The JUBILE cohort: Quality of life after more than 40 years with type 1 diabetes.

AIM: The incidence of type 1 diabetes is increasing, and more people are going to live many years with the disease. Quality of life might become the most challenging long-term complication. The JUBILE study describes the quality of life of people living with type 1 diabetes for more than 40 years. METHODS: Patients were recruited from 35 French regional or university hospitals: patients and physicians completed questionnaires, validated by the Delphi method. From 1200 questionnaires circulated, 808 patients and their physicians returned questionnaires. RESULTS: The duration of type 1 diabetes was 49 ± 6 years (mean±SD), age at diagnosis 15 ± 10 years, HbA1c 7.4 ± 0.9% [58 ± 10 mmol/mol] and 52% were men. Macrovascular disease was present in 32%, 46% had no or only mild non proliferative retinopathy. Insulin pumps were used by 25% and insulin pen/syringe users injected 3.9 ± 2.1 times per day. Blood glucose was self monitored at least five times per day by 67% of patients. Men had 1.8 ± 1.2 children, women 1.4 ± 1.0. More than half (55%) of this population was working, 38% had a university degree. Patients still had a busy life, going out (59%), eating out (82%), playing sports (38%) and travelling (66%). No differences appeared based on age, duration of diabetes, demography or social features. CONCLUSIONS: Living a long and pleasant life is possible with type 1 diabetes. Diabetes does not prevent people from having children, working at highly qualified jobs, travelling abroad: a message of hope that is comforting for patients, their family, relatives and the medical teams.

Prenatal education of overweight or obese pregnant women to prevent childhood overweight (the ETOIG study): an open-label, randomized controlled trial.

BACKGROUND: We aimed to evaluate whether pre and perinatal education of pregnant women would reduce childhood overweight. METHODS: Four French centers included women at ≤21 gestational weeks (GWs) with body mass index (BMI) >25 kg/m2 before pregnancy. Patients were randomized to a control group (routine care including at least one dietary visit) or an intervention group (2 individuals (26 and 30 GW) and 4 group sessions (21, 28, 35 GW, 2 months postpartum)) aimed at educating the future mother regarding infant and maternal nutrition. The primary objective was to reduce post-natal excessive weight gain in the infant from birth to 2 years (NCT00804765). This project was funded by a grant from the National Programme for Hospital Research (PHRC-2007 French Ministry of Health). RESULTS: We included 275 women (BMI: 32.5 kg/m2). The rate of post-natal excessive weight gain was similar in the intervention (n = 132) and control (n = 136) groups by intention to treat (ITT: 59.1% vs 60.3% respectively, p = 0.84) in available data (AD, n = 206) and by per-protocol analysis (PP, n = 177). Two years after delivery, normalization of maternal BMI and number of infants with BMI < 19 kg/m2 were not significantly different in the interventional group in ITT and in the control group. Although not significantly different in ITT, normalization of maternal BMI was more frequent in AD (n = 149: 12.9% vs 3.8%, p = 0.04) and 2-year-old infant BMIs were less likely to be >19 kg/m2 in the intervention group in AD (n = 204: 0% vs 6.8%, p = 0.014) and PP (n = 176: 0% vs 6.4%, p = 0.03). CONCLUSIONS: An education and nutritional counseling program for overweight women, starting after 3 months of gestation, did not significantly change post-natal excessive weight gain of infants or prevent overweight in mothers and children 2 years after delivery.

[LY2963016 insulin glargine: The first biosimilar insulin approved in the European Union]. / Développement des biosimilaires de l'insuline : exemple de l'insuline glargine LY2963016.

Biosimilars are not generics. They are similar, but not exactly identical to the biological reference product. The development plan of a biosimilar should assess the physical, chemical and biological properties (quality), as well as toxicological (safety), pharmacodynamic, pharmacokinetic, and clinical (efficacy and safety) characteristics of the biosimilar developed. The development of generics requires bioequivalence studies in healthy volunteers. Abasaglar®, a biosimilar of insulin glargine, is the first insulin biosimilar approved in the European Union. Phase III studies, ELEMENT 1 in patients with type 1 diabetes mellitus and ELEMENT 2 in patients with type 2 diabetes mellitus, showed LY2963016 insulin glargine to have similar efficacy and a comparable safety profile to the insulin glargine Lantus®. Policies for interchangeability/substitutability between a biosimilar and the reference product are decided at national level in Europe (LFSP, ANSM).

Delay discounting of gains and losses, glycemic control and therapeutic adherence in type 2 diabetes.

OBJECTIVE: Delay discounting is the tendency to prefer smaller, sooner rewards to larger, later ones. Poor adherence in type 2 diabetes could be partially explained by a discounted value of health, as a function of delay. Delay discounting can be described with a hyperbolic model characterized by a coefficient, k. The higher k, the less future consequences are taken into account when making decisions. This study aimed to determine whether k would be correlated with glycated hemoglobin and adherence in type 2 diabetes. METHODS: Ninety-three patients were recruited in two diabetology departments. Delay discounting coefficients were measured with a computerized task. HbA1c was recorded and adherence was assessed by questionnaires. Potential socio-demographic and clinical confounding factors were collected. RESULTS: There was a positive correlation between delay discounting of gains and HbA1c (r=0.242, P=0.023). This association remained significant after adjusting for potential confounding factors (F=4.807, P=0.031, η2=0.058). This association was partially mediated by adherence to medication (ß=0.048, 95% CI [0.004-0.131]). CONCLUSIONS: Glycemic control is associated with delay discounting in patients suffering from type 2 diabetes. Should these findings be replicated with a prospective design, they could lead to new strategies to improve glycemic control among these patients.

Do the EMA accelerated assessment procedure and the FDA priority review ensure a therapeutic added value? 2006-2015: a cohort study.

PURPOSE: The Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have both implemented procedures in order to shorten review time for marketing authorizations with potential therapeutic added value, called priority review and accelerated assessment procedure, respectively. The aim of this study is to compare the new molecular entities (NME) assessed in shorter review time by both agencies and to investigate whether granting a shorter review time status subsequently predicts its therapeutic value attributed by a health technology assessment agency, the French Haute Autorité de Santé (HAS). METHODS: All NME approved by the EMA and the FDA with a therapeutic added value between 2007 and June 30, 2015 were extracted. We assessed the sensibility, the positive predictive value, and the EMA review time. RESULTS: One hundred seventy-eight NME were approved by the FDA and the EMA and a therapeutic value was available for 160 NME. Eighty-eight (55.0 %) NME were on FDA priority review, 24 (15.0 %) on EMA accelerated procedure and 43 (26.9 %) were considered of high clinical added value. The sensibility was 86.0 % for the FDA and 30.2 % for the EMA. The positive predictive value was, respectively, 42.0 and 54.2 %. Twenty-five NME on FDA priority review and of high therapeutic added value were not on EMA accelerated assessment procedure, leading to a supplementary mean EMA review time of 146 days. CONCLUSION: The EMA was restrictive to grant a shorten review time status for products with therapeutic interest during the study period.

Observations and lessons learnt from non health professionals evaluating a health search engine.

This article presents the results of one of the stages of the user-centered evaluation conducted in a framework of the EU project Khresmoi. In a controlled environment, users were asked to perform health-related tasks using a search engine specifically developed for trustworthy online health information. Twenty seven participants from largely the Czech Republic and France took part in the evaluation. All reported overall a positive experience, while some features caused some criticism. Learning points are summed up regarding running such types of evaluations with the general public and specifically with patients.

High vitamin D deficiency rate in metabolic inpatients: is bariatric surgery planning found guilty?

BACKGROUND: High rates of vitamin D insufficiency are usually found in obese patients, even before any malabsorptive bariatric surgery. It is not clear whether they lack vitamin D because of different food intake, different solar exposure, or different storage pathways or bioavailability in adipose tissue. To better understand vitamin D deficiency, we studied different categories of inpatients. METHODS: We collected clinical and biological data from 457 consecutive inpatients during a year: 217 nonobese diabetic patients, 159 obese nonsurgical diabetic patients, 46 obese surgical nondiabetic patients, and 35 obese surgical diabetic patients. Statistically significant differences between two mean 25-hydroxyvitamin D (25(OH)D) levels were defined at the 5 % level using a Z-test. RESULTS: Vitamin D deficiency was found in 69 % of the patients, while 24 % had a normal level and 7 % an optimal level. A significant difference was found between obese (25(OH)D = 40.3 nmol/l) and nonobese patients (25(OH)D = 46.8 nmol/l). Patients undergoing bariatric surgery were not different from the other obese patients. CONCLUSION: No significant difference in 25(OH) vitamin D level could be demonstrated between obese patients before bariatric surgery and obese patients with no obesity surgery project. No difference was found between our Parisian obese population and a Spanish obese population, which benefits from a better solar exposure. Both findings suggest that obesity itself is the link with vitamin D deficiency, independently from behavioral differences.

[Insulin therapy among inpatients]. / L'insulinothérapie à l'hôpital.

To identify patients with known diabetes or hospital-related hyperglycemia. To establish blood glucose targets according to patient's clinical state. To draw up protocols by using basal, bolus (nutritional/prandial), and supplemental insulin and not "sliding scale insulin". To avoid hypoglycaemia particularly during intravenous insulin protocols in intensive care unit. To set up glucose monitoring with a regular training of medical staff. To perform HbA1c during hospital stay to plan the treatment after discharge. To organize follow-up of the patients with hospital-related hyperglycemia.

Cross-sectional assessment of the roles of comorbidities in resting and activity-related dyspnea in severely obese women.

OBJECTIVES: Obesity has been associated with a lesser degree of asthma control that may be biased by other comorbidities. The objectives of this cross-sectional study were to describe resting and activity-related dyspnea complaints according to the presence of obesity-related comorbidities (asymptomatic airway hyperresponsiveness (AHR), asthma, gastroesophageal reflux disease (GERD) and sleep-disordered breathing (SDB)). We hypothesized that obese women can exhibit both resting and activity-related dyspnea, independently of the presence of asthma. METHODS: Severely obese (body mass index (BMI) > 35 kg m(-2)) women prospectively underwent description of resting and activity-related dyspnea (verbal descriptors and Medical Research Council (MRC) scale), pulmonary function testing (spirometry, absolute lung volumes, and methacholine challenge test), oesogastro-duodenal fibroscopy, and overnight polygraphy. Thirty healthy lean women without airway hyperresponsiveness were enrolled. RESULTS: Resting dyspnea complaints were significantly more prevalent in obesity (prevalence 41%) than in healthy lean women (prevalence 3%). Chest tightness and the need for deep inspirations were independently associated with both asthma and GERD while wheezing and cough were related to asthma only in obese women. Activity-related dyspnea was very prevalent (MRC score > 1, 75%), associated with obesity, with the exception of wheezing on exertion due to asthma. Asymptomatic AHR and SDB did not affect dyspneic complaints. CONCLUSIONS: In severely obese women referred for bariatric surgery, resting dyspnea complaints are observed in association with asthma or GERD, while activity-related dyspnea was mainly related to obesity only. Consequently, asthma does not explain all respiratory complaints of obese women.

Risk factors for airway hyperresponsiveness in severely obese women.

Obesity affects airway diameter and tidal ventilation pattern, which could perturb smooth muscle function. The objective was to assess the pathophysiology of airway hyperresponsiveness in obesity while controlling for gastro-oesophageal reflux disease. Obese women (n=118, mean±SD BMI 46.1±6.8kg/m(-2)) underwent pulmonary function testing (including tidal ventilation monitoring and methacholine challenge) and oesogastro-duodenal fibroscopy. Fifty-seven women (48%, 95% CI: 39-57%) exhibited hyperresponsiveness (dose-response slope ≥2.39% decrease/µmol) that was independently and positively correlated with predicted % FRC, Raw0.5 and negatively correlated with sigh frequency during tidal ventilation. Obese women had an increased breathing frequency but a similar sigh frequency than healthy lean women (n=30). Twenty-two obese women (19%, 95% CI: 12-26%) were classified as asthmatics (hyperresponsiveness and suggestive symptoms) without confounding effect of gastro-oesophageal reflux disease. In conclusion, in women referred for bariatric surgery, unloading of bronchial smooth muscle (reduced airway calibre and sigh frequency) is associated with hyperresponsiveness.

Vitamin D deficiency before bariatric surgery: should supplement intake be routinely prescribed?

BACKGROUND: Before bariatric surgery, we demonstrate a 96% rate of vitamin D deficiency in morbidly obese French patients: should supplement intake be routinely prescribed? We conducted a prospective observational study to demonstrate the prevalence of vitamin D deficiency in morbidly obese patients awaiting bariatric surgery. METHODS: Clinical and biological data were collected on 50 successive patients. RESULTS: Data showed vitamin D deficiency in 96% (25-OH vitamin D = 31 ± 13 nmol/l), with a cut-point of 50 nmol/l. Secondary hyperparathyroidism was found in 44% of patients with hypovitaminosis D (parathyroid hormone (PTH), 59 ± 24 pg/ml). Impaired PTH level concerned 89% of this group, considering the cut-point at 30 pg/ml. No significant correlation appeared between vitamin D and calcium or phosphate levels. CONCLUSIONS: Before surgery, we demonstrated a higher incidence of vitamin D deficiency in morbidly obese French patients as compared to the general population. The incidence was also higher than previous American studies. Screening for hypovitaminosis D may routinely be considered in morbid obesity. Long-term observation is, however, needed to assess the advantages and potential side effects of systematic vitamin D supplements.

[Glycemic emergencies]. / Urgences glycémiques.

Emergency conditions such as hyper or hypoglycemic states are less and less frequent in industrialized countries, for type 1 and type 2 patients as well. Hospital admissions become the exception. Educational programs are the basis of this outstanding improvement. Type 1 diabetic patients are able to treat themselves initial ketonuria to prevent established keto-acidosis. The same patients, type 2, and their familial and professional environment learn how to diagnose, treat, prevent and not be afraid of hypoglycaemic attacks. This unpleasant symptomatic condition without real seriousness (as opposed to chronic asymptomatic but dangerous elevation of blood glucose) should led to less psycho-social impairment than before. For all patients, new research, new molecules and most of all tailored educational programs, give hope than therapeutic goals close to normoglycemia can be reached without the worries of hyper or hypoglycaemic states.

Complications after laparoscopic adjustable gastric banding for morbid obesity: experience with 1,000 patients over 7 years.

BACKGROUND: Laparoscopic adjustable gastric banding (LAGB) is considered the least invasive surgical option for morbid obesity. It is less efficient than gastric bypass in weight loss, but has the advantage of being potentially reversible and can improve the quality of life if mortality and morbidity are low. METHODS: Between 1996 and 2003, 1,000 patients underwent LAGB. There were 896 women and 104 men with mean age 40.4 years (16.3-66.3). Preoperative mean BMI was 44.3 kg/m(2). RESULTS: There were no deaths. Cumulative rate of complications was 192 (19.2%). 12 were life-threatening (1.2%): gastric perforation (n=4), acute respiratory distress (n=2), pulmonary embolism (n=2), migration (n=3), and gastric necrosis (n=1). 111 patients required an abdominal reoperation (11.1%) for perforation (n=2), slippage (n=78), migration (n=3), necrosis (n=1), esophageal dilatation (n=2), incisional hernias (n=4) and port problems (n=21). Before October 2000, we used the perigastric technique, and the slippage rate was 24% (91 / 378 ).Then, we changed to the pars flaccida approach and the slippage rate fell to 2% (13 / 622). The pars flaccida approach demonstrated safety in relation to both risks of perforation and slippage. CONCLUSION: The cumulative complication rate increased to 3-4 years, and then decreased with experience and technical improvement. Concerns of long-term follow-up should be migration and esophageal dilatation, which seem to be rare at 3 years.

Laparoscopic gastric banding: a minimally invasive surgical treatment for morbid obesity: prospective study of 500 consecutive patients.

OBJECTIVE: To evaluate early and late morbidity of laparoscopic adjustable gastric banding for morbid obesity and to assess the efficacy of this procedure by analyzing its results. SUMMARY BACKGROUND DATA: Laparoscopic adjustable gastric banding is considered the least invasive surgical option for morbid obesity. It is effective, with an average loss of 50% of excessive weight after 2 years of follow-up. It is potentially reversible and safe; major morbidity is low and there is no mortality. METHODS: Between April 1997 and June 2001, 500 patients underwent laparoscopic surgery for morbid obesity with application of an adjustable gastric band. There were 438 women and 62 men (sex ratio = 0.14) with a mean age of 40.4 years. Preoperative mean body weight was 120.7 kg and mean body mass index (BMI) was 44.3 kg. m. RESULTS: Mean operative time was 105 minutes, 84 minutes during the last 300 operations. Mean hospital stay was 4.5 days. There were no deaths. There were 12 conversions (2.4%), 2 during the last 300 operations. Fifty-two patients (10.4%) had complications requiring an abdominal reoperation. Forty-nine underwent a reoperation for minor complications: slippage (n = 43, incisional hernias (n = 3), and reconnection of the catheter (n = 3). Three patients underwent a reoperation for major complications: gastroesophageal perforation (n = 2) and gastric necrosis (n = 1). Seven patients had pulmonary complications and 36 patients experienced minor problems related to the access port. At 1-, 2-, and 3-year follow-up, mean BMI decreased from 44.3 kg. m to 34.2, 32.8, and 31.9, respectively, and mean excess weight loss reached 42.8%, 52%, and 54.8%. CONCLUSIONS: Laparoscopic adjustable gastric banding is a beneficial operation in terms of excessive weight loss, with an acceptably low complication rate. It can noticeably improve the quality of life in obese patients. Half of the excess body weight can be effortlessly lost within 2 years.