Objective Home-Monitoring of Physical Activity, Cardiovascular Parameters, and Sleep in Pediatric Obesity.

Introduction: Clinical research and treatment of childhood obesity is challenging, and objective biomarkers obtained in a home-setting are needed. The aim of this study was to determine the potential of novel digital endpoints gathered by a home-monitoring platform in pediatric obesity. Methods: In this prospective observational study, 28 children with obesity aged 6-16 years were included and monitored for 28 days. Patients wore a smartwatch, which measured physical activity (PA), heart rate (HR), and sleep. Furthermore, daily blood pressure (BP) measurements were performed. Data from 128 healthy children were utilized for comparison. Differences between patients and controls were assessed via linear mixed effect models. Results: Data from 28 patients (average age 11.6 years, 46% male, average body mass index 30.9) and 128 controls (average age 11.1 years, 46% male, average body mass index 18.0) were analyzed. Patients were recruited between November 2018 and February 2020. For patients, the median compliance for the measurements ranged from 55% to 100% and the highest median compliance was observed for the smartwatch-related measurements (81-100%). Patients had a lower daily PA level (4,597 steps vs. 6,081 steps, 95% confidence interval [CI] 862-2,108) and peak PA level (1,115 steps vs. 1,392 steps, 95% CI 136-417), a higher nighttime HR (81 bpm vs. 71 bpm, 95% CI 6.3-12.3) and daytime HR (98 bpm vs. 88 bpm, 95% CI 7.6-12.6), a higher systolic BP (115 mm Hg vs. 104 mm Hg, 95% CI 8.1-14.5) and diastolic BP (76 mm Hg vs. 65 mm Hg, 95% CI 8.7-12.7), and a shorter sleep duration (difference 0.5 h, 95% CI 0.2-0.7) compared to controls. Conclusion: Remote monitoring via wearables in pediatric obesity has the potential to objectively measure the disease burden in the home-setting. The novel endpoints demonstrate significant differences in PA level, HR, BP, and sleep duration between patients and controls. Future studies are needed to determine the capacity of the novel digital endpoints to detect effect of interventions.

Serum hepcidin concentrations in relation to iron status in children with type 1 diabetes.

Chronic low-grade inflammation in type 1 diabetes (T1D) might increase hepcidin synthesis, possibly resulting in functional iron deficiency (FID). We hypothesized that in T1D children with FID, hepcidin concentrations are increased compared to those with normal iron status and those with absolute iron deficiency (AID). We evaluated hepcidin concentrations in T1D children in relation to iron status, and investigated whether hepcidin is useful in assessing FID. A cross-sectional study was conducted. FID was defined as elevated zinc protoporphyrin/heme ratio and/or red blood cell distribution width, and AID as low serum ferritin concentration. Post-hoc analyses with different definitions of FID were performed, using transferrin saturation and reticulocyte hemoglobin content. Serum hepcidin concentrations were measured using mass-spectrometry. The IRODIAB-study is registered at www.trialregister.nl (NTR4642). This study included 215 T1D children with a median age of 13.7 years (Q1-Q3: 10.1-16.3). The median (Q1-Q3) hepcidin concentration in patients with normal iron status was 1.8 nmol/l (0.9-3.3), in AID-patients, 0.4 nmol/l (0.4-0.4) and in FID-patients, 1.6 nmol/l (0.7-3.5). Hepcidin concentrations in FID-patients were significantly higher than in AID-patients (p < 0.001). Irrespective of FID-definition used, hepcidin concentrations did not differ between FID-patients and patients with normal iron status. This might be explained by the influence of various factors on hepcidin concentrations, and/or by differences in response of iron parameters over time. Single hepcidin measurements do not seem useful in assessing FID in T1D children. Multiple hepcidin measurements over time in future studies, however, might prove to be more useful in assessing FID in children with T1D.

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.

The influence of food order on postprandial glucose levels in children with type 1 diabetes.

OBJECTIVE: To evaluate the effect of the order of intake of carbohydrates, protein, and fat on postprandial glucose levels in children with type 1 diabetes (T1D). Our hypothesis was that postprandial glucose levels would be lower when fat and protein are consumed prior to carbohydrates, compared to a meal where all macronutrients are combined. METHODS: A randomized, open-label, within-subject crossover study was conducted. Twenty patients aged 7 to 17 years diagnosed with T1D for >1 year consumed 2 isocaloric meals (with similar composition) in random order. In 1 meal, the protein and fat part was consumed 15 minutes prior to the carbohydrates (test meal). In the other meal, all macronutrients were consumed together (standard meal). Capillary blood glucose measurements and continuous glucose monitoring system were used to assess multiple glucose levels during a 3-hour postprandial period. RESULTS: Overall, mean glucose levels were 1 mmol/L lower following the test meal compared to the standard meal (9.30 ± 3.20 vs 10.24 ± 3.35 mmol/L; P < .001). No significant difference in peak glucose was found. Glucose excursions were 1.5 and 1 mmol/L lower at 30 and 120 minutes following the test meal. A reduction in the total time period in which glucose levels exceeded 10 and 12 mmol/L of 28.7 (P = .001) and 22.3 minutes (P = .004), respectively, after the test meal was found. CONCLUSIONS: This study shows that consumption of protein and fat prior to carbohydrates results in lower postprandial glucose levels and reduced glycemic variability in children with T1D.

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.

The effect of family-based multidisciplinary cognitive behavioral treatment on health-related quality of life in childhood obesity.

PURPOSE: To evaluate the effect of multidisciplinary treatment on obesity and health-related quality of life (HRQOL). METHODS: Obese children were randomized to a multidisciplinary lifestyle treatment, including medical, nutritional, physical, and psychological counseling during 3 months, (n = 40, BMI-SDS; 4.2 ± 0.7, age; 13.3 ± 2.0) or standard care, including an initial advice on nutrition and physical activity by the pediatrician (n = 39, BMI-SDS; 4.3 ± 0.7, age; 13.1 ± 1.9). At baseline, after 3 months of treatment and at 12 months follow-up, data were collected for BMI-SDS and a European validated questionnaire for assessing HRQOL (DISABKIDS). RESULTS: A significantly reduced BMI-SDS was found for the intervention group after 3 months treatment (4.0 ± 0.9 vs. 4.2 ± 0.7, P = 0.02) and at 12 months follow-up (3.8 ± 1.1 vs. 4.2 ± 0.7, P = 0.03). HRQOL in the intervention group was significantly improved at 12 months follow-up and unchanged in the obese control group. Agreement between child and parent report was moderate (67-85%), with parents reporting a lower HRQOL for their obese children than children themselves in both groups. CONCLUSION: Multidisciplinary treatment is effective in reducing BMI-SDS and improving HRQOL after 12 months follow-up.

The predictive value of the individual components of the metabolic syndrome for insulin resistance in obese children.

BACKGROUND/AIMS: The usefulness of the concept of the metabolic syndrome (MS) in its current form has recently been questioned, and its association with insulin resistance is unknown. We assessed whether a multivariate model based on all components of MS expressed on a continuous scale would be a better predictor of a common marker of insulin resistance than the current dichotomous MS definitions. METHODS: Data from 78 obese Dutch teenagers (age 13.0 ± 2.1 years) were used for model development, and the model was validated in 40 obese Hindustani children (age 12.6 ± 2.0 years). MS components and homeostasis model assessment-insulin resistance (HOMA-IR) were expressed as standard deviation scores (SDSs), based on gender- and age-specific reference values. RESULTS: Using the three dichotomous models, the prevalence of MS was found to be 36, 65 and 18%, with low mutual agreement. None of these dichotomous models was a significant predictor for increased HOMA-IR SDS. The multivariate model incorporating MS components expressed as SDSs explained 58% of the variance of increased HOMA-IR SDS. In the validation group, the predicted and observed HOMA-IR SDS (2.4 ± 1.2 vs. 2.6 ± 2.2) did not differ significantly. CONCLUSION: A multivariate prediction model based on MS components expressed as SDSs has a good predictive value for increased HOMA-IR SDS.

The effect of family-based multidisciplinary cognitive behavioral treatment in children with obesity: study protocol for a randomized controlled trial.

BACKGROUND: The prevalence of childhood obesity has increased rapidly during the last three decades in the Netherlands. It is assumed that mainly environmental factors have contributed to this trend. Parental overweight and low social economic status are risk factors for childhood obesity. Childhood obesity affects self-esteem and has negative consequences on cognitive and social development. Obese children tend to become obese adults, which increases the risk for developing cardiovascular complications, type 2 diabetes mellitus, and psychosocial problems. Additionally, the secretion of several gastrointestinal hormones, responsible for appetite and food intake, is impaired in obese subjects. Weight reduction through lifestyle changes in order to change health risks is, until now, suggested as the preferred treatment for childhood obesity.The objective of this study is the effect evaluation of a family-based cognitive behavioral multidisciplinary lifestyle treatment. The intervention aims to establish long-term weight reduction and stabilization, reduction of obesity-related health consequences and improvement of self-image by change of lifestyle and learning cognitive behavioral techniques. STUDY DESIGN/METHODS: In this randomized clinical trial newly presented children with obesity (8-17 years old) are divided, by randomization, in an intervention and control group, both consisting of 40 obese children. The intervention is carried out in groups of 8-11 children, and consists of respectively 7 and 5 separate group meetings for the children and their parents and 1 joint group meeting of 2 ½ hours. Main topics are education on nutrition, self-control techniques, social skills, physical activity and improvement of self-esteem. The control group is given advice on physical activity and nutrition. For normal data comparison, data were collected of 40 normal-weight children, 8-17 years old. DISCUSSION: Because of the increasing prevalence of childhood obesity and the impact on the individual as well as on society, prevention and treatment of obesity in children is of great importance. For evaluation of short- and long-term effects of the treatment, measurements are taken before and after 3 months of treatment, and after 12 and 24 months follow-up. During these visits clinical and biochemical data are determined, cardiovascular fitness tests are performed and quality of life questionnaires are completed. TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number Register ISRCTN36146436

The effect of multidisciplinary lifestyle intervention on the pre- and postprandial plasma gut Peptide concentrations in children with obesity.

Objective. This study aims to evaluate the effect of a multidisciplinary treatment of obesity on plasma concentrations of several gut hormones in fasting condition and in response to a mixed meal in children. Methods. Complete data were available from 36 obese children (age 13.3 ± 2.0 yr). At baseline and after the 3-month multidisciplinary treatment, fasting and postprandial blood samples were taken for glucose, insulin, ghrelin, peptide YY (PYY), and glucagon-like peptide 1 (GLP-1). Results. BMI-SDS was significantly reduced by multidisciplinary treatment (from 4.2 ± 0.7 to 4.0 ± 0.9, P < .01). The intervention significantly increased the area under the curve (AUC) of ghrelin (from 92.3 ± 18.3 to 97.9 ± 18.2 pg/L, P < .01), but no significant changes were found for PYY or GLP-1 concentrations (in fasting or postprandial condition). The insulin resistance index (HOMA-IR) remained unchanged as well. Conclusion. Intensive multidisciplinary treatment induced moderate weight loss and increased ghrelin secretion, but serum PYY and GLP-1 concentrations and insulin sensitivity remained unchanged.