Hybrid Closed Loop Overcomes the Impact of Missed or Suboptimal Meal Boluses on Glucose Control in Children with Type 1 Diabetes Compared to Sensor-Augmented Pump Therapy.

Background: It is unclear whether hybrid closed-loop (HCL) therapy attenuates the metabolic impact of missed or suboptimal meal insulin bolus compared with sensor-augmented pump (SAP) therapy in children with type 1 diabetes in free-living conditions. Methods: This is an ancillary study from a multicenter randomized controlled trial that compared 24/7 HCL with evening and night (E/N) HCL for 36 weeks in children between 6 and 12 years old. In the present study, the 60 children from the E/N arm underwent a SAP phase, an E/N HCL for 18 weeks, then a 24/7 phase for 18 weeks, extended for 36 more weeks. The last 28-30 days of each of the four phases were analyzed according to meal bolus management (cumulated 6817 days). The primary endpoint was the percentage of time that the sensor glucose was in the target range (TIR, 70-180 mg/dL) according to the number of missed boluses per day. Findings: TIR was 54% ± 10% with SAP, 63% ± 7% with E/N HCL, and steadily 67% ± 7% with 24/7 HCL. From the SAP phase to 72 weeks of HCL, the percentage of days with at least one missed meal bolus increased from 12% to 22%. Estimated marginal (EM) mean TIR when no bolus was missed was 54% (95% confidence intervals [CI] 53-56) in SAP and it was 13% higher (95% CI 11-15) in the 24/7 HCL phase. EM mean TIR with 1 and ≥2 missed boluses/day was 49.5% (95% CI 46-52) and 45% (95% CI 39-51) in SAP, and it was 15% (95% CI 14-16) and 17% higher (95% CI 6-28), respectively, in the 24/7 HCL phase (P < 0.05 for all comparisons vs. SAP). Interpretation: HCL persistently improves glycemic control compared with SAP, even in case of meal bolus omission. ClinicalTrials.gov (NCT03739099).

Outcomes of hybrid closed-loop insulin delivery activated 24/7 versus evening and night in free-living prepubertal children with type 1 diabetes: A multicentre, randomized clinical trial.

AIM: To assess the safety and efficacy of hybrid closed-loop (HCL) insulin delivery 24/7 versus only evening and night (E/N), and on extended 24/7 use, in free-living children with type 1 diabetes. MATERIALS AND METHODS: Prepubertal children (n = 122; 49 females/73 males; age, 8.6 ± 1.6 years; diabetes duration, 5.2 ± 2.3 years; insulin pump use, 4.6 ± 2.5 years; HbA1c 7.7% ± 0.7%/61 ± 5 mmol/mol) from four centres were randomized for 24/7 versus E/N activation of the Tandem Control-IQ system for 18 weeks. Afterwards, all children used the activated system 24/7 for 18 more weeks. The primary outcome was the percentage of time spent in the 70-180 mg/dL glucose range (TIR). RESULTS: HCL was active 94.1% and 51.1% of the time in the 24/7 and E/N modes, respectively. TIR from baseline increased more in the 24/7 versus the E/N mode (52.9% ± 9.5% to 67.3% ± 5.6% [+14.4%, 95% CI 12.4%-16.7%] vs. 55.1% ± 10.8% to 64.7% ± 7.0% [+9.6%, 95% CI 7.4%-11.6%]; P = .001). Mean percentage time below range was similarly reduced, from 4.2% and 4.6% to 2.7%, and the mean percentage time above range decreased more in the 24/7 mode (41.9% to 30.0% [-11.9%, 95% CI 9.7%-14.6%] vs. 39.8% to 32.6% [-7.2%, 95% CI 5.0%-9.9%]; P = .007). TIR increased through the whole range of baseline levels and always more with 24/7 use. The results were maintained during the extension phase in those initially on 24/7 use and improved in those with initial E/N use up to those with 24/7 use. Neither ketoacidosis nor severe hypoglycaemia occurred. CONCLUSIONS: The current study shows the safety and efficacy of the Tandem Control-IQ system in free-living children with type 1 diabetes for both E/N and 24/7 use; 24/7 use shows better outcomes, sustained for up to 36 weeks with no safety issues.

How to collect non-medical data in a pediatric trial: diaries or interviews.

BACKGROUND: Non-medical data, such as the amount of time that patients and caregivers spend managing their condition, may be relevant when assessing therapeutic strategies. For chronic pediatric conditions, the time that patients and caregivers spend in seeking and providing care (which are the indirect costs in an economic evaluation) can be significantly different depending on the treatment arm. To explore methods for collecting information on the care burden for caregivers and patients, we investigated whether a patient diary provided additional information compared to retrospective investigator-led interviews and whether a diary that was completed intermittently produced more or less information than a diary completed continually. The main objective of this study was to identify which type of data collection was most effective for measuring the time spent by caregivers and for estimating indirect treatment costs over 9 months. METHODS: Start-In! is a randomized controlled trial comparing the efficacy of three strategies of real-time continuous glucose monitoring for 12 months in children and adolescents with type 1 diabetes. We designed an ancillary study to assess methods of collecting information on the time spent by patients and caregivers in managing their condition (indirect costs). Data were entered retrospectively in case report forms (CRFs) by investigators during quarterly follow-up visits, which were supplemented with diaries completed prospectively by children or caregivers either continuously or intermittently. Data about absences from school and work as well as the time that caregivers spent on diabetes care were collected and the three collection methods were compared. RESULTS: At the end of the 9-month study, 42% of the study participants failed to return their diary. For the diaries that were received, less than 10% of expected data were collected versus 82% during investigators'interviews. Based on all the information collected, we calculated that over 9 months, caregivers lost on average 3.9 days of working time (€786) and 4 days of personal time, i.e. the equivalent of €526, and spent around 15 min of time on care per day, i.e. the equivalent of €1700. CONCLUSIONS: The CRFs completed by investigators during quarterly visits cannot be replaced by a diary. Completing the diaries appeared to represent an important additional burden to children and their caregivers, and the diaries provided little additional information compared to investigators' entries in the CRF. TRIAL REGISTRATION: ClinicalTrials.gov, NCT00949221. Registered on 30 July 2009. Registry name: Study of Insulin Therapy Augmented by Real Time Sensor in Type 1 Children and Adolescents (START-IN!).

Validation of the "Good2Go": the first French-language transition readiness questionnaire.

The use of transition readiness questionnaires is strongly recommended in adolescents with chronic conditions. The aim of our study was to validate "Good2Go," the first French-language transition readiness questionnaire. We analyzed the data from 2 multicentric studies (Canada and France) involving adolescents with chronic conditions (type 1 diabetes, inflammatory bowel disease, cystic fibrosis, epilepsy, juvenile idiopathic arthritis). Content and construct validity were examined using factorial and Rasch analysis (structural validity), Spearman's correlation, and Mann-Whitney test (external validity). Cronbach's α and intra-class correlation coefficients explored reliability. Cognitive interviews assessed wording comprehension and item appropriateness. Good2Go was completed by 321 participants (boys = 51%; mean age = 16.4 years (standard deviation = 1.5; min = 14.0; max = 18.0); Canada = 51.1%). Factor analysis identified 3 domains: "health self-advocacy," "knowledge about chronic conditions," and "self-management skills." The 3-domain structure showed a satisfying Rasch fit, internal consistency, and test-retest reliability. Good2Go domain scores were significantly higher in participants over 17 years of age, indicating satisfactory external validity.Conclusion: Good2Go is a valid 20-item questionnaire to assess transition readiness in adolescents with chronic conditions and may be useful in routine care to propose individually tailored preparation for their transfer to adult healthcare. Further research is now needed to analyze correlation between domain scores and success of transition.What is Known:• In adolescents with chronic conditions, the use of transition readiness questionnaires is recommended to propose individually tailored preparation for their transfer to adult healthcare.• However, no French-language questionnaire has been so far validated.What is New:• Based on a complete validation methodology, this study highlights that the French-language 20-items Good2Go questionnaire has good psychometric properties.• It explores all transition key points though 3 scored domains: "health self-advocacy", "knowledge about chronic disease" and "self-management skills".

Is there an optimal strategy for real-time continuous glucose monitoring in pediatrics? A 12-month French multi-center, prospective, controlled randomized trial (Start-In!).

AIM: To compare the efficacy of three strategies for real-time continuous glucose monitoring (RT-CGM) over 12 months in children and adolescents with type 1 diabetes. METHODS: A French multicenter trial (NCT00949221) with a randomized, controlled, prospective, open, and parallel-group design was conducted. After 3 months of RT-CGM, patients were allocated to one of three groups: return to self-monitoring of blood glucose, continuous CGM (80% of the time), or discontinuous CGM (40% of the time). The primary outcome was hemoglobin A1c (HbA1c) levels from 3 to 12 months. The secondary outcomes were acute metabolic events, hypoglycemia, satisfaction with CGM and cost. RESULTS: We included 151 subjects, aged 2 to 17 years, with a mean HbA1c level of 8.5% (SD0.7; 69 mmol/mol). The longitudinal change in HbA1c levels was similar in all three groups, at 3, 6, 9 and 12 months. The medical secondary endpoints did not differ between groups. The rate of severe hypoglycemia was significantly lower than that for the pretreatment year for the entire study population. Subjects reported consistent use and good tolerance of the device, regardless of age or insulin treatment. The use of full-time RT-CGM for 3 months costs the national medical insurance system €2629 per patient. CONCLUSION: None of the three long-term RT-CGM strategies evaluated in pediatric type 1 diabetes was superior to the others in terms of HbA1c levels. CGM-use for 3 months decreased rates of severe hypoglycemia. Our results confirm the feasibility of long-term RT-CGM-use and the need to improve educational support for patients and caregivers.

Closed-loop driven by control-to-range algorithm outperforms threshold-low-glucose-suspend insulin delivery on glucose control albeit not on nocturnal hypoglycaemia in prepubertal patients with type 1 diabetes in a supervised hotel setting.

This randomized control trial investigated glucose control with closed-loop (CL) versus threshold-low-glucose-suspend (TLGS) insulin pump delivery in pre-pubertal children with type 1 diabetes in supervised hotel conditions. The patients [n = 24, age range: 7-12, HbA1c: 7.5 ± 0.5% (58 ± 5 mmol/mol)] and their parents were admitted twice at a 3-week interval. CL control to range or TLGS set at 3.9 mmoL/L were assessed for 48 hour in randomized order. Admissions included three meals and one snack, and physical exercise. Meal boluses followed individual insulin/carb ratios. While overnight (22:00-08:00) per cent continuous glucose monitoring (CGM) time below 3.9 mmol/L (primary outcome) was similar, time in ranges 3.9 to 10.0 and 3.9 to 7.8 mmoL/L and mean CGM were all significantly improved with CL (P < 0.001). These results were confirmed over the whole 48 hour. Disconnections between devices and limited accuracy of glucose sensors in the hypoglycaemic range appeared as limiting factors for optimal control. CL mode was well accepted while fear of hypoglycaemia was unchanged. CL did not minimize nocturnal hypoglycaemia exposure but improved time in target range compared to TLGS. Although safe and well-accepted, CL systems would benefit from more integrated devices.

How Should We Assess Glycemic Variability in Type 1 Diabetes? Contribution of Principal Component Analysis for Interstitial Glucose Indices in 142 Children.

BACKGROUND: Glycemic variability (GV) can be used to assess glycemic control in diabetes, but there is no clear consensus concerning the methods to use for its assessment. Methodological differences have resulted in differences in the outcome of GV metrics used in research studies, controversies over clinical impact, and an absence of integration into routine care. AIM: To identify the indicators of GV most meaningful for clinicians, patients, and clinical researchers. MATERIALS AND METHODS: Continuous glucose monitoring data were collected during the first 3 months of a pediatric diabetes clinical trial (Start-In!; n = 142). We used principal component analysis (PCA) to analyze weekly averages for 22 parameters relating to GV. RESULTS: PCA identified five groups of parameters and three components explaining 85.7% of the variance. These components represented the amplitude, direction (hypoglycemia vs. hyperglycemia), and timing (within-day vs. between-days) of glucose excursions. CONCLUSIONS: This study provides elements that could make GV parameters more useful in clinical practice and research. No single parameter was sufficient to represent the complexity of GV, but it was possible to restrict the number of indicators required. The five groups of parameters identified by PCA could facilitate the choice of the most relevant outcomes for GV analysis in pediatric diabetes according to the purpose of the analysis (e.g., exploration of GV associated with hypo- or hyperglycemia, with short- or long-term periodicity, or GV in its entirety).

High Prevalence of Polycystic Ovary Syndrome in Type 1 Diabetes Mellitus Adolescents: Is There a Difference Depending on the NIH and Rotterdam Criteria?

BACKGROUND: Polycystic ovary syndrome (PCOS) is more frequently observed in type 1 diabetes mellitus (T1DM) adult women than in nondiabetic women. No such prevalence has yet been studied in adolescent girls with T1DM. AIM: The aim of this study was to evaluate the prevalence of PCOS in adolescent girls with T1DM and to determine the clinical and hormonal features associated with the disorder. METHODS: A cross-sectional study of 53 adolescent girls (gynecological age >2 years) referred for routine evaluation for T1DM was conducted. We diagnosed PCOS using the National Institutes of Health (NIH) and Rotterdam criteria. RESULTS: 26.4 and 47.9% of adolescents had PCOS according to NIH (NIH-PCOS) and Rotterdam (Rotterdam-PCOS) criteria. 66.7% of NIH-PCOS adolescents had a complete phenotype associated with hyperandrogenism, oligomenorrhea, and polycystic ovarian morphology, unlike only 33.3% of the Rotterdam-PCOS adolescents. A family history of type 2 diabetes mellitus (T2DM) was more frequent in PCOS than in non-PCOS girls, whichever criteria were used. Late pubertal development and a T1DM diagnosis close to puberty were factors associated with NIH-PCOS. CONCLUSION: Adolescents with T1DM had a high prevalence of PCOS. More differences between PCOS and non-PCOS patients were found using the NIH criteria, suggesting that clinical characteristics might be more accurate for diagnosing PCOS in girls with T1DM. A family history of T2DM is associated with a high risk of PCOS.

[Technological innovations in the treatment of type 1 diabetes in pediatrics]. / Innovations technologiques dans le traitement du diabète de type 1 en pédiatrie.

Insulin pumps, continuous glucose monitoring sensors and algorithms for managing the doses of insulin necessary to control blood sugar levels within target values: more and more research is being carried out into "closed loop" systems. The artificial pancreas is today at the stage of clinical trials in adults and children.

A simple and fast non-radioactive bridging immunoassay for insulin autoantibodies.

Type 1 diabetes (T1D) is an autoimmune disease which results from the destruction of pancreatic beta cells. Autoantibodies directed against islet antigens are valuable diagnostic tools. Insulin autoantibodies (IAAs) are usually the first to appear and also the most difficult to detect amongst the four major islet autoantibodies. A non-radioactive IAA bridging ELISA was developed to this end. In this assay, one site of the IAAs from serum samples is bound to a hapten-labeled insulin (GC300-insulin), which is subsequently captured on anti-GC300 antibody-coated 96-well plates. The other site of the IAAs is bound to biotinylated insulin, allowing the complex to be detected by an enzyme-streptavidin conjugate. In the present study, 50 serum samples from patients with newly diagnosed T1D and 100 control sera from non-diabetic individuals were analyzed with our new assay and the results were correlated with an IAA radioimmunoassay (RIA). Using IAA bridging ELISA, IAAs were detected in 32 out of 50 T1D children, whereas with IAA RIA, 41 out of 50 children with newly diagnosed T1D were scored as positive. In conclusion, the IAA bridging ELISA could serve as an attractive approach for rapid and automated detection of IAAs in T1D patients for diagnostic purposes.

Neuropsychological dysfunction and developmental defects associated with genetic changes in infants with neonatal diabetes mellitus: a prospective cohort study [corrected].

BACKGROUND: Neonatal diabetes mellitus is a rare genetic form of pancreatic ß-cell dysfunction. We compared phenotypic features and clinical outcomes according to genetic subtypes in a cohort of patients diagnosed with neonatal diabetes mellitus before age 1 year, without ß-cell autoimmunity and with normal pancreas morphology. METHODS: We prospectively investigated patients from 20 countries referred to the French Neonatal Diabetes Mellitus Study Group from 1995 to 2010. Patients with hyperglycaemia requiring treatment with insulin before age 1 year were eligible, provided that they had normal pancreatic morphology as assessed by ultrasonography and negative tests for ß-cell autoimmunity. We assessed changes in the 6q24 locus, KATP-channel subunit genes (ABCC8 and KCNJ11), and preproinsulin gene (INS) and investigated associations between genotype and phenotype, with special attention to extra-pancreatic abnormalities. FINDINGS: We tested 174 index patients, of whom 47 (27%) had no detectable genetic defect. Of the remaining 127 index patients, 40 (31%) had 6q24 abnormalities, 43 (34%) had mutations in KCNJ11, 31 (24%) had mutations in ABCC8, and 13 (10%) had mutations in INS. We reported developmental delay with or without epilepsy in 13 index patients (18% of participants with mutations in genes encoding KATP channel subunits). In-depth neuropsychomotor investigations were done at median age 7 years (IQR 1-15) in 27 index patients with mutations in KATP channel subunit genes who did not have developmental delay or epilepsy. Developmental coordination disorder (particularly visual-spatial dyspraxia) or attention deficits were recorded in all index patients who had this testing. Compared with index patients who had mutations in KATP channel subunit genes, those with 6q24 abnormalities had specific features: developmental defects involving the heart, kidneys, or urinary tract (8/36 [22%] vs 2/71 [3%]; p=0·002), intrauterine growth restriction (34/37 [92%] vs 34/70 [48%]; p<0·0001), and early diagnosis (median age 5·0 days, IQR 1·0-14·5 vs 45·5 days, IQR 27·2-95·0; p<0·0001). Remission of neonatal diabetes mellitus occurred in 89 (51%) index patients at a median age of 17 weeks (IQR 9·5-39·0; median follow-up 4·7 years, IQR 1·5-12·8). Recurrence was common, with no difference between the groups who had 6q24 abnormalities versus mutations in KATP channel subunit genes (82% vs 86%; p=0·36). INTERPRETATION: Neonatal diabetes mellitus is often associated with neuropsychological dysfunction and developmental defects that are specific to the underlying genetic abnormality. A multidisciplinary assessment is therefore essential when patients are diagnosed. Features of neuropsychological dysfunction and developmental defects should be tested for in adults with a history of neonatal diabetes mellitus. FUNDING: Agence Nationale de la Recherche-Maladies Rares Research Program Grant, the Transnational European Research Grant on Rare Diseases, the Société Francophone du Diabète-Association Française du Diabète, the Association Française du Diabète, Aide aux Jeunes Diabétiques, a CIFRE grant from the French Government, HRA-Pharma, the French Ministry of Education and Research, and the Société Française de Pédiatrie.

Assessment of patient-led or physician-driven continuous glucose monitoring in patients with poorly controlled type 1 diabetes using basal-bolus insulin regimens: a 1-year multicenter study.

OBJECTIVE: The benefits of real-time continuous glucose monitoring (CGM) have been demonstrated in patients with type 1 diabetes. Our aim was to compare the effect of two modes of use of CGM, patient led or physician driven, for 1 year in subjects with poorly controlled type 1 diabetes. RESEARCH DESIGN AND METHODS: Patients with type 1 diabetes aged 8-60 years with HbA(1c) ≥ 8% were randomly assigned to three groups (1:1:1). Outcomes for glucose control were assessed at 1 year for two modes of CGM (group 1: patient led; group 2: physician driven) versus conventional self-monitoring of blood glucose (group 3: control). RESULTS: A total of 257 subjects with type 1 diabetes underwent screening. Of these, 197 were randomized, with 178 patients completing the study (age: 36 ± 14 years; HbA(1c): 8.9 ± 0.9%). HbA(1c) improved similarly in both CGM groups and was reduced compared with the control group (group 1 vs. group 3: -0.52%, P = 0.0006; group 2 vs. group 3: -0.47%, P = 0.0008; groups 1 + 2 vs. group 3: -0.50%, P < 0.0001). The incidence of hypoglycemia was similar in the three groups. Patient SF-36 questionnaire physical health score improved in both experimental CGM groups (P = 0.004). Sensor consumption was 34% lower in group 2 than in group 1 (median [Q1-Q3] consumption: group 1: 3.42/month [2.20-3.91] vs. group 2: 2.25/month [1.27-2.99], P = 0.001). CONCLUSIONS: Both patient-led and physician-driven CGM provide similar long-term improvement in glucose control in patients with poorly controlled type 1 diabetes, but the physician-driven CGM mode used fewer sensors.

Childhood onset diabetes posttransplant in a girl with TCF2 mutation.

Heterozygous mutations of TCF2 (transcription factor 2) have been associated with maturity onset diabetes of the young, renal malformations, hyperuricemia, and occasionally internal genital malformations in female. We report a female patient with bilateral renal hypodysplasia and de novo heterozygous TCF2 gene mutation. At the age of 9 yr, she developed transient ketoacidosis immediately posttransplant, temporarily requiring insulin. During glucocorticoid tapering, impaired glucose tolerance persisted and overt insulin-dependent diabetes mellitus developed 1 yr later. Pathogenic factors which might have played a role in the acceleration of diabetes were (i) switch from cyclosporine to tacrolimus, (ii) weight excess, and (iii) cytomegalovirus infection. TCF2 analysis might, therefore, be of interest in patients with congenital abnormalities of the kidney and the urinary tract in order to improve posttransplant management in terms of steroid and tacrolimus exposure.

High prevalence of hirsutism and menstrual disorders in obese adolescent girls and adolescent girls with type 1 diabetes mellitus despite different hormonal profiles.

OBJECTIVES: To compare the pubertal development, the hormonal profiles and the prevalence of hirsutism and menstrual disorders in obese adolescent girls and adolescent girls with type 1 diabetes mellitus (T1DM). METHODS: Data were collected from 96 obese adolescent girls and 78 adolescent girls with T1DM at Tanner stage IV or V, whose ages ranged between 11.9 and 17.9 years. RESULTS: High prevalence of hirsutism and menstrual disorder was found in the obese adolescent girls (36.5 and 42% respectively) and the adolescent girls with T1DM (21 and 44% respectively). The obese girls were significantly younger at pubarche, thelarche and menarche than the girls with T1DM. Hirsutism in the obese girls and those with T1DM was associated with hyperandrogenaemia and a raised free androgen index (FAI). When the cause of the raised FAI was investigated in both the groups of girls with hirsutism, the raised FAI in the obese girls was due to low serum sex hormone-binding globulin (SHBG) levels. In contrast, the raised FAI of the girls with T1DM and hirsutism was due to hyperandrogenaemia. Menstrual disorders in the T1DM girls were associated also with hyperandrogenaemia unlike obese girls. CONCLUSIONS: Hirsutism and menstrual disorders are common in obese adolescent girls and adolescent girls with T1DM. Although hyperandrogenaemia is present in both groups of girls, the androgenic profiles of the two groups differ. The hyperandrogenaemia in the obese girls is primarily due to their decreased serum SHBG levels, whereas the hyperandrogenaemia in the girls with T1DM is due to their increased androgen production.

[The Ceduc, a multi-pathology therapeutic education centre]. / Le Ceduc, un centre d'éducation thérapeutique multipathologies.

The Ceduc, a multi-pathology therapeutic education centre. Patient therapeutic education has undergone rapid development in France. In 2005, at the Robert-Debré hospital in Paris, the professionals involved in education activities grouped together to create a multipathology centre, the Ceduc. This centre benefits from experiences and resources of the various actors who take care of sick children and their families.

Resistance to leptin-replacement therapy in Berardinelli-Seip congenital lipodystrophy: an immunological origin.

CONTEXT: Recently, in a 4-month proof-of-concept trial, beneficial metabolic effects were reported in non-diabetic children with Berardinelli-Seip congenital lipodystrophy (BSCL); this information prompted us to hypothesize that long-term leptin-replacement therapy might improve or reverse the early complications of the disease in these patients. PATIENTS AND METHODS: A 28-month trial was implemented in eight patients. Efficacy assessment was based on a decrease in serum triglyceride concentrations, and/or a decrease in liver volume and/or an increase in insulin sensitivity of at least 30% respectively. The response was defined as follows: total (3/3 positive criteria), partial (1 or 2/3), or negative (0/3). Anti-leptin antibodies were measured with a radiobinding assay, and a neutralizing effect was assessed in primary cultures of embryonic neurons incubated with an apoptotic agent (N-methyl-D-aspartate) and the patient serum, with or without leptin. RESULTS: A negative or partial response to treatment was observed in five of eight patients even when leptin dosages were increased. A displaceable leptin binding was detectable in all patients after 2 months of treatment. At 28 months, binding was higher in the patients with a negative response than in the total responders, and it paralleled both the increase in leptin dosage and serum leptin concentrations. Co-incubation of embryonic neurons with serum from two patients with a negative response inhibited the neuroprotective effect of leptin. CONCLUSION: Under leptin therapy, patients with BSCL may develop a resistance to leptin, which could be partly of immunological origin, blunting the previously reported beneficial effects.

[Patient education for children and adolescents with chronic diseases]. / Education thérapeutique des enfants et adolescents atteints de maladie chronique.

The education of children with chronic diseases and of their parents is a treatment procedure that must be integrated into the management of the child's disease: it is essential for his or her physical and psychological health and quality of life. This continuous process is part of long-term follow-up and of the child's development; it is not a procedure that can be carried out once and for all. The program must include initial, follow-up, and advanced education. Treatment education for parents occurs simultaneously with the child's medical management and has the same requirements as that of the child (which means that the time spent in this education requires financial support). The role of the pediatrics departments serving these children is essential, and they must work with other participants, whose roles are not identical to they perform in education for adult patients. Pediatric patient education requires an interdisciplinary pediatric team with specific skills and appropriate liaison with those involved in other aspects of the child's life (e.g., daycare and school). The child's psychological development is central to the design and implementation of pediatric patient education programs. Knowledge of child development is critical in providing these services for children and adolescents; training in this field is required in addition to that necessary for adult patient education. Epidemiologic findings of the increased incidence of several chronic diseases in children must be considered in decisions about the resources allocated to coping with them. The particularities and requirements of adolescence and its interactions with chronic disease must also be considered in specific patient education programs for adolescents, and in the training and skills of healthcare professionals.

Insulin pump therapy in neonatal diabetes.

Neonatal diabetes mellitus is rare. Typically, infants are of low birth weight and develop hyperglycemia requiring exogenous insulin within the first 6 weeks. Although pediatricians face numerous difficulties in managing insulin therapy at this age, very few data are available on possible methods of insulin delivery in neonatal diabetes. We report our experience over 18 years of continuous subcutaneous insulin infusion (CSII) in cases of neonatal diabetes requiring insulin therapy for more than 15 days (n=17; 8 permanent). CSII therapy in neonatal diabetes allows easy adaptation of insulin delivery, closely following the current feeding regimen (a basal infusion only being needed when using continuous enteral or parenteral feeding; preprandial boluses being started with intermittent bottle feeding). Management of the very small insulin doses (for example: bolus=0.20 U and basal rate=0.02 U/h) required is possible after insulin dilution (5-10 U/ml) and is more accurate with CSII than with syringes. Controlling blood glucose with few hypoglycemic events, which are particularly frequent and dangerous at this age, is more efficient with CSII than with injections. Infants tolerate the subcutaneous infusion lines well and we did not observe any side effects. For all children, CSII was utilized throughout the whole period of insulin therapy. In conclusion, during the neonatal period, and under the supervision of an experienced team, CSII is safe, more physiological and accurate and easier to manage than injections allowing easier matching of the insulin requirements of a newborn.

Metabolic correction induced by leptin replacement treatment in young children with Berardinelli-Seip congenital lipoatrophy.

OBJECTIVE: Berardinelli-Seip syndrome is a rare congenital lipoatrophy with a severe prognosis and no efficient therapy. Children present with low leptin levels and severe metabolic complications (insulin resistance, elevated triglyceride levels, and hepatic steatosis). The objective of this study was to test safety and efficacy of recombinant-methionyl-human leptin replacement in children with Berardinelli-Seip syndrome before development of severe metabolic disease METHODS: As part of an open trial, recombinant-methionyl-human leptin was given daily for 4 months to children who did not have diabetes and had Berardinelli-Seip congenital lipoatrophy and metabolic complications at a dosage that was meant to achieve physiologic levels. Six boys and 1 girl (age: 2.4-13.6 years), with a mean fasting insulin level of >15 mIU/L and hypertriglyceridemia, were included. RESULTS: At the end of the recombinant-methionyl-human leptin treatment, a 63% reduction of fasting triglycerides level was achieved. A simultaneous 30% increase in insulin sensitivity was seen, and liver volume was reduced by 20.3%. More remarkable, values of insulin sensitivity and triglyceride level were in the reference range in 4 patients. CONCLUSIONS: Leptin replacement is able to reverse metabolic complications in the majority of children with Berardinelli-Seip congenital lipoatrophy and with insulin resistance or dyslipidemia before the development of overt diabetes.