Longitudinal analysis of vitamin D levels considering sunshine duration and suggestion for a standardised approach for vitamin D supplementation in children and adolescents with obesity.

BACKGROUND: Children with obesity have low 25 hydroxy-vitamin D (25-OH-D3) levels compared to lean children. Recommendations on when to start vitamin D supplementation differ largely between countries. Longitudinal data on 25-OH-D3 levels to guide treatment decisions are scarce since they are largely influenced by solar radiation and are difficult to compare. METHODS: We carried out a retrospective analysis of multiple 25-OH-D3 and parathyroid hormone (PTH) measurements in a cohort of 543 patients without vitamin D supplementation. All measurements were taken at the local paediatric obesity clinic as documented in the German-Austrian-Swiss APV (Prospective Documentation of Overweight Children and Adolescents) registry from 2009 to 2019. Serial 25-OH-D3 and PTH levels were adjusted for sunshine duration over the last 30 days to account for seasonal variation, as well as for sex and body mass index (BMI). We further performed an exploratory analysis of the association of sunshine duration, sex, BMI SDS (standard deviation score), abnormal lipid levels or dysglycemia with the 25-OH-D3 trend. RESULTS: 229 obese patients (mean BMI SDS: 2,58 (± 0,56), 53% females, mean age: 12 (± 3) years, range: 2-21 years) with two, 115 with three and 96 with four repeated 25-OH-D3 measurements were identified. Mean adjusted 25-OH-D3 (48.2 nmol/l) and PTH (34.9 ng/l) levels remained stable over 120 weeks. 5% of the patients had an elevated PTH > 65 ng/l. High total cholesterol ≥ 200 mg/dl and high triglycerides ≥ 130 mg/dl were associated with higher 25-OH-D3 levels. CONCLUSION: We propose a simple method to include sunshine duration in the analysis of 25-OH-D3 levels to minimise the bias of seasonal variation. Based on our data we established the pragmatic strategy of limiting vitamin D supplementation to patients with biochemical signs of mineralisation disorders such as elevated PTH and alkaline phosphatase (AP). In children with normal PTH and AP we recommend adjustment of calcium intake and increase of outdoor activity instead.

Poorly controlled pediatric type 1 diabetes mellitus is a risk factor for metabolic dysfunction associated steatotic liver disease (MASLD): An observational study.

OBJECTIVES: Recent studies have suggested a link between type 1 diabetes mellitus (T1D) and metabolic dysfunction associated steatotic liver disease (MASLD) in children and adolescent, but longitudinal evidence is lacking. This study aimed to investigate the potential association between poorly controlled T1D and elevated alanine aminotransferase (ALT), serving as a proxy for MASLD in children and adolescents over time. METHODS: The study included 32,325 children aged 2-17 years with T1D from Germany, Austria, and Switzerland who had undergone at least one assessment of liver enzyme levels recorded in the Diabetes-Patienten- Verlaufsdokumentation registry. Multivariable logistic and Cox regression models were calculated to show possible associations between T1D and elevated ALT values (>26 U/L in males, >22 U/L in females) as a proxy for MASLD. RESULTS: Children with poorly controlled T1D (HbA1c > 11%) exhibited increased odds of elevated ALT values, after adjustment for age, sex, diabetes duration and overweight (odds ratio [OR] 2.54; 95% confidence interval [CI], 2.10-3.10; p < 0.01). This finding is substantiated by a longitudinal analysis, which reveals that inadequately controlled T1D was associated with a higher hazard ratio (HR) of elevated ALT values compared to children with controlled T1D over an observation period extending up to 5.5 (HR: 1.54; 95% CI, 1.19-2.01; p < 0.01). CONCLUSION: In conclusion, the current study strongly links poorly controlled T1D in children and adolescents to MASLD irrespective of overweight. This association is not only present cross-sectionally but also increases over time. The study underscores the critical role of effective diabetes management in reducing the risk of MASLD in this population.

Insulin Secretion Defect in Children and Adolescents with Obesity: Clinical and Molecular Genetic Characterization.

Introduction: Childhood obesity is increasing worldwide and presents as a global health issue due to multiple metabolic comorbidities. About 1% of adolescents with obesity develop type 2 diabetes (T2D); however, little is known about the genetic and pathophysiological background at young age. The objective of this study was to assess the prevalence of impaired glucose regulation (IGR) in a large cohort of children and adolescents with obesity and to characterize insulin sensitivity and insulin secretion. We also wanted to investigate adolescents with insulin secretion disorder more closely and analyze possible candidate genes of diabetes in a subcohort. Methods: We included children and adolescents with obesity who completed an oral glucose tolerance test (OGTT, glucose + insulin) in the outpatient clinic. We calculated Matsuda index, the area under the curve (AUC (Ins/Glu)), and an oral disposition index (ISSI-2) to estimate insulin resistance and beta-cell function. We identified patients with IGR and low insulin secretion (maximum insulin during OGTT < 200 mU/l) and tested a subgroup using next generation sequencing to identify possible mutations in 103 candidate genes. Results: The total group consisted of 903 children and adolescents with obesity. 4.5% showed impaired fasting glucose, 9.4% impaired glucose tolerance, and 1.2% T2D. Matsuda index and Total AUC (Ins/Glu) showed a hyperbolic relationship. Out of 39 patients with low insulin secretion, we performed genetic testing on 12 patients. We found five monogenetic defects (ABCC8 (n = 3), GCK (n = 1), and GLI2/PTF1A (n = 1)). Conclusion: Using surrogate parameters of beta-cell function and insulin resistance can help identify patients with insulin secretion disorder. A prevalence of 40% mutations of known diabetes genes in the subgroup with low insulin secretion suggests that at least 1.7% of patients with adolescent obesity have monogenic diabetes. A successful molecular genetic diagnosis can help to improve individual therapy.

Psychosocial Burden During the COVID-19 Pandemic in Adolescents With Type 1 Diabetes in Germany and Its Association With Metabolic Control.

PURPOSE: To investigate the psychosocial burden during the COVID-19 pandemic in adolescents with type 1 diabetes and its association with metabolic control. METHODS: Prospective multicenter observational cohort study based on data from the German Diabetes Prospective Follow-up Registry. Adolescents aged 12-20 years with type 1 diabetes were asked during routine follow-up visits to complete a questionnaire on psychosocial distress and daily use of electronic media during the COVID-19 pandemic from June 2021 to November 2022. Well-being, anxiety, and depression symptoms were assessed using World Health Organization Five Well-Being Index (WHO-5), General Anxiety Disorder scale 7 (GAD-7), and Patient Health Questionnaire-9 questionnaires. The impact of mental health symptoms on metabolic control was analyzed by using multivariable linear regression models adjusted for sex, diabetes duration, treatment, socioeconomic deprivation, and immigrant background. RESULTS: Six hundred eighty eight adolescents (45.6% females) from 20 diabetes centers participated. Compared with a prepandemic cohort, WHO-5 scores were lower during the COVID-19 pandemic (estimated mean difference -9.6 [95% confidence interval -11.6; -7.6], p < .001), but GAD-7 scores were not different (estimated mean difference 0.6 [95% confidence interval -0.2; 1.5], p = .14). HbA1c was significantly positively associated with GAD-7 and Patient Health Questionnaire-9 and negatively associated with WHO-5 scores (all p < .001). Daily electronic media use was positively associated with adjusted mental health symptoms (all p < .01). DISCUSSION: Although the overall well-being of adolescents with type 1 diabetes was reduced during the later phase of the COVID-19 pandemic, the additional psychological burden was relatively low. However, mental health symptoms were associated with poorer metabolic control and higher use of electronic media.

Clinical characteristics and outcomes of children, adolescents and young adults with overweight or obesity and mental health disorders.

BACKGROUND: Mental disorders are important comorbidities in youth with obesity. Aim was to describe the clinical characteristics and outcome of youth with overweight or obesity having comorbid mental disorders. METHODS: Data from children, adolescents, and young adults (age 6-30 years) with overweight or obesity and mental disorders (depression, anxiety disorder, eating disorder, attention deficit disorder (ADHD)) from 226 centers in Germany and Austria participating in the Adiposity Patient Registry (APV) were analyzed and compared with those without reported mental disorders using regression modeling. RESULTS: Mental health comorbidity was reported in a total of 3969 out of 114,248 individuals with overweight or obesity: 42.5% had ADHD, 31.3% anxiety disorders, 24.3% depression, and 12.9% eating disorders. Being male (OR 1.39 (95%CI 1.27;1.52)), of older age (1.42 (1.25;1.62)), or with extreme obesity (1.45 (1.30;1.63)) were most strongly associated with mental health comorbidity. Regression analysis showed that mean BMI-SDS was significantly higher in the group of individuals with depression and eating disorders (BMI-SDS 2.13 (lower; upper mean:2.09;2.16) and 2.22 (2.17;2.26)) compared to those without reported mental health comorbidity (BMI-SDS 2.008 (2.005;2.011); p < 0.001). In youth with ADHD, BMI-SDS was lower compared to those without reported mental disorders (BMI-SDS 1.91 (1.89;1.93) vs 2.008 (2.005;2.011); p < 0.001). Proportion of severe obesity was higher in individuals with depression (23.7%), anxiety disorders (17.8%), and eating disorders (33.3%), but lower in ADHD (10.3%), compared to those without reported mental disorders (13.5%, p < 0.002). Proportions of dyslipidaemia and abnormal carbohydrate metabolism were not different in youth with and without reported mental health comorbidity. BMI-SDS change after one year of lifestyle intervention program ranged between -0.22 and -0.16 and was similar in youth without and with different mental disorders. CONCLUSION: Health care professionals caring for youth with overweight or obesity should be aware of comorbid mental disorders and regular mental health screening should be considered.

BMI Z-Score (SDS) versus Calculated Body Fat Percentage: Association with Cardiometabolic Risk Factors in Obese Children and Adolescents.

INTRODUCTION: BMI or BMI-standardized deviation score (SDS) in children and adolescents is still the standard for weight classification. [BMJ. 2019;366:4293] developed a formula to calculate body fat percentage (%BF) based on age, sex, height, weight, and ethnicity. Using data from the German/Austrian APV registry, we investigated whether the calculated %BF is superior to BMI-SDS in predicting arterial hypertension, dyslipidaemia, and impaired glucose metabolism. METHODS: 94,586 children and adolescents were included (12.5 years, 48.3% male). Parental birth country (BC) was used to depict ethnicity (15.8% migration background); 95.67% were assigned to the ethnicity "white." %BF was calculated based on the Hudda formula. The relationship between BMI-SDS or %BF quartiles and outcome variables was investigated by logistic regression models, adjusted for age, sex, and migration background. Vuong test was applied to analyse predictive power. RESULTS: 58.4% had arterial hypertension, 33.5% had dyslipidaemia, and 11.6% had impaired glucose metabolism. Boys were significantly more often affected, although girls had higher calculated %BF (each p < 0.05). After adjustment, both models revealed significant differences between the quartiles (all p < 0.001). The predictive power of BMI-SDS was superior to %BF for all three comorbidities (all p < 0.05). DISCUSSION: The prediction of cardiometabolic comorbidities by calculated %BF was not superior to BMI-SDS. This formula developed in a British population may not be suitable for a central European population, which is applicable to this possibly less heterogeneous collective. Additional parameters, especially puberty status, should be taken into account. However, objective determinations such as bioimpedance analysis may possibly be superior to assess fat mass and cardiometabolic risk than calculated %BF.