECTIVE: Long before clinical complications of type 1 diabetes (T1D) develop, oxygen supply and use can be altered during activities of daily life. We examined in patients with uncomplicated T1D all steps of the oxygen pathway, from the lungs to the mitochondria, using an integrative ex vivo (muscle biopsies) and in vivo (during exercise) approach. RESEARCH DESIGN AND METHODS: We compared 16 adults with T1D with 16 strictly matched healthy control subjects. We assessed lung diffusion capacity for carbon monoxide and nitric oxide, exercise-induced changes in arterial O2 content (SaO2, PaO2, hemoglobin), muscle blood volume, and O2 extraction (via near-infrared spectroscopy). We analyzed blood samples for metabolic and hormonal vasoactive moieties and factors that are able to shift the O2-hemoglobin dissociation curve. Mitochondrial oxidative capacities were assessed in permeabilized vastus lateralis muscle fibers. RESULTS: Lung diffusion capacity and arterial O2 transport were normal in patients with T1D. However, those patients displayed blunted exercise-induced increases in muscle blood volume, despite higher serum insulin, and in O2 extraction, despite higher erythrocyte 2,3-diphosphoglycerate. Although complex I- and complex II-supported mitochondrial respirations were unaltered, complex IV capacity (relative to complex I capacity) was impaired in patients with T1D, and this was even more apparent in those with long-standing diabetes and high HbA1c. [Formula: see text]O2max was lower in patients with T1D than in the control subjects. CONCLUSIONS: Early defects in microvascular delivery of blood to skeletal muscle and in complex IV capacity in the mitochondrial respiratory chain may negatively impact aerobic fitness. These findings are clinically relevant considering the main role of skeletal muscle oxidation in whole-body glucose disposal.

Remote Monitoring of Diabetes: A Cloud-Connected Digital System for Individuals With Diabetes and Their Health Care Providers.

Benefits of telemedicine have been proven in the field of diabetes. Among a number of technical solutions, Diabeo® has been studied in both type 1 and type 2 diabetes with intensive insulin therapy. This digital therapeutic system contains a self-monitoring glucose logbook and offers automated insulin dose recommendations thanks to a fully customizable algorithm. In addition, the cloud-based dedicated software also has features to facilitate remote monitoring, including a platform for diabetes nurses who perform coaching and treatment adjustment. A detailed description of this telemedicine system is provided, as well as results of completed clinical studies. In particular, TeleDiab 1's positive results on HbA1c in type 1 diabetes are detailed. We conclude with a discussion of the role of this telemedicine system within the landscape of mobile apps for diabetes.

DIABEO App Software and Telemedicine Versus Usual Follow-Up in the Treatment of Diabetic Patients: Protocol for the TELESAGE Randomized Controlled Trial.

BACKGROUND: Self-management of diabetes minimizes the risk of macrovascular and microvascular complications, but understanding and/or adherence to self-management recommendations is often suboptimal. DIABEO is a smartphone app (downloaded via the internet) used to calculate bolus insulin doses. A previous study (TELEDIAB 1) showed that the use of DIABEO was associated with a significant improvement in glycemic control in patients with poorly controlled type 1 diabetes mellitus, particularly when combined with teleconsultations with physicians. OBJECTIVE: Here, we present the protocol for a new study (Suivi A Grande Echelle d'une cohorte de diabétiques de type 1 et de type 2 sous schéma insulinique basal bolus par la TELEmédecine; abbreviated TELESAGE), conducted in a larger population of diabetic patients with poorly controlled basal-bolus insulin levels. METHODS: TELESAGE is a multicenter, double-randomized, open-label, three parallel-arms study, conducted in approximately 100 centers in France. The study will compare a control group (arm 1: usual follow-up) with two DIABEO telemedicine systems: (1) physician-assisted telemedicine (arm 2), and (2) nurse-assisted telemonitoring and teleconsultations by a diabetologist's task delegation (arm 3). Initial randomization will allocate the study arms in 12 French regions. A second randomization will assign patients in the groups allocated to each studied region. The primary objective of TELESAGE will be to investigate the effect of the DIABEO telemedicine system versus usual follow-up, with respect to improvements in the glycated hemoglobin levels of approximately 696 diabetic patients with poorly controlled basal-bolus insulin levels. RESULTS: The TELESAGE study is sponsored by Sanofi (Gentilly, France). A primary completion date is expected in June 2018, and publication of results is expected within 6 months of work completion. CONCLUSIONS: The TELESAGE study is expected to confirm the previous results of the TELEDIAB 1 study using a larger sample of diabetic patients. It is also expected to evaluate a nurse-assisted telemonitoring system. We will assess the potential of the DIABEO telemedicine service in terms of its utility and explore whether it can become an integral part of diabetes care for patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT02287532; https://clinicaltrials.gov/ct2/show/NCT02287532 (Archived by WebCite at http://www.webcitation.org/6ykajhJKd).

Influence of glycaemic control on the outcomes of patients treated by intravenous thrombolysis for cerebral ischaemia.

Whether the glycaemic control during the first hours of cerebral ischaemia treated by thrombolysis influences outcomes remains unsettled. We aimed at evaluating the quality of the glycaemic control and whether patients with well-controlled glycaemia after thrombolysis for acute cerebral ischaemia have better outcomes. We retrospectively analysed data prospectively collected in consecutive stroke patients who received i.v. thrombolysis at the Lille University Hospital. Patients with glycaemia >1.6 g/l (8.9 mmol/l) at any point during the first 48 h received insulin. We used 2 definitions of well controlled glycaemia: (i) "well controlled 100 %" when 100 % glycaemia were <1.6 g/l (8.9 mmol/l), and (ii) "well controlled 70 %" when at least 70 % glycaemia were <1.6 g/l (8.9 mmol/l). The outcome measures at 3 months were (1) independence [modified Rankin scale (mRS) score 0 or 1], (2) absence of handicap (mRS 0-2), (3) death, and (4) symptomatic intracerebral haemorrhage (sICH). Of 875 consecutive patients, 657 (75.2 %) were considered as well controlled with a threshold at 100 % and 736 (84.2 %) with a threshold at 70 %. The glycaemic control was not independently associated with any of the four outcome measures. In patients treated by insulin, hypoglycaemic events were rare (2.1 % of all patients) and of moderate intensity [>0.5 g/l (2.8 mmol/l)]. The quality of the glycaemic control was not associated with outcomes in patients treated by thrombolysis. A possible explanation is that the glycaemic control after thrombolysis has minor influence compared with glycaemic control before thrombolysis when the artery is not yet re-open and the penumbra area at maximum.

The multinational second Diabetes, Attitudes, Wishes and Needs study: results of the French survey.

AIM: The second Diabetes, Attitudes, Wishes and Needs (DAWN2™) multinational cross-sectional study was aimed at generating insights to facilitate innovative efforts by people with diabetes (PWD), family members (FMs), and health care professionals (HCPs) to improve self-management and psychosocial support in diabetes. Here, the French data from the DAWN2™ study are described. METHODS: In France, 500 PWD (80 with type 1 diabetes [T1] and 420 with type 2 diabetes [T2]), 120 FMs, and 288 HCPs were recruited. The questionnaires assessed the impact of diabetes on quality of life and mood, self-management, attitudes/beliefs, and care/support. RESULTS: Diabetes negatively impacted the emotional well-being of 59% of people with T1 versus 45% of people with T2 (P<0.05) and about half of FMs. A high level of distress was felt by about half of PWD and FMs. About half of HCPs reported assessing depression in their patients. Sixty-two percent of FMs considered managing diabetes to be a burden. Hypoglycemia was a source of concern for 64% of people with T1 and 73% of FMs of insulin users. About two-thirds of non-insulin-medicated people with T2 agreed to start insulin if prescribed, while half of HCPs preferred to delay insulin initiation. A discrepancy between HCPs' perceptions of their interactions with their patients and PWD's recollection of these interactions with regard to patients' personal needs and distress was also observed. CONCLUSION: While distress remains under-assessed by HCPs, the negative impact of diabetes on the lives of PWD and FMs clearly induces distress on both groups. These findings provide new understanding of barriers precluding optimal management of diabetes. Developing strategies to overcome these barriers is now warranted.