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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.

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.

Type 1 diabetes mellitus (T1DM) is associated with a high risk of cardiovascular (CV) complications, even after controlling for traditional CV risk factors. Therefore, determinants of the residual increased CV morbidity and mortality remain to be discovered. This prospective cohort of people living with T1DM in France (SFDT1) will include adults and children aged over six years living with T1DM, recruited throughout metropolitan France and overseas French departments and territories. The primary objective is to better understand the parameters associated with CV complications in T1DM. Clinical data and biobank samples will be collected during routine visits every three years. Data from connected tools, including continuous glucose monitoring, will be available during the 10-year active follow-up. Patient-reported outcomes, psychological and socioeconomic information will also be collected either at visits or through web questionnaires accessible via the internet. Additionally, access to the national health data system (Health Data Hub) will provide information on healthcare and a passive 20-year medico-administrative follow-up. Using Health Data Hub, SFDT1 participants will be compared to non-diabetic individuals matched on age, gender, and residency area. The cohort is sponsored by the French-speaking Foundation for Diabetes Research (FFRD) and aims to include 15,000 participants.

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.

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. 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. 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

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 $\pm$ 0.02 and 0.82 $\pm$ 0.02 vs. 0.75 $\pm$ 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.

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 of metformin-DPP4i combination therapy was observed (14% of dual therapies in 2008 versus 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 2 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.

Resume L’objectif de cet observatoire dynamique etait d’obtenir une vue d’ensemble recente de la prise en charge des patients diabetiques de type 2 en France, en particulier traites par injectables. Il etait egalement de determiner le role de l’hopital et des medecins liberaux, diabetologues/endocrinologues et medecins generalistes, dans l‘initiation et la modification des traitements injectables chez ces patients. L’analyse a ete basee sur les informations de toutes delivrances de medicaments au sein d’un panel representatif de 7 100 pharmacies des 21 regions administratives metropolitaines (hors Corse) entre decembre 2014 a novembre 2015.

International audience; 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.

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. 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.

170 Background: Few epidemiological studies address differences in outcomes by gender in locoregional esophageal cancer (LEC) for which the current standard of care is chemoradiation followed by surgical resection. Although male gender is associated with the majority of LEC cases, we sought to determine if gender could impact clinical presentation as well as surgical and oncologic outcomes in our single institution 20 year experience. Methods: A retrospective query of our institution’s IRB-approved database of patients that had surgical therapy between 2008 and 2019 for esophageal cancer (EC) was performed. Patients were stratified by gender and analyzed based on characteristics such as tumor histology, tumor location, clinical stage at presentation, age at diagnosis, receipt of neoadjuvant therapy, surgical intent, surgical complications, length of post-operative hospital stay, response to neoadjuvant therapy, final pathology, and recurrence. Chi-square, ANOVA and Kaplan Meier survival analysis were performed on the previously defined groups. Results: The cohort studied included 1180 patients with resection for EC. Of those, 1005 (85.2%) had adenocarcinoma, 145 (12.3%) had squamous cell cancer (SCC), 10 (0.8%) had adenosquamous carcinoma, and 20 (1.7%) had other histological variants. There were 985 (83.5%) male patients and 195 (16.5%) female patients. SCC was more common in females (29.2% in females vs. 8.9% in males, p = 0.000) and females tended to have tumor location in the upper thoracic esophagus more often (4.7% in females vs. 0.9% of males, p = 0.000). Additionally, females developed surgical complications more often than males (72.2% vs. 64.7%, p = 0.045). Staging at diagnosis (p = 0.508), receipt of neoadjuvant treatment (p = 0.676), and age at diagnosis (65.3 years in males vs. 66.3 years in females, p = 0.934) had no association with gender. Response to neoadjuvant therapy (p = 0.157) and cancer recurrence (p = 0.434) did not have significant associations with gender. The median overall survival was not statistically significantly different but trended to be longer for females (73.4 months in females [95% CI: 51.5-95.4] vs. 47.0 months in males [95% CI: 39.6-54.5], p = 0.160). Conclusions: Based on our high-volume cancer center study, female patients were more likely to have SCC, upper thoracic esophageal lesions, and surgical complications following resection. While univariate analysis did not demonstrate significant differences in overall survival between genders, there are plans to report additional data after controlling for other variables. Further studies are warranted to validate these findings, given the potential for higher prioritization of an organ preservation approach for this patient population.

Aim DIALOG assessed the prevalence and predictors of hypoglycaemia in patients with type 1 (T1DM) or insulin-treated type 2 diabetes mellitus (T2DM) in a real-life setting. Methods In this observational study, insulin-treated patients ( n =3048) completed prospective daily questionnaires reporting the frequency and consequences of severe/confirmed non-severe hypoglycaemia over 30 days. Patients ( n =3743) also retrospectively reported severe hypoglycaemia over the preceding year. Results In this prospective survey, 85.3% and 43.6% of patients with T1DM and T2DM, respectively, reported experiencing at least one confirmed hypoglycaemic event over 30 days, while 13.4% and 6.4%, respectively, reported at least one severe event. Hypoglycaemia frequency increased with longer duration of diabetes and insulin therapy. Strongly predictive factors for hypoglycaemia were previous hypoglycaemia, >2 injections/day, BMI 2 and duration of insulin therapy>10 years. HbA 1c level was not predictive of hypoglycaemia in either T1DM or T2DM. The confirmed hypoglycaemia rate was increased in the lowest compared with the highest tertile of HbA 1c in T1DM, but not T2DM. At the time of enrolment, physicians reported severe hypoglycaemia in 23.6% and 11.9% of T1DM and T2DM patients, respectively, during the preceding year; the retrospective survey yielded frequencies of 31.5% and 21.7%, respectively. Also, severe hypoglycaemia led to medical complications in 10.7% and 7.8% of events in T1DM and T2DM patients, respectively, over 30 days. Conclusion Using a unique combined prospective and retrospective approach, the DIALOG study found a relatively high frequency of hypoglycaemia among insulin-treated patients. These findings emphasize the importance of a patient-centred approach for managing diabetes in which hypoglycaemia risk evaluation is critical. Trial registration ClinicalTrials.gov: NCT01628341.

The beneficial effects of physical activity and the advantages of good physical fitness are well established both in healthy individuals and in those with chronic disease (20,21). Aerobic fitness, as measured by maximal oxygen (O2) uptake (V˙O2max), is a strong predictor of cardiovascular risk (2). In patients with type 1 diabetes, poor fitness represents an important barrier to regular physical activity (9). Consequently, better understanding of the underlying factors involved in the possible impairment of V˙O2max in patients with type 1 diabetes is warranted. Low aerobic fitness levels have been reported in several (28,32), albeit not all (21,39), studies in adults with type 1 diabetes and seem to be associated with poor glycemic control, as reflected by high glycated hemoglobin (HbA1c) levels (5,24,30). A high HbA1c level is indeed an important factor in the initiation and progression of micro- and macrovascular complications. In turn, these complications may alter the functioning of tissues that are important for exercise adaptations, such as blood vessels, lungs, and heart (11,41) and, consequently, reduce V˙O2max. However, there may be other factors involved in the impairment of aerobic fitness observed in individuals with poor glycemic control. In this respect, the HbA1c– V˙O2max relation has been found even in the absence of diabetic complications in young patients with type 1 diabetes (24,35). O2 supply, including arterial O2 delivery and O2 release (i.e., oxyhemoglobin (O2Hb) dissociation) to active muscles, is a well-established factor influencing V˙O2max in healthy subjects or subjects with a chronic disease (17,29). In adolescents with type 1 diabetes, one study reported reduction in forearm blood flow after local exercise (rhythmic handgrip) despite the absence of any otherwise clinically detectable vascular disorders (33). To our knowledge, arterial O2 transport capacity has never been investigated during exercise in patients with type 1 diabetes and with different levels of HbA1c. Several in vitro studies suggest possibly increased O2Hb affinity (i.e., a leftward shift of the O2 dissociation curve) and/or decreased sensitivity of hemoglobin to the allosteric effect of organic phosphates as a result of hemoglobin glycation at a degree corresponding to HbA1c levels in patients with poor glycemic control (i.e., 8%) (10,25,26,36). Some further insight into muscle O2Hb dissociation in type 1 diabetes is required, particularly in vivo during maximal exercise and in accordance with HbA1c levels. In this respect, near-infrared spectroscopy (NIRS) allows noninvasive and functional monitoring of changes in skeletal muscle oxygenation including O2Hb dissociation (18). Besides hemoglobin glycation, it is important to take into account the erythrocyte 2,3-diphosphoglycerate (2,3-DPG) level. This stimulus for a rightward shift of the O2Hb dissociation curve has been found to be, contradictorily, either reduced (15,16) or elevated in patients with type 1 diabetes (8), especially in cases of chronically impaired glycemic control (1). Therefore, we aimed to determine whether O2 delivery and/or release to an active muscle during maximal exercise is altered in patients with uncomplicated type 1 diabetes and high levels of HbA1c and whether any subsequent relation to impairment in V˙O2max exists.

181 Background: Neoadjuvant chemoradiation (NCRT) and surgery is standard treatment for esophageal cancer (EC) in the U.S. The role of adjuvant chemotherapy (ACT) is unclear. Providers assign ACT inconsistently, and both its rationales and benefits have yet to be clearly defined. We sought to evaluate rationales and benefits for ACT in EC. Methods: This single institution retrospective review included 382 patients (pts) with EC who were treated at our tertiary referral center. All pts received NCRT and 46 received ACT. We reviewed medical records to obtain demographic and clinical information. Survival outcomes were analyzed with Kaplan-Meier method from date of death or last follow up and log-rank analysis. Case-control analysis was performed using a 2:1 nearest neighbor propensity score matching algorithm, and included 113 pts, 41 of which received ACT. Results: 46 of the 382 pts in our study who received NCRT and surgery for EC also underwent ACT; two pts had single agent paclitaxel, 9 had 5-F/U and leucovorin, 7 had 5-F/U and cisplatin, 5 had carboplatin and paclitaxel, 2 had carboplatin alone, and the remainder had other combinations. Pts who received ACT were younger (med. age = 60.2 v 63.8 yr, p = 0.047), more likely to have adenocarcinoma (91.3% v 85.1%, p = 0.034), and less likely to have positive LNs on pre-treatment EUS (60.1% v 77.4%, p = 0.018). Pts with pCR were less likely to receive further treatment (6.5% v 45.8%, p < 0.001), and pts with R1 resection were more likely to do so (15.2% v 4.2%, p = 0.007). With case-control analysis, no variables were significantly different between the two groups. The median follow-up times for the entire cohort and case-control analysis were 7.98 years and 8.89 years, respectively. There were no significant differences in overall (p = 0.975) or recurrence-free (p = 0.824) survival associated with ACT in either analysis. Conclusions: The role of CT following NCRT and surgical resection in pts with locally advanced ECis unclear. In the largest series to date, our single institution retrospective review found no significant difference in survival in pts who received ACT and those who did not. Prospective studies are needed to further identify the rationales for delivery of ACT, and to investigate any potential survival benefits.

Morbid obesity increases the risk of cardiovascular disease (CVD). The receptor for advanced glycation end-products (RAGE) is implicated in proinflammatory processes that underlie CVD. Its soluble form (sRAGE) has been proposed as a vascular biomarker. Recently, anti-sRAGE autoantibodies were described and found to be increased in diseases where RAGE is overexpressed. This study aimed to investigate serum levels of anti-sRAGE autoantibodies in morbidly obese patients.After exclusion based on specific criteria, 150 subjects (50 normoglycemics, 50 glucose-intolerants and 50 diabetics) were randomly recruited from a cohort of 750 obese patients (ABOS). Serum sRAGE and anti-sRAGE autoantibodies were measured before bariatric surgery. Sixty-nine patients were followed for up to 1year after gastric bypass, and their levels of sRAGE and anti-sRAGE autoantibodies measured. The control group consisted of healthy blood donors.Compared with controls, baseline levels of sRAGE and anti-sRAGE autoantibodies were significantly higher in all obese patients independently of glucose regulation (P0.001). At 1year after gastric bypass, sRAGE and anti-sRAGE were decreased (P0.001). The decrease in anti-sRAGE autoantibodies was correlated with an increase in high-density lipoprotein (HDL; P=0.02).Independently of previous diabetic status, morbid obesity increases sRAGE and anti-sRAGE levels. Weight loss after gastric bypass is followed by a decrease in both titres. The decrease in anti-sRAGE correlates with an increase in HDL.

Background Obesity, characterized by low grade inflammation, induces adipose tissue macrophage (ATM) infiltration in white adipose tissue (AT) in both humans and rodents, thus contributing to insulin resistance. Previous studies have shown altered prolactin secretion in obesity, however, studies linking ATM infiltration and prolactin (PRL) secretion to the pathogenesis of the metabolic syndrome, obesity and diabetes are lacking. Methods/Results In vivo, qPCR and Western blot analysis demonstrated that prolactin expression was increased in AT of obese rats and also in human AT from obese, obese pre-diabetic and obese diabetic compared to lean counterparts. Immunohistochemistry of obese rat and human AT sections demonstrated a specific expression of prolactin in macrophages. In vitro, we demonstrated that hyperglycemia and inflammation stimulated macrophages (human THP-1 cell line and sorted rat ATM) to express PRL, when challenged with different glucose concentrations with or without IL1β. In in vivo and in vitro experiments, we assessed the expression of Pit-1 (PRL-specific transcription factor) and found that its expression was parallel to PRL expression. Conclusions In this study, we show that rodent and human macrophages synthesize prolactin in response to inflammation and high glucose concentrations. General significance Our data shed new light on the potential role of macrophages in the physiopathology of diabesity via the PRL expression and on its expression mechanism and regulation.

Growing evidence indicates that maternal pathophysiological conditions, such as diabetes, influence fetal growth and could program metabolic disease in adulthood. Placental cells, particularly Hofbauer cells (HBCs), which are placental macrophages characterized by an anti-inflammatory profile (M2), can sense the modified maternal environment. The goal of this study was to investigate the direct effect of hyperglycemia on HBCs. We studied, at mRNA and protein levels, some markers of M2 and M1 (pro-inflammatory) macrophages in placentae from control and diabetic patients to assess the balance between pro- and anti-inflammatory macrophages: an imbalance of M2 to M1 macrophages has been observed in humans. We used pregnant rats, receiving a single injection of streptozotocin (STZ), as a model of maternal diabetes. We noticed a M2-to-M1 macrophage unbalance as we observed in human. An in vitro model of isolated rat HBCs was used to identify the direct effects of high glucose. We found that high glucose stimulation activated genes belonging to TLR (Toll-Like Receptor)-dependent inflammatory pathways. Moreover, the HBCs stimulated by high glucose switched their M2 profile towards M1, with increased expression of pro-inflammatory cytokines and markers. We also noticed that the oxidative-stress pathway was activated in response to high glucose driven by Hif-1α. In this study, we demonstrated that diabetes/hyperglycemia affect the anti-inflammatory profile of HBCs, by stimulating these cells to acquire an inflammatory profile leading to adverse consequences for the fetal–placental–maternal axis.

We compared pathologic complete response (pCR) rate, toxicity, and postoperative complications between patients treated preoperatively with 50.4 Gy versus dose escalation with dose-painting intensity-modulated radiation therapy (dp-IMRT) to 56 Gy in locally advanced esophageal cancer. We evaluated esophageal cancer patients treated between 2006 and 2014 with preoperative IMRT chemoradiation to a dose of 50.4 Gy versus 56 Gy. The endpoints were pCR and toxicity. We identified 113 patients (50.4 Gy: n = 40; 56 Gy: n = 73). There were no significant differences in tumor or patient characteristics. Patients treated with 56 Gy demonstrated a higher pCR rate (56.2% vs. 30.0%) and lower pathologic nonresponse rate (4.1% vs. 20.0%) compared to patients treated to 50.4 Gy (P = 0.008). This remained significant on multivariate analysis (OR 3.375 95%CI 1.3-8.8, P = 0.013). Patients treated to 56 Gy also had an improved 3-year locoregional control rate compared to those treated to 50.4 Gy (93.8% vs. 78.5%; P = 0.022). The estimated 3-year freedom from failure was also superior in the 56 Gy arm (73.7% vs. 52.2%; P = 0.051), approaching significance. There were no differences in treatment related grade ≥3 toxicities, hospital admissions, feeding tube, esophageal stent placement, or dilation. There was, however, a statistically significant increase in postoperative atrial fibrillation in patients treated with 56 Gy (30.1% vs. 12.5%; P = 0.036). There was no difference in postoperative 30 or 60 day mortality. Dose escalation to 56 Gy with dp-IMRT is safe and results in significantly higher complete pathologic response rates in esophageal cancer without an increase in treatment-related toxicity. Prospective trials using dp-IMRT are needed to address the role of dose escalation on pCR rate and survival in esophageal cancer.

La grossesse presente un risque d’apparition et d’aggravation d’une retinopathie diabetique (RD) dont la frequence et les facteurs predictifs varient selon les etudes. L’objectif de l’etude est d’evaluer la prevalence et les facteurs de risque d’apparition ou d’aggravation d’une RD pendant la grossesse chez des patientes diabetiques de type 1. L’etude inclut 499 grossesses chez 375 patientes diabetiques de type 1 suivies dans une structure multidisciplinaire au CHRU de Lille, ayant accouche entre 1997 et 2015. Les donnees diabetologiques, obstetricales et ophtalmologiques ont ete recueillies a partir des dossiers medicaux. Le suivi ophtalmologique consistait en la realisation trimestrielle d’un fond d’œil et/ou angiographie, mensuelle en cas de retinopathie initiale severe ou d’aggravation pendant la grossesse. Une progression de la RD a ete observee dans 21,8 % des grossesses (24,4 % d’apparition parmi les 348 grossesses sans retinopathie initiale et 15,9 % d’aggravation parmi les 151 grossesses avec retinopathie preexistante). On note une regression dans le post-partum pour 9,3 % des grossesses. L’anciennete du diabete ( p p p p p

Les donnees epidemiologiques et anatomopathologiques ont montre que le patient diabetique est expose precocement aux complications liees a l’atherosclerose, suggerant que la presence d’un diabete equivaut a un vieillissement arteriel de 15 ans en termes de risque cardiovasculaire. Diabete et vieillissement physiologique partagent des anomalies communes. Sur le plan structural, ces anomalies sont representees par l’augmentation de l’epaisseur intima-media, le remodelage matriciel et les calcifications. Sur le plan fonctionnel, la rigidite arterielle et la dysfonction endotheliale sont observees conjointement dans les deux situations. Ces anomalies resultent egalement de mecanismes physiopathologiques communs, tels que la voie des produits finaux de la glycation et le stress oxydatif, ouvrant de nouvelles perspectives therapeutiques.

Resume La grossesse chez la patiente diabetique reste une grossesse a haut risque puisque le diabete influence le devenir materno-fœtal. Puisque le degre d’hyper glycemie conditionne ces risques, le monitoring des glycemies est devenu imperatif dans la prise en charge. En effet, les principales complications restent la macrosomie, les malformations congenitales, l’accouchement premature et les complications du travail et de l’accouchement. Ces risques sont reduits lors d’une prise en charge intensive associant la dietetique, l’insulinotherapie et l’autosurveillance glycemique (ASG). Obtenir une normoglycemie est necessaire tout au long de la grossesse, mais egalement au cours du travail et de l’accouchement. Il a ete demontre que l’hyperglycemie postprandiale est davantage associee a la genese des complications materno-fœtales que ne l’est la glycemie a jeun. L’ASG permet une optimisation therapeutique permettant un meilleur controle des hyperglycemies, notamment postprandiales. Bien que les modalites pratiques (horaires et frequences) restent a ce jour discute puisque nous manquons d’etudes avec haut niveau de preuves, il convient d’effectuer au moins quatre glycemies capillaires au cours du diabete gestationnel traite par dietetique, et au moins six glycemies capillaires en cas d’insulinotherapie associee. Par ailleurs, l’avancee des nouvelles technologies comme la mesure continue de glucose devrait etre un outil complementaire dans la prise en charge du diabete au cours de la grossesse.

146 Background: Radiomic data extraction from medical images has the potential to differentiate tumor phenotypes. We investigated the potential of esophageal cancer radiomic features to differentiate clinical outcomes following neoadjuvant chemoradiation (NACRT). Methods: We retrospectively reviewed 68 biopsy-proven mid-distal esophageal/gastroesophageal junction (GEJ) cancer patients treated from 2007-2014 with NACRT followed by esophagectomy on an IRB approved study in which patients were eligible if imaging was performed at our institution. The primary tumor was segmented on baseline computed tomography (CT) and 18-Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) scans with contour review by two independent radiation oncologists. A total of 126 quantitative 3-D shape and intensity-based radiomics features were extracted using in-house data algorithm software. Locoregional control (LRC), metastasis free survival (DFS), metastasis free survival (MFS) and overall survival (OS) were estimated by Kaplan-Meier analysis and multivariate Cox proportion hazard. Results: Estimated actuarial 5-year RFS, LRC, MFS, OS was 56.6% (mean: 67.8 months, 95% CI 53.7-81.8 months), 83.1% (mean: 92.8 months, 95% CI 81.4-104.2 months), 64.9% (mean: 76.4 months, 95% CI 62.2-90.7 months), 39.5% (median survival 40 months, 95% CI 24.59-55.40), respectively. Pathological complete response (pCR) was achieved in 34 (50%) patients. Tumor Regression Grade (TRG) 0-1 indicative of complete response was associated with improved LRC [p = 0.04; Hazard Ratio (HR) 4.24 (1.01-19.01)]. On univariate analysis, 16 PET-based and 14 CT-based radiomics features were found to independently predict pCR. On multivariate analysis (MVA), three PET-CT based radiomic features [sphericity (p = 0.04), compactness (p = .05) and PET_TGV (p = 0.08)] were found to closely predict pCR. When grouped by median, PET sphericity independently predicted RFS [p = 0.014; Hazard Ratio (HR) 0.31 95% Confidence Interval (CI) 0.11-0.83]. Conclusions: This study suggests pre-treatment radiomic features in esophageal cancer may be prognostic for response assessment (pCR) and overall outcome following NACRT.

PREDICTIVE (an ongoing multinational observational study) provides an opportunity to explore the impact of insulin detemir use in routine clinical practice. Here, we report on long-term (52-week) data from a French cohort of patients (n=1772), comprising 643 with type 1 diabetes and 1129 with type 2 diabetes.Patients were prescribed insulin detemir at their physician's discretion and assessed at various visits (baseline, 12 weeks, 26 weeks and 52 weeks). The primary endpoint was the frequency of serious adverse drug reactions, including major hypoglycaemia. Secondary endpoints included minor and nocturnal hypoglycaemia, glycaemic control (HbA(1c), fasting blood glucose and variability of fasting blood glucose) and weight change.The incidence of serious adverse drug reactions was low throughout the study, seen in 10 patients with type 1 diabetes (14 events, 1.6%) and seven with type 2 diabetes (seven events, 0.6%). In both type 1 and type 2 diabetes cohorts, the overall minor and nocturnal hypoglycaemic events were reduced from baseline (P0.001), with no clinically significant changes in weight from baseline to endpoint. After 52 weeks of treatment with insulin detemir, glycaemic control improved, with reductions in: HbA(1c), by -0.6% and -0.8% in type 1 and type 2 diabetes patients, respectively; fasting blood glucose, by -1.4mmol/L and -1.9mmol/L respectively; and FBG variability, by -0.8mmol/L and -0.3mmol/L, respectively (P0.0001 for all).Patients treated with insulin detemir in a clinical healthcare setting improved their glycaemic control with no increases in hypoglycaemia, adverse events or weight compared with baseline.

The aim was to compare clinical outcomes by different dosing frequencies of insulin detemir (detemir) used over 52 weeks in various regimens. Methods: This analysis involved French patients enrolled in PREDICTIVE (a large-scale, multinational, observational study of empirical use of detemir in everyday clinical practice) for whom data have been collected over 52 weeks. Three cohorts were considered: patients with type 1 diabetes; patients with type 2 diabetes using detemir in a basal insulin plus oral antidiabetic drug (OAD) regimen; patients with type 2 diabetes using detemir as part of basal-bolus insulin therapy. In each cohort, data were stratified according to detemir dosing frequency at the beginning and end of 52 weeks: once daily (o.d.) at the beginning and end; twice daily (b.i.d.) at the beginning and end; o.d. at the beginning, but b.i.d. at the end. Endpoints assessed included glycated hemoglobin, fasting plasma glucose, hypoglycemia, weight, and insulin dose. There were improvements in glycemic control and tolerability in all subgroups. Patients completing on o.d. dosing tended to have better outcomes than those completing on b.i.d. dosing in all cohorts, and o.d. administration was associated with lower insulin dosing. There was little evidence that switching from o.d. to b.i.d. dosing influenced outcomes other than insulin dose. However, there were some baseline differences between subgroups selected for o.d. and b.i.d. dosing that might have influenced outcomes: many patients appeared to have been continued on previous basal dosing frequencies; for others, b.i.d. detemir dosing seemed to be used to intensify previous therapy. With the caveat that empirical choices of dose frequency were made, this analy-sis shows that empirical use of o.d. detemir produces results at least as good as empirical use of b.i.d. detemir in basal-bolus-treated type 1 and type 2 diabetes, and in basal plus OAD-treated type 2 diabetes.

Aims To estimate the prevalence of diagnosed type 2 diabetes mellitus in the French general population. Secondary objectives were to evaluate treatments and diabetic complications. Methods In this cross-sectional epidemiological survey, a representative sample of the French adult population was selected using a stratified quota method: 10,038 individuals were evaluated by a standardized face-to-face interview. The diagnosis of type 2 diabetes was determined on the basis of replies to six questions using a specific algorithm. Data were collected on risk factors, diabetes history, familial antecedents and diabetic complications. These patients also identified their treatments from an exhaustive list. Results The prevalence of type 2 diabetes was 5.08% in men and 4.11% in women, and rose progressively after the age of 50. Of these, 79patients (13.4%) received no pharmacological treatment, 477 (80.9%) were taking an oral antidiabetic drug and 134 (22.7%) were taking insulin. Renal and ocular complications were reported by 6.8% and 21.0%, respectively, of the patients. Also, 10.4% had been hospitalized at some time of that year for a diabetes-related problem. The most frequently reported treatments were metformin and sulphonylureas, used by more than 50% of the patients. In addition, 380 patients (65.9%) claimed to be following a diet and 228 (39.2%) were consulting a dietitian. Conclusion The prevalence of treated and untreated type 2 diabetes mellitus in France was 4.57%.

OBJECTIVE—The purpose of this study was to compare effects of insulin detemir once daily versus twice a day in a basal-bolus insulin regimen. RESEARCH DESIGN AND METHODS—In this open-label, 7-month study, 520 patients with type 1 diabetes were randomly assigned to receive detemir once daily or twice daily with mealtime insulin aspart. Insulin doses were titrated over 1 month, with patients followed up over the subsequent 3 months. Thereafter, patients were able to switch from one regimen to the other, with an additional nonrandomized 3-month follow-up, to a total of 7 months. The primary end point was A1C at 4 months, with noninferiority defined as a difference RESULTS—A1C at 4 months was 8.1 ± 0.9 versus 8.0 ± 1.0% with once- and twice-daily detemir, respectively, with an adjusted between-group difference of 0.12% (95% CI −0.01 to 0.25%), showing noninferiority for once-daily dosing. Similar results were found in the per protocol population. Improvement in A1C was similar in both groups (−0.4 ± 0.8 vs. −0.5 ± 0.8%; P = 0.09, NS) but with differences in the 7-point glucose profile. Detemir doses were lower (29 ± 18 vs. 39 ± 20 units/day, P < 0.001), but aspart doses were higher (34 ± 17 vs. 26 ± 14 IU/day, P < 0.001) with once-daily detemir. At 7 months, A1C decreased slightly in patients switched from once-daily to twice-daily administration (8.2 ± 0.8 vs. 8.0 ± 0.8%; P = 0.34, NS) in association with increased total insulin doses (P < 0.05), but A1C increased in those switched from twice-daily to once-daily administration (7.2 ± 0.9 vs. 7.6 ± 0.8%, P < 0.05) in association with decreased doses (P < 0.05). CONCLUSIONS—Although some individuals may benefit from twice-daily dosing, the most suitable routine starting schedule for detemir in a basal-bolus regimen for type 1 diabetes is once-daily injection.

OBJECTIVE—The purpose of this article was to identify criteria predictive of remission in nonsurgical treatment of diabetic foot osteomyelitis. RESEARCH DESIGN AND METHODS—Diabetic patients who were initially treated without orthopedic surgery for osteomyelitis of the toe or metatarsal head of a nonischemic foot between June 2002 and June 2003 in nine French diabetic foot centers were identified, and their medical records were reviewed. Remission was defined as the absence of any sign of infection at the initial or contiguous site assessed at least 1 year after the end of treatment. A total of 24 demographic, clinical, and therapeutic variables including bone versus swab culture–based antibiotic therapy were analyzed. RESULTS—Fifty consecutive patients aged 62.2 ± 11.1 years (mean ± SD) with diabetes duration of 16 ± 10.9 years were included. The mean duration of antibiotic treatment was 11.5 ± 4.21 weeks. Bone biopsy was routinely available in four of the nine centers. Overall patient management was similar in the different centers except for the use of rifampin, which was recorded more frequently in patients from centers in which a bone biopsy was available. At the end of a 12.8-month posttreatment mean follow-up, 32 patients (64%) were in remission. Bone culture–based antibiotic therapy was the only variable associated with remission, as determined by both univariate (18 of 32 [56.3%] vs. 4 of 18 [22.2%], P = 0.02) and multivariate analyses (odds ratio 4.78 [95% CI 1.0–22.7], P = 0.04). CONCLUSIONS—Bone culture–based antibiotic therapy is a factor predictive of success in diabetic patients treated nonsurgically for osteomyelitis of the foot.

The IDAHO 2 epidemiological survey was conducted in departments of diabetology in insulin-naïve type 2 diabetics for whom insulin was initiated. The objective was to assess the patients' profile, the treatments proposed during hospital stay and after one year.797 patients were analysed. Their characteristics were: age 64+/-12 years, 49% males, weight: 78+/-17 kg, BMI: 29+/-6 kg/m2, diabetes duration 11 years, prevalence of complications: 68%, fasting blood glucose 13+/-6 mmol/l, HbA1c: 10+/-2.2%; treatment prior to insulin comprised: at least 2 OHA: 71% of cases, one: 21%, no OAD: 8%. At hospital discharge, 54% of the patients used basal insulin. After 1 year, 670 continued on insulin. The insulin initiation was accompanied by a decrease in the FBG level (baseline: 13+/-6 mmol/l; final: 8.5+/-2.75 mmol/l; P0.0001) and a HbA1c improvement (baseline: 10+/-2.2%; final: 7.9+/-1.4%; P0.0001). This was observed du-ring the first 6 months (HbA1c: 7.8%, P0.0001 versus baseline). 80% of the patients remained on the same insulin regimen after 1 year: 35% had 1 injection/day, 44% had 2, 12% had 3 and 9% had a complex regimen. The weight gain, the final daily dose and hypoglycaemias increased with the number of injections. The mean daily insulin dose was 33 U/day (24 U with 1 injection/day).The IDAHO study shows that insulin is effective in type 2 diabetics however, management is inadequate with insulin therapy being initiated too late and at doses which are low after one year.

Summary Objective Self monitoring of blood glucose (SMBG) in type 2 diabetes is a topic of current interest (imbalance between increased health-care costs and improvement in compliance with treatment and diet). An open label randomized prospective study was designed to compare changes in metabolic control over 6 months in patients managed with usual recommendations alone (conventional assessment group) or combined with SMBG. Research design and methods Patients not treated with insulin or previously self monitored, 40 to 75 years of age, with a diagnosis of type 2 diabetes > 1 year and standardized HbA 1c level ≥ 7.5 and ≤ 11% were randomized to either a control group or SMBG group. They were followed up every 6 weeks over 24 weeks. Patients in the SMBG group were given the same device (Ascensia Esprit® Discmeter, Bayer) and were required to perform at least 6 capillary assays a week (3 different days of the week, including weekend). Management of patients was standardized, including drugs, diet and physical activity. The primary efficacy criterion was change in HbA 1c level in Intent To Treat (ITT) patients. Assays were performed at baseline, at 3 and 6 months using the calibrated DCA 2000® device (Bayer). Results Two hundred sixty five general practitioners randomized 988 patients (ITT Population), but 689 patients were evaluable for the primary criterion. At the endpoint, HbA 1c was lower in the SMBG group (8.1 ± 1.6%) than in the conventional treatment group (8.4 ± 1.4%, P = 0.012). The change in HbA 1c levels between baseline and endpoint was classified into two classes: improvement if a change > 0.5% occurred, stability or worsening in case of a change ≤ 0.5%; 57.1% of patients in the SMBG group vs 46.8% in the control group had an improvement in HbA 1c level ( P = 0.007) after 3 months. A steady state was reached during the last 3 months. A multivariate logistic regression analysis was performed and identified factors predictive of improvement in HbA 1c levels: HbA 1c at baseline: odd ratio (OR) = 1.749 ( P P = 0.015), duration of diabetes: OR=0.953 ( P = 0.001) and BMI: OR=0.962 ( P = 0.039). Conclusions This study is the first multicenter, controlled, prospective trial conducted on a large number of patients demonstrating that SMBG was statistically associated with a better quality of metabolic control than usual traditional recommendations alone in type 2 diabetes.

OBJECTIVE—To evaluate perinatal outcome in pregnancies in women with type 1 and type 2 diabetes and the influence of preconception care 10 years after the St. Vincent’s declaration.RESEARCH DESIGN AND METHODS—A cross-sectional study was conducted in 12 perinatal centers in France in 2000-2001. The main investigated outcomes were perinatal mortality, major congenital malformations, and preterm delivery.RESULTS—Among 435 single pregnancies, 289 (66.4%) were from women with type 1 and 146 (33.6%) from women with type 2 diabetes. Perinatal mortality rate was 4.4% (0.7% national rate), severe congenital malformations rate was 4.1% (2.2% national rate), and preterm delivery rate was 38.2% (4.7% national rate). Preconception care was provided in 48.5% women with type 1 diabetes and in 24.0% women with type 2 diabetes. Women whose first trimester HbA1c was >8% had higher rates of perinatal mortality (9.2 vs. 2.5%; odds ratio 3.9; 95% CI 1.5–9.7; P < 0.005), major congenital malformations (8.3 vs. 2.5%; 3.5; 1.3–8.9; P < 0.01), and preterm delivery (57.6 vs. 24.8%; 1.4; 1.1–1.7; P < 0.005) than those with first trimester HbA1c CONCLUSIONS—Pregnancies in women with diabetes are still poorly planned and complicated by higher rates of perinatal mortality and major congenital malformations. Despite knowledge of the importance of intensified glycemic control before pregnancy, reaching the St. Vincent’s target needs further implementation in France.

Summary Several studies have demonstrated an association of cytotoxic T lymphocyte-associated molecule 4 (CTLA-4) (IDDM 12) alanine 17 with type 1 diabetes, but we wished to study the parental effect of CTLA-4 49 A/G dimorphism in diabetic families. The CTLA-4 exon 1 polymorphism (49 A/G), HLA-DRB1 and insulin gene (INS) variable number tandem repeats (VNTR) were analysed in 134 type 1 diabetic patients vs. 273 control subjects. The segregation analysis for transmission was carried out in 70 informative diabetic families using the transmission distortion test (TDT). All genotyping was performed by PCR-RFLP. CTLA-4 49 G allele frequency was not increased in diabetic patients compared to controls (41 vs. 38%, not significant). The distribution of GG, AG and AA CTLA-4 genotypes was similar in the two groups (13, 57 and 30% vs. 11, 54 and 35%, respectively) and was independent of HLA-DRB1 or INS VNTR polymorphism. The CTLA-4 49 G allele showed weak distorted transmission to the diabetic offspring, whereas random transmission was observed in unaffected offspring. This distortion is attributable to a maternal effect (71% compared to the 50% expected ratio; tdt = 4.8; P

Objective : To determine the relationship between pregnancy induced hypertension (PIH) and gestational glucose intolerance. Methods : A 50 g, 1 h glucose loading test was offered to all pregnant women between 24 and 28 weeks of gestation in 15 centres in northern France during 8 months in 1992. If the test was positive (≥7.2 mmol/l), the woman underwent a 3 h oral glucose tolerance test (OGTT) as soon as possible. Using the criteria of Carpenter and Coustan, gestational diabetes mellitus (GDM) was defined by two abnormal values ( n =218) and gestational mild hyperglycemia (GMH) by one abnormal value ( n =130). Each control group was defined by a 50 g, 1 h loading test result of n =108). PIH included gestational hypertension (GH) and preeclampsia (PE). GH was defined as a diastolic pressure of more than 85 mmHg on at least two occasions arising during pregnancy. PE was defined as GH with proteinuria ≥500 mg/24 h. Results : The rate of PIH in the three groups (GDM; GMH and control group, C) was, respectively 17.0, 10.8, and 4.6%. All the six PE occured in the GDM group. Univariate analysis showed significantly higher rate of hypertension in women with a history of PE, increasing body mass index before pregnancy (BMI) and glucose intolerance. In multivariate analysis with adjustment for primiparity, independant risk factors for PIH were a history of PE, BMI>27 and GDM, contrary to GMH and maternal age. Conclusions : PIH appears to be linked to the level of glucose intolerance during pregnancy, independently of other known factors of hypertension.

Introduction/objectivesThe role of the placenta in diabetic mothers on fetal development and programming is unknown. Prolactin (PRL) produced by decidual endometrial cells may have an impact. Although full-length PRL is angiogenic, the processed form by bone morphogenetic protein-1 (BMP-1) and/or cathepsin D (CTSD) is antiangiogenic.The objectives were to investigate the involvement of decidual PRL and its antiangiogenic fragments in placentas from type-1 diabetic women (T1D) and from pregnant diabetic rats with lower offspring weights than controls.MethodsPRL, BMP-1, and CTSD gene expressions and PRL protein level were assessed in T1D placentas (n=8) at delivery and compared to controls (n=5). Wistar rats received, at day 7 of pregnancy, streptozotocin (STZ) (n=5) or nicotinamide (NCT) plus STZ (n=9) or vehicle (n=9). Placental whole-genome gene expression and PRL western blots were performed at birth.ResultsIn human placentas, PRL (p

To study the influence of energy and macronutrient intake on infant birthweight in women with gestational diabetes mellitus undergoing intensive management.This prospective study evaluated the impact of intensive management of gestational diabetes on maternal and fetal morbidity, and addressed the relationship between food intake and infant birthweight.Fifteen maternity hospitals in northern France.Ninety-nine women with gestational diabetes or gestational mild hyperglycemia diagnosed between 24 and 34 weeks of gestation were surveyed. After 1 was excluded because of a premature birth and 18 were excluded as underreporters, 80 women were included in the final analysis. Diet intake was assessed by a dietary history at the first interview, and by two 3-day diet records at the 3rd and 7th week after diagnosis.In a forward-stepwise regression analysis (controlling for maternal age; smoking; parity; prepregnancy BMI; pregnancy weight gain; gestational duration; infant sex; fasting and 2-hour postprandial serum glucose; insulin therapy; and energy, fat, protein and carbohydrate intake during treatment) infant birthweight was positively associated with gestational duration (beta = +0.34, P.002), and negatively with smoking (beta = -0.27, P.02) and carbohydrate intake (beta = -0.24, P.03). There were no large-for-gestational-age infants among women whose carbohydrate intake exceeded 210 g/day.For women with gestational diabetes undergoing intensive management, higher carbohydrate intake is associated with decreased incidence of macrosomia.These findings suggest that nutrition counseling in gestational diabetes must be directed to maintain a sufficient carbohydrate intake (at least 250 g per day), which implies a low-fat diet to limit energy intake. A careful distribution of carbohydrate throughout the day and the use of low-glycemic index foods may help limit postprandial hyperglycemia.

Changes of the tissue factor (TF) pathway of blood coagulation have been described in diabetes and could be involved in its vascular complications. In order to evaluate the influence of the type of diabetes and of the obesity index and age on these changes, factor VII coagulant activity, factor VII antigen, activated factor VII, monocyte TF expression, and plasma Tissue Factor Pathway Inhibitor (TFPI) were examined in 18 Type 1 and 16 Type 2 diabetic patients compared to non-diabetic control subjects matched for age, sex, and obesity index (Types 1 and 2 controls, respectively). Multicomplicated patients were excluded. FVIIc, FVIIAg, and FVIIa were higher in Type 2 diabetic patients and controls than in Type 1 diabetic patients and controls (P< .03). However, FVIIc and FVIIAg were lower in diabetic patients than in their matched controls (P< .03). Monocyte expression of TF was not different between Types 1 and 2 diabetic patients and their matched controls except for LPS-stimulated monocyte TF activity which was lower in Type 2 diabetic patients than in Type 2 controls (P< .05). Plasma TFPI was slightly but significantly higher in Type 1 diabetic patients than in Type 1 controls (P= .01) and was correlated to glycemia. However, both in Type 2 diabetic patients and controls, TFPI was higher than in Type 1 controls and was correlated with BMI (P< .0003). These results indicate that in not multicomplicated patients, the increase of FVII and TFPI was highly dependent on obesity index and age rather than on diabetes by itself.

Introduction Malgre l’amelioration des pratiques, la grossesse reste associee a une morbidite materno-fœtale elevee chez la DT1. Notre objectif a ete d’evaluer l’equilibre metabolique et le devenir materno-fœtal chez des DT1 traitees par pompe a insuline Patients et methodes Nous avons etudie retrospectivement 241 grossesses DT1 issues des CHRU de Lille et Toulouse entre 2006 et 2012, toutes prises en charge dans le cadre d’une structure multidisciplinaire selon le referentiel de la SFD. Nous avons compare deux groupes : G1 (n = 180) traite par pompe avant la conception et G0 (n = 61) initiant ce traitement en cours de grossesse. Resultats Les patientes de G1 etaient plus âgees (30,4 ± 5,0 vs 28,4 ± 5,3 ans, p Conclusion L’utilisation de l’insulinotherapie par pompe avant la grossesse permet une amelioration de l’equilibre metabolique sans augmenter le risque d’acidocetose. Cependant, compte-tenu du faible nombre d’evenements, notre etude n’a pas mis en evidence de reduction significative de la morbidite materno-fœtale. Declaration d’interet Les auteurs declarent ne pas avoir d’interet direct ou indirect (financier ou en nature) avec un organisme prive, industriel ou commercial en relation avec le sujet presente.