Cilius Esmann Fonvig

Changes in lipidemia during chronic care treatment of childhood obesity.

BACKGROUND Childhood obesity and related co-morbidities are increasing. This intervention study assessed the associations between weight changes and lipidemia in obese children and adolescents. METHODS A total of 240 obese children and adolescents (median age, 11.3 years; range, 3.9-20.9) were enrolled in a best-practice multidisciplinary chronic care treatment program. The concentrations of total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglycerides (TGs) and anthropometric data comprising height and weight were collected at baseline and after up to 39 months of continuous treatment. RESULTS The BMI standard deviation score (SDS) decreased in 51% of patients and maintained unchanged in 32% of patients during the treatment. At baseline, 65 (27.1%) of the patients exhibited dyslipidemia defined as increased concentrations of total cholesterol (>200 mg/dL), LDL (>130 mg/dL), or TGs (>150 mg/dL), or decreased HDL concentration (<35 mg/dL). Dyslipidemia improved with weight loss; the odds ratio (OR) was 0.37 per BMI SDS (p = 0.014) after adjusting for age, sex, and baseline BMI SDS. Baseline TG concentration correlated positively and HDL concentration correlated negatively with baseline BMI SDS. Weight loss was associated with a decrease in the concentrations of total cholesterol (p = 0.0005), LDL (p < 0.0001), non-HDL (p < 0.0001), and TGs (p < 0.0001), and with an increase in HDL concentration (p < 0.0001). CONCLUSION High lipid concentrations were associated with childhood obesity. The lipid profile improved during weight loss independently of the baseline BMI SDS and baseline lipid concentration.

Muscle fat content and abdominal adipose tissue distribution investigated by magnetic resonance spectroscopy and imaging in obese children and youths

The degree of fat deposition in muscle and its implications for obesity-related complications in children and youths are not well understood. One hundred and fifty-nine patients (mean age: 13.3 years; range: 6–20) with a body mass index (BMI) >90th percentile for age and sex were included. Muscle fat content (MFC) was measured in the psoas muscle by proton magnetic resonance spectroscopy. The patients were assigned to two groups: MFC <5% or ≥5%. Visceral adipose tissue volume (VAT) and subcutaneous adipose tissue volume (SAT) were measured by magnetic resonance imaging. The data were analysed to detect associations between MFC and BMI standard deviation scores, VAT and SAT, blood values, pubertal stages, and physical activity scores. The mean BMI standard deviation score (SDS) was 3.04 (range 1.32–5.02). The mean MFC was 8.9% (range 0.8–46.7), and 118 (74.2%) of 159 patients had an MFC ≥5%. Children with an MFC ≥5%, compared with children with an MFC <5%, had a higher BMI SDS (P=0.03), a higher VAT (P=0.04), and elevated intramyocellular lipid (IMCL) and extramyocellular lipid (EMCL) contents (both P<0.0001). SAT, SAT/VAT ratio, blood values, pubertal stages and physical activity scores did not differ between the two groups. Severely obese children and youths tend to have a high MFC, which is associated with elevated VAT, IMCL, and EMCL contents. An increased MFC may be associated with impaired metabolic processes, which may predispose these young people to obesity-related complications.

Environmental spread of microbes impacts the development of metabolic phenotypes in mice transplanted with microbial communities from humans.

Microbiota transplantation to germ-free animals is a powerful method to study involvement of gut microbes in the aetiology of metabolic syndrome. Owing to large interpersonal variability in gut microbiota, studies with broad coverage of donors are needed to elucidate the establishment of human-derived microbiotas in mice, factors affecting this process and resulting impact on metabolic health. We thus transplanted faecal microbiotas from humans (16 obese and 16 controls) separately into 64 germ-free Swiss Webster mice caged in pairs within four isolators, with two isolators assigned to each phenotype, thereby allowing us to explore the extent of microbial spread between cages in a well-controlled environment. Despite high group-wise similarity between obese and control human microbiotas, transplanted mice in the four isolators developed distinct gut bacterial composition and activity, body mass gain, and insulin resistance. Spread of microbes between cages within isolators interacted with establishment of the transplanted microbiotas in mice, and contributed to the transmission of metabolic phenotypes. Our findings highlight the impact of donor variability and reveal that inter-individual spread of microbes contributes to the development of metabolic traits. This is of major importance for design of animal studies, and indicates that environmental transfer of microbes between individuals may affect host metabolic traits.

The Role of the Gut Microbiota in Childhood Obesity

BACKGROUND Childhood and adolescent obesity has reached epidemic proportions worldwide. The pathogenesis of obesity is complex and multifactorial, in which genetic and environmental contributions seem important. The gut microbiota is increasingly documented to be involved in the dysmetabolism associated with obesity. METHODS We conducted a systematic search for literature available before October 2015 in the PubMed and Scopus databases, focusing on the interplay between the gut microbiota, childhood obesity, and metabolism. RESULTS The review discusses the potential role of the bacterial component of the human gut microbiota in childhood and adolescent-onset obesity, with a special focus on the factors involved in the early development of the gut bacterial ecosystem, and how modulation of this microbial community might serve as a basis for new therapeutic strategies in combating childhood obesity. A vast number of variables are influencing the gut microbial ecology (e.g., the host genetics, delivery method, diet, age, environment, and the use of pre-, pro-, and antibiotics); but the exact physiological processes behind these relationships need to be clarified. CONCLUSIONS Exploring the role of the gut microbiota in the development of childhood obesity may potentially reveal new strategies for obesity prevention and treatment.

1H-MRS Measured Ectopic Fat in Liver and Muscle in Danish Lean and Obese Children and Adolescents.

Objectives This cross sectional study aims to investigate the associations between ectopic lipid accumulation in liver and skeletal muscle and biochemical measures, estimates of insulin resistance, anthropometry, and blood pressure in lean and overweight/obese children. Methods Fasting plasma glucose, serum lipids, serum insulin, and expressions of insulin resistance, anthropometry, blood pressure, and magnetic resonance spectroscopy of liver and muscle fat were obtained in 327 Danish children and adolescents aged 8–18 years. Results In 287 overweight/obese children, the prevalences of hepatic and muscular steatosis were 31% and 68%, respectively, whereas the prevalences in 40 lean children were 3% and 10%, respectively. A multiple regression analysis adjusted for age, sex, body mass index z-score (BMI SDS), and pubertal development showed that the OR of exhibiting dyslipidemia was 4.2 (95%CI: [1.8; 10.2], p = 0.0009) when hepatic steatosis was present. Comparing the simultaneous presence of hepatic and muscular steatosis with no presence of steatosis, the OR of exhibiting dyslipidemia was 5.8 (95%CI: [2.0; 18.6], p = 0.002). No significant associations between muscle fat and dyslipidemia, impaired fasting glucose, or blood pressure were observed. Liver and muscle fat, adjusted for age, sex, BMI SDS, and pubertal development, associated to BMI SDS and glycosylated hemoglobin, while only liver fat associated to visceral and subcutaneous adipose tissue and intramyocellular lipid associated inversely to high density lipoprotein cholesterol. Conclusion Hepatic steatosis is associated with dyslipidemia and liver and muscle fat depositions are linked to obesity-related metabolic dysfunctions, especially glycosylated hemoglobin, in children and adolescents, which suggest an increased cardiovascular disease risk.

Liver fat content investigated by magnetic resonance spectroscopy in obese children and youths included in multidisciplinary treatment.

What is already known about this subject •  Investigations of non‐alcoholic fatty liver disease (NAFLD) by non‐invasive imaging procedures have limited evidence. •  Thirty percent of obese children are estimated to have NAFLD and implications for future morbidity are uncertain.

Reference values for serum total adiponectin in healthy non-obese children and adolescents.

BACKGROUND Adiponectin is an abundant adipocyte-secreted hormone that modulates a number of metabolic processes and is correlated to various metabolic disorders. Pediatric reference levels are needed for the risk stratification and interpretation of individual serum adiponectin levels. METHODS A total of 1193 healthy, non-obese Danish schoolchildren (730 girls, 463 boys) aged 6-18 years (median 11.9) were examined by trained medical staff. Total serum adiponectin concentrations in venous fasting blood samples were quantitated by a DuoSet® ELISA human Adiponectin/Acrp30 (R&D Systems) following optimization. RESULTS In a generalized linear model adjusted for BMI SDS, total serum adiponectin concentrations were correlated to age in girls (p<0.0001) and boys (p=<0.0001) and for both sexes combined (p<0.0001). No significant difference between sexes was found. Reference intervals were calculated using age as a continuous variable. The best fitted reference curve for both sexes was: 50th percentile: Y=-0.1478 ∗ X+6.046; 2.5th percentile: Y=-0.06256 ∗ X+2.34; 97.5th percentile: Y=-0.4086 ∗ X+22.39, where Y=adiponectin in μg/mL and X=years of age (from 6 to 18 years). CONCLUSION We developed a pediatric reference levels for total serum adiponectin in a sample of 1193 Danish children and adolescents aged 6-18 years. A correlation with age was demonstrated in children, but no significant difference was seen between the sexes.

Reference values for serum leptin in healthy non-obese children and adolescents

Abstract Background: Adipokines are biologically active, low-molecular weight peptides, which play a major role in metabolic homeostasis in humans. Leptin has gained increasing attention in pediatrics as a biomarker for various metabolic pathologies. Yet, its usefulness is hampered by the relative lack of reference values from pediatric settings. Accordingly, this study aims to evaluate serum concentrations of leptin, soluble leptin receptor (sOB-R), and free leptin index (FLI) in healthy Danish schoolchildren aged 6–18 years and subsequently to establish reference intervals across sex and age groups. Methods: A total of 1193 healthy, non-obese Danish schoolchildren (730 girls, 463 boys) aged 6–18 years (median 11.9) were examined by trained medical staff. Serum leptin and sOB-R concentrations in venous fasting blood samples were quantitated by immunoassay. Percentile curves of leptin, sOB-R, and free leptin index were calculated using the General Additive Model for Location Scale and Shape (GAMLSS). Results: Significant age and sex-dependent differences in circulating leptin levels were found. In boys, the median leptin concentration for all ages combined was 3.35 μg/L (95%-interval: 0.71–22.47) and in girls, it was 9.89 ng/L (95%-interval: 2.06–41.49). For SOB-R, no sex-specific difference was found, and the median sOB-R concentration was 8.24 μg/L (IQR: 3.58–23.74; range: < 1.56–744.15). Conclusion: We demonstrated an age-dependent correlation with both serum leptin concentration and free leptin index with a gradual and significant increase in girls throughout childhood and adolescence and a significantly higher leptin concentration and free leptin index bell-shaped peak in early adolescence in boys.

Effects of a Family-Based Childhood Obesity Treatment Program on Parental Weight Status

Objective The aim of this study was to investigate the prevalence of overweight/obesity among parents of children entering childhood obesity treatment and to evaluate changes in the parents’ weight statuses during their child’s treatment. Methods The study included parents of 1,125 children and adolescents aged 3–22 years, who were enrolled in a multidisciplinary childhood obesity treatment program. At baseline, weight and height of the parents were obtained by self-reported information and parental body mass index (BMI) was calculated. Weight and height of the children were measured in the clinic and BMI standard deviation scores were calculated. Furthermore, anthropometric data from parents of 664 children were obtained by telephone interview after a mean of 2.5 years of treatment (ranging 16 days to 7 years), and changes in parental BMI were analyzed. Results Data on changes in BMI were available in 606 mothers and 479 fathers. At baseline, the median BMI of the mothers was 28.1 kg/m2 (range: 16.9–66.6), and the median BMI of the fathers was 28.9 kg/m2 (range: 17.2–48.1). Seventy percent of the mothers and 80% of the fathers were overweight or obese at the time of their child’s treatment initiation. Both the mothers and fathers lost weight during their child’s treatment with a mean decrease in BMI in the mothers of 0.5 (95% CI: 0.2–0.8, p = 0.0006) and in the fathers of 0.4 (95% CI: 0.2–0.6, p = 0.0007). Of the overweight/obese parents, 60% of the mothers and 58% of the fathers lost weight during their child’s treatment. Conclusion There is a high prevalence of overweight/obesity among parents of children entering childhood obesity treatment. Family-based childhood obesity treatment with a focus on the child has a positive effect on parental BMI with both mothers and fathers losing weight. Trial Registration ClinicalTrials.gov NCT00928473

Obesity is associated with vitamin D deficiency in Danish children and adolescents.

Abstract Background: Sufficient serum concentrations of vitamin D are required to maintain bone health during growth. The aims of this study were to determine whether vitamin D deficiency is more prevalent among children and adolescents with obesity compared to their normal weight peers and to identify clinical and biochemical variables associated with vitamin D deficiency. Methods: One thousand four hundred and eighty-four children and adolescents with overweight/obesity and 2143 population-based controls were recruited from the Danish Childhood Obesity Biobank. Anthropometric variables and fasting concentrations of serum 25-hydroxy vitamin D (25-OH-D), plasma parathyroid hormone (PTH), calcium and phosphate were assessed at baseline. Vitamin D deficiency was defined as serum 25-OH-D concentrations <30 nmol/L. Linear and logistic regressions were used to identify variables associated with vitamin D deficiency. Results: A total of 16.5% of the children and adolescents with obesity (body mass index [BMI] standard deviation score [SDS]>2.33) exhibited vitamin D deficiency, with an odds ratio (OR) 3.41 (confidence interval [CI]: 2.27–5.71; p<0.0001) for being vitamin D deficient compared to their normal weight peers. BMI-SDS was independently and inversely associated with serum 25-OH-D concentrations. Other independent risk factors for vitamin D deficiency were being older than 14 years (OR: 2.39; CI: 1.28–4.48; p=0.006), more than 4 daily hours of screen time (OR: 4.56; CI: 2.59–8.05; p<0.0001) and blood sample assessment during winter-spring (OR: 6.44; CI: 4.47–9.26; p<0.0001). Conclusions: Vitamin D deficiency was common among Danish children and adolescents with obesity. The degree of obesity was independently associated with lower serum 25-OH-D concentrations.