Veren rasva-arvojen yhteys tyypin 1 diabeteksen liitännäissairauksiin

Background: Cardiovascular disease is the most common cause of death in patients with type 1 diabetes, and the premature mortality rates are especially high in patients with diabetic nephropathy. Diabetic retinopathy is the leading cause of vision loss among the working-age population in industrialized countries. Early identification and aggressive treatment of risk factors are crucial to reduce the incidence of diabetic complications. Aims: To examine the relationships between lipid profiles and diabetic nephropathy, diabetic retinopathy, and incident coronary artery disease (CAD) events in a large nationwide cohort of patients with type 1 diabetes. Subjects and methods: These studies are part of the ongoing Finnish Diabetic Nephropathy Study (FinnDiane). Studies I (N=2927) and III (N=1465) have a cross-sectional design. At follow-up, renal status was verified by a review of all available medical files (Study II, N=2304), and data on CAD events were retrieved from the Finnish Hospital Discharge Register and the Causes of Death Register (Study IV, N=3520). Results: The recommended lipid concentrations of current treatment guidelines were poorly met, especially regarding the target for LDL cholesterol. Triglycerides and apolipoprotein (Apo) B were independent predictors of progression to micro- and macroalbuminuria, and total cholesterol was an independent predictor of progression to end-stage renal disease. HDL and HDL2 cholesterol were independently associated with proliferative diabetic retinopathy (PDR). In patients with PDR, the correlations between albumin excretion rate (AER) and lipid variables were strong. However, in patients without retinopathy no significant correlations were observed. In multivariate models, ApoB, triglycerides, non-HDL cholesterol, ApoB/ApoA-I ratio, and triglyceride/HDL cholesterol ratio were the strongest lipid predictors of an incident CAD event. Conclusions: Lipid abnormalities were associated with an increased risk of all three diabetic complications studied, i.e. diabetic nephropathy, retinopathy, and incident CAD events. Triglycerides and ApoB were independently associated with AER and estimated glomerular filtration rate (eGFR) and predicted the progression to micro- and macroalbuminuria as well as incident CAD events. Far lower concentrations of triglycerides than the currently recommended cut-off level (less than 1.7 mmol/l) increased the risk of progression of renal disease. Total and LDL cholesterol were poor predictors of an incident CAD event in patients with normal AER, in patients with HbA1c below the median (8.3%, 67mmol/l) of the cohort, and in women, in whom the ratios of atherogenic and anti-atherogenic lipoproteins and lipids performed better. Current treatment recommendations may need to be revised to reflect residual CAD risk in patients with type 1 diabetes.Tausta: Sydän- ja verisuonitaudit ovat yleisin kuolinsyy tyypin 1 diabeetikoilla, ja ennenaikainen kuolleisuus on erityisen suuri potilailla, joilla on diabeettinen munuaistauti eli nefropatia. Diabetekseen liittyvä silmäsairaus, retinopatia, on sokeutumisen yleisin syy länsimaiden työikäisessä väestössä. Riskitekijöiden varhainen tunnistaminen ja tehokas hoito ovat ratkaisevassa asemassa jotta voisimme vähentää diabeettisten liitännäissairauksien syntyä. Tavoitteet: Tavoitteina oli tutkia veren rasva-arvojen ja diabeettisen nefropatian, retinopatian, ja sepelvaltimotautitapahtumien (ensimmäinen sydäninfarkti, sepelvaltimoiden pallolaajennus tai ohitusleikkaus) yhteyttä suuressa valtakunnallisessa tyypin 1 diabetespopulaatiossa. Aineisto ja menetelmät: Tutkimukset ovat osa FinnDiane-tutkimusta (Finnish Diabetic Nephropathy Study). Seurantatutkimuksissa tieto munuaistaudin vaikeusasteesta varmennettiin kaikista käytettävissä olevista sairaskertomuksista, ja tiedot sepelvaltimotautitapahtumista saatiin hoitoilmoitusjärjestelmästä (HILMO) sekä kuolinsyyrekisteristä. Tulokset: Hoitosuositusten mukaiset kolesterolipitoisuudet ylittyivät monella potilaalla ja erityisen huonosti toteutuivat LDL-kolesterolin suositukset. Kohonneet triglyseridi- ja apolipoproteiini (Apo) B-pitoisuudet (ApoB on aterogeenisten lipoproteiinihiukkasten, erityisesti LDL hiukkasen, rakenneproteiini) ennustivat varhaisen nefropatian (mikroalbuminuria) sekä nefropatian (makroalbuminuria) kehittymistä. Kohonnut kokonaiskolesteroli oli itsenäinen riskitekijä loppuvaiheen munuaistaudin kehittymiselle. Matalat HDL- ja HDL2-kolesterolipitoisuudet olivat yhteydessä diabeettiseen retinopatiaan. ApoB, triglyseridit, ei-HDL-kolesteroli ja ApoB/ApoA-I-suhde (ApoA-I on HDL hiukkasen rakenneproteiini) olivat vahvimpia ensimmäisen sepelvaltimotautitapahtuman ennustajia tyypin 1 diabeetikoilla. Päätelmät: Epäsuotuisat veren rasva-arvot olivat yhteydessä kaikkiin kolmeen tutkittuun diabeteskomplikaatioon, eli diabeettiseen nefropatiaan, retinopatiaan, ja sepelvaltimotautiin. Koholla olevat triglyseridi- ja ApoB-pitoisuudet ennustivat munuaistaudin etenemistä sekä sepelvaltimotautitapahtumaa. Jo nykyisiä suosituksia (alle 1.7 mmol/l) huomattavasti matalampi triglyseridipitoisuus ennusti munuaistaudin etenemistä ja sepelvaltimotautitapahtumia. Kun potilaat jaettiin ryhmiin sukupuolen, munuaistaudin tai sokeritasapainon mukaan, kokonais- ja LDL-kolesteroliarvot eivät olleet yhteydessä sepelvaltimotautitapahtumaan naisilla, potilailla joilla ei ollut munuaistautia, eikä potilailla joilla sokeritasapaino oli kohtalaisen hyvä (HbA1c alle 8.3 %). Näillä potilailla ApoB/ApoA-I- sekä triglyseridi/HDL-kolesterolisuhteet olivat parempia sepelvaltimotautitapahtuman ennustajia. Nykyisiä hoitosuosituksia tulisi tarkistaa, jotta mahdollinen suurentunut sepelvaltimotautiriski tyypin 1 diabeetikoilla havaittaisiin paremmin

The Association Between Dietary Sodium Intake, ESRD, and All-Cause Mortality in Patients With Type 1 Diabetes

OBJECTIVE: Many guidelines recommend reduced consumption of salt in patients with type 1 diabetes, but it is unclear whether dietary sodium intake is associated with mortality and end-stage renal disease (ESRD). RESEARCH DESIGN AND METHODS: In a nationwide multicenter study (the FinnDiane Study) between 1998 and 2002, 2,807 enrolled adults with type 1 diabetes without ESRD were prospectively followed. Baseline urinary sodium excretion was estimated on a 24-h urine collection. The predictors of all-cause mortality and ESRD were determined by Cox regression and competing risk modeling, respectively. RESULTS: The median follow-up for survival analyses was 10 years, during which 217 deaths were recorded (7.7%). Urinary sodium excretion was nonlinearly associated with all-cause mortality, such that individuals with the highest daily urinary sodium excretion, as well as the lowest excretion, had reduced survival. This association was independent age, sex, duration of diabetes, the presence and severity of chronic kidney disease (CKD) (estimated glomerular filtration rate [eGFR] and log albumin excretion rate), the presence of established cardiovascular disease, and systolic blood pressure. During follow-up, 126 patients developed ESRD (4.5%). Urinary sodium excretion was inversely associated with the cumulative incidence of ESRD, such that individuals with the lowest sodium excretion had the highest cumulative incidence of ESRD. CONCLUSIONS: In patients with type 1 diabetes, sodium was independently associated with all-cause mortality and ESRD. Although we have not demonstrated causality, these findings support the calls for caution before applying salt restriction universally. Clinical trials must be performed in diabetic patients to formally test the utility/risk of sodium restriction in this setting

Arterial stiffness and vascular complications in patients with type 1 diabetes: The finnish diabetic nephropathy (FinnDiane) study

While patients with type 1 diabetes (T1D) are known to suffer from early cardiovascular disease (CVD), we examined associations between arterial stiffness and diabetic complications in a large patient group with T1D.This study included 807 subjects (622 T1D and 185 healthy volunteers (age 40.6 ± 0.7 versus 41.6 ± 1.2 years; P = NS)). Arterial stiffness was measured by pulse wave analysis from each participant. Furthermore, information on diabetic retinopathy, nephropathy, and CVD was collected. The renal status was verified from at least two out of three urine collections.Patients with T1D without signs of diabetic nephropathy had stiffer arteries measured as the augmentation index (AIx) than age-matched control subjects (17.3% ± 0.6% versus 10.0% ± 1.2%; P0.001). Moreover, AIx (OR 1.08; 95% CI 1.03-1.13; P = 0.002) was associated with diabetic laser-treated retinopathy in patients with normoalbuminuria in a multivariate logistic regression analysis. The same was true for AIx and diabetic nephropathy (1.04 (1.01-1.08); P = 0.004) as well as AIx and CVD (1.06 (1.00-1.12); P = 0.01) in patients with T1D.Arterial stiffness was associated with microvascular and macrovascular complications in patients with T1D

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

Association of dietary sodium intake with atherogenesis in experimental diabetes and with cardiovascular disease in patients with Type 1 diabetes

Abstract It is recommended that individuals with diabetes restrict their dietary sodium intake. However, although salt intake is correlated with BP (blood pressure), it also partly determines the activation state of the RAAS (reninangiotensin-aldosterone system), a key mediator of diabetes-associated atherosclerosis. apoE KO (apolipoprotein E knockout) mice were allocated for the induction of diabetes with streptozotocin or citrate buffer (controls) and further randomized to isocaloric diets containing 0.05 %, 0.3 % or 3.1 % sodium with or without the ACEi [ACE (angiotensin-converting enzyme) inhibitor] perindopril. After 6 weeks of study, plaque accumulation was quantified and markers of atherogenesis were assessed using RT-PCR (reverse transcription-PCR) and ELISA. The association of sodium intake and adverse cardiovascular and mortality outcomes were explored in 2648 adults with Type 1 diabetes without prior CVD (cardiovascular disease) from the FinnDiane study. A 0.05 % sodium diet was associated with increased plaque accumulation in diabetic apoE KO mice, associated with activation of the RAAS. By contrast, a diet containing 3.1 % sodium suppressed atherogenesis associated with suppression of the RAAS, with an efficacy comparable with ACE inhibition. In adults with Type 1 diabetes, low sodium intake was also associated with an increased risk of all-cause mortality and new-onset cardiovascular events. However, high sodium intake was also associated with adverse outcomes, leading to a J-shaped relationship overall. Although BP lowering is an important goal for the management of diabetes, off-target actions to activate the RAAS may contribute to an observed lack of protection from cardiovascular complications in patients with Type 1 diabetes with low sodium intake

Vesistö- ja valuma-aluekunnostukset Natura 2000 -alueilla: suunnittelun toimintamalli

Vesienhoidon ja luonnonsuojelun tavoitteet ovat useimmiten yhdenmukaisia. Ne tähtäävät paitsi vesiekosysteemien hyvään tilaan, myös lajien ja luontotyyppien suotuisaan suojelutasoon. Vesien ja luontotyyppien tilan parantamisen ohella vesistökunnostustoimenpiteitä voidaan suunnitella myös virkistyskäyttöedellytysten kohentamiseksi ja maisemansuojelun edistämiseksi. Vesistöjen ekologisen tilan parantaminen edellyttää useimmiten riittävää ulkoisen kuormituksen vähentämistä. Näin ollen vesiensuojelutoimet valuma-alueella ovat keskeisiä hoitotoimia vesistökunnostuksissa ja valuma-aluetasoisen kunnostussuunnittelun tarve on nostettu esille useissa ohjelmissa ja strategioissa. Toistaiseksi Natura 2000 -alueiden huomioiminen on kuitenkin jäänyt valuma-aluetason kunnostussuunnittelun ohjeistuksessa vähälle huomiolle. Vesienhoidon ja virkistyskäytön toimenpiteet voivat toisinaan aiheuttaa luontodirektiivin lajien lisääntymis- ja levähdyspaikkojen paikallista heikentymistä ja maisemansuojelulliset hoitotoimenpiteet voivat puolestaan olla ristiriidassa vesiensuojelutavoitteiden kanssa. Myös luonto- ja lintudirektiivin tavoitteet saattavat ajoittain olla ristiriidassa toistensa kanssa. Natura 2000 -alueilla tehtävien vesistökunnostusten ja vesiensuojelutoimenpiteiden tulisi parantaa paitsi vesistön tilaa, myös alueen suojeluperusteena olevan luontotyypin tilaa, sekä edistää luontotyypille ominaisten lajien elinmahdollisuuksia. Luontodirektiivin lajien suotuisan suojelutason sekä lajien lisääntymis- ja levähdyspaikkojen säilyminen on turvattava. Freshabit LIFE IP -hankkeessa (2016–2022) toteutettiin vesistö- ja valuma-aluekunnostuksia yhteensä 33 Natura 2000 -alueella, jotka sijoittuivat 11 vesistöalueelle eri puolille Suomea. Hankkeen tavoitteena oli parantaa Suomen sisävesien luonnon monimuotoisuutta ja kohdevesistöjen ekologista tilaa kehittämällä valuma-aluetason suunnittelun toimintatapoja ja testaamalla niitä hankkeen kohdevesistöissä. Hankkeen kokemusten perusteella koottiin tämä toimintamalli, jossa kuvataan vesistö- ja valuma-aluekunnostusten suunnittelun periaatteet Natura 2000 -alueilla, jotta mahdolliset ristiriidat pystytään huomioimaan ja ratkaisemaan. Natura 2000 -alueilla valuma-aluetason kunnostussuunnittelun keskiössä ovat paitsi erityistä huomiota vaativien lajien ja luontotyyppien tunnistaminen ja huomioiminen toimenpiteiden ajoituksessa ja sijoittamisessa, myös sidosryhmien osallistaminen jo suunnittelun alkuvaiheessa. Sidosryhmistä oleellisimpia ovat maa- ja vesialueiden omistajat. Vesistökunnostusmenetelmät valitaan kohdekohtaisesti, seurantatietojen perusteella tunnistettujen ongelmien ja niiden pohjalta muodostettujen tavoitteiden mukaisesti. Kunnostusten seurantaan tulee varata riittävästi resursseja, jotta vaikuttavuutta pystytään arvioimaan. Seurantaa tulisi tehdä niin vedenlaadun ja biologisten tekijöiden kuin direktiivilajien osalta myös kunnostusten jälkeen. Ulkoisen kuormituksen vähentäminen on avainasemassa, jotta kunnostuksilla voidaan saavuttaa vaikuttavuutta pitkällä tähtäimellä. Restoration and water protection of aquatic ecosystems at Natura 2000 sites: framework for planning The goals of water resource management and nature conservation are most often consistent. Both can aim at a good status of aquatic ecosystems, and at a favorable conservation status of species and habitats. In addition to improving the condition of aquatic ecosystems, restoration measures can also be targeted to improve the prerequisites for recreational use and to promote landscape protection. Improving the ecological status of water bodies typically requires a sufficient reduction of the external loading. Consequently, water protection measures in the catchment area are key management measures on a watershed level. The need for planning restoration measures at the catchment scale has been brought up in several national programs and strategies. However, the consideration of Natura 2000 sites has so far received less attention in such guidelines. Some restoration measures targeted to improve the status of water bodies and their recreational value can sometimes cause a local deterioration of breeding and resting habitats for species that are included in the European Union’s Birds and Habitats Directives. Also, some landscape protection measures can, in turn, conflict with the goals of water protection. Additionally, the objectives of the Birds and Habitats Directives may sometimes conflict with each other. The restoration of water bodies and water protection measures carried out at sites under Natura 2000 network should not only improve the status of aquatic ecosystems and certain habitat types to which protection of the areas are based on, but they should also promote the survival of species that are typical for the given habitat types. A favorable conservation status for species and habitats must be secured. In the Freshabit LIFE IP -project (2016–2022), restoration and water protection measures were carried out at a total of 33 Natura 2000 sites located in 11 separate watersheds around the country. The aim of the project was to improve the biodiversity of Finnish inland waters and the ecological status of the target lakes and streams by developing and implementing planning procedures at a catchment scale. Based on the project’s experiences, this framework for planning was put together to describe the principles of planning restoration and water protection measures at Natura 2000 sites, so that possible conflicts can be considered and resolved. At Natura 2000 sites, the focus of planning restorations at the catchment level is not only about identification and consideration of species and habitats that require special attention in the timing and placement of different measures. It is also about the involvement of stakeholders, most importantly the owners of land and water areas, already in the initial stages of planning. The restoration methods are selected site-specifically, according to the problems identified and targets set on the basis of validated monitoring data. Sufficient resources should always be set aside for monitoring the impacts of restorations, that should be carried out before, during and after the easures allowing for evaluating their effectiveness. Monitoring should include both water quality, morphology and the species included in the Directives. Reducing the external loading is always a key to achieve effectiveness in the long term

Association Testing of Previously Reported Variants in a Large Case-Control Meta-analysis of Diabetic Nephropathy

We formed the GEnetics of Nephropathy–an International Effort (GENIE) consortium to examine previously reported genetic associations with diabetic nephropathy (DN) in type 1 diabetes. GENIE consists of 6,366 similarly ascertained participants of European ancestry with type 1 diabetes, with and without DN, from the All Ireland-Warren 3-Genetics of Kidneys in Diabetes U.K. and Republic of Ireland (U.K.-R.O.I.) collection and the Finnish Diabetic Nephropathy Study (FinnDiane), combined with reanalyzed data from the Genetics of Kidneys in Diabetes U.S. Study (U.S. GoKinD). We found little evidence for the association of the EPO promoter polymorphism, rs161740, with the combined phenotype of proliferative retinopathy and end-stage renal disease in U.K.-R.O.I. (odds ratio [OR] 1.14, P = 0.19) or FinnDiane (OR 1.06, P = 0.60). However, a fixed-effects meta-analysis that included the previously reported cohorts retained a genome-wide significant association with that phenotype (OR 1.31, P = 2 × 10−9). An expanded investigation of the ELMO1 locus and genetic regions reported to be associated with DN in the U.S. GoKinD yielded only nominal statistical significance for these loci. Finally, top candidates identified in a recent meta-analysis failed to reach genome-wide significance. In conclusion, we were unable to replicate most of the previously reported genetic associations for DN, and significance for the EPO promoter association was attenuated

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

EU-wide exposure data of 11 chemical substance groups from the HBM4EU Aligned Studies (2014–2021)

Funding Information: The authors would like to thank everybody who contributed to the HBM4EU Aligned Studies: the participating children, teenagers, adults and their families, the fieldworkers that collected the samples and database managers that made the information available to HBM4EU, the HBM4EU project partners, especially those from WP7 for developing all materials supporting the fieldwork, WP9 for organizing the QA/QC scheme under HBM4EU and all laboratories who performed the analytical measurements. We would like to acknowledge Sun Kyoung Jung from the National Institute of Environmental Research of South-Korea for providing the KoNEHS Cycle III results (crt adjusted). HBM4EU is co-financed under Horizon 2020 (grant agreement No 733032). The authors thank all principal investigators of the contributing studies for their participation and contribution to the HBM4EU Aligned Studies and the national program owners for their financial support. Further details on funding for all the participating studies can be found in the Supplemental Material, Table S12.As one of the core elements of the European Human Biomonitoring Initiative (HBM4EU) a human biomonitoring (HBM) survey was conducted in 23 countries to generate EU-wide comparable HBM data. This survey has built on existing HBM capacity in Europe by aligning national or regional HBM studies, referred to as the HBM4EU Aligned Studies. The HBM4EU Aligned Studies included a total of 10,795 participants of three age groups: (i) 3,576 children aged 6–12 years, (ii) 3,117 teenagers aged 12–18 years and (iii) 4,102 young adults aged 20–39 years. The participants were recruited between 2014 and 2021 in 11–12 countries per age group, geographically distributed across Europe. Depending on the age group, internal exposure to phthalates and the substitute DINCH, halogenated and organophosphorus flame retardants, per- and polyfluoroalkyl substances (PFASs), cadmium, bisphenols, polycyclic aromatic hydrocarbons (PAHs), arsenic species, acrylamide, mycotoxins (deoxynivalenol (total DON)), benzophenones and selected pesticides was assessed by measuring substance specific biomarkers subjected to stringent quality control programs for chemical analysis. For substance groups analyzed in different age groups higher average exposure levels were observed in the youngest age group, i.e., phthalates/DINCH in children versus teenagers, acrylamide and pesticides in children versus adults, benzophenones in teenagers versus adults. Many biomarkers in teenagers and adults varied significantly according to educational attainment, with higher exposure levels of bisphenols, phthalates, benzophenones, PAHs and acrylamide in participants (from households) with lower educational attainment, while teenagers from households with higher educational attainment have higher exposure levels for PFASs and arsenic. In children, a social gradient was only observed for the non-specific pyrethroid metabolite 3-PBA and di-isodecyl phthalate (DiDP), with higher levels in children from households with higher educational attainment. Geographical variations were seen for all exposure biomarkers. For 15 biomarkers, the available health-based HBM guidance values were exceeded with highest exceedance rates for toxicologically relevant arsenic in teenagers (40%), 3-PBA in children (36%), and between 11 and 14% for total DON, Σ (PFOA + PFNA + PFHxS + PFOS), bisphenol S and cadmium. The infrastructure and harmonized approach succeeded in obtaining comparable European wide internal exposure data for a prioritized set of 11 chemical groups. These data serve as a reference for comparison at the global level, provide a baseline to compare the efficacy of the European Commission's chemical strategy for sustainability and will give leverage to national policy makers for the implementation of targeted measures.publishersversionpublishe