Zusammenhang zwischen dem Val66Met-Polymorphismus im Neurotrophin BDNF und metabolischen Faktoren im Kindes- und Jugendalter

Background: The exonic variant rs6265 in the brain-derived neurotrophic factor (BDNF) has repeatedly been linked to obesity. Objective: To discern the factors by which this effect is conveyed we aimed to investigate its correlation with obesity and metabolic parameters as well as with serum levels of BDNF and measures of energy intake in children. Secondly, we aimed to compare levels of circulating BDNF with metabolic parameters. Methods: We genotyped the variant in 2131 obese and lean children and adolescents (age 6-18 years). In 177 subjects, we determined BDNF serum levels by ELISA and assessed the association with metabolic parameters and data on eating habits from self-reported food diaries. Results: The minor Met-allele was associated with lower body weight (p=0.002). In the entire study cohort none of the investigated metabolic parameters was associated with the variant. When looking at postpubertal subjects, we observed decreased postprandial glucose levels and a decreased HbA1c in Met-allele-carriers after adjusting for BMI (p=0.046 and p=0.012, respectively). Serum BDNF did not differ between homozygous Val/Val-individuals and carriers of the Met-allele. We neither found a correlation of serum BDNF with different genotypes nor with any of the metabolic parameters. Conclusion: We confirmed the association of the minor Met-allele with decreased body weight in children and additionally observed alterations in postprandial glucose metabolism in postpubertal subjects. However, variations in serum levels of BDNF were neither related to the genotype nor to the phenotype of food intake or glucose metabolism.:Inhaltsverzeichnis 2 Abkürzungsverzeichnis 3 1 Einführung in die Thematik 4 1.1 Genetische Ursachen von Adipositas 4 1.2 Der neuronale Wachstumsfaktor BDNF 5 1.3 BDNF und Regulation von Nahrungsaufnahme und Glukosemetabolismus 6 1.4 Der exonisch gelegene Val66Met-Polymorphismus in BDNF 7 1.5 Oraler Glukosetoleranztest und HbA1c als Marker des Glukosestoffwechsels 9 1.5.1 Physiologische Grundlagen der Glukosehomöostase 9 1.5.2 OGTT und Insulinsensitivitätsindizes 10 1.5.3 HbA1c – das „Langzeitgedächtnis“ des Blutzuckerspiegels 10 1.6 Basisdiagnostik des Fettstoffwechsels 11 1.7 Einschätzung der Nährstoffaufnahme mittels Ernährungstagebuch 11 2 Überleitung zur Publikation 13 2.1 Ziel der Arbeit, Rationale und Fragestellung 13 2.2 Charakterisierung der Kohorten 14 2.3 Kurzbeschreibung der Methoden 15 2.4 Ergebnisse 15 2.5 Fazit 16 3 Originalpublikation 17 4 Zusammenfassung 30 5 Literaturverzeichnis 35 6 Anlagen 39 6.1 Erklärung über die eigenständige Abfassung der Arbeit 39 6.2 Spezifizierung des eigenen wissenschaftlichen Beitrages 40 6.3 Danksagung 4

Socioeconomic Status Is Related to Pubertal Development in a German Cohort

Introduction: Current health literature suggests that there has been a decline in the age of pubertal onset and that pubertal onset/duration of puberty may, besides weight status, be influenced by socioeconomic context. Objective: The goal of this study was to determine whether pubertal onset/ duration and puberty-triggering hormones luteinizing hormone (LH) and follicle-stimulating hormone (FSH) vary according to socioeconomic status (SES). Moreover, we aimed to propose cutoff values of serum LH and FSH for predicting gonadarche in boys. Methods: 2,657 apparently healthy children and adolescents between 5.5 and 18 years from the area of Leipzig were recruited from the LIFE Child study. Age at pubertal onset/end of puberty was given in 738/573 children, respectively. Anthropometric parameters of puberty, blood measurements of LH and FSH, and questionnaires assessing SES were evaluated. Results: Lower SES was associated with earlier thelarche and longer duration of puberty in overweight/obese girls, whereas age of menarche was not affected. In boys with low SES, a trend versus earlier puberty onset can be seen. Lower SES was significantly associated with boys’ age at mutation. No significant differences in boys’ and girls’ serum levels of LH and FSH during puberty according to SES were observed. Serum LH levels of 0.56 IU/L and serum FSH levels of 1.74 IU/L showed the best prediction of gonadarche in boys. Conclusion: Puberty onset/duration and boys’ age at mutation is affected by SES. The proposed cutoff levels for serum LH and FSH could provide a serological tool to determine gonadarche in boy

Socioeconomic Status Is Related to Pubertal Development in a German Cohort

Introduction: Current health literature suggests that there has been a decline in the age of pubertal onset and that pubertal onset/duration of puberty may, besides weight status, be influenced by socioeconomic context. Objective: The goal of this study was to determine whether pubertal onset/ duration and puberty-triggering hormones luteinizing hormone (LH) and follicle-stimulating hormone (FSH) vary according to socioeconomic status (SES). Moreover, we aimed to propose cutoff values of serum LH and FSH for predicting gonadarche in boys. Methods: 2,657 apparently healthy children and adolescents between 5.5 and 18 years from the area of Leipzig were recruited from the LIFE Child study. Age at pubertal onset/end of puberty was given in 738/573 children, respectively. Anthropometric parameters of puberty, blood measurements of LH and FSH, and questionnaires assessing SES were evaluated. Results: Lower SES was associated with earlier thelarche and longer duration of puberty in overweight/obese girls, whereas age of menarche was not affected. In boys with low SES, a trend versus earlier puberty onset can be seen. Lower SES was significantly associated with boys’ age at mutation. No significant differences in boys’ and girls’ serum levels of LH and FSH during puberty according to SES were observed. Serum LH levels of 0.56 IU/L and serum FSH levels of 1.74 IU/L showed the best prediction of gonadarche in boys. Conclusion: Puberty onset/duration and boys’ age at mutation is affected by SES. The proposed cutoff levels for serum LH and FSH could provide a serological tool to determine gonadarche in boy

Socioeconomic Status Is Related to Pubertal Development in a German Cohort

Introduction: Current health literature suggests that there has been a decline in the age of pubertal onset and that pubertal onset/duration of puberty may, besides weight status, be influenced by socioeconomic context. Objective: The goal of this study was to determine whether pubertal onset/ duration and puberty-triggering hormones luteinizing hormone (LH) and follicle-stimulating hormone (FSH) vary according to socioeconomic status (SES). Moreover, we aimed to propose cutoff values of serum LH and FSH for predicting gonadarche in boys. Methods: 2,657 apparently healthy children and adolescents between 5.5 and 18 years from the area of Leipzig were recruited from the LIFE Child study. Age at pubertal onset/end of puberty was given in 738/573 children, respectively. Anthropometric parameters of puberty, blood measurements of LH and FSH, and questionnaires assessing SES were evaluated. Results: Lower SES was associated with earlier thelarche and longer duration of puberty in overweight/obese girls, whereas age of menarche was not affected. In boys with low SES, a trend versus earlier puberty onset can be seen. Lower SES was significantly associated with boys’ age at mutation. No significant differences in boys’ and girls’ serum levels of LH and FSH during puberty according to SES were observed. Serum LH levels of 0.56 IU/L and serum FSH levels of 1.74 IU/L showed the best prediction of gonadarche in boys. Conclusion: Puberty onset/duration and boys’ age at mutation is affected by SES. The proposed cutoff levels for serum LH and FSH could provide a serological tool to determine gonadarche in boy