Susanna Wiegand

Cardiovascular risk in 26,008 European overweight children as established by a multicenter database.

Objective: Although the obesity epidemic is progressing in European children too, there is no consensus on the population‐specific prevalence of comorbidities or efficient diagnostic strategies. Therefore, weight‐related risk factors, their interrelationship, and association with biological parameters were assessed in a large group of overweight (OW) children, documented by an electronic database.

β-cell autoantibodies in children with type 2 diabetes mellitus: subgroup or misclassification?

Background: In adults, a fraction of diabetic individuals with β-cell autoantibodies has initially non-insulin requiring diabetes clinically appearing as type 2 diabetes mellitus (T2DM), named latent autoimmune diabetes in adulthood (LADA). The occurrence of β-cell autoantibodies in European children and adolescents with T2DM has not been reported so far. Methods: The frequency of β-cell autoantibodies (anti-GAD, anti-IA-2, and anti-ICA) was determined in 7050 diabetic children and adolescents. The type of diabetes was classified by paediatric diabetic specialists based on the clinical presentation. Children with non-insulin dependent T2DM over a one year period were studied separately. Results: A total of 6922 children were clinically classified as having type 1 diabetes (T1DM) and 128 children as having T2DM. Thirty six per cent of the children with T2DM had at least one detectable β-cell autoantibody. These children did not differ significantly from the children with T2DM and without autoantibodies in respect of age, gender, weight status, lipids, blood pressure, C-peptide, glucose, and HbA1c at manifestation, as well as frequency of anti-thyroidal antibodies and insulin treatment during follow up. In the subgroup of the 38 children with T2DM without insulin requirement over a one year period, autoantibodies occurred in 32%. These 12 children were predominantly obese (67%), female (67%), and in the pubertal age range. Conclusion: β-cell autoantibodies were detectable in a subgroup of initially non-insulin dependent diabetic children and adolescents with the clinical appearance of T2DM. Following the terminology “latent autoimmune diabetes in adulthood (LADA)”, this subgroup might be classified as “LADY” (latent autoimmune diabetes in youth).

An Alu Element–Associated Hypermethylation Variant of the POMC Gene Is Associated with Childhood Obesity

The individual risk for common diseases not only depends on genetic but also on epigenetic polymorphisms. To assess the role of epigenetic variations in the individual risk for obesity, we have determined the methylation status of two CpG islands at the POMC locus in obese and normal-weight children. We found a hypermethylation variant targeting individual CpGs at the intron2–exon3 boundary of the POMC gene by bisulphite sequencing that was significantly associated with obesity. POMC exon3 hypermethylation interferes with binding of the transcription enhancer P300 and reduces expression of the POMC transcript. Since intron2 contains Alu elements that are known to influence methylation in their genomic vicinity, the exon3 methylation variant seems to result from an Alu element–triggered default state of methylation boundary definition. Exon3 hypermethylation in the POMC locus represents the first identified DNA methylation variant that is associated with the individual risk for obesity.

Proopiomelanocortin Deficiency Treated with a Melanocortin-4 Receptor Agonist

Patients with rare defects in the gene encoding proopiomelanocortin (POMC) have extreme early-onset obesity, hyperphagia, hypopigmentation, and hypocortisolism, resulting from the lack of the proopiomelanocortin-derived peptides melanocyte-stimulating hormone and corticotropin. In such patients, adrenal insufficiency must be treated with hydrocortisone early in life. No effective pharmacologic treatments have been available for the hyperphagia and obesity that characterize the condition. In this investigator-initiated, open-label study, two patients with proopiomelanocortin deficiency were treated with setmelanotide, a new melanocortin-4 receptor agonist. The patients had a sustainable reduction in hunger and substantial weight loss (51.0 kg after 42 weeks in Patient 1 and 20.5 kg after 12 weeks in Patient 2).

Body Mass Index, Waist Circumference, and Waist-to- Height Ratio as Predictors of Cardiometabolic Risk in Childhood Obesity Depending on Pubertal Development

CONTEXT The predictive value of body mass index (BMI), waist circumference (WC), and waist-to-height ratio (WtHR) to define cardiometabolic risk is unclear in childhood obesity. OBJECTIVE [corrected] The associations between BMI, WtHR, or WC and cardiometabolic risk markers were analyzed in a multicenter data collection of obese youth. DESIGN AND SUBJECTS BMI, WtHR, and WC were retrospectively evaluated in 1278 patients (11-18 years, 53% boys) from the German/Austrian/Swiss Adiposity Patients Registry. MAIN OUTCOME MEASURES Parameters were correlated with homeostasis model assessment for insulin resistance, fasting insulin, blood pressure, transaminases, lipids and uric acid, applying adjusted regression models, with age group, pubertal stage and gender as covariates. RESULTS Homeostasis model assessment for insulin resistance and fasting insulin were most strongly correlated with BMI, independent of age group or gender. Lipids, transaminases, and uric acid were most strongly correlated with WC with stronger associations for boys. Correlations between BMI and WC as well as metabolic markers and systolic blood pressure showed only minor differences. The pattern of relationship changed during the course of pubertal development with the strongest associations for pubertal children. None of the parameters showed a dependency on WtHR that was superior to BMI or WC. CONCLUSIONS There is only small additional benefit in using WC measurements for routine pediatric care in addition to BMI for predicting metabolic risk. For all parameters, the relationship is strongest during midpuberty, emphasizing that among obese pubertal adolescents, anthropometric measures (BMI and WC) best predict cardiometabolic comorbidities. WtHR does not seem to be superior to BMI or WC in predicting metabolic or cardiovascular risk related to childhood obesity.

Obese boys at increased risk for nonalcoholic liver disease: evaluation of 16 390 overweight or obese children and adolescents

Objective:Comorbidities of childhood obesity challenge health-care systems in Europe. Further, there is a lack of population-specific prevalence data and diagnostic strategies available, especially for obesity-related disturbances of liver function. Therefore, the prevalence of elevated liver enzymes and their relationship to biological parameters were studied in a large pediatric obesity cohort.Methods:In 111 specialized pediatric obesity centers in Germany, Austria and Switzerland, 16 390 children and adolescents (age 12.4±2.6 years, 58% boys) were categorized as overweight (body mass index (BMI) >90th percentile) and obese (>97th percentile) and studied for related comorbidities, especially nonalcoholic fatty liver disease (NAFLD; as defined by aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) >50 U l−1). Data were collected using a standardized software program (APV) for longitudinal multicenter documentation. Pseudonymized data were transmitted for central statistical analysis.Results:In this pediatric cohort, 16% of the study population was overweight, 46% obese and 35% extremely obese (>99.5th percentile extreme obesity (Xob)). NAFLD was present in 11% of the study population, but predominantly in boys (boys vs girls; 14.4:7.4%; P<0.001), in Xob (obese vs Xob; 9.5:17.0%; P<0.001) and in older age (< 12 vs ⩾12 years; 8:12%; P<0.001; adjusted for BMI). ALT >50 U l−1 was significantly associated with fasting insulin and BMI-SDS. In multiple logistic regression models, Xob and male gender were strongly associated with NAFLD (odds ratio Xob vs normal weight=3.2; boys vs girls OR=2.3).Conclusion:In a large cohort of overweight and obese European children and adolescents, markers of nonalcoholic liver disease, especially ALT, are frequent and predicted by Xob and male gender. The results underline the epidemiological dimension of this obesity-related morbidity even in childhood. Therefore, at least ALT is recommended as a screening parameter in basic care.

Type 2 diabetes in children and adolescents in a 2-year follow-up: insufficient adherence to diabetes centers.

Background/Aims: To study the 2-year course of children and adolescents with type 2 diabetes mellitus (T2DM) in general practice to present (1) the treatment modalities, (2) patient adherence, and (3) the occurrence of comorbidities. Methods: HBA1c, lipids, blood pressure, treatment modalities, occurrence of retinopathy and nephropathy were analyzed in 129 children and adolescents with T2DM (median age 13.4 years, 75% female) in specialized diabetes centers in Germany. Results: Seventy-eight (60%) children dropped out of care after a mean of 7.1 months. Drug treatment was not stopped in any of the 64 children initially treated with antidiabetic drugs. Sixteen (12%) children were treated solely by lifestyle intervention over the 2-year course. In the 51 children with complete follow-up, median HbA1c was 7.7% at diagnosis and 6.3% after 2 years. Less than 5% of all children were treated with antihypertensive or lipid-lowering drugs, while 65% suffered from hypertension and 44% from dyslipidemia. Over the course of the disease, retinopathy was not observed, while microalbuminuria occurred in 25%. Conclusions: In general practice, many children and adolescents with T2DM were lost of follow-up. Lifestyle intervention as sole treatment was not often useful for long-term metabolic control. Dyslipidemia and hypertension were seldom treated as recommended.

Is there a further acceleration in the age at onset of menarche? A cross-sectional study in 1840 school children focusing on age and bodyweight at the onset of menarche

OBJECTIVE More than 30 years ago Frisch and Revelle proposed a body weight threshold for the onset of menarche. Based on this hypothesis, a further acceleration of age at menarche can be expected in times of childhood obesity. DESIGN A cross-sectional study of 1840 healthy school girls (Berlin school childrens cohort, BSCOC) within the age groups 10-15 years was conducted in 2006-2007. METHODS Median age of menarche was calculated by Kaplan-Meier survival analysis. Bi- and multivariate analyses were performed to analyze the associations between menarche age and weight status. A locally weighted regression was used to analyze the relationship respectively between height, weight, and body mass index (BMI)-SDS and age stratified by menarche status. RESULTS Nine hundred and thirty six (50.9%) girls had already experienced menarche at a median age of 12.8 years. Two hundred and thirty six of these girls reached their menarche recently. Obese/overweight girls reached menarche significantly earlier (12.5 years), than normal weight (12.9 years), and underweight girls (13.7 years). The mean total body weight was similar in all girls at menarche irrespective of age (mean 51.1 kg, s.d. 8.1) and height. BMI-SDS remained the only significant factor for onset of menarche within a multiple regression model for early menarche (OR 2.1, 95% confidence interval 1.3-3.3, P=0.002). CONCLUSIONS Age at onset of menarche did not accelerate even in a childhood population with more than 10% obesity prevalence. Nevertheless, a negative correlation of BMI-SDS with age at onset of menarche exists.

Differences in taste sensitivity between obese and non-obese children and adolescents

Background Taste sensitivity varies between individuals. Several studies describe differences between obese and non-obese subjects concerning their taste perception. However, data are partly contradictory and insufficient. Therefore, in this study taste sensitivity of obese and non-obese children/adolescents was analysed. Methods In a cross-sectional study gustatory sensitivity of n=99 obese subjects (body mass index (BMI) >97th percentile) and n=94 normal weight subjects (BMI <90th percentile), 6–18 years of age, was compared. Sensitivity for the taste qualities sweet, sour, salty, umami and bitter was analysed by means of impregnated ‘taste strips’ in different concentrations. A total score was determined for all taste qualities combined as well as for each separately. Furthermore, the possible influence of sex, age and ethnicity on taste perception was analysed. An intensity rating for sweet was performed on a 5-point rating scale. Results Obese subjects showed—compared to the control group—a significantly lower ability to identify the correct taste qualities regarding the total score (p<0.001). Regarding individual taste qualities there was a significantly lower detection rate for salty, umami and bitter by obese subjects. Furthermore, the determinants age and sex had a significant influence on taste perception: older age and female sex was associated with better ability to identify taste qualities. Concerning the sweet intensity rating obese children gave significantly lower intensity ratings to three of the four concentrations. Conclusions Obese and non-obese children and adolescents differ in their taste perception. Obese subjects could identify taste qualities less precisely than children and adolescents of normal weight.

Comorbidities Related to BMI Category in Children and Adolescents: German/Austrian/Swiss Obesity Register APV Compared to the German KiGGS Study

Purpose: To assess cardiovascular risk factors in overweight or obese children and adolescents in Germany, Austria and Switzerland and to investigate the relationship to BMI category. Methods: Data of 63,025 overweight or obese patients (APV population) were compared to normal-weight subjects from a representative study on health status of 14,298 children and adolescents in Germany (KiGGS survey). The weight status was assessed by BMI, and BMI-SDS values were cal-culated using national reference data. Results: In normal-weight KiGGS subjects, mean BMI was 17.3 ± 2.5 (BMI-SDS -0.1 ± 0.8). In the overweight or obese APV population, mean BMI was 30.2 ± 5.6 (BMI-SDS 2.5 ± 0.6). In normal-weight subjects blood pressure, total cholesterol, LDL-cholesterol, and triglycerides were elevated in 6.1, 8.6, 7.0 and 3.0%, respectively, and HDL-cholesterol was reduced in 3.0%, whereas in overweight/obese subjects the percentages of abnormal values were 35.3, 13.8, 14.5, 13.6, and 10.1%, respectively. Conclusions: Cardiovascular risk is increased in obese children and adolescents. There is a strong need to monitor blood pressure and serum lipids in this group of patients. Our results emphasize the importance of prevention of obesity in order to reduce cardiovascular risk.