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<p>Interleukin 6 (IL-6) is a multifunctional cytokine with both pro- and anti-inflammatory properties with a heritability estimate of up to 61%. The circulating levels of IL-6 in blood have been associated with an increased risk of complex disease pathogenesis. We conducted a two-staged, discovery and replication meta genome-wide association study (GWAS) of circulating serum IL-6 levels comprising up to 67428 (n_discovery=52654 and n_replication=14774) individuals of European ancestry. The inverse variance fixed effects based discovery meta-analysis, followed by replication led to the identification of two independent loci, IL1F10/IL1RN rs6734238 on chromosome (Chr) 2q14, (P_combined=1.8x10^-11), HLA-DRB1/DRB5 rs660895 on Chr6p21 (P_combined=1.5x10^-10) in the combined meta-analyses of all samples. We also replicated the IL6R rs4537545 locus on Chr1q21 (P_combined=1.2x10^-122). Our study identifies novel loci for circulating IL-6 levels uncovering new immunological and inflammatory pathways that may influence IL-6 pathobiology.</p>...

<p><strong>Objective</strong> <br></p><p>To evaluate the role of autoantibodies to N-terminally truncated glutamic acid decarboxylase GAD₆₅(96-585) (t-GADA) as a marker for type 1 diabetes (T1D) and to assess the potential HLA-associations with such autoantibodies.<br></p><p><strong>Design</strong><br></p><p>In this cross-sectional study combining data from the Finnish Pediatric Diabetes Register, the Type 1 Diabetes Prediction and Prevention (DIPP) Study, the DIABIMMUNE Study, and the Early Dietary Intervention and Later Signs of Beta-Cell Autoimmunity (EDIA) Study, venous blood samples from 760 individuals (53.7% males) were analyzed for t-GADA, autoantibodies to full-length GAD₆₅ (f-GADA), and islet cell antibodies. Epitope-specific GAD autoantibodies were analyzed from 189 study participants.<br></p><p><strong>Results</strong><br></p><p>T1D had been diagnosed in 174 (23%) participants. Altogether 631 (83%) individuals tested positive for f-GADA and 451 (59%) for t-GADA at a median age of 9.0 years (range 0.2-61.5). t-GADA demonstrated higher specificity (46%) and positive predictive value (30%) for T1D than positivity for f-GADA alone (15% and 21%, respectively). Among participants positive for f-GADA, those who tested positive for t-GADA carried more frequently HLA genotypes conferring increased risk for T1D than those who tested negative for t-GADA (77 vs. 53%; P<0.001).<br></p><p><strong>Conclusions</strong><br></p><p>Autoantibodies to N-terminally truncated GAD improve the screening for T1D compared to f-GADA and may facilitate the selection of participants for clinical trials. HLA class II-mediated antigen presentation of GAD(96-585)-derived or structurally similar peptides might comprise an important pathomechanism in T1D.</p>...

<p>Diet and gut microbiota are known to modulate metabolic health. Our aim was to apply a metagenomics approach to investigate whether the diet-gut microbiota-metabolism and inflammation relationships differ in pregnant overweight and obese women. This cross-sectional study was conducted in overweight (n = 234) and obese (n = 152) women during early pregnancy. Dietary quality was measured by a validated index of diet quality (IDQ). Gut microbiota taxonomic composition and species diversity were assessed by metagenomic profiling (Illumina HiSeq platform). Markers for glucose metabolism (glucose, insulin) and low-grade inflammation (high sensitivity C-reactive protein [hsCRP], glycoprotein acetylation [GlycA]) were analyzed from blood samples. Higher IDQ scores were positively associated with a higher gut microbiota species diversity (r = 0.273, P = 0.007) in obese women, but not in overweight women. Community composition (beta diversity) was associated with the GlycA level in the overweight women (P = 0.04) but not in the obese. Further analysis at the species level revealed a positive association between the abundance of species Alistipes finegoldii and the GlycA level in overweight women (logfold change = 4.74, P = 0.04). This study has been registered at ClinicalTrials.gov under registration no. NCT01922791 (<a href="https://clinicaltrials.gov/ct2/show/NCT01922791">https://clinicaltrials.gov/ct2/show/NCT01922791</a>).<br></p>...

The randomized controlled Special Turku Coronary Risk Factor Intervention Project (STRIP) has completed a 20-year infancy-onset dietary counselling intervention to reduce exposure to atherosclerotic cardiovascular disease ...

<p>Genes in the HLA class II region include the most important inherited risk factors for type 1 diabetes (T1D) although also polymorphisms outside the HLA region modulate the predisposition to T1D. This study set out to ...

<p>The association between child temperament characteristics and total diurnal saliva cortisol in 84 children (M = 2.3 years, SD = 0.6) attending out-of-home, center-based child care and 79 children (M = 2.0 years, SD = ...

<div>Background/Objectives: Obesity in early childhood is associated with increased risk of chronic diseases, but studies of body composition at preschool ages are sparse. Therefore, we examined differences in body composition by sex and obesity status in Finnish preschool-aged children and within-individual changes in body composition in normal and overweight children.<br></div><div><br></div><div>Subject/Methods: Body composition was measured using segmental multifrequency bioimpedance analysis (BIA) in 476 children and in 781 children at age 3 and 5 years, respectively. Of those, 308 had repeated BIA measurements at both ages. BMI-SDS was used for classification of normal weight and overweight children.<br></div><div><br></div><div>Results: Sex difference in the amount of lean mass (LM) was already seen at 3 years of age (boys 11.7 kg, girls 11.3 kg; p < 0.001). At 5 years of age, boys had lower fat mass (FM; 3.6 kg vs. 3.9 kg, p < 0.001), lower percent fat mass (%FM; 17.2% vs. 19.1%; p < 0.001), and higher LM (16.0 kg vs. 15.2 kg; p < 0.001) than girls. Overweight children had higher values in FM, %FM, and LM compared with normal weight peers at both ages. Among normal weight children, the increase of LM by age was associated with only minor changes in FM, whereas children who were or became overweight both LM and FM was substantially increased between 3 and 5 years of age.<br></div><div><br></div><div>Conclusions: BIA-assessed body composition differs by sex and obesity status already at age of 3 years. For children who are or become overweight at very young age, the patterns for the changes in LM and FM by age are different than for normal weight children.</div>...

PCB 180 is a persistent and abundant non-dioxin-like PCB (NDL-PCB). We determined the developmental toxicity profile of ultrapure PCB 180 in developing offspring following in utero and lactational exposure with the focus ...

<p><strong>Context: </strong>Circulating levels of liver-enriched antimicrobial peptide 2 (LEAP2), a ghrelin receptor antagonist, decrease under caloric restriction and increase in obesity. The role of LEAP2 in male puberty, a phase with accelerated energy demand, is unclear.</p><p><strong>Objective: </strong>This work aimed to investigate whether circulating LEAP2 levels are downregulated in boys following the onset of puberty to respond to the energy need required for growth.</p><p><strong>Methods: </strong>We determined circulating LEAP2 levels in 28 boys with constitutional delay of growth and puberty (CDGP) who participated in a randomized controlled trial (<a href="http://clinicaltrials.gov/show/NCT01797718" title="See in ClinicalTrials.gov">NCT01797718</a>), and were treated with letrozole (n = 15) or intramuscular low-dose testosterone (T) (n = 13) for 6 months. Blood sampling and dual-energy x-ray absorptiometry-measured body composition were performed at 0-, 6-, and 12-month visits.</p><p><strong>Results: </strong>Serum LEAP2 levels decreased statistically significantly during pubertal progression (0-6 months: mean decrease -4.3 [10.3] ng/mL, P = .036 and 0-12 months: -3.9 [9.3] ng/mL, P = .033). Between 0 and 6 months, the changes in serum LEAP2 levels correlated positively with changes in percentage of body fat (r _s = 0.48, P = .011), and negatively with growth velocity and estradiol levels (r _s = -0.43, P = .022, r _s = -0.55, P = .003, respectively). In the T group only, the changes in serum LEAP2 correlated negatively with changes in T and estradiol levels. Between 0 and 12 months, the change in LEAP2 levels correlated negatively with the change in high-density lipoprotein levels (r _s = -0.44, P = .022) and positively with the change in insulin (r _s = 0.50, P = .009) and HOMA-IR (r_s = 0.51, P = .007) levels.</p><p><strong>Conclusion: </strong>Circulating LEAP2 levels decreased after induction of puberty reciprocally with increased growth rate and energy demand, reflecting the metabolic state of the adolescent. Further, the results suggest that estradiol levels may have a permissive role in downregulating circulating LEAP2 levels.</p>...

STUDY QUESTION: Does treatment of constitutional delay of growth and puberty (CDGP) in boys with aromatase inhibitor letrozole (Lz) or conventional low-dose testosterone (T) have differing effects on developing seminiferous ...