Vitamin D and type 1 diabetes : Serum 25- hydroxyvitamin D contentreations and risk of type 1 diabetes in children

The aims of this study were to get an overall view of 25-hydroxyvitamin D (25[OH]D) concentrations in healthy Finnish children, to find the major factors influencing the levels, and to find if there are differences in 25(OH) concentrations already at birth or later in childhood between children who develop islet autoimmunity (IA) or type 1 diabetes (T1D) and autoantibody negative children. The study population comprised of children born in 1994-2004 participating in Type 1 Diabetes Prediction and Prevention study (DIPP) clinics in Turku, Oulu and Tampere University Hospitals, Finland. In this study we showed there was a marked increase in the 25(OH)D concentrations in healthy children, who were over the age of two years, in year 2003. Seasonal variation was significant, and it remained the same after year 2003. A largescale program for vitamin D fortification of dairy products and other foodstuffs was begun in Finland in 2003. The median 25(OH)D concentrations were lowest at birth and highest at the age of six months, and they were not associated with the development of IA or T1D during childhood in follow-up lasting up to 14 years. The concentrations were associated with geographical location, sampling year and month, age of the child and for the samples taken at birth also with maternal age and maternal intake of vitamin D during pregnancy.D-vitamiini ja tyypin 1 diabetes. Seerumin 25-hydroksi-D-vitamiinipitoisuus ja tyypin 1 diabeteksen riski lapsilla. Tutkimuksen tavoitteina oli luoda yleiskatsaus terveiden suomalaislasten seerumin 25-hydroksi-D-vitamiinin (25[OH]D) pitoisuuksista, pitoisuuksiin vaikuttavien tekijöiden kartoittaminen, ja sen selvittäminen eroavatko 25(OH)D pitoisuudet syntymähetkellä tai myöhemmin lapsuudessa niillä lapsilla, joille kehittyy saarekesoluvasta-aineita (IA) tai jotka sairastuvat tyypin 1 diabetekseen (T1D), kun heitä verrataan vasta-ainenegatiivisiin lapsiin. Työssä tutkittiin vuosina 1994 - 2004 syntyneitä lapsia, jotka osallistuivat tyypin 1 diabeteksen ehkäisemiseen ja ennustamiseen tähtäävään DIPP-tutkimukseen Turun, Oulun ja Tampereen yliopistosairaaloissa. Terveillä yli kaksivuotiailla lapsilla seerumin 25(OH)D pitoisuudet olivat merkittävästi korkeammat vuodesta 2003 alkaen kuin sitä ennen. Vuodenaikavaihtelu oli huomattavaa ja pysyi samanlaisena vuoden 2003 jälkeen. Vuonna 2003 Suomessa aloitettiin maitotuotteiden ja muutamien muiden elintarvikkeiden laajamittainen D-vitaminointiohjelma. Tutkimuksessa havaittiin, että seerumin 25(OH)D-mediaanipitoisuudet ovat alimmillaan syntymähetkellä ja korkeammillaan puolivuotiailla lapsilla, mutta pitoisuudet eivät assosioituneet IA:n tai T1D:n kehittymiseen lapsilla. Pitoisuuksiin vaikuttivat maantieteellinen sijainti, näytteenottovuosi ja –kuukausi, lapsen ikä sekä syntymäpitoisuuteen myös äidin ikä ja raskaudenaikainen D-vitamiininsaanti

D-vitamiini ja tyypin 1 diabetes : Seerumin 25-hydroksi-D-vitamiinipitoisuus ja tyypin 1 diabeteksen riski lapsilla

Seerumin D-vitamiinin on todettu olevan yhteydessä joihinkin autoimmuunisairauksiin. Kirjoittaja havaitsi, että seerumin D-vitamiinitasot olivat DIPPtutkimukseen osallistuneilla lapsilla matalia. Suoraa yhteyttä tyypin 1 diabetekseen ei kuitenkaan löytynyt.</p

Torque Teno Virus Primary Infection Kinetics in Early Childhood

Human torque teno viruses (TTVs) are a diverse group of small nonenveloped viruses with circular, single-stranded DNA genomes. These elusive anelloviruses are harbored in the blood stream of most humans and have thus been considered part of the normal flora. Whether the primary infection as a rule take(s) place before or after birth has been debated. The aim of our study was to determine the time of TTV primary infection and the viral load and strain variations during infancy and follow-up for up to 7 years. TTV DNAs were quantified in serial serum samples from 102 children by a pan-TTV quantitative PCR, and the amplicons from representative time points were cloned and sequenced to disclose the TTV strain diversity. We detected an unequivocal rise in TTV-DNA prevalence, from 39% at 4 months of age to 93% at 2 years; all children but one, 99%, became TTV-DNA positive before age 4 years. The TTV-DNA quantities ranged from 5 × 101 to 4 × 107 copies/mL, both within and between the children. In conclusion, TTV primary infections occur mainly after birth, and increase during the first two years with high intra- and interindividual variation in both DNA quantities and virus strains

Torque Teno Virus Primary Infection Kinetics in Early Childhood

Human torque teno viruses (TTVs) are a diverse group of small nonenveloped viruses with circular, single-stranded DNA genomes. These elusive anelloviruses are harbored in the blood stream of most humans and have thus been considered part of the normal flora. Whether the primary infection as a rule take(s) place before or after birth has been debated. The aim of our study was to determine the time of TTV primary infection and the viral load and strain variations during infancy and follow-up for up to 7 years. TTV DNAs were quantified in serial serum samples from 102 children by a pan-TTV quantitative PCR, and the amplicons from representative time points were cloned and sequenced to disclose the TTV strain diversity. We detected an unequivocal rise in TTV-DNA prevalence, from 39% at 4 months of age to 93% at 2 years; all children but one, 99%, became TTV-DNA positive before age 4 years. The TTV-DNA quantities ranged from 5 x 10(1) to 4 x 10(7) copies/mL, both within and between the children. In conclusion, TTV primary infections occur mainly after birth, and increase during the first two years with high intra- and interindividual variation in both DNA quantities and virus strains.Peer reviewe

Xylo-Oligosaccharides in Prevention of Hepatic Steatosis and Adipose Tissue Inflammation: Associating Taxonomic and Metabolomic Patterns in Fecal Microbiomes with Biclustering

We have shown that prebiotic xylo-oligosaccharides (XOS) increased beneficial gut microbiota (GM) and prevented high fat diet-induced hepatic steatosis, but the mechanisms associated with these effects are not clear. We studied whether XOS affects adipose tissue inflammation and insulin signaling, and whether the GM and fecal metabolome explain associated patterns. XOS was supplemented or not with high (HFD) or low (LFD) fat diet for 12 weeks in male Wistar rats (n = 10/group). Previously analyzed GM and fecal metabolites were biclustered to reduce data dimensionality and identify interpretable groups of co-occurring genera and metabolites. Based on our findings, biclustering provides a useful algorithmic method for capturing such joint signatures. On the HFD, XOS-supplemented rats showed lower number of adipose tissue crown-like structures, increased phosphorylation of AKT in liver and adipose tissue as well as lower expression of hepatic miRNAs. XOS-supplemented rats had more fecal glycine and less hypoxanthine, isovalerate, branched chain amino acids and aromatic amino acids. Several bacterial genera were associated with the metabolic signatures. In conclusion, the beneficial effects of XOS on hepatic steatosis involved decreased adipose tissue inflammation and likely improved insulin signaling, which were further associated with fecal metabolites and GM

Xylo-Oligosaccharides in Prevention of Hepatic Steatosis and Adipose Tissue Inflammation: Associating Taxonomic and Metabolomic Patterns in Fecal Microbiomes with Biclustering

We have shown that prebiotic xylo-oligosaccharides (XOS) increased beneficial gut microbiota (GM) and prevented high fat diet-induced hepatic steatosis, but the mechanisms associated with these effects are not clear. We studied whether XOS affects adipose tissue inflammation and insulin signaling, and whether the GM and fecal metabolome explain associated patterns. XOS was supplemented or not with high (HFD) or low (LFD) fat diet for 12 weeks in male Wistar rats (n = 10/group). Previously analyzed GM and fecal metabolites were biclustered to reduce data dimensionality and identify interpretable groups of co-occurring genera and metabolites. Based on our findings, biclustering provides a useful algorithmic method for capturing such joint signatures. On the HFD, XOS-supplemented rats showed lower number of adipose tissue crown-like structures, increased phosphorylation of AKT in liver and adipose tissue as well as lower expression of hepatic miRNAs. XOS-supplemented rats had more fecal glycine and less hypoxanthine, isovalerate, branched chain amino acids and aromatic amino acids. Several bacterial genera were associated with the metabolic signatures. In conclusion, the beneficial effects of XOS on hepatic steatosis involved decreased adipose tissue inflammation and likely improved insulin signaling, which were further associated with fecal metabolites and GM

Twenty-five year trends in body mass index by education and income in Finland

ABSTRACT: BACKGROUND: The socioeconomic gradient in obesity and overweight is amply documented. However, the contribution of different socioeconomic indicators on trends of body mass index (BMI) over time is less well known. The aim of this study was to investigate the associations of education and income with (BMI) from the late 1970s to the early 2000s. METHODS: Data were derived from nationwide cross-sectional health behaviour surveys carried out among Finns annually since 1978. This study comprises data from a 25-year period (1978-2002) that included 25 339 men and 25 330 women aged 25-64 years. BMI was based on self-reported weight and height. Education in years was obtained from the questionnaire and household income from the national tax register. In order to improve the comparability of the socioeconomic position measures, education and income were divided into gender-specific tertiles separately for each study year. Linear regression analysis was applied. RESULTS: An increase in BMI was observed among men and women in all educational and income groups. In women, education and income were inversely associated with BMI. The magnitudes of the associations fluctuated but stayed statistically significant over time. Among the Finnish men, socioeconomic differences were more complicated. Educational differences were weaker than among the women and income differences varied according to educational level. At the turn of the century, the high income men in the lowest educational group had the highest BMI whereas the income pattern in the highest educational group was the opposite. CONCLUSION: No overall change in the socio-economic differences of BMI was observed in Finland between 1978 and 2002. However, the trends of BMI diverged ini sub-groups of the studied population: the most prominent increase in BMI took place in high income men with low education and in low income men with high education. The results encourage further research on the pathways between income, education, living conditions and the increasing BMI.Peer reviewe

Mlh1 deficiency in normal mouse colon mucosa associates with chromosomally unstable colon cancer

Colorectal cancer (CRC) genome is unstable and different types of instabilities, such as chromosomal instability (CIN) and microsatellite instability (MSI) are thought to reflect distinct cancer initiating mechanisms. Although 85% of sporadic CRC reveal CIN, 15% reveal mismatch repair (MMR) malfunction and MSI, the hallmarks of Lynch syndrome with inherited heterozygous germline mutations in MMR genes. Our study was designed to comprehensively follow genome-wide expression changes and their implications during colon tumorigenesis. We conducted a long-term feeding experiment in the mouse to address expression changes arising in histologically normal colonic mucosa as putative cancer preceding events, and the effect of inherited predisposition (Mlh1(+/-)) and Western-style diet (WD) on those. During the 21-month experiment, carcinomas developed mainly in WD-fed mice and were evenly distributed between genotypes. Unexpectedly, the heterozygote (B6.129-Mlh1tm1Rak) mice did not show MSI in their CRCs. Instead, both wildtype and heterozygote CRC mice showed a distinct mRNA expression profile and shortage of several chromosomal segregation gene-specific transcripts (Mlh1, Bub1, Mis18a, Tpx2, Rad9a, Pms2, Cenpe, Ncapd3, Odf2 and Dclre1b) in their colon mucosa, as well as an increased mitotic activity and abundant numbers of unbalanced/atypical mitoses in tumours. Our genome-wide expression profiling experiment demonstrates that cancer preceding changes are already seen in histologically normal colon mucosa and that decreased expressions of Mlh1 and other chromosomal segregation genes may form a field-defect in mucosa, which trigger MMR-proficient, chromosomally unstable CRC.Peer reviewe

Torque Teno Virus Primary Infection Kinetics in Early Childhood

Human torque teno viruses (TTVs) are a diverse group of small nonenveloped viruses with circular, single-stranded DNA genomes. These elusive anelloviruses are harbored in the blood stream of most humans and have thus been considered part of the normal flora. Whether the primary infection as a rule take(s) place before or after birth has been debated. The aim of our study was to determine the time of TTV primary infection and the viral load and strain variations during infancy and follow-up for up to 7 years. TTV DNAs were quantified in serial serum samples from 102 children by a pan-TTV quantitative PCR, and the amplicons from representative time points were cloned and sequenced to disclose the TTV strain diversity. We detected an unequivocal rise in TTV-DNA prevalence, from 39% at 4 months of age to 93% at 2 years; all children but one, 99%, became TTV-DNA positive before age 4 years. The TTV-DNA quantities ranged from 5 × 101 to 4 × 107 copies/mL, both within and between the children. In conclusion, TTV primary infections occur mainly after birth, and increase during the first two years with high intra- and interindividual variation in both DNA quantities and virus strains