Impact of Early Growth on Postprandial Responses in Later Life

Peer reviewe

FINRISKI 2002 : Tutkimus kroonisten kansantautien riskitekijöistä, niihin liittyvistä elintavoista, oireista, psykososiaalisista tekijöistä ja terveyspalvelujen käytöstä : tutkimuksen toteutus ja tulokset 2 : Taulukkoliite

Sama sarjanumero kuin perusraportilla. Tästä tutkimuksen Perusraporttiin</a

Whole blood microRNA levels associate with glycemic status and correlate with target mRNAs in pathways important to type 2 diabetes

We analyzed the associations between whole blood microRNA profiles and the indices of glucose metabolism and impaired fasting glucose and examined whether the discovered microRNAs correlate with the expression of their mRNA targets. MicroRNA and gene expression profiling were performed for the Young Finns Study participants (n= 871). Glucose, insulin, and glycated hemoglobin (HbA1c) levels were measured, the insulin resistance index (HOMA2-IR) was calculated, and the glycemic status (normoglycemic [n = 534]/impaired fasting glucose [IFG] [n = 252]/type 2 diabetes [T2D] [n = 24]) determined. Levels of hsa-miR-144-5p, -122-5p, -148a-3p, -589-5p, and hsa-let-7a-5p associated with glycemic status. hsa-miR-144-5p and -148a-3p associated with glucose levels, while hsa-miR-144-5p, -122-5p, -184, and -339-3p associated with insulin levels and HOMA2-IR, and hsa-miR-148a-3p, -15b-3p, -93-3p, -146b-5p, -221-3p, -18a-3p, -642a-5p, and -181-2-3p associated with HbA1c levels. The targets of hsa-miR-146b-5p that correlated with its levels were enriched in inflammatory pathways, and the targets of hsa-miR-221-3p were enriched in insulin signaling and T2D pathways. These pathways showed indications of co-regulation by HbA1c-associated miRNAs. There were significant differences in the microRNA profiles associated with glucose, insulin, or HOMA-IR compared to those associated with HbA1c. The HbA1c-associated miRNAs also correlated with the expression of target mRNAs in pathways important to the development ofT2D.Peer reviewe

Metabonomic, transcriptomic, and genomic variation of a population cohort

Peer reviewe

Blood hsa-miR-122-5p and hsa-miR-885-5p levels associate with fatty liver and related lipoprotein metabolism : The Young Finns Study

MicroRNAs are involved in disease development and may be utilized as biomarkers. We investigated the association of blood miRNA levels and a) fatty liver (FL), b) lipoprotein and lipid pathways involved in liver lipid accumulation and c) levels of predicted mRNA targets in general population based cohort. Blood microRNA profiling (TaqMan OpenArray), genome-wide gene expression arrays and nuclear magnetic resonance metabolomics were performed for Young Finns Study participants aged 34-49 years (n = 871). Liver fat status was assessed ultrasonographically. Levels of hsa-miR-122-5p and -885-5p were up-regulated in individuals with FL (fold change (FC) = 1.55, p = 1.36 * 10-14 and FC = 1.25, p = 4.86 * 10-4, respectively). In regression model adjusted with age, sex and BMI, hsa-miR-122-5p and -885-5p predicted FL (OR = 2.07, p = 1.29 * 10-8 and OR = 1.41, p = 0.002, respectively). Together hsa-miR-122-5p and -885-5p slightly improved the detection of FL beyond established risk factors. These miRNAs may be associated with FL formation through the regulation of lipoprotein metabolism as hsa-miR-122-5p levels associated with small VLDL, IDL, and large LDL lipoprotein subclass components, while hsa-miR-885-5p levels associated inversely with XL HDL cholesterol levels. Hsa-miR-885-5p levels correlated inversely with oxysterol-binding protein 2 (OSBPL2) expression (r = -0.143, p = 1.00 * 10-4) and suppressing the expression of this lipid receptor and sterol transporter could link hsa-miR-885-5p with HDL cholesterol levels

The use of fasting vs. non-fasting triglyceride concentration for estimating the prevalence of high LDL-cholesterol and metabolic syndrome in population surveys

<p>Abstract</p> <p>Background</p> <p>For practical reasons it is not easy to obtain fasting samples in large population health surveys. Non-fasting triglyceride (Tg) values are difficult to interpret. The authors compared the accuracy of statistically corrected non-fasting Tg values with true fasting values and estimated the misclassification of subjects with high low-density lipoprotein cholesterol (LDL-C) and the metabolic syndrome.</p> <p>Methods</p> <p>Non-fasting blood was obtained from a population-based sample of 4282 individuals aged 24-75 years in the National FINRISK 2007 Study. Fasting blood samples were drawn from the same persons 3 months later. Non-fasting serum Tg values were converted into fasting values using previously published formula. LDL-C was calculated and classification of the metabolic syndrome was carried out according to three different latest guidelines.</p> <p>Results</p> <p>The median (25^th, 75th percentile) non-fasting serum Tg concentration was 1.18 (0.87, 1.72) mmol/L and after postprandial correction 1.06 (0.78, 1.52) mmol/L. The true-fasting serum Tg concentration was 1.00 (0.75, 1.38) mmol/L (<it>P </it>< 0.001) vs. non-fasting and corrected value. Bias of the corrected value was +5.9% compared with the true-fasting Tg. Of the true fasting subjects, 56.4% had LDL-C ≥3.00 mmol/L. When calculated using non-fasting serum Tg, the prevalence of high LDL-C was 51.3% and using statistically corrected Tg it was 54.8%. The prevalence of metabolic syndrome was 35.5% among fully fasted persons and among non-fasting subjects 39.7%, which after statistical correction of Tg decreased to 37.6% (P < 0.001 for all comparisons).</p> <p>Conclusions</p> <p>Correction of non-fasting serum Tg to fasting values plays a minor role in population studies but nevertheless reduces misclassification of calculated high LDL-C from 5.1 to 1.6% and the metabolic syndrome from 4.2 to 2.1%.</p

Altered Activation of Innate Immunity Associates with White Matter Volume and Diffusion in First-Episode Psychosis

First-episode psychosis (FEP) is associated with inflammatory and brain structural changes, but few studies have investigated whether systemic inflammation associates with brain structural changes in FEP. Thirty-seven FEP patients (median 27 days on antipsychotic medication), and 19 matched controls were recruited. Serum levels of 38 chemokines and cytokines, and cardiovascular risk markers were measured at baseline and 2 months later. We collected T1-and diffusion-weighted MRIs with a 3 T scanner from the patients at baseline. We analyzed the association of psychosis-related inflammatory markers with gray and white matter (WM) volume using voxel-based morphometry and WM diffusion using tract-based spatial statistics with whole-brain and region-of-interest (ROI) analyses. FEP patients had higher CCL22 and lower TGFa, CXCL1, CCL7, IFN-alpha 2 and ApoA-I than controls. CCL22 decreased significantly between baseline and 2 months in patients but was still higher than in controls. The association between inflammatory markers and FEP remained significant after adjusting for age, sex, smoking and BMI. We did not observe a correlation of inflammatory markers with any symptoms or duration of antipsychotic treatment. Baseline CCL22 levels correlated negatively with WM volume and positively with mean diffusivity and radial diffusivity bilaterally in the frontal lobes in ROI analyses. Decreased serum lan association between circulating chemokine levels and WM in FEP patients. Interestingly, CCL22 has been previously implicated in autoimmune diseases associated with WM pathology. The results suggest that an altered activation of innate immunity may contribute to WM damage in psychotic disorders.evel of ApoA-I was associated with smaller volume of the medial temporal WM. In whole-brain analyses, CCL22 correlated positively with mean diffusivity and radial diffusivity, and CXCL1 associated negatively with fractional anisotropy and positively with mean diffusivity and radial diffusivity in several brain regions. This is the first report to demonstratePeer reviewe

Laboratory Diagnostics of Dyslipidemi : From Cholesterol to Apolipoproteins

Dyslipidemia - high serum cholesterol, LDL-cholesterol (LDL-C), or triglycerides or low HDL-cholesterol (HDL-C) concentration - is one among the most important factors increasing the risk for cardiovascular disease. Apolipoprotein A-I (apoA-I) is the main apolipoprotein of atheroprotective HDL particles and apoB is the main apolipoprotein in all other atherogenic lipoprotein particles. An increased number of apoB-containing particles and low HDL-C together with almost normal LDL-C is a common feature in obesity, metabolic syndrome, and type 2 diabetes. The first aim of this study was to assess the systematic errors in cholesterol, triglycerides, and HDL-C measurements. Secondly, the effect of fasting and non-fasting triglyceride values on the prevalences of high LDL-C and metabolic syndrome was estimated. The reference intervals for apoA-I, apoB, and apoB/apoA-I ratio were calculated and they were compared with the traditional lipid and lipoprotein concentrations in different pathophysiological conditions. Finally, two direct HDL-C methods and two turbidimetric apoA-I methods in two independent laboratories were compared to discover the concordance between these methods. The data for estimating accuracy of cholesterol, triglycerides, and HDL-C measurements was obtained from different external quality assessment (EQA) programs, in which the Laboratory of Analytical Biochemistry at the National Institute for Health and Welfare has participated since 1978. The laboratory data for lipid and lipoprotein population trends was obtained from the FINRISK population-based health surveys during 1982 2012. During this time systematic error for cholesterol and triglyceride measurements remained within the range of 4% but for HDL-C error was larger. Comparison of two direct HDL-C methods showed a concentration-dependent difference between these methods. At low HDL-C concentrations difference between methods was negative -12.0 %, but at higher concentrations turned out to be positive: +9.0 %. However, apoA-I methods demonstrated better agreement than HDL-C in the method comparisons. Obese men and women had the highest apoB concentrations and apoB/apoA-I ratios compared to the healthy reference group. Men with self-reported cardiovascular disease (CVD) or diabetes had lower apoB concentrations and apoB/apoA-I ratio than the averages in the healthy reference group. In contrast women had higher apoB concentrations and apoB/apoA-I ratios in obesity, CVD, hypertension, or diabetes than in the healthy reference group. Participating in the external quality assessment programs with target values measured by the reference methods was essential, when interpreting the effects of the systematic errors on the population lipid trends. The concentration-dependent differences in homogeneous HDL-C methods may cause misclassificatios in the risk assessment of cardiovascular disease. Because an increased number of apoB-containing lipoproteins but a normal or even low LDL-cholesterol is a common feature in obesity, metabolic syndrome and type 2 diabetes, apoB measurements may produce more specific information in the risk assessment for CVD in these conditions than total cholesterol and LDL-C measurements.Dyslipidemia on yksi tärkeimmistä sydän- ja verisuonitautiriskiä lisäävistä tekijöistä. Dyslipidemialla tarkoitetaan seerumin kohonnutta kokonaiskolesteroli-, LDL-kolesteroli- tai triglyseridipitoisuutta tai alentunutta HDL-kolesterolipitoisuutta sekä näiden yhdistelmiä. Apolipoproteiini A-I (apoA-I) on HDL-partikkeleiden tärkein apolipoproteiini ja apoB vastaavasti kaikkien muiden sydän- ja verisuonitautien riskiä lisäävien lipoproteiinien (esim. LDL) tärkein apolipoproteiini. Lisääntynyt apoB:n määrä ja alentunut HDL-kolesteroli, mutta normaali tai vähän koholla oleva LDL-kolesteroli on tyypillinen ilmiö ylipainossa, metabolisen oireyhtymässä ja tyypin 2 diabeteksessa. Väitöstyön tavoitteena oli arvioida systemaattisen virheen vaikutuksia kolesteroli-, triglyseridi- ja HDL-kolesterolimäärityksissä sekä paaston pituuden vaikutuksia triglyseridipitoisuuksiin. Tavoitteena oli myös määrittää apoA-I:n, apoB:n ja apoB/apoA-I-suhteen viitearvot suomalaisessa väestössä ja verrata niitä kolesteroli-, LDL-kolesteroli-, HDL-kolesteroli- ja triglyseridipitoisuuksiin eri tautiryhmissä. Lopuksi verrattiin kahta suoraa HDL-kolesterolimenetelmää ja kahta apoA-I-menetelmää kahdessa eri laboratoriossa. Kolesteroli-, triglyseridi- ja HDL-kolesterolimenetelmien systemaattisen virheen arviointiin käytettiin Terveyden ja hyvinvoinnin laitoksen (THL) analyyttisen biokemian laboratorion laadunarviointikierrosten sekä FINRISKI-tutkimusten lipidi- ja lipoproteiinimittausten tuloksia vuosilta 1978 2012. Tutkittuna aikana kolesteroli- ja triglyseridimittausten systemaattinen virhe pysyi n. 4 %:n vaihteluvälin sisällä, mutta HDL-kolesterolimittauksissa oli suurempaa vaihtelua. Nykyisin käytössä olevien kahden suoran HDL-kolesterolimenetelmän vertailussa havaittiin konsentraatioriippuvainen ero: matalilla HDL-kolesterolipitoisuuksilla menetelmien välinen ero oli negatiivinen -12 % mutta korkeammilla HDL-kolesterolipitoisuuksilla ero oli keskimäärin +9 %. Normaalialueella menetelmien välinen ero oli pienempi. ApoA-I-menetelmissä vastaavaa eroa ei havaittu. Lihavilla miehillä ja naisilla havaittiin korkeimmat apoB-pitoisuudet ja korkeimmat apoB/apoA-I suhteet verrattuna terveeseen viitearvoaineistoon. Niillä miehillä, joilla oli jo todettu sydän- ja verisuonitauti tai diabetes, oli matalammat apoB-pitoisuudet ja apoB/apoA-I suhde kuin terveillä, mutta naisilla tilanne oli päinvastainen. Väitöstutkimuksessa määritettiin myös FINRISKI 2007 tutkimukseen perustuvat suomalaisen väestön apoA-I:n, apoB:n ja apoB/apoA-I-suhteen viitearvot. Osallistuminen ulkoisen laadunarvioinnin kierroksiin, joissa käytetään referenssimenetelmiin jäljitettäviä tavoitearvoja, on välttämätöntä, jotta muutoksia väestön lipiditasoissa pystytään tulkitsemaan oikein. Suorissa HDL-kolesterolimenetelmissä havaitut konsentraatiosta riippuvaiset tulostasoerot voivat aiheuttaa virheellisiä tulkintoja sydän- ja verisuonitautien riskin arvioinnissa. ApoB:n määrityksellä voidaan saada tarkempaa tietoa sydän- ja verisuonitautiriskistä kuin kolesteroli- tai LDL-kolesterolimäärityksillä erityisesti ylipainoisilla, metabolista oireyhtymää sairastavilla tai tyypin 2 diabeetikoilla

Dyslipidemioiden laboratoriodiagnostiikka : kolesterolista apolipoproteiineihin

Dyslipidemia - high serum cholesterol, LDL-cholesterol (LDL-C), or triglycerides or low HDL-cholesterol (HDL-C) concentration - is one among the most important factors increasing the risk for cardiovascular disease. Apolipoprotein A-I (apoA-I) is the main apolipoprotein of atheroprotective HDL particles and apoB is the main apolipoprotein in all other atherogenic lipoprotein particles. An increased number of apoB-containing particles and low HDL-C together with almost normal LDL-C is a common feature in obesity, metabolic syndrome, and type 2 diabetes. The first aim of this study was to assess the systematic errors in cholesterol, triglycerides, and HDL-C measurements. Secondly, the effect of fasting and non-fasting triglyceride values on the prevalences of high LDL-C and metabolic syndrome was estimated. The reference intervals for apoA-I, apoB, and apoB/apoA-I ratio were calculated and they were compared with the traditional lipid and lipoprotein concentrations in different pathophysiological conditions. Finally, two direct HDL-C methods and two turbidimetric apoA-I methods in two independent laboratories were compared to discover the concordance between these methods. The data for estimating accuracy of cholesterol, triglycerides, and HDL-C measurements was obtained from different external quality assessment (EQA) programs, in which the Laboratory of Analytical Biochemistry at the National Institute for Health and Welfare has participated since 1978. The laboratory data for lipid and lipoprotein population trends was obtained from the FINRISK population-based health surveys during 1982 2012. During this time systematic error for cholesterol and triglyceride measurements remained within the range of 4% but for HDL-C error was larger. Comparison of two direct HDL-C methods showed a concentration-dependent difference between these methods. At low HDL-C concentrations difference between methods was negative -12.0 %, but at higher concentrations turned out to be positive: +9.0 %. However, apoA-I methods demonstrated better agreement than HDL-C in the method comparisons. Obese men and women had the highest apoB concentrations and apoB/apoA-I ratios compared to the healthy reference group. Men with self-reported cardiovascular disease (CVD) or diabetes had lower apoB concentrations and apoB/apoA-I ratio than the averages in the healthy reference group. In contrast women had higher apoB concentrations and apoB/apoA-I ratios in obesity, CVD, hypertension, or diabetes than in the healthy reference group. Participating in the external quality assessment programs with target values measured by the reference methods was essential, when interpreting the effects of the systematic errors on the population lipid trends. The concentration-dependent differences in homogeneous HDL-C methods may cause misclassificatios in the risk assessment of cardiovascular disease. Because an increased number of apoB-containing lipoproteins but a normal or even low LDL-cholesterol is a common feature in obesity, metabolic syndrome and type 2 diabetes, apoB measurements may produce more specific information in the risk assessment for CVD in these conditions than total cholesterol and LDL-C measurements.Dyslipidemia on yksi tärkeimmistä sydän- ja verisuonitautiriskiä lisäävistä tekijöistä. Dyslipidemialla tarkoitetaan seerumin kohonnutta kokonaiskolesteroli-, LDL-kolesteroli- tai triglyseridipitoisuutta tai alentunutta HDL-kolesterolipitoisuutta sekä näiden yhdistelmiä. Apolipoproteiini A-I (apoA-I) on HDL-partikkeleiden tärkein apolipoproteiini ja apoB vastaavasti kaikkien muiden sydän- ja verisuonitautien riskiä lisäävien lipoproteiinien (esim. LDL) tärkein apolipoproteiini. Lisääntynyt apoB:n määrä ja alentunut HDL-kolesteroli, mutta normaali tai vähän koholla oleva LDL-kolesteroli on tyypillinen ilmiö ylipainossa, metabolisen oireyhtymässä ja tyypin 2 diabeteksessa. Väitöstyön tavoitteena oli arvioida systemaattisen virheen vaikutuksia kolesteroli-, triglyseridi- ja HDL-kolesterolimäärityksissä sekä paaston pituuden vaikutuksia triglyseridipitoisuuksiin. Tavoitteena oli myös määrittää apoA-I:n, apoB:n ja apoB/apoA-I-suhteen viitearvot suomalaisessa väestössä ja verrata niitä kolesteroli-, LDL-kolesteroli-, HDL-kolesteroli- ja triglyseridipitoisuuksiin eri tautiryhmissä. Lopuksi verrattiin kahta suoraa HDL-kolesterolimenetelmää ja kahta apoA-I-menetelmää kahdessa eri laboratoriossa. Kolesteroli-, triglyseridi- ja HDL-kolesterolimenetelmien systemaattisen virheen arviointiin käytettiin Terveyden ja hyvinvoinnin laitoksen (THL) analyyttisen biokemian laboratorion laadunarviointikierrosten sekä FINRISKI-tutkimusten lipidi- ja lipoproteiinimittausten tuloksia vuosilta 1978 2012. Tutkittuna aikana kolesteroli- ja triglyseridimittausten systemaattinen virhe pysyi n. 4 %:n vaihteluvälin sisällä, mutta HDL-kolesterolimittauksissa oli suurempaa vaihtelua. Nykyisin käytössä olevien kahden suoran HDL-kolesterolimenetelmän vertailussa havaittiin konsentraatioriippuvainen ero: matalilla HDL-kolesterolipitoisuuksilla menetelmien välinen ero oli negatiivinen -12 % mutta korkeammilla HDL-kolesterolipitoisuuksilla ero oli keskimäärin +9 %. Normaalialueella menetelmien välinen ero oli pienempi. ApoA-I-menetelmissä vastaavaa eroa ei havaittu. Lihavilla miehillä ja naisilla havaittiin korkeimmat apoB-pitoisuudet ja korkeimmat apoB/apoA-I suhteet verrattuna terveeseen viitearvoaineistoon. Niillä miehillä, joilla oli jo todettu sydän- ja verisuonitauti tai diabetes, oli matalammat apoB-pitoisuudet ja apoB/apoA-I suhde kuin terveillä, mutta naisilla tilanne oli päinvastainen. Väitöstutkimuksessa määritettiin myös FINRISKI 2007 tutkimukseen perustuvat suomalaisen väestön apoA-I:n, apoB:n ja apoB/apoA-I-suhteen viitearvot. Osallistuminen ulkoisen laadunarvioinnin kierroksiin, joissa käytetään referenssimenetelmiin jäljitettäviä tavoitearvoja, on välttämätöntä, jotta muutoksia väestön lipiditasoissa pystytään tulkitsemaan oikein. Suorissa HDL-kolesterolimenetelmissä havaitut konsentraatiosta riippuvaiset tulostasoerot voivat aiheuttaa virheellisiä tulkintoja sydän- ja verisuonitautien riskin arvioinnissa. ApoB:n määrityksellä voidaan saada tarkempaa tietoa sydän- ja verisuonitautiriskistä kuin kolesteroli- tai LDL-kolesterolimäärityksillä erityisesti ylipainoisilla, metabolista oireyhtymää sairastavilla tai tyypin 2 diabeetikoilla