Background: Anxiety and depression are more common in children with obesity than in children of normal weight, but it is unclear whether this association is independent of other known risk factors. Interpretation of results from previous studies is hampered by methodological limitations, including self-reported assessment of anxiety, depression, and anthropometry. The aim of this study was to investigate whether obesity increases the risk of anxiety or depression independently of other risk factors in a large cohort of children and adolescents, using robust measures with regard to exposure and outcome. Methods: Children aged 6-17 years in the Swedish Childhood Obesity Treatment Register (BORIS, 2005-2015) were included (n = 12,507) and compared with a matched group (sex, year of birth, and area of residence) from the general population (n = 60,063). The main outcome was a diagnosis of anxiety or depression identified through ICD codes or dispensed prescribed medication within 3 years after the end of obesity treatment. Hazard ratios (HRs) with 95% confidence intervals (CIs) from Cox proportional models were adjusted for several known confounders. Results: Obesity remained a significant risk factor for anxiety and depression in children and adolescents after adjusting for Nordic background, neuropsychiatric disorders, family history of anxiety/depression, and socioeconomic status. Girls in the obesity cohort had a 43% higher risk of anxiety and depression compared to girls in the general population (adjusted HR 1.43, 95% CI 1.31-1.57; p < 0.0001). The risk in boys with obesity was similar (adjusted HR 1.33, 95% CI 1.20-1.48; p < 0.0001). In sensitivity analyses, excluding subjects with neuropsychiatric disorders and a family history of anxiety/depression, the estimated risks in individuals with obesity were even higher compared with results from the main analyses (adjusted HR [95% CI]: girls = 1.56 [1.31-1.87], boys = 2.04 [1.64-2.54]). Conclusions: Results from this study support the hypothesis that obesity per se is associated with risk of both anxiety and depression in children and adolescents.

Objective:Impaired fasting glucose (IFG), a pre-stage to type 2 diabetes in adults, is also present in obese children. A large variation of the occurrence has been recorded, but the true prevalence is unknown due to lack of larger representative cohort studies. This study was implemented to investigate the prevalence of IFG in two nationwide cohorts of obese children and to find factors that affect the risk of IFG.Design:A cross-sectional study based on data collected from two nationwide registers of obese children in Germany and Sweden, respectively.Subjects:Subjects included were 2–18 years old. 32 907 subjects with fasting glucose were eligible in Germany and 2726 in Sweden. Two cutoff limits for IFG were used: 5.6–6.9 mmol l−1 according to the American Diabetes Association (ADA) and 6.1–6.9 mmol l−1according to the World Health Organization (WHO). Variables collected were gender, age and degree of obesity. Logistic regression was used to calculate odds ratios.Results:The total prevalence of IFG among obese children in the German cohort according to the ADA was 5.7% and according to the WHO it was 1.1%. In Sweden, the corresponding prevalence was 17.1% and 3.9%, respectively. IFG risk was correlated with increasing age, male sex and degree of obesity.Conclusions:IFG is highly prevalent among obese children. Age and degree of obesity are positively correlated with the risk of having IFG. There are large regional differences. After adjustments, obese children in Sweden, due to unknown reasons, have a 3.4- to 3.7-fold higher risk of having IFG than obese children in Germany.

Background Pediatric obesity is associated with increased risk of premature death from middle age onward, but whether the risk is already increased in young adulthood is unclear. The aim was to investigate whether individuals who had obesity in childhood have an increased mortality risk in young adulthood, compared with a population-based comparison group. Methods and findings In this prospective cohort study, we linked nationwide registers and collected data on 41,359 individuals. Individuals enrolled at age 3-17.9 years in the Swedish Childhood Obesity Treatment Register (BORIS) and living in Sweden on their 18th birthday (start of followup) were included. A comparison group was matched by year of birth, sex, and area of residence. We analyzed all-cause mortality and cause-specific mortality using Cox proportional hazards models, adjusted according to group, sex, Nordic origin, and parental socioeconomic status (SES). Over 190,752 person-years of follow-up (median follow-up time 3.6 years), 104 deaths were recorded. Median (IQR) age at death was 22.0 (20.0-24.5) years. In the childhood obesity cohort, 0.55% (n = 39) died during the follow-up period, compared to 0.19% (n = 65) in the comparison group (p < 0.001). More than a quarter of the deaths among individuals in the childhood obesity cohort had obesity recorded as a primary or contributing cause of death. Male sex and low parental SES were associated with premature all-cause mortality. Suicide and self-harm with undetermined intent were the main cause of death in both groups. The largest difference between the groups lay within endogenous causes of death, where children who had undergone obesity treatment had an adjusted mortality rate ratio of 4.04 (95% CI 2.00-8.17, p < 0.001) compared with the comparison group. The main study limitation was the lack of anthropometric data in the comparison group.

BackgroundExperimental and natural human adenovirus-36 (Adv36) infection of multiple animal species results in obesity through increasing adipogenesis and lipid accumulation in adipocytes. Presence of Adv36 antibodies detected by serum neutralization assay has previously been associated with obesity in children and adults living in the USA, South Korea and Italy, whereas no association with adult obesity was detected in Belgium/the Netherlands nor among USA military personnel. Adv36 infection has also been shown to reduce blood lipid levels, increase glucose uptake by adipose tissue and skeletal muscle biopsies, and to associate with improved glycemic control in non-diabetic individuals.Principal FindingsUsing a novel ELISA, 1946 clinically well-characterized individuals including 424 children and 1522 non-diabetic adults, and 89 anonymous blood donors, residing in central Sweden representing the population in Stockholm area, were studied for the presence of antibodies against Adv36 in serum. The prevalence of Adv36 positivity in lean individuals increased from ∼7% in 1992–1998 to 15–20% in 2002–2009, which paralleled the increase in obesity prevalence. We found that Adv36-positive serology was associated with pediatric obesity and with severe obesity in females compared to lean and overweight/mildly obese individuals, with a 1.5 to 2-fold Adv36 positivity increase in cases. Moreover, Adv36 positivity was less common among females and males on antilipid pharmacological treatment or with high blood triglyceride level. Insulin sensitivity, measured as lower HOMA-IR, showed a higher point estimate in Adv36-positive obese females and males, although it was not statistically significant (p = 0.08).ConclusionUsing a novel ELISA we show that Adv36 infection is associated with pediatric obesity, severe obesity in adult females and lower risk of high blood lipid levels in non-diabetic Swedish individuals.

Background In order to achieve improved weight status, behavioral pediatric obesity treatment is resource intensive. Mobile Health (mHealth) is more accessible than standard care but effective approaches are scarce. Therefore, the aim of this feasibility trial was to study trial design, mHealth usage, compliance, and acceptability of a novel mHealth approach in pediatric obesity treatment. Methods This six-month parallel two-arm feasibility trial took place at three pediatric outpatient clinics in Stockholm, Sweden. Participants, 5–12 years, starting obesity treatment were randomized to using an mHealth support system as an addition to standard care (intervention) or to standard care alone (control). The intervention included daily self-monitoring of weight transferred to a mobile application (app) used by parents, a website in which clinicians could track treatment progress, prespecified treatment goals for change in degree of obesity shown in the app and on the website, and text message interactions between clinicians and parents. The main outcome was description of feasibility. Height and weight were measured at baseline, three, and 6 months to explore changes in body mass index standard deviation score (BMI SDS). Results Of 40 children eligible for inclusion, 28 agreed to participate (54% girls) and were randomized to intervention (n = 15) or control (n = 13). Weight was measured at home regularly throughout the entire trial period by 12/15 children in the intervention group. Attendance at appointments were better in the intervention group (p = 0.024). Both parents and clinicians had a positive experience and found the mHealth support system accessible. At 6 months the intervention group had a greater reduction of 0.24 units in BMI SDS than standard care (− 0.23 vs. 0.01, p = 0.002). Conclusions The mHealth support system was a feasible and innovative treatment approach which, in addition to standard care, generated better treatment results than standard care alone. Future research should evaluate the treatment effects over a longer follow-up time in a larger study sample. Trial registration This trial was retrospectively registered at ClinicalTrials.gov, ID: NCT03380598, on November 8, 2017.

Objectives:In adults, impaired fasting glycemia (IFG) increases the risk for type 2 diabetes mellitus (T2DM). This study aimed to investigate to which extent children with obesity develop T2DM during early adulthood, and to determine whether IFG and elevated hemoglobin A1c (HbA1c) in obese children are risk markers for early development of T2DM.Methods:In this prospective cohort study, 1620 subjects from the Swedish Childhood Obesity Treatment Registry – BORIS who were ⩾18 years at follow-up and 8046 individuals in a population-based comparison group, matched on gender age and living area, were included. IFG was defined according to both ADA (cut-off 5.6 mmol l−1) and WHO (6.1 mmol l−1). Elevated HbA1c was defined according to ADA (cut-off 39 mmol l−1). Main outcome was T2DM medication, as a proxy for T2DM. Data on medications were retrieved from a national registry.Results:The childhood obesity cohort were 24 times more likely to receive T2DM medications in early adulthood compared with the comparison group (95% confidence interval (CI): 12.52–46). WHO-defined IFG predicted future use of T2DM medication with an adjusted hazard ratio (HR) of 3.73 (95% CI: 1.87–7.45) compared with those who had fasting glucose levels <5.6 mmol l−1. A fasting glucose level of 5.6–6.0 mmol l−1, that is, the IFG-interval added by American Diabetes Association (ADA), did not increase the use of T2DM medication more than pediatric obesity itself, adjusted HR=1.72 (0.84–3.52). Elevated levels of HbA1c resulted in an adjusted HR=3.12 (1.50–6.52). More severe degree of obesity also increased the future T2DM risk.CONCLUSION:IFG according to WHO and elevated HbA1c (39–48 mmol l−1), but not the additional fasting glucose interval added by ADA (5.6–6.0 mmol l−1), can be considered as prediabetes in the obese pediatric population in Sweden.

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Aims In this study, we investigated whether adipose tissue insulin resistance (IR) is affected by the degree of obesity during the fasting and post-prandial state, independent of glucose tolerance among obese children and adolescents. We also tested whether systemic subclinical inflammation is associated with adipose tissue IR. Methods Subjects were recruited to the Yale Pathophysiology of Type 2 Diabetes in Youth Study (NCT01967849). An oral glucose-tolerance test was performed to establish glucose-tolerance status and blood samples were drawn for measurement of free fatty acids (FFAs), to calculate the area under the curve (AUC) of FFA. Adipose tissue insulin resistance was calculated as the product of insulin and FFA concentrations. Results In total, 671 children and adolescents (58.6% females) were included with a mean age of 13.3(2.7) years and BMI Z score of 2.45(0.31). The degree of obesity emerged as an independent predictor of both fasting and post-prandial adipose IR, p < 0.0001. Higher degree of obesity was associated with greater AUC FFA (lower suppression) compared to lower degree of obesity, p = 0.01. Furthermore, higher levels of IL-6 were positively associated with post-prandial adipose tissue IR, p = 0.02. Conclusions The degree of obesity in childhood and adolescence is strongly associated with adipose tissue IR independent of glucose tolerance. This is reflected not only in calculated indices of adipose IR but also in lower suppression of FFAs during the OGTT regardless of glucose tolerance or fasting adipose tissue IR. Furthermore, markers of subclinical inflammation such as IL-6 are associated with adipose tissue IR, independent of other factors. Electronic supplementary material The online version of this article (10.1007/s00592-018-01285-3) contains supplementary material, which is available to authorized users.