Synnynnäisiä aineenvaihduntatauteja on seulottu Suomessa jo lähes neljännesmiljoonalta vauvalta

Synnynnäisiä aineenvaihduntasairauksia on seulottu Suomessa vuodesta 2015. Seulonta tehdään hiussuoniverinäytteestä, joka otetaan kantapään ihopistolla 2–5 päivän iässä. Noin yhdeltä lapselta viidestätuhannesta löydetään synnynnäinen aineenvaihduntasairaus tai lisämunuaiskuoren hyperplasia. Fenyyliketonuria on Suomessa poikkeuksellisen harvinainen, mutta mm. pitkäketjuisten rasvahappojen oksidaatiohäiriö ja tyypin 1 tyrosinemia ovat meillä jopa yleisempiä kuin muualla. Seulonnan mahdollistama varhainen hoito turvaa joka vuosi usean lapsen tulevaisuuden.</p

Comparison of glucose metabolism and anthropometry in women with previous gestational diabetes treated with metformin vs. insulin: 9-year follow-up of two randomized trials

Introduction: The main aim was to study whether the long-term incidences of type 2 diabetes, pre-diabetes and metabolic syndrome differed between women who were treated with metformin or insulin for gestational diabetes.Material and methods: This 9-year follow-up study of two open-label randomized trials compares metformin and insulin treatments of gestational diabetes. In all, 165 women, 88 previously treated with insulin and 77 treated with metformin in the index pregnancy, were included in the analyses. An oral glucose tolerance test was performed, and measures of anthropometry, glucose metabolism, serum lipids and inflammatory markers were compared between the treatment groups. Disorders of glucose metabolism (pre-diabetes and type 2 diabetes) at the 9-year follow-up was the primary outcome of this study. This study was registered at ClinicalTrials.gov: NCT02417090.Results: The incidences of pre-diabetes and type 2 diabetes (40.3% vs. 46.6%, odds ratio [OR] 0.77, 95% CI 0.40-1.50, p = 0.51), type 2 diabetes (14.3% vs. 15.9%, OR 0.88, 95% CI 0.34-2.26, p = 0.94), pre-diabetes (26.0% vs. 30.7%, OR 0.79, 95% CI 0.38-1.65, p = 0.62), and metabolic syndrome (45.9% vs. 55.2%, OR 0.69, 95% CI 0.35-1.35, p = 0.31) were comparable between the metformin and insulin groups. Moreover, there were no evident differences in the individual measures of anthropometry, glucose metabolism including HOMA-insulin resistance, serum lipids or inflammatory markers between the two treatment groups.Conclusions: Treatment of gestational diabetes with metformin vs. insulin during pregnancy is unlikely to have diverging long-term effects on maternal anthropometry, glucose metabolism or serum lipids. From this perspective, both treatments may be considered in gestational diabetes.</p

Metformin versus insulin therapy for gestational diabetes: Effects on offspring anthropometrics and metabolism at the age of 9 years: A follow-up study of two open-label, randomized controlled trials

AimsTo compare anthropometrics, and lipid and glucose metabolism in the 9-year-old offspring of mothers treated with metformin or insulin for gestational diabetes mellitus (GDM).Materials and MethodsThis was a Finnish two-centre, 9-year follow-up study of two open-label, randomized controlled trials comparing the effects observed in the offspring of mothers who received metformin and insulin treatment for GDM. Measurements included anthropometrics, blood pressure, lipoproteins, and oral glucose tolerance tests. This study was registered with ClinicalTrials.gov, number NCT02417090.ResultsAt the age of 9 years 172 children (55% of the original study cohort, 82 from the metformin and 90 from the insulin group) participated in the study. No differences were found between the 9-year-old offspring groups in anthropometric variables, including body mass index and waist-to-height ratio. The offspring in the metformin group had higher high-density lipoprotein (HDL) cholesterol concentrations (1.72 vs. 1.54 mmol/L; P = 0.039) but lower low-density lipoprotein cholesterol (2.39 vs. 2.58 mmol/L; P = 0.046) and apolipoprotein B concentrations (0.63 vs. 0.67 g/L; P = 0.043) than the offspring in the insulin group. The difference in HDL cholesterol concentration was found to be significant only in boys (P = 0.003). The 2-hour glucose value in the oral glucose tolerance test was 0.6-mmol/L lower in boys from the metformin group than in those from the insulin group (P = 0.015).ConclusionsMetformin treatment for GDM is associated with similar offspring growth and glucose metabolism but a more favourable lipid profile at the age of 9 years as compared to insulin treatment.</p

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

Childhood Exposure to Passive Smoking and Bone Health in Adulthood : The Cardiovascular Risk in Young Finns Study

Context: Passive smoke exposure has been linked to the risk of osteoporosis in adults. Objective: We examined the independent effects of childhood passive smoke exposure on adult bone health. Design/Setting: Longitudinal, the Cardiovascular Risk in Young Finns Study. Participants: The study cohort included 1422 individuals followed for 28 years since baseline in 1980 (age 3 to 18 years). Exposure to passive smoking was determined in childhood. In adulthood, peripheral bone traits were assessed with peripheral quantitative CT (pQCT) at the tibia and radius, and calcaneal mineral density was estimated with quantitative ultrasound. Fracture data were gathered by questionnaires. Results: Parental smoking in childhood was associated with lower pQCT-derived bone sum index in adulthood (beta +/- SE, -0.064 +/- 0.023 per smoking parent; P= 0.004) in multivariate models adjusted for age, sex, active smoking, body mass index, serum 25-OH vitamin D concentration, physical activity, and parental socioeconomic position. Similarly, parental smoking was associated with lower heel ultrasound estimated bone mineral density in adulthood (beta +/- SE, -0.097 +/- 0.041 per smoking parent; P = 0.02). Parental smoking was also associated with the incidence of low-energy fractures (OR, 1.28; 95% CI, 1.01 to 1.62). Individuals with elevated cotinine levels (3 to 20 ng/mL) in childhood had lower bone sum index with pQCT (beta +/- SE, -0.206 +/- 0.057; P = 0.0003). Children whose parents smoked and had high cotinine levels (3 to 20 ng/mL) had significantly lower pQCT-derived bone sum index compared with those with smoking parents but had low cotinine levels ( Conclusions and Relevance: Children of parents who smoke have evidence of impaired bone health in adulthood.Peer reviewe

Long-term tracking and population characteristics of lipoprotein (a) in the Cardiovascular Risk in Young Finns Study

Background and aims: Lipoprotein (a) (Lp(a)) is a causal risk factor for cardiovascular diseases and its levels are under strict genetic control. Therefore, it is hypothesized that the concentration of Lp(a) remains stable throughout life. Finns have lower Lp(a) levels than central Europeans, but it is unknown whether there are differences within Finland, especially between the eastern and western parts of the country with known genetic duality and persistent differences in cardiovascular disease rates. We have examined the long-term stability of Lp(a) levels over 25 years in the Cardiovascular Risk in Young Finns Study (YFS), and the characteristics of individuals with different Lp(a) levels, including their geographical origin within Finland. Methods: In YFS, the first large baseline examination was conducted in 1980 (baseline age, 3–18 years). Several follow-ups during the past 40 years have been conducted to investigate the determinants of cardiometabolic health. Lp(a) levels have been measured in study years 1986 (N = 2464, ages 9–24 years), 2001 (N = 2281, ages 24–39 years), 2007 (N = 2204, ages 35–45 years) and 2011 (N = 2044, ages 39–49 years). Tracking of Lp(a) was estimated by calculating Spearman's rank order correlations between the study years, and by cross-tabulating how many individuals diagnosed with either elevated or non-elevated Lp(a) levels in 1986, 2001 and 2007 remained in the same category in the latest follow-up in 2011. Results: Spearman's correlation coefficients varied between r = 0.84–0.96. Most individuals (87–94%) who had a high Lp(a) level (>30 mg/dl) in any of the previous study years had a high level also in 2011. On average, the median Lp(a) levels were consistently ∼20% higher in the individuals originating from eastern Finland compared to those from western Finland, but there were no differences in the distribution of known genetic determinants between eastern and western Finns that would have explained the observed difference. Conclusions: These data confirm that Lp(a) levels remain very stable over the life-course. In line with the genetic duality between eastern and western parts of Finland, we observed about 20% higher Lp(a) levels in individuals originating from eastern Finland compared to those originating from western Finland.publishedVersionPeer reviewe

Long-term tracking and population characteristics of lipoprotein (a) in the Cardiovascular Risk in Young Finns Study

Background and aimsLipoprotein (a) (Lp(a)) is a causal risk factor for cardiovascular diseases and its levels are under strict genetic control. Therefore, it is hypothesized that the concentration of Lp(a) remains stable throughout life. Finns have lower Lp(a) levels than central Europeans, but it is unknown whether there are differences within Finland, especially between the eastern and western parts of the country with known genetic duality and persistent differences in cardiovascular disease rates. We have examined the long-term stability of Lp(a) levels over 25 years in the Cardiovascular Risk in Young Finns Study (YFS), and the characteristics of individuals with different Lp(a) levels, including their geographical origin within Finland.MethodsIn YFS, the first large baseline examination was conducted in 1980 (baseline age, 3–18 years). Several follow-ups during the past 40 years have been conducted to investigate the determinants of cardiometabolic health. Lp(a) levels have been measured in study years 1986 (N = 2464, ages 9–24 years), 2001 (N = 2281, ages 24–39 years), 2007 (N = 2204, ages 35–45 years) and 2011 (N = 2044, ages 39–49 years). Tracking of Lp(a) was estimated by calculating Spearman's rank order correlations between the study years, and by cross-tabulating how many individuals diagnosed with either elevated or non-elevated Lp(a) levels in 1986, 2001 and 2007 remained in the same category in the latest follow-up in 2011.ResultsSpearman's correlation coefficients varied between r = 0.84–0.96. Most individuals (87–94%) who had a high Lp(a) level (>30 mg/dl) in any of the previous study years had a high level also in 2011. On average, the median Lp(a) levels were consistently ∼20% higher in the individuals originating from eastern Finland compared to those from western Finland, but there were no differences in the distribution of known genetic determinants between eastern and western Finns that would have explained the observed difference.ConclusionsThese data confirm that Lp(a) levels remain very stable over the life-course. In line with the genetic duality between eastern and western parts of Finland, we observed about 20% higher Lp(a) levels in individuals originating from eastern Finland compared to those originating from western Finland.</p

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

Childhood Exposure to Passive Smoking and Bone Health in Adulthood: The Cardiovascular Risk in Young Finns Study

Context: Passive smoke exposure has been linked to the risk of osteoporosis in adults.Objective: We examined the independent effects of childhood passive smoke exposure on adult bone health.Design/Setting: Longitudinal, the Cardiovascular Risk in Young Finns Study.Participants: The study cohort included 1422 individuals followed for 28 years since baseline in 1980 (age 3 to 18 years). Exposure to passive smoking was determined in childhood. In adulthood, peripheral bone traits were assessed with peripheral quantitative CT (pQCT) at the tibia and radius, and calcaneal mineral density was estimated with quantitative ultrasound. Fracture data were gathered by questionnaires.Results: Parental smoking in childhood was associated with lower pQCT-derived bone sum index in adulthood (beta +/- SE, -0.064 +/- 0.023 per smoking parent; P= 0.004) in multivariate models adjusted for age, sex, active smoking, body mass index, serum 25-OH vitamin D concentration, physical activity, and parental socioeconomic position. Similarly, parental smoking was associated with lower heel ultrasound estimated bone mineral density in adulthood (beta +/- SE, -0.097 +/- 0.041 per smoking parent; P = 0.02). Parental smoking was also associated with the incidence of low-energy fractures (OR, 1.28; 95% CI, 1.01 to 1.62). Individuals with elevated cotinine levels (3 to 20 ng/mL) in childhood had lower bone sum index with pQCT (beta +/- SE, -0.206 +/- 0.057; P = 0.0003). Children whose parents smoked and had high cotinine levels (3 to 20 ng/mL) had significantly lower pQCT-derived bone sum index compared with those with smoking parents but had low cotinine levels (Conclusions and Relevance: Children of parents who smoke have evidence of impaired bone health in adulthood.</div