Preclinical Aortic Atherosclerosis in Adolescents With Chronic Disease.

Background Adolescents with chronic disease are often exposed to inflammatory, metabolic, and hemodynamic risk factors for early atherosclerosis. Since postmortem studies have shown that atherogenesis starts in the aorta, the CDACD (Cardiovascular Disease in Adolescents with Chronic Disease) study investigated preclinical aortic atherosclerosis in these adolescents. Methods and Results The cross-sectional CDACD study enrolled 114 adolescents 12 to 18 years old with chronic disorders including juvenile idiopathic arthritis, cystic fibrosis, obesity, corrected coarctation of the aorta, and healthy controls with a corrected atrial septal defect. Cardiovascular magnetic resonance was used to assess aortic pulse wave velocity and aortic wall thickness, as established aortic measures of preclinical atherosclerosis. Cardiovascular magnetic resonance showed a higher aortic pulse wave velocity, which reflects aortic stiffness, and higher aortic wall thickness in all adolescent chronic disease groups, compared with controls (P<0.05). Age (ß=0.253), heart rate (ß=0.236), systolic blood pressure (ß=-0.264), and diastolic blood pressure (ß=0.365) were identified as significant predictors for aortic pulse wave velocity, using multivariable linear regression analysis. Aortic wall thickness was predicted by body mass index (ß=0.248) and fasting glucose (ß=0.242), next to aortic lumen area (ß=0.340). Carotid intima-media thickness was assessed using ultrasonography, and was only higher in adolescents with coarctation of the aorta, compared with controls (P<0.001). Conclusions Adolescents with chronic disease showed enhanced aortic stiffness and wall thickness compared with controls. The enhanced aortic pulse wave velocity and aortic wall thickness in adolescents with chronic disease could indicate accelerated atherogenesis. Our findings underscore the importance of the aorta for assessment of early atherosclerosis, and the need for tailored cardiovascular follow-up of children with chronic disease.

Immunometabolic factors in adolescent chronic disease are associated with Th1 skewing of invariant Natural Killer T cells.

Invariant Natural Killer T (iNKT) cells respond to the ligation of lipid antigen-CD1d complexes via their T-cell receptor and are implicated in various immunometabolic diseases. We considered that immunometabolic factors might affect iNKT cell function. To this end, we investigated iNKT cell phenotype and function in a cohort of adolescents with chronic disease and immunometabolic abnormalities. We analyzed peripheral blood iNKT cells of adolescents with cystic fibrosis (CF, n = 24), corrected coarctation of the aorta (CoA, n = 25), juvenile idiopathic arthritis (JIA, n = 20), obesity (OB, n = 20), and corrected atrial septal defect (ASD, n = 25) as controls. To study transcriptional differences, we performed RNA sequencing on a subset of obese patients and controls. Finally, we performed standardized co-culture experiments using patient plasma, to investigate the effect of plasma factors on iNKT cell function. We found comparable iNKT cell numbers across patient groups, except for reduced iNKT cell numbers in JIA patients. Upon ex-vivo activation, we observed enhanced IFN-γ/IL-4 cytokine ratios in iNKT cells of obese adolescents versus controls. The Th1-skewed iNKT cell cytokine profile of obese adolescents was not explained by a distinct transcriptional profile of the iNKT cells. Co-culture experiments with patient plasma revealed that across all patient groups, obesity-associated plasma factors including LDL-cholesterol, leptin, and fatty-acid binding protein 4 (FABP4) coincided with higher IFN-γ production, whereas high HDL-cholesterol and insulin sensitivity (QUICKI) coincided with higher IL-4 production. LDL and HDL supplementation in co-culture studies confirmed the effects of lipoproteins on iNKT cell cytokine production. These results suggest that circulating immunometabolic factors such as lipoproteins may be involved in Th1 skewing of the iNKT cell cytokine response in immunometabolic disease.

Prevalence and course of mood and anxiety disorders, and correlates of symptom severity in adolescents with type 1 diabetes: Results from diabetes LEAP.

OBJECTIVES: We aim to determine the prevalence and the course of anxiety and mood disorders in Dutch adolescents (12-18 years old) with type 1 diabetes, and to examine correlates of symptom severity, including parental emotional distress. METHODS: Participants were 171 adolescents and 149 parents. The Diagnostic Interview Schedule for Children-IV was used to assess current, past year and lifetime anxiety and mood disorders in adolescents. Symptom severity and diabetes distress were measured with validated questionnaires. Correlates of these symptoms were examined using hierarchical regression analyses and included demographics (adolescent sex and age), clinical factors (diabetes duration, treatment modality, most recent glycated hemoglobin A1c ; all extracted from medical charts), adolescent diabetes distress, and parent emotional distress. RESULTS: Twenty-four (14%) adolescents met the criteria for ≥1 disorder(s) in the previous 12 months. Anxiety disorders were more prevalent than mood disorders (13% vs. 4%). Lifetime prevalence of anxiety and mood disorders was 29% (n = 49). The presence of any of these disorders earlier in life (from 5 years old up to 12 months prior to assessment) was associated with disorders in the past 12 months (OR = 4.88, p = 0.001). Higher adolescent diabetes distress was related to higher symptoms of anxiety (b = 0.07, p = 0.001) and depression (b = 0.13, p = 0.001), while demographics, clinical characteristics, and parental emotional distress were not related. CONCLUSIONS: Anxiety and mood disorders are common among adolescents and related to earlier disorders. Higher diabetes distress was related to higher symptom severity. Clinicians are advised to address past psychological problems and remain vigilant of these problems.

Study protocol of Diabetes LEAP: a longitudinal study examining emotional problems in adolescents with type 1 diabetes and their parents/caregivers.

BACKGROUND: Type 1 diabetes (T1D) is a chronic metabolic condition requiring intensive daily self-care to avoid both high and low blood glucose levels. Self-care and glycemic outcomes are particularly problematic in adolescence, a period known for its increased risk of emotional problems. However, the true scope of mood and anxiety disorders in adolescents with T1D is unknown. Earlier studies are limited by a small sample size, lack of diagnostic interview data, a focus on depression only, non-adolescent specific estimates, lack of information about parental emotional problems and/or a cross-sectional design. Diabetes LEAP is a two-year prospective observational cohort study examining (a) the prevalence and course of depression and anxiety in adolescents with T1D and their parents/caregivers, (b) the risk factors predicting the presence of these emotional problems, (c) their longitudinal relation with diabetes outcomes, and (d) the psychosocial care currently in place. METHODS: Adolescents (12-18 years) from 8 Dutch pediatric diabetes clinics are interviewed using the DISC-IV to establish the presence of mood and anxiety disorders in the previous 4 weeks, the previous 12 months, and lifetime. They also complete questionnaires, including CDI-2, GAD-7, and PAID-T. Parents/caregivers complete PHQ-9, GAD-7, and PAID-PR. Follow-up assessments take place after 1 and 2 years. DISCUSSION: This longitudinal study with diagnostic interviews in a large cohort of adolescents with T1D in the Netherlands will provide much needed information regarding the prevalence and course of depression and anxiety in this group, thereby opening avenues for proper recognition, prevention and timely treatment.

Youth With Type 1 Diabetes Taking Responsibility for Self-Management: The Importance of Executive Functioning in Achieving Glycemic Control: Results From the Longitudinal DINO Study.

OBJECTIVE: Successful self-management of type 1 diabetes requires cognitive skills such as executive functioning (EF). In the transition to adolescence, youth take over responsibility for diabetes management. We set out to test: 1) the association between EF and glycemic control over time and 2) whether this association was moderated by: a) youth, shared, or parent responsibility for diabetes management and b) youth's age. RESEARCH DESIGN AND METHODS: Within the Diabetes IN DevelOpment study (DINO), parents of youth with type 1 diabetes (8-15 years at baseline; N = 174) completed a yearly assessment over 4 years. Glycemic control (HbA1c) was derived from hospital charts. Youth's EF was measured using the Behavior Rating Inventory of Executive Functioning (BRIEF)-parent report. The Diabetes Family Responsibility Questionnaire (DFRQ)-parent report was used to assess diabetes responsibility (youth, shared, and parent). Linear generalized estimating equations were used to analyze data including youth's sex, age, and age of diabetes onset as covariates. RESULTS: Relatively more EF problems are significantly associated with higher HbA1c over time (ß = 0.190; P = 0.002). More EF problems in combination with less youth responsibility (ß = 0.501; P = 0.048) or more parental responsibility (ß = -0.767; P = 0.006) are significantly associated with better glycemic control over time. Only age significantly moderates the relationship among EF problems, shared responsibility, and glycemic control (ß = -0.024; P = 0.019). CONCLUSIONS: Poorer EF is associated with worse glycemic control over time, and this association is moderated by responsibility for diabetes management tasks. This points to the importance of EF when youth take over responsibility for diabetes management in order to achieve glycemic control.

Differential adipokine receptor expression on circulating leukocyte subsets in lean and obese children.

BACKGROUND: Childhood obesity prevalence has increased worldwide and is an important risk factor for type 2 diabetes (T2D) and cardiovascular disease (CVD). The production of inflammatory adipokines by obese adipose tissue contributes to the development of T2D and CVD. While levels of circulating adipokines such as adiponectin and leptin have been established in obese children and adults, the expression of adiponectin and leptin receptors on circulating immune cells can modulate adipokine signalling, but has not been studied so far. Here, we aim to establish the expression of adiponectin and leptin receptors on circulating immune cells in obese children pre and post-lifestyle intervention compared to normal weight control children. METHODS: 13 obese children before and after a 1-year lifestyle intervention were compared with an age and sex-matched normal weight control group of 15 children. Next to routine clinical and biochemical parameters, circulating adipokines were measured, and flow cytometric analysis of adiponectin receptor 1 and 2 (AdipoR1, AdipoR2) and leptin receptor expression on peripheral blood mononuclear cell subsets was performed. RESULTS: Obese children exhibited typical clinical and biochemical characteristics compared to controls, including a higher BMI-SD, blood pressure and circulating leptin levels, combined with a lower insulin sensitivity index (QUICKI). The 1-year lifestyle intervention resulted in stabilization of their BMI-SD. Overall, circulating leukocyte subsets showed distinct adipokine receptor expression profiles. While monocytes expressed high levels of all adipokine receptors, NK and iNKT cells predominantly expressed AdipoR2, and B-lymphocytes and CD4+ and CD8+ T-lymphocyte subsets expressed AdipoR2 as well as leptin receptor. Strikingly though, leukocyte subset numbers and adipokine receptor expression profiles were largely similar in obese children and controls. Obese children showed higher naïve B-cell numbers, and pre-intervention also higher numbers of immature transition B-cells and intermediate CD14++CD16+ monocytes combined with lower total monocyte numbers, compared to controls. Furthermore, adiponectin receptor 1 expression on nonclassical CD14+CD16++ monocytes was consistently upregulated in obese children pre-intervention, compared to controls. However, none of the differences in leukocyte subset numbers and adipokine receptor expression profiles between obese children and controls remained significant after multiple testing correction. CONCLUSIONS: First, the distinct adipokine receptor profiles of circulating leukocyte subsets may partly explain the differential impact of adipokines on leukocyte subsets. Second, the similarities in adipokine receptor expression profiles between obese children and normal weight controls suggest that adipokine signaling in childhood obesity is primarily modulated by circulating adipokine levels, instead of adipokine receptor expression.

Sugarsquare, a Web-Based Patient Portal for Parents of a Child With Type 1 Diabetes: Multicenter Randomized Controlled Feasibility Trial.

BACKGROUND: Raising a child with type 1 diabetes (T1D) means combining the demands of the disease management with everyday parenting, which is associated with increased levels of distress. A Web-based patient portal, Sugarsquare, was developed to support parents, by providing online parent-professional communication, online peer support and online disease information. OBJECTIVE: The first aim of this study was to assess the feasibility of conducting a multicenter, randomized controlled trial in Dutch parents of a child with T1D. The second aim was to assess the feasibility of implementing Sugarsquare in clinical practice. METHODS: The parents of 105 children (N=105) with T1D below the age of 13 participated in a 6-month multicenter randomized controlled feasibility trial. They were randomly assigned to an experimental (n=54, usual care and Sugarsquare) or a control group (n=51, usual care). Attrition rates and user statistics were gathered to evaluate feasibility of the trial and implementation. To determine potential efficacy, the parenting stress index (PSI-SF) was assessed at baseline (T0) and after 6 months (T1). RESULTS: Of a potential population of parents of 445 children, 189 were willing to participate (enrollment refusal=57.5%, n=256), 142 filled in the baseline questionnaire (baseline attrition rate=25%, n=47), and 105 also filled in the questionnaire at T1 (post randomization attrition rate during follow-up=26%, n=32). As such, 24% of the potential population participated. Analysis in the experimental group (n=54) revealed a total of 32 (59%) unique users, divided into 12 (38%) frequent users, 9 (28%) incidental users, and 11 (34%) low-frequent users. Of the total of 44 professionals, 34 (77%) logged in, and 32 (73%) logged in repeatedly. Analysis of the user statistics in the experimental group further showed high practicability and integration in all users, moderate acceptability and demand in parents, and high acceptability and demand in health care professionals. Baseline parenting stress index scores were related to the parents' frequency of logging on (ρ=.282, P=.03) and page-views (ρ=.304, P=.01). No significant differences in change in parenting stress between experimental and control group were found (F3,101=.49, P=.49). CONCLUSIONS: The trial can be considered feasible, considering the average enrollment refusal rate, baseline attrition rate and postrandomization attrition rate, compared to other eHealth studies, although lower than hypothesized. Implementing Sugarsquare in clinical practice was partly feasible, given moderate demand and acceptability in parent users and lack of potential efficacy. Parents who reported higher levels of parenting stress used Sugarsquare more often than other parents, although Sugarsquare did not reduce parenting stress. These results indicate that Web-based interventions are a suitable way of providing parents of children with T1D with additional support. Future studies should determine how Sugarsquare could reduce parenting stress, for instance by adding targeted interventions. Factors potentially contributing to successful implementation are suggested. TRIAL REGISTRATION: Nederlands Trial Register Number: NTR3643; http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=3643 (Archived by WebCite at http://www.webcitation.org/6qihOVCi6).

Disturbed eating behaviors in adolescents with type 1 diabetes. How to screen for yellow flags in clinical practice?

BACKGROUND: Adolescents with type 1 diabetes are at an increased risk of disturbed eating behaviors (DEBs). OBJECTIVE: The aims of this study are to (i) explore the prevalence of DEBs and associated 'yellow flags', and (ii) establish concordance between adolescents-parents and adolescents-clinicians with respect to DEBs. METHODS: Adolescents (11-16 yr) and parents completed questionnaires. A stepwise approach was used to assess DEBs: only adolescents whose answers raised psychological yellow flags for DEBs completed the Diabetes Eating Problems Scale - Revised and questions from the AHEAD study. Parents and clinicians shared their observations regarding possible DEBs. Kruskal-Wallis tests, post hoc Mann-Whitney U test, and chi-squared tests were utilized to examine clinical yellow flags. Cohen's kappa was used to assess concordance. RESULTS: Of 103 adolescents participated (51.5% girls), answers of 47 (46.5%) raised psychological yellow flags, indicating body and weight concerns. A total of 8% scored above cut-off for DEBs. Clinical yellow flags were elevated glycated hemoglobin A1c (p = 0.004), older age (p = 0.034), dieting frequency (p = 0.001), reduced quality of life (p = 0.007), less diabetes self-confidence (p = 0.015), worsened diabetes management (p < 0.001), and body dissatisfaction (p < 0.001). Body Mass Index (BMI) z-scores and gender were no yellow flags. Concordance between parents and adolescents was slight (k = 0.126 and 0.141), and clinicians and adolescents was fair (k = 0.332). DISCUSSION: Half of the adolescents reported body and weight concerns, less than 1 in 10 reported DEBs. Screening for yellow flags for DEBs as a part of clinical routine using a stepwise approach and early assistance is recommended to prevent onset or deterioration of DEBs.

Parental Diabetes Behaviors and Distress Are Related to Glycemic Control in Youth with Type 1 Diabetes: Longitudinal Data from the DINO Study.

OBJECTIVE: To evaluate (1) the longitudinal relationship between parental well-being and glycemic control in youth with type 1 diabetes and (2) if youth's problem behavior, diabetes parenting behavior, and parental diabetes-distress influence this relationship. RESEARCH DESIGN AND METHODS: Parents of youth 8-15 yrs (at baseline) (N = 174) participating in the DINO study completed questionnaires at three time waves (1 yr interval). Using generalized estimating equations, the relationship between parental well-being (WHO-5) and youth's HbA1c was examined. Second, relationships between WHO-5, Strength and Difficulties Questionnaire (SDQ), Diabetes Family Behavior Checklist (DFBC), Problem Areas In Diabetes-Parent Revised (PAID-Pr) scores, and HbA1c were analyzed. RESULTS: Low well-being was reported by 32% of parents. No relationship was found between parents' WHO-5 scores and youth's HbA1c (ß = -0.052, p = 0.650). WHO-5 related to SDQ (ß = -0.219, p < 0.01), DFBC unsupportive scale (ß = -0.174, p < 0.01), and PAID-Pr (ß = -0.666, p < 0.01). Both DFBC scales (supportive ß = -0.259, p = 0.01; unsupportive ß = 0.383, p = 0.017), PAID-Pr (ß = 0.276, p < 0.01), and SDQ (ß = 0.424, p < 0.01) related to HbA1c. CONCLUSIONS: Over time, reduced parental well-being relates to increased problem behavior in youth, unsupportive parenting, and parental distress, which negatively associate with HbA1c. More unsupportive diabetes parenting and distress relate to youth's problem behavior.

Diabetes IN develOpment (DINO): the bio-psychosocial, family functioning and parental well-being of youth with type 1 diabetes: a longitudinal cohort study design.

BACKGROUND: Strict glycemic control during adolescence decreases the risk of developing complications later in life, even if this level of control is not maintained afterwards. However, the majority of adolescents with type 1 diabetes (T1D) are in poor control and so far medical or psychological interventions have shown limited success. Adolescence is characterized by major biological, psychosocial, cognitive and parent-child relationship changes and the complex interaction between these developmental trajectories, and its impact on health outcomes is still poorly understood. A specific topic of interest in this context is the timing of diagnosis. The longitudinal study DINO (Diabetes IN develOpment) aims to examine: 1) If and how the onset of T1D before vs. during puberty results in different outcomes of glycemic control, self-management, psychological functioning and diabetes-related quality of life. 2) The timing of onset of disturbed eating behavior, its risk factors and its prospective course in relation to glycemic and psychological consequences. 3) If and how the onset of T1D before vs. during puberty results in different family functioning and parental well-being. 4) If and how the cognitive development of youth with T1D relates to glycemic control and diabetes self-management. METHODS/DESIGN: DINO, a longitudinal multi-center cohort study is conducted in youth with T1D in the age range 8-15 years at baseline. Participants will be divided into two subgroups: pre-pubertal and pubertal. Both groups will be followed for 3 years with assessments based on a bio-psychosocial model of diabetes, scheduled at baseline, 12 months, 24 months and 36 months examining the biological, psychosocial -including disturbed eating behaviors- and cognitive development, family functioning and parental well-being. DISCUSSION: A better understanding of how the different trajectories affect one another will help to gain insight in the protective and risk factors for glycemic outcomes and in who needs which support at what moment in time. First results are expected in 2016.

[Fever with a rash caused by chronic meningococcemia]. / Koorts en huiduitslag door chronische meningokokkemie.

BACKGROUND: Fever with a rash is a common clinical presentation, which can be caused by various medical conditions. CASE DESCRIPTION: A 14-year old boy presented at the outpatient clinic with a two-week history of fever, myalgia and purpuric skin lesions. Blood cultures showed an infection with Neisseria meningitidis. After antibiotic treatment, his symptoms resolved promptly. CONCLUSION: Chronic meningococcemia is a rare manifestation of meningococcal infection and should be considered in patients with prolonged fever, purpuric skin lesions and joint involvement.

[Diabetes treatment in children: intensive therapy is not always best]. / Diabetesbehandeling bij kinderen: intensief is niet altijd beter.

Since the 'Diabetes Complications and Control Trial' results were published in 1993, intensive insulin therapy has been the standard treatment for paediatric patients with insulin-dependent diabetes mellitus. This therapy significantly lowers the risk of long term complications of diabetes. The intensive therapy occurs by either continuous insulin infusion via a pump or a 4-times daily injection regime. In three young patients--two girls of 16 and a boy aged 12 years--the intensive treatment option appeared to be inadequate due to a variety of factors including lack of parental support and an eating disorder. All patients were put on a 2 or 3-times daily regime, which resulted in great improvements to their HbA1c levels and sense of well being. To the boy and one of the girls, extra support was given by a home care nurse. We recommend an individualized approach to the paediatric diabetic patient when it comes to the degree of intensity of the treatment.

Tooth discoloration in patients with neonatal diabetes after transfer onto glibenclamide: a previously unreported side effect.

OBJECTIVE To assess if tooth discoloration is a novel side effect of sulfonylurea therapy in patients with permanent neonatal diabetes due to mutations in KCNJ11. RESEARCH DESIGN AND METHODS A total of 67 patients with a known KCNJ11 mutation who had been successfully transferred from insulin injections onto oral sulfonylureas were contacted and asked about the development of tooth discoloration after transfer. RESULTS Altered tooth appearance was identified in 5 of the 67 patients. This was variable in severity, ranging from mild discoloration/staining (n = 4) to loss of enamel (n = 1) and was only seen in patients taking glibenclamide (glyburide). CONCLUSIONS These previously unreported side effects may relate to the developing tooth and/or to the high local concentrations in the children who frequently chewed glibenclamide tablets or took it as a concentrated solution. Given the multiple benefits of sulfonylurea treatment for patients with activating KCNJ11 mutations, this association warrants further investigation but should not preclude such treatment.

Co-morbidity obese children in family practice in The Netherlands: the results of a pilot study.

OBJECTIVES: The aim of this pilot study was to assess the prevalence of co-morbidity in obese children. Particular emphasis was on cardiovascular risk. METHOD: In this retrospective, cross-sectional, observational study the data of 155 obese children, who visited a paediatric obesity outdoor clinic, have been studied. RESULTS: In all, 92% of the population had at least one cardiovascular risk factor. In all, 48% showed a high systolic and 9% a high diastolic blood pressure, while 18% had an increased fasting glucose. In 60%, we diagnosed insulin resistance: the homeostasis model assessment was elevated. DISCUSSIONS: The prevalence of high blood pressure, dyslipidaemia, abnormal fasting glucose and insulin resistance are high in this retrospective study. Outcomes of foreign studies on this object are difficult to compare because various populations and cut-off points are used. A new, prospective, study will be conducted to asses the prevalence of co-morbidity in obese children in general practice.

Effects of insulin pump vs. injection treatment on quality of life and impact of disease in children with type 1 diabetes mellitus in a randomized, prospective comparison.

OBJECTIVE: Effects of pump treatment vs. four times daily injections were explored in children with diabetes with regard to quality of life and impact of disease as well as adverse effects and parameters of metabolic control. METHODS: An open, parallel, randomized controlled prospective comparative study lasting 14 months was completed by 38 type 1 children with diabetes (age 4-16 yr) following a 3.5-months run-in phase. Standardized quality-of-life Pediatric Quality of life Inventory (PedsQL) and impact of disease scores were obtained every 3.5 months as well as regular medical parameters. Parallel treatment group data and longitudinal within-patient data were analysed for each treatment modality. RESULTS: Within-patient comparisons of the two treatment modalities showed significant improvement in PedsQL and impact scores after pump treatment. Treatment group comparisons did not show significant improvement. Pump treatment resulted in decreased symptomatic hypoglycaemia and lowered haemoglobin A1c by 0.22% after run in. CONCLUSIONS: Within-patient comparison suggests that metabolic control, frequency of severe hypoglycaemia (a threefold decrease), quality of life and impact of disease scores are improved by pump treatment in comparison to regular treatment with four daily insulin injections.

Cost-effectiveness of continuous subcutaneous insulin infusion (CSII) in children: illusion or delusion?

Cost-effectiveness of continuous subcutaneous insulin infusion (CSII) in children is reviewed in the context of possible improvement of percentage of hemoglobin A1c (HbA1c) and of other clinical benefits over multiple daily injections (MDI). Cost-effectiveness depends on clinical efficacy but reported clinical efficacy parameters may overlook definite benefits perceived by children and parents using CSII. There are few detailed reports on cost comparisons between CSII and MDI in adults, even less in children or adolescents. Review of direct extra costs for CSII over conventional treatment, including MDI, suggest that these may double, 5000-6000 EUR vs. 3000 EUR per patient year. An example is given of how to calculate direct cost differences, showing local differences. Randomized comparisons between CSII and MDI in childhood and adolescence show few marked clinical effects, but non-randomized comparisons favor CSII. Quality of life parameters fall short in any such comparison in children and adolescents alike. The reasons for the apparent discrepancy between non-randomized childhood studies and the randomized prospective ones are given. There is a dire need for better parameters to assess the well-being of diabetic children treated by CSII or MDI. Only then is it warranted to estimate the cost-effectiveness of CSII vs. MDI in childhood and adolescence.