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Leptin levels in children and adults with classic galactosaemia.

ABSTRACT: Among the long-term complications of Classic Galactosaemia (Gal) is premature ovarian insufficiency (POI) in female patients with subtle abnormalities of reproductive function also reported in male patients. Leptin is a circulating hormone which reflects body energy stores and which affects the neuroendocrine reproductive axis and pubertal development.We measured serum leptin in 28 children (10 girls, 18 boys; mean age 7.6 years, range 0.5-17.9 years) and in 22 adults (10 females, 12 males; mean age 23.9 years, range 18-37 years) with Gal on a strict galactose-restricted diet in comparison with control data.Leptin levels (expressed as SDS for gender and pubertal stage) were lower in Gal children than controls (mean leptin-SDS = -0.71 for girls, p < 0.05, -0.97 for boys compared with SDS = 0 for controls, p < 0.05). In an age-related analysis, leptin levels did not correlate with age in children with Gal for both sexes as it did for matched controls.As expected, females had higher leptin levels than males in either group. In adults with Gal, leptin concentrations were within normal limits for both sexes when adjusted for gender and BMI. There was a linear relationship between log-leptin and BMI in children with Gal and in controls. For Gal women, log-leptin was also associated with BMI. However, for Gal men, and hence for the entire group of adult Gal patients, this association between log-leptin and BMI was not detectable. Our findings suggest that leptin dysregulation may play a role in fertility issues in individuals with Gal from an early age.

SUBMITTER: Knerr I

PROVIDER: S-EPMC3565669 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Leptin levels in children and adults with classic galactosaemia.

Knerr Ina I Coss Karen P KP Doran Peter P PP Hughes Joanne J Wareham Nick N Burling Keith K Treacy Eileen P EP

JIMD reports 20121107

Among the long-term complications of Classic Galactosaemia (Gal) is premature ovarian insufficiency (POI) in female patients with subtle abnormalities of reproductive function also reported in male patients. Leptin is a circulating hormone which reflects body energy stores and which affects the neuroendocrine reproductive axis and pubertal development.We measured serum leptin in 28 children (10 girls, 18 boys; mean age 7.6 years, range 0.5-17.9 years) and in 22 adults (10 females, 12 males; mean ...[more]

PMID: 23430559

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Project description:IntroductionAccumulating evidence has shown that maternal metabolic conditions, such as pre-pregnancy overweight, diabetes mellitus, and hypertensive disorders of pregnancy (HDP) are potential risk factors of autism spectrum disorder (ASD). However, it remains unclear how these maternal conditions lead to neurodevelopmental outcomes in the offspring, including autistic symptoms. Leptin, an adipokine that has pro-inflammatory effects and affects fetal neurodevelopment, is a candidate mediator of the association between maternal metabolic factors and an increased risk of ASD. However, whether prenatal exposure to leptin mediates the association between maternal metabolic conditions and autistic symptoms in children has not been investigated yet.MethodsThis study investigated the associations between mothers' metabolic conditions (pre-pregnancy overweight, diabetes mellitus during or before pregnancy, and HDP), leptin concentrations in umbilical cord serum, and autistic symptoms among 762 children from an ongoing cohort study, using generalized structural equation modeling. We used the Social Responsive Scale, Second Edition (SRS-2) at 8-9 years old to calculate total T-scores. Additionally, we used the T-scores for two subdomains: Social Communication and Interaction (SCI) and Restricted Interests and Repetitive Behavior (RRB).ResultsUmbilical cord leptin levels were associated with pre-pregnancy overweight [coefficient = 1.297, 95% confidence interval (CI) 1.081-1.556, p = 0.005] and diabetes mellitus (coefficient = 1.574, 95% CI 1.206-2.055, p = 0.001). Furthermore, leptin levels were significantly associated with SRS-2 total T-scores (coefficient = 1.002, 95% CI 1.000-1.004, p = 0.023), SCI scores (coefficient = 1.002, 95% CI 1.000-1.004, p = 0.020), and RRB scores (coefficient = 1.001, 95% CI 1.000-1.003, p = 0.044) in children. Associations between maternal metabolic factors and autistic symptoms were not significant.DiscussionThe present study uncovered an association between cord leptin levels and autistic symptoms in children, while maternal metabolic conditions did not have an evident direct influence on the outcome. These results imply that prenatal pro-inflammatory environments affected by maternal metabolic conditions may contribute to the development of autistic symptoms in children. The findings warrant further investigation into the role of leptin in the development of autistic symptoms.

Project description:BackgroundIn Sub-Saharan African countries, rapid urbanization and increasing socio-economic status are associated with a transition to decreased physical activity (PA). A more sedentary lifestyle is linked to increased body fat leading to increments in leptin levels. Since rodent and human studies in high-income countries have shown that starvation-induced hypoleptinemia triggers high PA, efforts are warranted to pursue the hypothesis that low leptin levels in lean children of low- and middle-income countries (LMIC) are also associated with high PA.MethodsIn this cross-sectional study, we assessed seven-day PA with triaxial accelerometry (ActiGraph GT3X) among 223 primary school children (9 to 12 years of age) in rural Tanzania. Moderate-to-vigorous PA (MVPA) and total accelerometer counts per day were outcome variables. Leptin was determined using enzyme linked immunosorbent assay tests from dried blood spots. Anthropometric assessments were conducted and food insecurity and socio-demographic data were gathered using semi-structured interviews.ResultsIn this sample of school children in rural Tanzania, leptin concentrations (median: 0.91 ng/mL, P25: 0.55, P75: 1.69), body mass index z-scores (median: -1.35, P25: -1.93, P75: -0.82), and height-for-age-z-scores (median: -1.16, P25: -1.96, P75: -0.61) were low. In contrast, PA levels were high with a median MVPA time of 119 min/day. Linear regression confirmed that leptin levels were negatively associated with MVPA (beta: -18.1; 95%CI: -29.7; -6.5; p = 0.002) and total accelerometer counts (beta: -90,256; 95%CI: -154,146; -26,365; p = 0.006). Children residing in areas with better infrastructure had lower MVPA levels (p < 0.001) and tended to have higher leptin levels (p = 0.062) than children residing in areas only reachable via dirt roads.ConclusionOur cross-sectional field study is the first that supports the hypothesis of low leptin levels as a potential endocrine trigger of high PA in lean children of a LMIC. We observed early signs of a PA transition towards a less active lifestyle in a subgroup residing in areas with better infrastructure that concomitantly tended to have higher leptin concentrations. Considering that area-dependent PA differences were more pronounced among girls than boys, whereas differences in leptin levels were less pronounced, not only biological, but also external factors explain PA transition.

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Leptin levels in children and adults with classic galactosaemia.

Publications

Leptin levels in children and adults with classic galactosaemia.

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