Decrease in TSH Receptor Autoantibodies during Antithyroid Treatment: Relationship with a Long Noncoding Heg RNA and Cdk1 mRNA in Mononuclear Cells

We have previously shown that a long noncoding RNA transcript Heg is negatively correlated with TSH receptor autoantibodies (TRAb) in patients with untreated Graves' disease and with CD14 mRNA in treated patients and controls. Thus patients with high concentrations of Heg RNA have low levels of TRAb or CD14 mRNA, respectively. Here we show that an additional factor, gene expression of Cdk1 in mononuclear cells, is positively related to concentrations of TRAb in patients with untreated Graves' disease. Cdk1 mRNA is very important for regulation of cell cycle activity. It is well known that TRAb decrease significantly during treatment with antithyroid drugs. This decrease during treatment cannot be explained by Heg RNA, which remains unchanged. Cdk1 mRNA decreased significantly during treatment to values below values obtained in normal subjects. Thus both Heg RNA and Cdk1 mRNA may influence the level of TSH receptor autoantibodies but by different mechanisms

Dyslipidemia and reference values for fasting plasma lipid concentrations in Danish/North-European White children and adolescents

Abstract Background Dyslipidemia is reported in 27 − 43% of children and adolescents with overweight/obesity and tracks into adulthood, increasing the risk of cardiovascular morbidity. Cut-off values for fasting plasma lipid concentrations are typically set at fixed levels throughout childhood. The objective of this cross-sectional study was to generate fasting plasma lipid references for a Danish/North-European White population-based cohort of children and adolescents, and investigate the prevalence of dyslipidemia in this cohort as well as in a cohort with overweight/obesity. Methods A population-based cohort of 2141 (1275 girls) children and adolescents aged 6 − 19 (median 11.5) years was recruited from 11 municipalities in Denmark. Additionally, a cohort of children and adolescents of 1421 (774 girls) with overweight/obesity aged 6 − 19 years (median 11.8) was recruited for the study. Height, weight, and fasting plasma lipid concentrations were measured on all participants. Smoothed reference curves and percentiles were generated using the Generalized Additive Models for Location Scale and Shape package in the statistical software R. Results In the population-based cohort, plasma concentrations of total cholesterol (TC) (P < 0.05), low-density lipoprotein cholesterol (LDL) (P < 0.005), and high-density lipoprotein cholesterol (HDL) (P < 0.005) were higher in the youngest compared to the oldest tertile. Fasting plasma levels of triglycerides (TG) (P < 0.005) increased with age in both sexes. In boys, non-HDL was lower in the oldest compared to the youngest tertile (P < 0.0005). Concentrations of TC, LDL, non-HDL, and TG were higher (P < 0.05), and HDL lower (P < 0.05) in the cohort with overweight/obesity in both sexes and for all ages except for TC in the youngest girls. The overall prevalence of dyslipidemia was 6.4% in the population-based cohort and 28.0% in the cohort with overweight/obesity. The odds ratio for exhibiting dyslipidemia in the cohort with overweight/obesity compared with the population-based cohort was 6.2 (95% CI: 4.9 − 8.1, P < 2*10−16). Conclusion Fasting plasma lipid concentrations change during childhood and adolescence and differ with sex and age. Children and adolescents with obesity have increased concentrations of circulating lipids and exhibit an increased prevalence of dyslipidemia. Trial registration The study is part of The Danish Childhood Obesity Biobank; ClinicalTrials.gov ID-no.: NCT00928473 retrospectively registered on June 25th 2009

Change in β 1 -adrenergic receptor protein concentration in adipose tissue correlates with diet-induced weight loss

A B S T R A C T The aim of the present study was to examine gene expression and protein concentrations of β 1 -and β 2 -adrenergic receptors in subcutaneous adipose tissue in obese subjects in response to weight loss. Eighteen obese subjects were studied during diet-induced weight loss. β-Adrenergic receptor mRNA levels were quantified by reverse transcription-PCR-HPLC. β-Adrenergic receptor protein concentrations were measured by Western blotting using fluorescence laser scanning for detection. Subjects lost 12.8 + − 0.8 kg (mean + − S.E.M.) during diet treatment. There was a 34% decrease in the β 1 -adrenergic receptor mRNA level (0.92 + − 0.09 compared with 0.61 + − 0.06 amol/µg of DNA; P &lt; 0.002). β 2 -Adrenergic receptor mRNA did not decrease significantly. β 2 -Adrenergic receptor protein concentration decreased 37 % (25.5 + − 7.1 compared with 16.0 + − 5.6 arbitrary units/ng of DNA; P = 0.008), whereas β 1 -adrenergic receptor protein concentration did not decrease significantly. The degree of weight loss was correlated with the concentration of β 1 -adrenergic receptor protein (r = 0.65, P &lt; 0.003) and changes in receptor protein concentration (r = 0.50, P = 0.035) during the very-low-calorie diet. In conclusion, the present study demonstrates a relationship between β 1 -adrenergic receptor protein concentration in adipose tissue and the degree of weight loss. This relationship is not directly related to energy expenditure and deserves further investigation

Variation in plasma 25-hydroxyvitamin D2 and D3 in normal pregnancy with gestational age, sampling season, and complications:A longitudinal cohort study

INTRODUCTION:Low levels of vitamin D in pregnancy have been associated with the risk of a variety of pregnancy outcomes. Few studies have investigated vitamin D concentrations throughout pregnancy in healthy women, and most guidelines recommend high vitamin D levels. In the present study, we investigated 25-hydroxyvitamin D concentrations in healthy Caucasian Danish women in relation to season, gestational age and possible vitamin D-linked complications. MATERIALS AND METHODS:Eight hundred and one healthy Caucasian Danish women with an expected normal pregnancy were recruited among 2147 women attending first trimester screening. Seven blood samplings were planned throughout the pregnancy and delivery period. The 25-hydroxyvitamin D2 (25(OH)D2) and 25-hydroxyvitamin D3 (25(OH)D3) concentrations were measured by LC-MS/MS and total 25-hydroxyvitamin D (25(OH)D) were calculated. RESULTS:A total of 3304 samples from 694 women were available for 25(OH)D measurements. The mean (25th-75th percentiles) concentrations of 25(OH)D, 25(OH)D3, and 25(OH)D2 were 54.6 (38.8-68.6) nmol/L, 52.2 (36.4-66.4) nmol/L, and 2.4 (2.2-2.2) nmol/L, respectively. Season was the strongest predictor of 25(OH)D concentration, with the lowest values observed in winter and spring, where only 42% and 41% of samples, respectively, were above 50 nmol/L. Nearly all women had values below the suggested optimal level of 75 nmol/L, independent of season. 25(OH)D peaked at gestational weeks 21-34. Plasma 25(OH)D2 levels were low in all seasons. Women with complications during pregnancy had higher 25(OH)D (estimated difference 9.8 nmol/L, standard error 2.7, p<0.001) than did women without complications, and women giving birth vaginally had lower 25(OH)D than did those delivering via elective (10.0 nmol/L, standard error 2.1, p<0.001) or emergency cesarean section (6.8 nmol/L, standard error 2.2, p<0.001). CONCLUSION:The 25(OH)D concentrations vary with both season and gestational age. Healthy women had lower 25(OH)D concentrations than recommended, without an association with an increased risk of pregnancy complications. Guidelines for vitamin D in pregnancy may require revision