Correlation between bioactive and immunoreactive leptin levels with selected indices of insulin secretion and insulin resistance.

<p>A—fasting serum insulin (logINS₀); B–HOMA-IR; C–QUICKI; D–free fatty acids insulin sensitivity index (ISI-FFA); E–C-peptide and fasting glucose ratio (CP₀/GLU₀); F– 120-minute values of insulin during a 75g oral glucose-tolerance test (INS₁₂₀); G–peak insulin levels during a 75g oral glucose-tolerance test (INS_MAX); H–oral disposition index (oDI); I–ratio of areas under the curve for insulin and glucose levels during a 75g oral glucose-tolerance test (AUC_INS/AUC_GLU); J–whole body insulin sensitivity index (WBISI Matsuda). Empty black icons symbolize bioactive leptin, and empty grey icons immunoreactive leptin levels, respectively. In the figure log values of all variables were used.</p

Partial correlation between bioactive or immunoreactive leptin levels controlled for sex, age, BMI SDS, pubertal stage, and HbA1c and selected insulin secretion or resistance indices.

<p>Partial correlation between bioactive or immunoreactive leptin levels controlled for sex, age, BMI SDS, pubertal stage, and HbA1c and selected insulin secretion or resistance indices.</p

Multiple regression analyses for insulin secretion and resistance indices and bioactive and immunoreactive leptin levels.

<p>Multiple regression analyses for insulin secretion and resistance indices and bioactive and immunoreactive leptin levels.</p

Phenotype characterization of 70 early-onset severely obese children and adolescents selected for the leptin measurements.

<p>Phenotype characterization of 70 early-onset severely obese children and adolescents selected for the leptin measurements.</p

Distribution of bioactive and immunoreactive leptin levels.

<p>A–the range of bioactive and immunoreactive leptin for individual patients is shown as indicated (lower part). Ratio between both forms ranged around 100% with few patients lower than 90% (upper part). B–Non-linear regression between bioactive and immunoreactive leptin serum levels with soluble leptin receptor (sobR).</p

Characteristics of the study population.

<p>*data previously published in the entire cohort (37);</p><p>^#average of 2 working days where recording lasted of >12 hours, LBM—lean body mass; RQ—respiratory quotient; delta RQ = steady state (EHC) RQ-fasting RQ. Data are shown as average +/- SEM. Diferent letters of latin alphabet (a,b,c) denote statistical significance with p<0.05 (ANOVA)</p><p>Characteristics of the study population.</p

Relationship of muscle carnosine with anthropometric or metabolic parameters.

<p>• Lean, ▲Obese, □ IGT, Δ T2D, LBM—lean body mass; Respiratory quotient measured in the fasted state represents metabolic substrate preference. Insulin sensitivity—M value (mg of Glucose/kg of Body Weight/minute).</p

Genetic analysis of single-minded 1 gene in early-onset severely obese children and adolescents

<div><p>Background</p><p>Inactivating mutations of the hypothalamic transcription factor singleminded1 (SIM1) have been shown as a cause of early-onset severe obesity. However, to date, the contribution of <i>SIM1</i> mutations to the obesity phenotype has only been studied in a few populations. In this study, we screened the functional regions of <i>SIM1</i> in severely obese children of Slovak and Moravian descent to determine if genetic variants within <i>SIM1</i> may influence the development of obesity in these populations.</p><p>Methods</p><p>The <i>SIM1</i> promoter region, exons and exon-intron boundaries were sequenced in 126 unrelated obese children and adolescents (2–18 years of age) and 41 adult lean controls of Slovak and Moravian origin. Inclusion criteria for the children and adolescents were a body mass index standard deviation score higher than 2 SD for an appropriate age and sex, and obesity onset at less than 5 years of age. The clinical phenotypes of the <i>SIM1</i> variant carriers were compared with clinical phenotypes of 4 <i>MC4R</i> variant carriers and with 27 unrelated <i>SIM1</i> and <i>MC4R</i> mutation negative obese controls that were matched for age and gender.</p><p>Results</p><p>Seven previously described <i>SIM1</i> variants and one novel heterozygous variant p.D134N were identified. The novel variant was predicted to be pathogenic by 7 <i>in silico</i> software analyses and is located at a highly conserved position of the SIM1 protein. The p.D134N variant was found in an 18 year old female proband (BMI 44.2kg/m²; +7.5 SD), and in 3 obese family members. Regardless of early onset severe obesity, the proband and her brother (age 16 years) did not fulfill the criteria of metabolic syndrome. Moreover, the variant carriers had significantly lower preferences for high sugar (<i>p</i> = 0.02) and low fat, low carbohydrate, high protein (<i>p</i> = 0.02) foods compared to the obese controls.</p><p>Conclusions</p><p>We have identified a novel <i>SIM1</i> variant, p.D134N, in 4 obese individuals from a single pedigree which is also associated with lower preference for certain foods.</p></div