The metabolic syndrome is frequent in children and adolescents with type 1 diabetes compared to healthy controls.

OBJECTIVE: There is a rise in overweight and obesity among children and adolescents with type 1 diabetes (T1D) in parallel with the rise in the metabolic syndrome (MetS) among children and adolescents. The aim of the study was to describe the prevalence and characteristics of MetS in children and adolescents with T1D compared to their healthy counterparts. RESEARCH DESIGN AND METHODS: The study includes two Danish cohorts; (i) the Copenhagen cross sectional cohort 2016 of 277 children and adolescents with T1D that attend the pediatric outpatient clinic at a large hospital in greater Copenhagen and (ii) the CHAMPS-study DK which is a population-based cohort study of Danish children and adolescents (control cohort). Participants were categorized to have MetS if at least two of the following criteria were met: (i) systolic and/or diastolic blood pressure ≥ 90th percentile, (ii) waist circumference ≥90th percentile, and (iii) triglyceride ≥90th percentile and/or HDL ≤10th percentile. RESULTS: The prevalence of children with Mets in the T1D cohort was higher than in the control cohort (p = 0.002). Moreover, participants with T1D had MetS at a lower level of BMI (p < 0.001) and waist circumference (p < 0.001) than participants with MetS from the control cohort (z-scores = 0.90 and 1.51). Participants with MetS were younger than the other T1D participants (median 12.8 [9.9,14.8] vs. median 14.6 [11.2,16.9] years, p = 0.006). CONCLUSIONS: Children and adolescents with T1D have an increased risk of MetS compared to healthy controls and clinicians and caretakers should consider early prevention and health promotion strategies.

[Obesity in children and adolescents is a chronic disease].

WHO declared obesity a disease in 1979 and has named childhood obesity one of the most pervasive health challenges in the 21st century. The Danish Paediatric Society concordantly declares childhood obesity a chronic disease. Early treatment of obesity can prevent the disease from escalating into significant psychosocial and somatic complications arising in most organs with the potential to compromise normal growth and development. As argued in this review, the recognition of childhood obesity as a disease will help to increase the development of new treatment measures and health policies to prevent and manage obesity.

Systemic TNFα correlates with residual ß-cell function in children and adolescents newly diagnosed with type 1 diabetes.

BACKGROUND: Type 1 diabetes (T1D) is caused by immune-mediated destruction of the ß-cells. After initiation of insulin therapy many patients experience a period of improved residual ß-cell function leading to partial disease remission. Cytokines are important immune-modulatory molecules and contribute to ß-cell damage in T1D. The patterns of systemic circulating cytokines during T1D remission are not clear but may constitute biomarkers of disease status and progression. In this study, we investigated if the plasma levels of various pro- and anti-inflammatory cytokines around time of diagnosis were predictors of remission and residual ß-cell function in children with T1D followed for one year after disease onset. METHODS: In a cohort of 63 newly diagnosed children (33% females) with T1D with a mean age of 11.3 years (3.3-17.7), ten cytokines were measured of which eight were detectable in plasma samples by Mesoscale Discovery multiplex technology at study start and after 6 and 12 months. Linear regression models were used to evaluate association of cytokines with stimulated C-peptide. RESULTS: Systemic levels of tumor necrosis factor (TNF)-α, interleukin (IL)-2 and IL-6 inversely correlated with stimulated C-peptide levels over the entire study (P < 0.05). The concentrations of TNFα and IL-10 at study start predicted stimulated C-peptide level at 6 months (P = 0.011 and P = 0.043, respectively, adjusted for sex, age, HbA1c and stage of puberty). CONCLUSIONS: In recent-onset T1D, systemic cytokine levels, and in particular that of TNFα, correlate with residual ß-cell function and may serve as prognostic biomarkers of disease remission and progression to optimize treatment strategies. TRIAL REGISTRATION: The study was performed according to the criteria of the Helsinki II Declaration and was approved by the Danish Capital Region Ethics Committee on Biomedical Research Ethics (journal number H-3-2014-052). The parents of all participants gave written consent.

High prevalence of disordered eating behavior in Danish children and adolescents with type 1 diabetes.

OBJECTIVE: A higher prevalence of disordered eating behavior (DEB) has been demonstrated in children and adolescents with type 1 diabetes (T1D) compared to healthy aged-matched peers. DEB is associated with higher HbA1c levels and increased risk of developing complications to T1D. The aim of this study was to determine the prevalence of DEB in a Danish cohort of children and adolescents with T1D aged 11 to 19 years and to characterize them regarding metabolic control and relevant clinical data. RESEARCH DESIGN AND METHODS: In a cross-sectional study, we determined the prevalence of DEB using the revised Diabetes Eating Problem Survey (DEPS-R) questionnaire. HbA1c and relevant clinical data were obtained at the time they filled in the questionnaire. RESULTS: Hundred and ninety-two children and adolescents (46% girls) aged 11 to 19 years with T1D were included from the pediatric diabetes outpatient clinic. A total of 40 participants (21%) had DEB. The prevalence was higher among girls compared with boys (34.1% vs 8.9%) and those who had DEB were older (16.7 vs 15.0 years, P < .001), had longer duration of T1D (7.5 vs 4.9 years, P < .001), higher BMI Z-scores (1.2 vs 0.3, P < .001), higher HbA1c (72.8 (8.8%) vs 62.0 (7.8%) mmol/mol, P < .001), higher total cholesterol (4.6 mmol/L vs 4.2 mmol/L, P = .0048), and LDL (2.7 vs 2.3, P = .001) compared with those with no signs of DEB. CONCLUSION: As in other countries, the prevalence of DEB is high in Danish adolescents with T1D. Early detection of DEB is essential to prevent short- and long-term complications to T1D.

Decreased markers of bone turnover in children and adolescents with type 1 diabetes.

BACKGROUND AND AIM: Adults with type 1 diabetes (T1D) have increased risk of bone fractures and decreased bone mineral density (BMD). Alterations in bone turnover have been suggested as the link between T1D and the impaired bone health. Furthermore, bone turnover has been suggested to have beneficial effects on glucose metabolism. This study aimed at describing bone turnover markers (BTM), and the relationship with glycemic control, in children and adolescents with T1D. METHODS: A total of 173 (47% girls) children and adolescents aged 7.7 to 17.5 years with T1D for more than 1 year were included. Participants were evaluated by BMD together with measurements of selected BTM; two formation markers: osteocalcin (OCN) and procollagen type-1 amino-terminal propeptide (P1NP) and one resorption marker, C-terminal cross-linked telopeptide of type-1 collagen (CTX). BTM were converted into Z-scores utilizing new national references. RESULTS: Mean OCN Z-score (-0.68 ± 1.31), P1NP Z-score (-0.33 ± 1.03) and CTX Z-score (-0.43 ± 1.10) were all significantly lower than the reference population (P < .001). No associations were seen between BTM and T1D duration. BMD Z-score was comparable to the reference population and associated with none of individual BTMs. CTX Z-score was negatively associated with HbA1c (P = .007) independent of both exogenous and residual endogenous insulin. CONCLUSIONS: Markers of bone formation and resorption were decreased in children and adolescents with T1D. CTX Z-score associated negatively with HbA1c adjusted for insulin treatment and endogenous insulin production indicating a potential association between CTX and insulin sensitivity. The long-term consequences of decreased BTM on BMD need further attention.

Unaffected bone mineral density in Danish children and adolescents with type 1 diabetes.

AIMS: Adults with type 1 diabetes mellitus (T1D) have decreased bone mineral density (BMD). Our study aimed at determining BMD and the association to metabolic control in children and adolescents with T1D. METHODS: 244 patients (113 girls) with a median age of 14.3 years and T1D duration of 1-16 years were included. A dual-energy X-ray absorptiometry scan assessed BMD Z-scores excluding the head (total body less head, TBLH). TBLH-BMD were then investigated for associations to diabetes relevant variables such as HbA1c, insulin treatment, anthropometry and physical activity. RESULTS: In all participants the TBLH-BMD Z-score (0.22 ± 0.96) was significantly higher than the references. Separated by sex, TBLH-BMD Z-score in boys (0.11 ± 0.84) was no different from healthy peers whereas TBLH-BMD Z-score was significantly higher in girls (0.36 ± 1.09). The higher TBLH-BMD Z-score in girls were explained by higher BMI Z-scores. Participants with assumed final height (based on age) had an average TBLH-BMD Z-score of 0.78 ± 1.06, significantly higher than references independent of gender, HbA1c, height- and weight Z-scores. Multiple regression analyses showed that TBLH BMD Z-score associated negatively to HbA1c (P = 0.003), pump treatment (P = 0.019) and screen-time (P = 0.005) and positively to weight Z-score (P < 0.001). Physical activity, sex and puberty did not significantly associate to TBLH-BMD Z-score. CONCLUSION: Unlike adults with T1D, BMD is not decreased in children and adolescents with T1D and even elevated after attained final height. As HbA1c negatively associates to BMD, decreased BMD may progress over time. Whether changes in microarchitecture or bone metabolism precede changes in BMD needs further investigation.

No Effect of an Automated Bolus Calculator in Pediatric Patients with Type 1 Diabetes on Multiple Daily Injections: The Expert Kids Study.

Background: This multicenter crossover study investigated the potential beneficial effect of an automated bolus calculator (ABC) in children and adolescents with type 1 diabetes (T1D) treated with multiple daily injections (MDI). Methods: Participants were randomized to either begin or end with a 5 months intervention versus their regular treatment regimen (control), separated by a 2 months washout period. During the intervention participants were carefully instructed to use the ABC (Accu-Check Aviva Expert) versus manual insulin calculations during the control period. Participants between 8 and 18 years of age with T1D were recruited from clinics in Denmark, Belgium, and Spain. Inclusion criteria included T1D for >1 year, a minimum of 3 months MDI treatment before inclusion, and HbA1c of 7.5%-11% (57-97 mmol/mol). Improvement in HbA1c was the main outcome, and improved quality of life (QoL) and glucose variability (time spent in target glucose) were secondary outcomes. Results: A total of 65 patients with a mean age of 13.25 years and a mean HbA1c of 8.25% (66.7 mmol/mol) were included. Midway evaluation after 2 months of intervention showed no significant difference from the standard care (0.297, 95% confidence interval [CI]: -0.645 to 0.054; P = 0.10). The difference remained insignificant after the 5 months of intervention (-0.143 [95% CI: -0.558 to 0.272; P = 0.51]). Using the ABC did not change the time spent in target glucose range, nor did it change the QoL. Conclusions: Our study did not demonstrate beneficial additive effects of an ABC in children and adolescents with T1D treated with MDI neither in HbA1c, nor in any other endpoint investigated.

CYP24A1 Mutation in a Girl Infant with Idiopathic Infantile Hypercalcemia.

Idiopathic infantile hypercalcemia (IIH) was associated with vitamin-D supplementation in the 1950's. Fifty years later, mutations in the CYP241A gene, involved in the degradation of vitamin-D, have been identified as being a part of the etiology. We report a case of a 21-month old girl, initially hospitalized due to excessive consumption of water and behavioral difficulties. Blood tests showed hypercalcemia and borderline high vitamin-D levels. Renal ultrasound revealed medullary nephrocalcinosis. An abnormality in vitamin-D metabolism was suspected and genetic testing was performed. This revealed the patient to be compound heterozygous for a common (p.E143del) and a novel (likely) disease-causing mutation (p.H83D) in the CYP24A1 gene. The hypercalcemia normalized following a calcium depleted diet and discontinuation of vitamin-D supplementation. Increased awareness of the typical symptoms of hypercalcemia, such as anorexia, polydipsia, vomiting and failure to thrive, is of utmost importance in diagnosing IHH early and preventing long-term complications such as nephrocalcinosis. Further identification of as many disease-causing mutations in the CYP24A1 gene as possible can help identification of predisposed individuals in whom vitamin-D supplementation should be reconsidered.

[Bullous pemphigoid may also be seen in children]. / Bulløs pemfigoid rammer også yngre patienter.

Bullous pemphigoid is most commonly seen in elderly patients, however, an increasing number of cases in children have been reported. In this article we present a case of a five-month-old boy who was admitted with red annular plaques over his entire body and vesicles and bullae on his hands and feet. Correct diagnosis was made by skin biopsy and after reviewing the literature high dose oral steroids therapy (1 mg/kg/day) was successfully initiated. The cause of the disease remains unknown. With correct treatment the prognosis is good with documented ten-year follow-up without relapse.

Habitual alcohol consumption associated with reduced semen quality and changes in reproductive hormones; a cross-sectional study among 1221 young Danish men.

OBJECTIVE: Study associations between three measures of alcohol consumption (recent, typical/habitual, binging), semen quality and serum reproductive hormones. DESIGN: Cross-sectional population based study. SETTING AND PARTICIPANTS: 1221 young Danish men, aged 18-28 years were recruited when they attended a compulsory medical examination to determine their fitness for military service from 2008 to 2012. Total alcohol consumption: (1) in the week preceding (habitual/typical) the visit (recent alcohol intake), (2) in a typical week and (3) frequency of 'binge drinking' (consuming more than 5 units/day)) in the past 30 days was estimated. MAIN OUTCOME MEASURES: Semen quality (volume, sperm concentration, total sperm count, and percentages of motile and morphologically normal spermatozoa) and serum concentration of reproductive hormones (follicle-stimulating hormone, luteinising hormone, testosterone, sex hormone binding globulin, oestradiol, free testosterone and inhibin B). RESULTS: Sperm concentration, total sperm count and percentage of spermatozoa with normal morphology were negatively associated with increasing habitual alcohol intake. This association was observed in men reporting at least 5 units in a typical week but was most pronounced for men with a typical intake of more than 25 units/week. Men with a typical weekly intake above 40 units had a 33% (95% CI 11% to 59%) reduction in sperm concentration compared to men with an intake of 1-5 units/week. A significant increase in serum free testosterone with increasing alcohol consumption the week preceding the visit was found. Binging was not independently associated with semen quality. CONCLUSIONS: Our study suggests that even modest habitual alcohol consumption of more than 5 units per week had adverse effects on semen quality although most pronounced associations were seen in men who consumed more than 25 units per week. Alcohol consumption was also linked to changes in testosterone and SHBG levels. Young men should be advised to avoid habitual alcohol intake.