Pediatric Diabetes

Background. Poor glycemic control in patients with type 1 diabetes (T1D) is associated with greater social deprivation. However, the evidence is inconsistent in terms of the type of social deprivation (individual-level or area-level) and whether glycemic control changes over time. Here, we investigated the impacts of individual-level and area-level social deprivation on the glycated hemoglobin (HbA1c) trajectory from the time of T1D diagnosis. Materials and Methods. We retrospectively analyzed a cohort of children who were diagnosed with T1D between 2017 and 2020 at Bordeaux University Hospital. Social deprivation was assessed using both parental individual indicator (EPICES score) and ecological indicator (European Deprivation Index (EDI) score). Piecewise linear mixed-effects models were used to estimate the effects of social deprivation on HbA1c trajectory. Results. We included 168 patients. The most-deprived group included 29% and 22% of all patients, as revealed by the respective EPICES and EDI scores. The two indicators were poorly correlated. The short-term decrease in HbA1c level tended to be smaller in the most-deprived patients over the first 4 months after diagnosis than in other patients (slope difference of 2.68% per year compared with the slope among the least-deprived patients, P=0.056). The long-term trajectory was influenced by area-level deprivation (EDI score); the least-deprived patients (quintile 1) exhibited more stable mean HbA1c levels. Conclusions. Social deprivation may partially explain poor glycemic control in some patients; both short-term individual deprivation and long-term area-level deprivation may be involved. Further research is needed to determine how to integrate this information into a therapeutic strategy

Altered Cortisol Metabolism Increases Nocturnal Cortisol Bioavailability in Prepubertal Children With Type 1 Diabetes Mellitus

ObjectiveDisturbances in the activity of the hypothalamus-pituitary-adrenal axis could lead to functional alterations in the brain of diabetes patients. In a later perspective of investigating the link between the activity of the hypothalamus-pituitary-adrenal axis and the developing brain in children with diabetes, we assessed here nocturnal cortisol metabolism in prepubertal children with type 1 diabetes mellitus (T1DM).MethodsPrepubertal patients (aged 6–12 years) diagnosed with T1DM at least 1 year previously were recruited, along with matched controls. Nocturnal urine samples were collected, with saliva samples taken at awakening and 30 minutes after awakening. All samples were collected at home over 5 consecutive days with no detectable nocturnal hypoglycaemia. The State-Trait Anxiety Inventory (trait scale only) and Child Depression Inventory were also completed. Glucocorticoid metabolites in the urine, salivary cortisol (sF) and cortisone (sE) were measured by liquid chromatography–tandem mass spectrometry. Metabolic data were analysed by logistic regression, adjusting for sex, age, BMI and trait anxiety score.ResultsUrine glucocorticoid metabolites were significantly lower in T1DM patients compared to controls. 11β-hydroxysteroid dehydrogenase type 1 activity was significantly higher, while 11β-hydroxysteroid dehydrogenase type 2, 5(α+β)-reductase and 5α-reductase levels were all lower, in T1DM patients compared to controls. There was a significant group difference in delta sE level but not in delta sF level between the time of awakening and 30 minutes thereafter.ConclusionsOur findings suggest that altered nocturnal cortisol metabolism and morning HPA axis hyperactivity in children with T1DM leads to greater cortisol bioavailability and lower cortisol production as a compensatory effect. This altered nocturnal glucocorticoid metabolism when cortisol production is physiologically reduced and this HPA axis hyperactivity question their impact on brain functioning

Cost-effectiveness of malaria microscopy and rapid diagnostic tests versus presumptive diagnosis: implications for malaria control in Uganda

BACKGROUND: Current Uganda National Malaria treatment guidelines recommend parasitological confirmation either by microscopy or rapid diagnostic test (RDT) before treatment with artemether-lumefantrine (AL). However, the cost-effectiveness of these strategies has not been assessed at rural operational primary care centres. METHODS: Three health centres (HCs) were randomized to three diagnostic arms (microscopy, RDT and presumptive diagnosis) in a district of low and another of high malaria transmission intensities in Uganda. Some 22,052 patients presenting with fever at outpatients departments were enrolled from March 2010 to February 2011. Of these, a random sample of 1,627 was selected to measure additional socio-economic characteristics. Costing was performed following the standard step-down cost allocation and the ingredients approach. Effectiveness was measured as the number and proportion of patients correctly diagnosed and treated. Incremental Cost-Effectiveness Ratios (ICERs) were estimated from the societal perspective (http://Clinicaltrials.gov, NCT00565071). RESULTS: Overall RDT was most cost-effective with lowest ICER US$5.0 compared to microscopy US$9.61 per case correctly diagnosed and treated. In the high transmission setting, ICER was US$4.38 for RDT and US$12.98 for microscopy. The corresponding ICERs in the low transmission setting were US$5.85 and US$7.63 respectively. The difference in ICERs between RDT and microscopy was greater in the high transmission area (US$8.9) than in low transmission setting (US$1.78). At a willingness to pay of US$2.8, RDT remained cost effective up to a threshold value of the cost of treatment of US$4.7. CONCLUSION: RDT was cost effective in both low and high transmission settings. With a global campaign to reduce the costs of AL and RDT, the Malaria Control Programme and stakeholders need a strategy for malaria diagnosis because as the cost of AL decreases, presumptive treatment is likely to become more attractive

Memory deficits in a juvenile rat model of type 1 diabetes are due to excess 11β-HSD1 activity, which is upregulated by high glucose concentrations rather than insulin deficiency

Aims/hypothesis: Children with diabetes may display cognitive alterations although vascular disorders have not yet appeared. Variations in glucose levels together with relative insulin deficiency in treated type 1 diabetes have been reported to impact brain function indirectly through dysregulation of the hypothalamus-pituitary-adrenal axis. We have recently shown that enhancement of glucocorticoid levels in children with type 1 diabetes is dependent not only on glucocorticoid secretion but also on glucocorticoid tissue concentrations, which is linked to 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) activity. Hypothalamus-pituitary-adrenal axis dysfunction and memory alteration were further dissected in a juvenile rat model of diabetes showing that excess 11β-HSD1 activity within the hippocampus is associated with hippocampal-dependent memory deficits. Here, to investigate the causal relationships between diabetes, 11β-HSD1 activity and hippocampus-dependent memory deficits, we evaluated the beneficial effect of 11β-HSD1 inhibition on hippocampal-related memory in juvenile diabetic rats. We also examined whether diabetes-associated enhancement of hippocampal 11β-HSD1 activity is due to an increase in brain glucose concentrations and/or a decrease in insulin signalling. Methods: Diabetes was induced in juvenile rats by daily i.p. injection of streptozotocin for 2 consecutive days. Inhibition of 11β-HSD1 was obtained by administrating the compound UE2316 twice daily by gavage for 3 weeks, after which hippocampal-dependent object location memory was assessed. Hippocampal 11β-HSD1 activity was estimated by the ratio of corticosterone/dehydrocorticosterone measured by LC/MS. Regulation of 11β-HSD1 activity in response to changes in glucose or insulin levels was determined ex vivo on acute brain hippocampal slices. The insulin regulation of 11β-HSD1 was further examined in vivo using virally mediated knockdown of insulin receptor expression specifically in the hippocampus. Results: Our data show that inhibiting 11β-HSD1 activity prevents hippocampal-related memory deficits in diabetic juvenile rats. A significant increase (53.0±9.9%) in hippocampal 11β-HSD1 activity was found in hippocampal slices incubated in high glucose conditions (13.9 mmol/l) vs normal glucose conditions (2.8 mmol/l) without insulin. However, 11β-HSD1 activity was not affected by variations in insulin concentration either in the hippocampal slices or after a decrease in hippocampal insulin receptor expression. Conclusions/interpretation: Together, these data demonstrate that an increase in 11β-HSD1 activity contributes to memory deficits observed in juvenile diabetic rats and that an excess of hippocampal 11β-HSD1 activity stems from high glucose levels rather than insulin deficiency. 11β-HSD1 might be a therapeutic target for treating cognitive impairments associated with diabetes

Photochemically produced SO2 in the atmosphere of WASP-39b

Photochemistry is a fundamental process of planetary atmospheres that regulates the atmospheric composition and stability1. However, no unambiguous photochemical products have been detected in exoplanet atmospheres so far. Recent observations from the JWST Transiting Exoplanet Community Early Release Science Program2,3 found a spectral absorption feature at 4.05 μm arising from sulfur dioxide (SO2) in the atmosphere of WASP-39b. WASP-39b is a 1.27-Jupiter-radii, Saturn-mass (0.28 MJ) gas giant exoplanet orbiting a Sun-like star with an equilibrium temperature of around 1,100 K (ref. 4). The most plausible way of generating SO2 in such an atmosphere is through photochemical processes5,6. Here we show that the SO2 distribution computed by a suite of photochemical models robustly explains the 4.05-μm spectral feature identified by JWST transmission observations7 with NIRSpec PRISM (2.7σ)8 and G395H (4.5σ)9. SO2 is produced by successive oxidation of sulfur radicals freed when hydrogen sulfide (H2S) is destroyed. The sensitivity of the SO2 feature to the enrichment of the atmosphere by heavy elements (metallicity) suggests that it can be used as a tracer of atmospheric properties, with WASP-39b exhibiting an inferred metallicity of about 10× solar. We further point out that SO2 also shows observable features at ultraviolet and thermal infrared wavelengths not available from the existing observations

Valeur prédictive du rapport 17-hydroxyprogestérone/cortisol sanguin au troisième jour de vie sur la survenue de troubles hémodynamiques sévères chez les prématurés de moins de 32 semaines d aménorrhée

La fonction surrénalienne des prématurés de moins de 32 semaines d'aménorrhée (SA) semble immature : les concentrations de cortisol sont souvent corrélées négativement avec le degré de sévérité de la pathologie. Ceci peut être expliqué par une immaturité enzymatique, dont la 11-hydroxylase, responsable d'une élévation de la 17-hydroxyprogestérone (17-OHP) et d'une baisse de la cortisolémie. Les grands prématurés sont cependant exposés à une morbidité hémodynamique et respiratoire importante. Nous avons réalisé une étude de cohorte prospective concernant les enfants prématurés de moins de 32 SA hospitalisés au centre hospitalo-universitaire de Bordeaux. Lors du dépistage néonatal de l'hyperplasie congénitale des surrénales (basé sur la 17-OHP), nous avons associé un dosage sanguin du cortisol. L'objectif principal de notre étude était de définir la valeur prédictive du rapport 17-OHP/cortisol sanguin au troisième jour de vie (J3) sur la survenue de troubles hémodynamiques sévères chez les prématurés de moins de 32 SA, afin d'établir un facteur pronostique d'insuffisance surrénalienne transitoire du prématuré. Nos objectifs secondaires étaient l'étude de la relation entre les variables dosées 17-OHP, cortisol ou le rapport 17-OHP/cortisol à J3 et la morbidité respiratoire, ainsi que l'analyse des facteurs pouvant influencer les dosages. Nous n'avons pas pu démontrer, dans notre population d'étude, que le rapport 17-OHP/cortisol à J3 soit prédictif de la morbidité hémodynamique ou respiratoire. Le dosage de cortisol à J3 est significativement plus élevé chez les patients requérant un soutien respiratoire. Nos analyses multivariées avec les dosages de 17-OHP et cortisol à J3 démontrent que seul l'âge gestationnel reste corrélé et ce de façon négative, avec la survenue de troubles hémodynamiques sévères. La dysplasie broncho-pulmonaire n'est corrélée en analyse multivariée qu'avec la présence d'un canal artériel perméable à J3.BORDEAUX2-BU Santé (330632101) / SudocSudocFranceF

Modes de révélation du panhypopituitarisme néonatal, à propos de quatre cas cliniques

Le panhypopituitarisme néonatal est une pathologie rare correspondant à un déficit d'au moins deux hormones anté-hypophysaires. Ses modes de révélation sont multiples, variables et fréquemment responsables d'un retard au diagnostic, dans une pathologie déjà peu connue en néonatologie. Certaines formes de panhypopituitarisme néonatal sont d'origine génétique. D'autres formes sont liées une anomalie syndromique telle que la dysplasie septo-optique, le syndrome d'interruption de la tige pituitaire, le syndrome de la selle turcique vide, le kyste de la poche de Rathke, ou s'associent à des malformations cérébrales. Le diagnostic repose sur les explorations hormonales et l'imagerie par résonance magnétique cérébrale et hypothalamo-hypophysaire. Le traitement hormonal substitutif permet une régression des symptômes et doit être instaurer précocement afin d'éviter les décompensations aiguës et les complications chroniques. La multiplicité des modes de révélations de cette pathologie et ses difficultés diagnostiques sont illustrées par les cas de quatre nouveau-nés, recensés dans les services de réanimation et de néonatologie du CHU de Bordeaux entre février 2001 et mai 2007. Les cas étudiés entrent tous dans le cadre d'un syndrome d'interruption de la tige pituitaire. Les symptômes les plus fréquents sont: les difficultés d'accouchement, les hypoglycémies récidivantes, l'ictère prolongé, l'hypotonie axiale, le micropénis et l'hypothermie. Les signes cliniques révélateurs du panhypopituitarisme sont peu spécifiques et variables pour une même étiologie. Pris isolément, ils sont souvent banalisés, ce qui est responsable du retard au diagnostic.POINTE A PITRE-BU (971202101) / SudocSudocFranceF

Incidence du diabète de type 1 chez l'enfant de moins de 15 ans en Aquitaine entre le 1er Janvier 1995 et le 31 Décembre 2004

BORDEAUX2-BU Santé (330632101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Description épidémiologique et du mode de présentation du diabète de type 1 chez les enfants de moins de 15 ans pris en charge à l'hôpital de Bordeaux de 1998 à 2002

BORDEAUX2-BU Santé (330632101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF