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As an indicator of general indoor air quality in industrial facilities, the concentrations of total volatile organic compounds (TVOC) were determined in the workplaces of 37 industry sectors during the years of 2006–2011. For comparison, the TVOC levels in office-type workplaces were also determined. Based on the results, the TVOC target and guideline values are proposed for industrial workplaces. The geometric mean and median concentrations in the industrial workplaces were 778 and 845 µg/m3, respectively, while the 90th, 25th percentiles were, respectively, 6616 and 270 µg/m3. In the office-type environments, the geometric mean and median concentrations were 55 and 50 µg/m3, and the 90th and 25th percentiles were 230 and 27 µg/m3. Based on the measured TVOC distributions and the target values previously set, we propose a TVOC target value of 300 µg/m3 and guideline value of 3000 µg/m3 for the general indoor air in industrial workplaces. The concentration of 3000 µg/m3 could be achieved with reasonable measures by most industry sectors, but does not guarantee that the inhalation exposure to volatile organic compounds in the occupational environments is free from health concerns or perceived discomfort. Therefore, when reasonably achievable, a TVOC concentration close to or below the target value is recommended. This would make the TVOC levels in industrial facilities similar to those in the non-occupational indoor environments. [ABSTRACT FROM AUTHOR]

Background: There is little previous information of the effects of size fractioned particulate air pollution and source specific fine particles (PM2.5 <2.5 µm) on asthma and chronic obstructive pulmonary disease (COPD) among children, adults and the elderly. Objectives: To determine the effects of daily variation in levels of different particle size fractions and gaseous pollutants on asthma and COPD by age group. Methods: Levels of particulate air pollution, NO2 and CO were measured from 1998 to 2004 at central outdoor monitoring sites in Helsinki, Finland. Associations between daily pollution levels and hospital emergency room visits were evaluated for asthma (ICD10: J45+J46) in children <15 years old, and for asthma and COPD (ICD10: J41+J44) in adults (15-64 years) and the elderly (⩾65 years). Results: Three to 5 day lagged increases in asthma visits were found among children in association with nucleation (<0.03 µm), Aitken (0.03-0.1 µm) and accumulation (0.1-0.29 µm) mode particles, gaseous pollutants and traffic related PM2.5 (7.8% (95% Cl 3.5 to 12.3) for 1.1 µg/m³ increase in traffic related PM2.5 at lag 4). Pooled asthma-COPD visits among the elderly were associated with lag 0 of PM2.5, coarse particles, gaseous pollutants and long range transported and traffic related PM2.5 (3.9% (95% Cl 0.28 to 7.7) at lag 0). Only accumulation mode and coarse particles were associated with asthma and COPD among adults. Conclusions: Among children, traffic related PM2.5 had delayed effects, whereas among the elderly, several types of particles had effects that were more immediate. These findings suggest that the mechanisms of the respiratory effects of air pollution, and responsible pollutants, differ by age group. [ABSTRACT FROM AUTHOR]

The aim of the study was 1) to establish the prevalence of GAD antibodies (GADab) in a population-based study of type 2 diabetes in western Finland, 2) to genetically and phenotypically characterize this subgroup, and 3) to provide a definition for latent autoimmune diabetes in adults (LADA). The prevalence of GADab was 9.3% among 1,122 type 2 diabetic patients, 3.6% among 558 impaired glucose tolerance (IGT) subjects, and 4.4% among 383 nondiabetic control subjects. Islet antigen 2 antibodies (IA2ab) or islet cell antibodies were detected in only 0.5% of the GADab- patients. The GADab+ patients had lower fasting C-peptide concentrations (median [interquartile range]: 0.46 [0.45] vs. 0.62 [0.44] nmol/l, P = 0.0002) and lower insulin response to oral glucose compared with GADab- patients. With respect to features of the metabolic syndrome, the GADab+ patients had lower systolic (140 [29.1] vs. 148 [26.0] mmHg, P = 0.009) and diastolic (79.2 [17.6] vs. 81.0 [13.1] mmHg, P = 0.030) blood pressure values, as well as lower triglyceride concentrations (1.40 [1.18] vs. 1.75 [1.25] mmol/l, P = 0.003). GADab+ men had a lower waist-to-hip ratio compared with GADab- patients. Compared with GADab- patients and control subjects, the GADab+ patients had an increased frequency HLA-DQB1*0201/0302 (13 vs. 4%; P = 0.002) and other genotypes containing the *0302 allele (22 vs. 12%; P = 0.010). However, the frequency of these high-risk genotypes was significantly lower in GADab+ type 2 patients than in type 1 diabetes of young or adult onset (0201/0302 or 0302/X: 36 vs. 66 vs. 64%, P < 0.001). The GADab+ type 2 group did not differ from control subjects with respect to genotypes containing the protective DQB1-alleles *0602 or *0603, nor with respect to the type 1 high-risk genotype in the IDDM1 (Hph1 +/+). We conclude that GADab+ patients differ from both GADab- type 2 diabetic patients and type 1 diabetic patients with respect to beta-cell function, features of the metabolic syndrome, and type 1 diabetes susceptibility genes. Further, we propose that LADA be defined as GADab positivity (>5 relative units) in patients older than 35 years at onset of type 2 diabetes. [ABSTRACT FROM AUTHOR]

In the search for differences between rheumatoid factors (RF) in patients with rheumatoid arthritis (RA) and in non-rheumatoid subjects, the reactivity of IgM- and IgA-class RF with rabbit IgG (rIgG) and Fc fragments of rabbit and human IgG (rFc, hFc) was studied by enzyme immunoassay. From a community-based cohort (n = 7124) representing the adult population of Finland. RA patients (n = 130), other subjects positive in the Waaler-Rose (WaRo, sensitized sheep cell agglutination) test (n = 137), and controls matched for age, sex and living area were selected for further study. In RA sera there was a good correlation between the results in the WaRo test and in the IgM-RF ELISA (rIgG, rFc and hFc). A considerable number of `false positive' sera, though positive in the WaRo test and the rIgG-ELISA, were negative in the rFc-ELISA. Twenty-two per cent of the false positive sera reacted with either hFc or rFc, both types being equally common. IgA-RF reacted more frequently with hFc than with rFc in both the RA and the 'false positive' sera. In some sera, IgM- and IgA-RFs reacted differently with human and rabbit Fc, e.g. IgM-RF reacted only with human Fc, and IgA-RF reacted with both hFc and rFc, thus suggesting different regulation of their formation. [ABSTRACT FROM AUTHOR]

Objectives: To assess the exposure to enzymes and prevalence of enzyme sensitisation in the baking industry.Methods: A cross sectional study was conducted in four bakeries, one flour mill, and one crispbread factory. Sensitisation to enzymes, flours, and storage mites was examined by skin prick and radioallergosorbent (RAST) tests. 365 workers were tested. The workers were interviewed for work related respiratory and skin symptoms. Total dust concentrations were measured by a gravimetric method, and the concentration of alpha-amylase in air was measured by a catalytic method. An immunochemical method was used for measuring cellulase and xylanase in air.Results: Total measured dust concentrations were from 0.1 to 18 mg/m3, with highest values in dough making areas of bakeries. The alpha-amylase concentrations generally followed the total dust concentrations and reached the highest values < 6.6 micrograms/m3 in the same areas. Cellulase and xylanase varied with concentrations < 180 ng/m3 and < 40 ng/m3, respectively, in the flour mill and the crispbread factory. No cellulase, but concentrations of 1-200 ng/m3 xylanase, were found in the bakeries, probably indicating the natural xylanase activity of wheat. 12 workers (8%) in the bakeries, three (5%) in the flour mill, and four (3%) in the crispbread factory were skin prick positive to enzymes. The corresponding percentages of positive reactions to flours were 12%, 5%, and 8%.Conclusions: The study confirmed that industrial enzymes in baking used as additives in a powdered form pose a risk of sensitisation. The no effect air concentrations for industrial enzymes are not known. Based on present knowledge, however, lowering exposures and eliminating short and high peaks by technical measures would lower the risk of sensitisation. This would be most effectively accomplished by shifting to non-dusty products. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus is a heterogeneous inherited disorder characterized by chronic hyperglycemia resulting from pancreatic b -cell dysfunction and insulin resistance. Although the pathogenic mechanisms are not fully un-derstood, manifestation of the disease most likely requires interaction between both environmental and genetic factors. In the search for such susceptibility genes, we have performed a genomewide scan in 58 multiplex families (comprising 440 individuals, 229 of whom were affected) from the Botnia region in Finland. Initially, linkage between chromosome 12q24 and impaired insulin secretion had been reported, by Mahtani et al., in a subsample of 26 families. In the present study, we extend the initial genomewide scan to include 32 additional families, update the affectation status, and fine map regions of interest, and we try to replicate the initial stratification analysis. In our analysis of all 58 families, we identified suggestive linkage to one region, chromosome 9p13-q21... [ABSTRACT FROM AUTHOR]

Optic neuritis (ON) is associated with numerous immune-mediated inflammatory diseases, but 50% patients are ultimately diagnosed with multiple sclerosis (MS). Differentiating MS-ON from non-MS-ON acutely is challenging but important; non-MS ON often requires urgent immunosuppression to preserve vision. Using data from the United Kingdom Biobank we showed that combining an MS-genetic risk score (GRS) with demographic risk factors (age, sex) significantly improved MS prediction in undifferentiated ON; one standard deviation of MS-GRS increased the Hazard of MS 1.3-fold (95% confidence interval 1.07-1.55, P < 0.01). Participants stratified into quartiles of predicted risk developed incident MS at rates varying from 4% (95%CI 0.5-7%, lowest risk quartile) to 41% (95%CI 33-49%, highest risk quartile). The model replicated across two cohorts (Geisinger, USA, and FinnGen, Finland). This study indicates that a combined model might enhance individual MS risk stratification, paving the way for precision-based ON treatment and earlier MS disease-modifying therapy., (© 2024. The Author(s).)

Background: Contrary to the presumption that type 1 diabetes leads to an absolute insulin deficiency, many individuals with type 1 diabetes have circulating C-peptide years after the diagnosis. We studied factors affecting random serum C-peptide concentration in individuals with type 1 diabetes and the association with diabetic complications., Methods: Our longitudinal analysis included individuals newly diagnosed with type 1 diabetes from Helsinki University Hospital (Helsinki, Finland) with repeated random serum C-peptide and concomitant glucose measurements from within 3 months of diagnosis and at least once later. The long-term cross-sectional analysis included data from participants from 57 centres in Finland who had type 1 diabetes diagnosed after 5 years of age, initiation of insulin treatment within 1 year from diagnosis, and a C-peptide concentration of less than 1·0 nmol/L (FinnDiane study) and patients with type 1 diabetes from the DIREVA study. We tested the association of random serum C-peptide concentrations and polygenic risk scores with one-way ANOVA, and association of random serum C-peptide concentrations, polygenic risk scores, and clinical factors with logistic regression., Findings: The longitudinal analysis included 847 participants younger than 16 years and 110 aged 16 years or older. In the longitudinal analysis, age at diagnosis strongly correlated with the decline in C-peptide secretion. The cross-sectional analysis included 3984 participants from FinnDiane and 645 from DIREVA. In the cross-sectional analysis, at a median duration of 21·6 years (IQR 12·5-31·2), 776 (19·4%) of 3984 FinnDiane participants had residual random serum C-peptide secretion (>0·02 nmol/L), which was associated with lower type 1 diabetes polygenic risk compared with participants without random serum C-peptide (p<0·0001). Random serum C-peptide was inversely associated with hypertension, HbA 1c , and cholesterol, but also independently with microvascular complications (adjusted OR 0·61 [95% CI 0·38-0·96], p=0·033, for nephropathy; 0·55 [0·34-0·89], p=0·014, for retinopathy)., Interpretation: Although children with multiple autoantibodies and HLA risk genotypes progressed to absolute insulin deficiency rapidly, many adolescents and adults had residual random serum C-peptide decades after the diagnosis. Polygenic risk of type 1 and type 2 diabetes affected residual random serum C-peptide. Even low residual random serum C-peptide concentrations seemed to be associated with a beneficial complications profile., Funding: Folkhälsan Research Foundation; Academy of Finland; University of Helsinki and Helsinki University Hospital; Medical Society of Finland; the Sigrid Juselius Foundation; the "Liv and Hälsa" Society; Novo Nordisk Foundation; and State Research Funding via the Helsinki University Hospital, the Vasa Hospital District, Turku University Hospital, Vasa Central Hospital, Jakobstadsnejdens Heart Foundation, and the Medical Foundation of Vaasa., Competing Interests: Declaration of interests P-HG has received investigator-initiated research grants from Eli Lilly and Roche, is an advisory board member for AbbVie, Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Cebix, Eli Lilly, Janssen, Medscape, Merck Sharp & Dohme, Mundipharma, Nestlé, Novartis, Novo Nordisk, and Sanofi; and has received lecture fees from AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Elo Water, Genzyme, Merck Sharp & Dohme, Medscape, Novartis, Novo Nordisk, PeerVoice, Sanofi, and Sciarc. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Aims/hypothesis: Monogenic forms of diabetes (MODY, neonatal diabetes mellitus and syndromic forms) are rare, and affected individuals may be misclassified and treated suboptimally. The prevalence of type 1 diabetes is high in Finnish children but systematic screening for monogenic diabetes has not been conducted. We assessed the prevalence and clinical manifestations of monogenic diabetes in children initially registered with type 1 diabetes in the Finnish Pediatric Diabetes Register (FPDR) but who had no type 1 diabetes-related autoantibodies (AABs) or had only low-titre islet cell autoantibodies (ICAs) at diagnosis., Methods: The FPDR, covering approximately 90% of newly diagnosed diabetic individuals aged ≤15 years in Finland starting from 2002, includes data on diabetes-associated HLA genotypes and AAB data (ICA, and autoantibodies against insulin, GAD, islet antigen 2 and zinc transporter 8) at diagnosis. A next generation sequencing gene panel including 42 genes was used to identify monogenic diabetes. We interpreted the variants in HNF1A by using the gene-specific standardised criteria and reported pathogenic and likely pathogenic findings only. For other genes, we also reported variants of unknown significance if an individual's phenotype suggested monogenic diabetes., Results: Out of 6482 participants, we sequenced DNA for 152 (2.3%) testing negative for all AABs and 49 (0.8%) positive only for low-titre ICAs (ICA low ). A monogenic form of diabetes was revealed in 19 (12.5%) of the AAB-negative patients (14 [9.2%] had pathogenic or likely pathogenic variants) and two (4.1%) of the ICA low group. None had ketoacidosis at diagnosis or carried HLA genotypes conferring high risk for type 1 diabetes. The affected genes were GCK, HNF1A, HNF4A, HNF1B, INS, KCNJ11, RFX6, LMNA and WFS1. A switch from insulin to oral medication was successful in four of five patients with variants in HNF1A, HNF4A or KCNJ11., Conclusions/interpretation: More than 10% of AAB-negative children with newly diagnosed diabetes had a genetic finding associated with monogenic diabetes. Because the genetic diagnosis can lead to major changes in treatment, we recommend referring all AAB-negative paediatric patients with diabetes for genetic testing. Low-titre ICAs in the absence of other AABs does not always indicate a diagnosis of type 1 diabetes., (© 2022. The Author(s).)

Population isolates such as those in Finland benefit genetic research because deleterious alleles are often concentrated on a small number of low-frequency variants (0.1% ≤ minor allele frequency < 5%). These variants survived the founding bottleneck rather than being distributed over a large number of ultrarare variants. Although this effect is well established in Mendelian genetics, its value in common disease genetics is less explored 1,2 . FinnGen aims to study the genome and national health register data of 500,000 Finnish individuals. Given the relatively high median age of participants (63 years) and the substantial fraction of hospital-based recruitment, FinnGen is enriched for disease end points. Here we analyse data from 224,737 participants from FinnGen and study 15 diseases that have previously been investigated in large genome-wide association studies (GWASs). We also include meta-analyses of biobank data from Estonia and the United Kingdom. We identified 30 new associations, primarily low-frequency variants, enriched in the Finnish population. A GWAS of 1,932 diseases also identified 2,733 genome-wide significant associations (893 phenome-wide significant (PWS), P < 2.6 × 10 -11 ) at 2,496 (771 PWS) independent loci with 807 (247 PWS) end points. Among these, fine-mapping implicated 148 (73 PWS) coding variants associated with 83 (42 PWS) end points. Moreover, 91 (47 PWS) had an allele frequency of <5% in non-Finnish European individuals, of which 62 (32 PWS) were enriched by more than twofold in Finland. These findings demonstrate the power of bottlenecked populations to find entry points into the biology of common diseases through low-frequency, high impact variants., (© 2023. The Author(s).)

Large variations in transportation noise tolerance have been reported between communities. In addition to population sensitivity, exposure-response functions (ERFs) for the effects of transportation noise depend on the exposure estimation method used. In the EU, the new CNOSSOS-EU method will change the estimations of exposure by changing the assignment of noise levels and populations to buildings. This method was officially used for the first time in the strategic noise mapping performed by Finnish authorities in 2017. Compared to the old method, the number of people exposed to traffic noise above 55 dB decreased by 50%. The main aim of this study, conducted in the Helsinki Capital Region, Finland, was to evaluate how the exposure estimation method affects ERFs for road traffic noise. As an example, with a façade road traffic noise level of 65 dB, the ERF based on the highest façade noise level of the residential building resulted in 5.1% being highly annoyed (HA V ), while the ERF based on the exposure estimation method that is similar to the CNOSSOS-EU method resulted in 13.6%. Thus, the substantial increase in the health effect estimate compensates for the reduction in the number of highly exposed people. This demonstrates the need for purpose-fitted ERFs when the CNOSSOS-EU method is used to estimate exposure in the health impact assessment of transportation noise.

In many countries, some people living in the vicinity of wind power production areas report having symptoms that they intuitively associate with wind turbines. Recently public discussions have focused especially on wind turbine infrasound. However, scientific evidence supporting an association is lacking. The aim of this study was to assess the association between exposure to wind turbines and the prevalence of self-reported symptoms, diseases and medications. A cross-sectional questionnaire study (n = 2,828) was conducted in the vicinity of five wind power production areas in Finland in 2015-2016. Each area had 3-16 turbines with a nominal power of 2.4-3.3 MW. The response rate was 50% (n = 1,411). Continuous and categorised (≤ 2.5, > 2.5-5, > 5-10 km) distance between the respondents' home and the closest wind turbine was used to represent exposure to wind turbines. Wind turbine sound pressure level outdoors could be reliably modelled only for the closest distance zone where the yearly average was 34 dB and maximum 43 dB. The data on symptoms (headache, nausea, dizziness, tinnitus, ear fullness, arrhythmia, fatigue, difficulties in falling asleep, waking up too early, anxiety, stress), diseases (hypertension, heart insufficiency, diabetes), and medications (analgesics for headache, joint/muscle pain and other pain, and medication for sleep disturbance, anxiety and depression, and hypertension) was obtained from the questionnaire. Logistic regression analyses were adjusted for age, sex, marital status, education, work situation, smoking, alcohol consumption, physical activity, body mass index, and hearing problems. Annoyance and sleep disturbance due to wind turbine noise were inversely associated with the distance to the closest wind turbine. The prevalence of symptoms, diseases and medications was essentially the same in all distance categories. In multivariate regression modelling, the odds ratio estimates were generally close to unity and statistically non-significant. Beyond annoyance and sleep disturbance, there were no consistent associations between exposure to wind turbines and self-reported health problems. The results do not support the hypothesis that broadband sound or infrasound from wind turbines could cause the proposed health problems., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Diabetes increases the risk of bacterial infections. We investigated whether common genetic variants associate with infection susceptibility in Finnish diabetic individuals. We performed genome-wide association studies and pathway analysis for bacterial infection frequency in Finnish adult diabetic individuals (FinnDiane Study; N = 5092, Diabetes Registry Vaasa; N = 4247) using national register data on antibiotic prescription purchases. Replication analyses were performed in a Swedish diabetic population (ANDIS; N = 9602) and in a Finnish non-diabetic population (FinnGen; N = 159,166). Genome-wide data indicated moderate but significant narrow-sense heritability for infection susceptibility (h 2  = 16%, P = 0.02). Variants on chromosome 2 were associated with reduced infection susceptibility (rs62192851, P = 2.23 × 10 -7 ). Homozygotic carriers of the rs62192851 effect allele (N = 44) had a 37% lower median annual antibiotic purchase rate, compared to homozygotic carriers of the reference allele (N = 4231): 0.38 [IQR 0.22-0.90] and 0.60 [0.30-1.20] respectively, P = 0.01). Variants rs6727834 and rs10188087, in linkage disequilibrium with rs62192851, replicated in the FinnGen-cohort (P < 0.05), but no variants replicated in the ANDIS-cohort. Pathway analysis suggested the IRAK1 mediated NF-κB activation through IKK complex recruitment-pathway to be a mediator of the phenotype. Common genetic variants on chromosome 2 may associate with reduced risk of bacterial infections in Finnish individuals with diabetes.

Urban dwellers are simultaneously exposed to several environmental health risk factors. This study aimed to examine the relationship between long-term exposure to fine particulate matter (PM 2.5 , diameter < 2.5 µm) of residential-wood-burning and road-traffic origin, road-traffic noise, green space around participants' homes, and hypertension. In 2015 and 2016, we conducted a survey of residents of the Helsinki Capital Region to determine their perceptions of environmental quality and safety, lifestyles, and health statuses. Recent antihypertensive medication was used as an indicator of current hypertensive illness. Individual-level exposure was estimated by linking residential coordinates with modelled outdoor levels of wood-smoke- and traffic-related PM 2.5 , road-traffic noise, and coverage of natural spaces. Relationships between exposure and hypertension were modelled using multi-exposure and single-exposure binary logistic regression while taking smooth functions into account. Twenty-eight percent of the participants were current users of antihypertensive medication. The odds ratios (95% confidence interval) for antihypertensive use were 1.12 (0.78-1.57); 0.97 (0.76-1.26); 0.98 (0.93-1.04) and 0.99 (0.94-1.04) for wood-smoke PM 2.5 , road-traffic PM 2.5 , road-traffic noise, and coverage of green space, respectively. We found no evidence of an effect of the investigated urban exposures on prevalent hypertension in the Helsinki Capital Region.

In many countries, a certain proportion of individuals living in the vicinity of wind power areas have reported symptoms that they have intuitively associated with infrasound from wind turbines. While the reason for these symptoms remains under debate, this is the first study to describe the phenomenon by assessing the prevalence and severity of these wind turbine infrasound related symptoms as well as factors associated with being symptomatic. Four wind power areas in Finland assessed to have the most problems intuitively associated with wind turbine infrasound were selected for the study. The questionnaire was mailed to 4847 adults in four distance zones (≤ 2.5 km, > 2.5-5 km, > 5-10 km, > 10-20 km from the closest wind turbine), and 28% responded. In the closest distance zone, 15% of respondents reported having symptoms that they have intuitively associated with wind turbine infrasound. In the whole study area, the symptom prevalence was 5%. Many of the symptomatic respondents were annoyed by audible wind turbine sound and associated their symptoms also with vibration or electromagnetic field from wind turbines. One third of the symptomatic respondents rated their symptoms severe, and the symptom spectrum was very broad covering several organ systems. In multivariate models, many factors such as proximity to wind turbines, impaired health status, being annoyed by different aspects of wind turbines and considering wind turbines as a health risk were associated with having wind turbine infrasound related symptoms. Although causal relationships cannot be assessed based on a cross-sectional questionnaire study, it can be speculated that interpretations of symptoms are affected by many other factors in addition to actual exposure., (Copyright © 2020. Published by Elsevier Inc.)

A six-month winter-spring study was conducted in a suburb of the northern European city of Kuopio, Finland, to identify and quantify factors determining daily personal exposure and home indoor levels of fine particulate matter (PM 2.5 , diameter <2.5 µm) and its light absorption coefficient (PM 2.5abs ), a proxy for combustion-derived black carbon. Moreover, determinants of home indoor ozone (O 3 ) concentration were examined. Local central site outdoor, home indoor, and personal daily levels of pollutants were monitored in this suburb among 37 elderly residents. Outdoor concentrations of the pollutants were significant determinants of their levels in home indoor air and personal exposures. Natural ventilation in the detached and row houses increased personal exposure to PM 2.5 , but not to PM 2.5abs , when compared with mechanical ventilation. Only cooking out of the recorded household activities increased indoor PM 2.5 . The use of a wood stove room heater or wood-fired sauna stove was associated with elevated concentrations of personal PM 2.5 and PM 2.5abs , and indoor PM 2.5abs . Candle burning increased daily indoor and personal PM 2.5abs , and it was also a determinant of indoor ozone level. In conclusion, relatively short-lasting wood and candle burning of a few hours increased residents' daily exposure to potentially hazardous, combustion-derived carbonaceous particulate matter., (© 2019 The Authors. Indoor Air published by published by John Wiley & Sons Ltd.)

Context: Early prediction of dysglycemia is crucial to prevent progression to type 2 diabetes. The 1-hour postload plasma glucose (PG) is reported to be a better predictor of dysglycemia than fasting plasma glucose (FPG), 2-hour PG, or glycated hemoglobin (HbA1c)., Objective: To evaluate the predictive performance of clinical markers, metabolites, HbA1c, and PG and serum insulin (INS) levels during a 75-g oral glucose tolerance test (OGTT)., Design and Setting: We measured PG and INS levels at 0, 30, 60, and 120 minutes during an OGTT in 543 participants in the Botnia Prospective Study, 146 of whom progressed to type 2 diabetes within a 10-year follow-up period. Using combinations of variables, we evaluated 1527 predictive models for progression to type 2 diabetes., Results: The 1-hour PG outperformed every individual marker except 30-minute PG or mannose, whose predictive performances were lower but not significantly worse. HbA1c was inferior to 1-hour PG according to DeLong test P value but not false discovery rate. Combining the metabolic markers with PG measurements and HbA1c significantly improved the predictive models, and mannose was found to be a robust metabolic marker., Conclusions: The 1-hour PG, alone or in combination with metabolic markers, is a robust predictor for determining the future risk of type 2 diabetes, outperforms the 2-hour PG, and is cheaper to measure than metabolites. Metabolites add to the predictive value of PG and HbA1c measurements. Shortening the standard 75-g OGTT to 1 hour improves its predictive value and clinical usability., (Copyright © 2019 Endocrine Society.)

Background: Seasonal variation in glucose metabolism might be driven by changes in daylight. Melatonin entrains circadian regulation and is directly associated with daylight. The relationship between melatonin receptor 1B gene variants with glycemic traits and type 2 diabetes is well established. We studied if daylight length was associated with glycemic traits and if it modified the relationship between melatonin receptor 1B gene rs10830963 variant and glycemic traits., Materials: A population-based sample of 3422 18-78-year-old individuals without diabetes underwent an oral glucose tolerance test twice, an average 6.8 years (SD = 0.9) apart and were genotyped for rs10830963. Daylight data was obtained from the Finnish Meteorological Institute., Results: Cross-sectionally, more daylight was associated with lower fasting glucose, but worse insulin sensitivity and secretion at follow-up. Longitudinally, individuals studied on lighter days at follow-up than at baseline showed higher glucose values during the oral glucose tolerance test and lower Corrected Insulin Response at follow-up. GG genotype carriers in the rs10830963 became more insulin resistant during follow-up if daylight length was shorter at follow-up than at baseline., Conclusions: Our study shows that individual glycemic profiles may vary according to daylight, MTNR1B genotype and their interaction. Future studies may consider taking daylight length into account. Key messages In Western Finland, the amount daylight follows an extensive annual variation ranging from 4 h 44 min to 20 h 17 min, making it ideal to study the associations between daylight and glycemic traits. Moreover, this allows researchers to explore if the relationship between the melatonin receptor 1B gene rs10830963 variant and glycemic traits is modified by the amount of daylight both cross-sectionally and longitudinally. This study shows that individuals, who participated in the study on lighter days at the follow-up than at the baseline, displayed to a greater extent worse glycemic profiles across the follow-up. Novel findings from the current study show that in the longitudinal analyses, each addition of the minor G allele of the melatonin receptor 1B gene rs10830963 was associated with worsening of fasting glucose values and insulin secretion across the 6.8-year follow-up. Importantly, this study shows that in those with the rs10830963 GG genotype, insulin sensitivity deteriorated the most significantly across the 6.8-year follow-up if the daylight length on the oral glucose tolerance testing date at the follow-up was shorter than at the baseline. Taken together, the current findings suggest that the amount of daylight may affect glycemic traits, especially fasting glucose and insulin secretion even though the effect size is small. The association can very according to the rs10830963 risk variant. Further research is needed to elucidate the mechanisms behind these associations.

Background: The association between depression and type 2 diabetes is bidirectional. Underlying biological determinants remain elusive. We examined whether a common melatonin receptor 1B gene diabetes risk variant rs10830963 influenced the associations between depressive symptoms and glycaemic traits., Materials: The Prevalence, Prediction and Prevention of Diabetes-Botnia Study participants (n = 4,455) with no diabetes who underwent an oral glucose tolerance test were genotyped for rs10830963 and completed the Mental Health Inventory on depressive symptoms., Results: The rs10830963 did not influence significantly the associations between depressive symptoms and glycaemic traits. Yet, the addition of each copy of the minor G allele of the rs1080963 and higher depressive symptoms were both, independent of each other, associated significantly with higher glucose response (glucose area under the curve), higher insulin resistance (Insulin Sensitivity Index) and lower insulin secretion (Disposition Index). Depressive symptoms, but not rs1080963, were also significantly associated with higher fasting insulin, insulin area under the curve and insulin resistance (Homeostasis Model Assessment, Homeostasis Model Assessment-2); rs1080963, but not depressive symptoms, was significantly associated with higher fasting glucose and lower Corrected Insulin Response., Conclusions: Our study shows that the diabetes risk variant rs10830963 does not contribute to the known comorbidity between depression and type 2 diabetes. Key messages The association between depression and type 2 diabetes is bidirectional. We tested whether a common variant rs10830963 in the gene encoding Melatonin Receptor 1B influences the known association between depressive symptoms and glycaemic traits in a population-based sample from Western Finland. The MTNR1B genetic diabetes risk variant rs10830963 does not contribute to the known comorbidity between depression and type 2 diabetes. Depressive symptoms and rs10830963 are associated with a worse glycaemic profile independently of each other.

Objective: To evaluate if obstructive sleep apnoea (OSA) modifies the risk of coronary heart disease, type 2 diabetes (T2D) and diabetic complications in a gender-specific fashion., Design and Setting: A longitudinal population-based study with up to 25-year follow-up data on 36 963 individuals (>500 000 person years) from three population-based cohorts: the FINRISK study, the Health 2000 Cohort Study and the Botnia Study., Main Outcome Measures: Incident coronary heart disease, diabetic kidney disease, T2D and all-cause mortality from the Finnish National Hospital Discharge Register and the Finnish National Causes-of-Death Register., Results: After adjustments for age, sex, region, high-density lipoprotein (HDL) and total cholesterol, current cigarette smoking, body mass index, hypertension, T2D baseline and family history of stroke or myocardial infarction, OSA increased the risk for coronary heart disease (HR=1.36, p=0.0014, 95% CI 1.12 to 1.64), particularly in women (HR=2.01, 95% CI 1.31 to 3.07, p=0.0012). T2D clustered with OSA independently of obesity (HR=1.48, 95% CI 1.26 to 1.73, p=9.11×[Formula: see text]). The risk of diabetic kidney disease increased 1.75-fold in patients with OSA (95% CI 1.13 to 2.71, p=0.013). OSA increased the risk for coronary heart disease similarly among patients with T2D and in general population (HR=1.36). All-cause mortality was increased by OSA in diabetic individuals (HR=1.35, 95% CI 1.06 to 1.71, p=0.016)., Conclusion: OSA is an independent risk factor for coronary heart disease, T2D and diabetic kidney disease. This effect is more pronounced even in women, who until now have received less attention in diagnosis and treatment of OSA than men., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Road-traffic noise can induce stress, which may contribute to mental health disorders. Mental health problems have not received much attention in noise research. People perceive noise differently, which may affect the extent to which noise contributes to poor mental health at the individual level. This paper aims to assess the relationships between outdoor traffic noise and noise annoyance and the use of psychotropic medication., Methods: We conducted a survey to assess noise annoyance and psychotropic medication among residents of the Helsinki Capital Region of Finland. We also assessed the associations of annoyance and road-traffic noise with sleep disorders, anxiety and depression. Respondents were randomly sampled from the Finnish Population registry, and data was collected using a self-administered questionnaire. Outdoor traffic noise was modelled using the Nordic prediction model. Associations between annoyance and modelled façade-noise levels with mental health outcome indicators were assessed using a binary logistic regression while controlling for socioeconomic, lifestyle and exposure-related factors., Results: A total of 7321 respondents returned completed questionnaires. Among the study respondents, 15%, 7% and 7% used sleep medication, anxiolytic and antidepressant medications, respectively, in the year preceding the study. Noise annoyance was associated with anxiolytic drug use, OR = 1.41 (95% CI: 1.02-1.95), but not with sedative or antidepressant use. There was suggestive association between modelled noise at levels higher than 60 dB and anxiolytic or antidepressant use. In respondents whose bedroom windows faced the street, modelled noise was definitively associated with antidepressant use. Noise sensitivity did not modify the effect of noise but was associated with an increased use of psychotropic medication., Conclusion: We observed suggestive associations between high levels of road-traffic noise and psychotropic medication use. Noise sensitivity was associated with psychotropic medication use., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

To reduce the incidence of occupational diseases related to exposure to respirable silica at work, the main industries in the EU associated with respirable silica agreed on measures to improve working conditions through the application of good practices. These practices were included in &ldquo;The Agreement on Workers Health Protection through the Good Handling and Use of Crystalline Silica and Products Containing it&rdquo; (NEPSI agreement), signed in April 2006. In Finland, we have previously seen a decline in exposure to respirable quartz in relevant industries upon the treaty coming into effect, during the years 2006⁻2013. The present paper examines trends in exposure to respirable crystalline silica in Finland from 2006 to the end of 2017. In addition, we looked at changes in the number of exposed workers and the prevalence of silicosis and lung cancer associated with the exposure during the same period. The aim was to find out whether the decline in exposure previously recorded had continued, and whether this, in addition to the previously reported descent in exposure, was reflected in the amount and prevalence of occupational diseases associated with inhaling respirable quartz. In the present study, during the period 2013 to 2017 no further improvements were observed. The exposure remained at an average level of 20⁻50% of the current OEL 8h . This is not necessarily sufficient to eliminate silicosis, lung cancer or other health effects associated with exposure to respirable silica in affected workplaces. To bring about further improvements in exposure, we suggest the present OEL 8h in Finland (0.05 mg/m³) and particularly in the many EU countries with an OEL 8h of 0.1 mg/m³ be lowered to 0.020⁻0.025 mg/m³. Secondly, branches outside of the NEPSI treaty where the number of exposed workers is increasing in Finland and possibly in some other EU countries as well, namely building and refinery industries, would be advised to sign the treaty. In addition, as a result of signing, good practices should be developed for work tasks where exposure to respirable silica is of concern in these industries.

To identify novel coding association signals and facilitate characterization of mechanisms influencing glycemic traits and type 2 diabetes risk, we analyzed 109,215 variants derived from exome array genotyping together with an additional 390,225 variants from exome sequence in up to 39,339 normoglycemic individuals from five ancestry groups. We identified a novel association between the coding variant (p.Pro50Thr) in AKT2 and fasting plasma insulin (FI), a gene in which rare fully penetrant mutations are causal for monogenic glycemic disorders. The low-frequency allele is associated with a 12% increase in FI levels. This variant is present at 1.1% frequency in Finns but virtually absent in individuals from other ancestries. Carriers of the FI-increasing allele had increased 2-h insulin values, decreased insulin sensitivity, and increased risk of type 2 diabetes (odds ratio 1.05). In cellular studies, the AKT2-Thr50 protein exhibited a partial loss of function. We extend the allelic spectrum for coding variants in AKT2 associated with disorders of glucose homeostasis and demonstrate bidirectional effects of variants within the pleckstrin homology domain of AKT2 ., (© 2017 by the American Diabetes Association.)

Introduction: The purpose of this study was to determine the incidence of, and risk factors for, surgical site infections in a contemporary cohort of women with endometrial carcinoma., Material and Methods: We retrospectively studied 1164 women treated for endometrial carcinoma by hysterectomy at a single institution in 2007-2013. In all, 912 women (78.4%) had minimally invasive hysterectomy. Data on surgical site infections were collected from medical records. Univariate and multivariate analyses were used to identify risk factors for incisional and organ/space infections., Results: Ninety-four women (8.1%) were diagnosed with a surgical site infection. Twenty women (1.7%) had an incisional infection and 74 (6.4%) had an organ/space infection. The associations of 17 clinico-pathologic and surgical variables were tested by univariate analyses. Those variables that were identified as potential risk factors in univariate analyses (p < 0.15) were used in logistic regression models with incisional and organ/space infections as dependent variables. Obesity (body mass index ≥ 30 kg/m(2)), diabetes, and long operative time (>80th centile) were independently associated with a higher risk of incisional infection, whereas minimally invasive surgery was associated with a smaller risk. Smoking, conversion to laparotomy, and lymphadenectomy were associated with a higher risk of organ/space infection., Conclusions: Organ/space infections comprised the majority of surgical site infections. Risk factors for incisional and organ/space infections differed. Minimally invasive hysterectomy was associated with a smaller risk of incisional infections but not of organ/space infections., (© 2015 Nordic Federation of Societies of Obstetrics and Gynecology.)

About 500,000 people suffer from diabetes in Finland, a number which is predicted to increase within the next decades. At the moment, diabetes can neither be prevented nor cured. Diabetes is associated with microvascular (kidney, eye and peripheral nerves) and macrovascular complications (coronary heart disease, stroke). These complications affect the quality of life of patients and account for a substantial proportion of healthcare costs in Finland. The.current guidelines offer recommendations for the diagnosis, screening, prevention and treatment of diabetes and its complications.

Little information is available on the concentrations of ambient fine particles (PM2.5) in residential areas where wood combustion is common for recreational purposes and secondary heating. Further, the validity of central site measurements of PM2.5 as a measure of exposure is unclear. Therefore, outdoor PM2.5 samples were repeatedly collected at a central site and home outdoor locations from a panel of 29 residents in a suburb in Kuopio, Finland. Source apportionment results from the central site were used to estimate the contributions from local sources, including wood combustion, to PM2.5 and absorption coefficient (ABS) at home outdoor locations. Correlations between the central and home outdoor concentrations of PM2.5, ABS, and their local components were analyzed for each home. At the central site, the average PM2.5 was 6.0 μg m(-)(3) during the heating season, and the contribution from wood combustion (16%) was higher than the contribution from exhaust emissions (12%). Central site measurements predicted poorly daily variation in PM2.5 from local sources. In conclusion, wood combustion significantly affects air quality also in areas where it is not the primary heating source. In epidemiological panel studies, central site measurements may not sufficiently capture daily variation in exposure to PM2.5 from local wood combustion.

Objective: To compare short-term effects of fine particles (PM2.5; aerodynamic diameter <2.5 µm) from different sources on the blood levels of markers of systemic inflammation., Methods: We followed a panel of 52 ischaemic heart disease patients from 15 November 2005 to 21 April 2006 with clinic visits in every second week in the city of Kotka, Finland, and determined nine inflammatory markers from blood samples. In addition, we monitored outdoor air pollution at a fixed site during the study period and conducted a source apportionment of PM2.5 using the Environmental Protection Agency's model EPA PMF 3.0. We then analysed associations between levels of source-specific PM2.5 and markers of systemic inflammation using linear mixed models., Results: We identified five source categories: regional and long-range transport (LRT), traffic, biomass combustion, sea salt, and pulp industry. We found most evidence for the relation of air pollution and inflammation in LRT, traffic and biomass combustion; the most relevant inflammation markers were C-reactive protein, interleukin-12 and myeloperoxidase. Sea salt was not positively associated with any of the inflammatory markers., Conclusions: Results suggest that PM2.5 from several sources, such as biomass combustion and traffic, are promoters of systemic inflammation, a risk factor for cardiovascular diseases., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

In order to better understand the relations between different risk factors in the predisposition to type 2 diabetes, we present a Bayesian Network analysis of a large dataset, composed of three European population studies. Our results show, together with a key role of metabolic syndrome and of glucose after 2 hours of an Oral Glucose Tolerance Test, the importance of education, measured as the number of years of study, in the predisposition to type 2 diabetes.

Rare-variant association studies in common, complex diseases are customarily conducted under an additive risk model in both single-variant and burden testing. Here, we describe a method to improve detection of rare recessive variants in complex diseases termed RAFT (recessive-allele-frequency-based test). We found that RAFT outperforms existing approaches when the variant influences disease risk in a recessive manner on simulated data. We then applied our method to 1,791 Finnish individuals with type 2 diabetes (T2D) and 2,657 matched control subjects. In BBS10, we discovered a rare variant (c.1189A>G [p.Ile397Val]; rs202042386) that confers risk of T2D in a recessive state (p = 1.38 × 10(-6)) and would be missed by conventional methods. Testing of this variant in an established in vivo zebrafish model confirmed the variant to be pathogenic. Taken together, these data suggest that RAFT can effectively reveal rare recessive contributions to complex diseases overlooked by conventional association tests., (Copyright © 2014 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)

To protect the health of those occupationally exposed to respirable crystalline silica, the main industries in European Union associated with exposure to respirable silica, agreed on appropriate measures for the improvement of working conditions through the application of good practices, as part of 'The Agreement on Workers Health Protection through the Good Handling and Use of Crystalline Silica and Products Containing it' (NEPSI agreement), signed in April 2006. The present paper examines trends in exposure to respirable crystalline silica in Finland prior to and following the implementation of the NEPSI agreement and includes a working example of the NEPSI approach in the concrete industry. Data derived from workplace exposure assessments during the years 1994-2013 are presented, including 2556 air samples collected mostly indoors, from either the breathing zone of workers or from stationary points usually at a height of 1.5 m above the floor, with the aim to estimate average exposure of workers to respiratory crystalline silica during an 8-h working day. The aim was, to find out how effective this unique approach has been in the management of one of the major occupational hazards in the concerned industries. Application of good practices as described by the NEPSI agreement coincides with a strong decline in the exposure to respirable crystalline silica in Finnish workplaces, as represented by the clientele of Finnish Institute of Occupational Health. During the years followed in the present study, we see a >10-fold decrease in the average and median exposures to respirable silica. Prior to the implementation of the NEPSI agreement, >50% of the workplace measurements yielded results above the OEL8 h (0.2mg m(-3)). As of present (2013), circa 10% of the measurements are above of or identical to the OEL8 h (0.05mg m(-3))., (© The Author 2014. Published by Oxford University Press on behalf of the British Occupational Hygiene Society.)

Objectives: Road traffic noise is a common environmental nuisance, which has been thought to increase the risk of many types of health problems. However, population-level evidence often remains scarce. This study examined whether road traffic noise is associated with self-rated health and use of psychotropic medication in a cohort of public sector employees., Methods: Data are from the Finnish Public Sector Study cohort. Geographical information system (GIS) was used to link modeled outdoor road traffic noise levels (L den) to residential addresses of 15 611 men and women with cross-sectional survey responses on self-rated health and register-based information on the use of antidepressants, anxiolytics, and hypnotics. High trait anxiety scores were used to identify potentially vulnerable individuals. The analyses were run with logistic regression models adjusting for individual and area-level variables. All participants were blind to the aim of the study., Results: Mean level of road traffic noise at participants' home addresses was 52 decibels (dB) (standard deviation 8.1). Noise level >60 dB versus ≤45 dB was associated with poor self-rated health in men [odds ratio (OR) 1.58, 95% confidence interval (95% CI) 1.14-2.21]. Further stratification revealed that the association was evident only among men with high trait anxiety scores (OR 2.23, 95% CI 1.28-3.89). No association was found with psychotropic medication use or among women., Conclusion: Exposure to road traffic noise was not associated with increased use of psychotropic medication, although it was associated with weakened self-rated health among men.

Objectives: To assess work-related exposure to tobacco smoke in Finnish restaurants, a series of nationwide questionnaire surveys were conducted among restaurant workers and the levels of indoor air nicotine concentrations were measured in restaurants. The survey aimed to evaluate the impact of the smoke-free legislation in general and in particular after the total smoking ban launched in 2007., Materials and Methods: In 2003-2010, four national questionnaire surveys were conducted among restaurant workers and the concentration of nicotine in indoor air was measured in different types of restaurants, bars and nightclubs., Results: Between 2003 and 2010, the proportion of restaurant workers reporting occupational exposure to tobacco smoke dropped from 59% to 11%. Among pub workers, the decrease was from 97% to 18% and in workers of dining restaurants from 49% to 10%, respectively. The median concentration of nicotine in indoor air of all restaurants decreased from 11.7 μg/m(3) to 0.1 μg/m(3). The most significant decrease was detected in pubs where the decrease was from 16.1 μg/m(3) to 0.1 μg/m(3). Among all restaurant workers, in 2003-2010 the prevalence of daily smokers was reduced from 39% to 31% in men and from 35% to 25% in women., Conclusion: Total prohibition of smoking but not partial restriction in restaurants was effective in reducing work-related exposure to tobacco smoke. Strict tobacco legislation may partly be associated with the significant decrease of daily smoking prevalence among restaurant workers.

Although meta-analyses of genome-wide association studies have identified >60 single nucleotide polymorphisms (SNPs) associated with type 2 diabetes and/or glycemic traits, there is little information on whether these variants also affect α-cell function. The aim of the current study was to evaluate the effects of glycemia-associated genetic loci on islet function in vivo and in vitro. We studied 43 SNPs in 4,654 normoglycemic participants from the Finnish population-based Prevalence, Prediction, and Prevention of Diabetes-Botnia (PPP-Botnia) Study. Islet function was assessed, in vivo, by measuring insulin and glucagon concentrations during oral glucose tolerance test, and, in vitro, by measuring glucose-stimulated insulin and glucagon secretion from human pancreatic islets. Carriers of risk variants in BCL11A, HHEX, ZBED3, HNF1A, IGF1, and NOTCH2 showed elevated whereas those in CRY2, IGF2BP2, TSPAN8, and KCNJ11 showed decreased fasting and/or 2-h glucagon concentrations in vivo. Variants in BCL11A, TSPAN8, and NOTCH2 affected glucagon secretion both in vivo and in vitro. The MTNR1B variant was a clear outlier in the relationship analysis between insulin secretion and action, as well as between insulin, glucose, and glucagon. Many of the genetic variants shown to be associated with type 2 diabetes or glycemic traits also exert pleiotropic in vivo and in vitro effects on islet function.

Aims: The aim was to evaluate the impact of family history of diabetes on the phenotype of patients diagnosed with Type 2 diabetes and the frequency of susceptibility genotypes., Methods: Patients with Type 2 diabetes with family history for both Type 1 and Type 2 diabetes (FH(MIX, n) = 196) or Type 2 diabetes only (FH(T2), n = 139) matched for age, sex, BMI and age at diagnosis, underwent an oral glucose tolerance test and a combined glucagon test and insulin tolerance test. Glutamic acid decarboxylase (GAD) antibodies and major Type 1 and Type 2 diabetes susceptibility gene variants were analysed. Patients were stratified into groups according to family history or GAD antibody positivity (GADA+, GADA-) or a combination of these (GADA+/FH(MIX), GADA+/FH(T2), GADA-/FH(MIX), GADA-/FH(T2))., Results: Compared with other patients, those with FH(MIX) more often had GAD antibodies (14.3 vs. 4.3%, P = 0.003), and those with both FH(MIX) and GAD antibodies had the highest frequency of insulin deficiency (stimulated serum C-peptide < 0.7 nmol/l, GADA+/FH(MIX) 46.4% vs. GADA-/FH(MIX) 9.5% (P < 0.00001), GADA-/FH(T2) 4.5% (P < 0.00001), GADA+/FH(T2) 0%). Patients with GADA+/FH(MIX) more often had HLA-DQB1 risk genotypes compared with patients with GADA-/FH(MIX) or GADA-/FH(T2D) (47 vs. 23 or 14%, P = 0.05 and P < 0.00001, respectively). In logistic regression analyses, FH(MIX), GAD antibody positivity and HLA risk genotypes were independently associated with insulin deficiency., Conclusion: A family history for both type 1 and type 2 diabetes was associated with higher prevalence of GAD antibodies and HLA-DQB1 risk genotypes than a family history of type 2 diabetes only, and was associated with earlier and more severe development of insulin deficiency, which was only partially explained by GAD antibodies and HLA., (© 2012 The Authors. Diabetic Medicine © 2012 Diabetes UK.)

Aim/hypothesis: Individuals at risk of developing type 2 diabetes show a progressive decline in insulin secretion and increased insulin resistance over time. However, inability of the beta cells to compensate for the increased insulin resistance represents a key defect leading to overt type 2 diabetes. The aims of the present study were to replicate the association between genetic variants of the PCSK2 gene and insulin secretion, and to explore the effect on risk of type 2 diabetes., Methods: Replication of PCSK2 variants against insulin secretion included 7,682 non-diabetic Scandinavian individuals. Insulin secretion was measured as the corrected insulin response or disposition index, i.e. insulin secretion adjusted for the degree of insulin resistance. Risk of type 2 diabetes was studied in 28,287 Scandinavian individuals., Results: The C-allele of PCSK2 rs2208203 was associated with reduced insulin secretion measured as the corrected insulin response (n = 8,151; β = -0.112, p = 1.3 × 10(-6)) as well as disposition index (n = 8,078, β = -0.128, p = 1.6 × 10(-7)). The variant was also associated with lower fasting glucagon levels (β = -0.084, p = 0.005) in non-diabetic individuals with a fasting plasma glucose of over 5.5 mmol/l. In human pancreatic islets, PCSK2 expression correlated negatively with HbA(1c) (n = 133, r = -0.196, p = 0.038), and showed a tendency to be lower in hyperglycaemic (HbA(1c) ≥6.0% or type 2 diabetes; n = 47, p = 0.13) than normoglycaemic (HbA(1c) >6.0%; n = 66) donors. The presence of the PCSK2 rs2208203 risk allele did not influence gene expression, nor did it show an apparent risk in terms of type 2 diabetes., Conclusions/interpretation: A variant of the PCSK2 gene was associated with reduced glucose-stimulated insulin secretion, but also with lower glucagon levels, which could potentially counteract the effects of decreased insulin secretion on the risk of type 2 diabetes.

Short-term exposure to ambient air pollution is associated with increased cardiovascular mortality and morbidity. This adverse health effect is suggested to be mediated by inflammatory processes. The purpose of this study was to determine if low levels of particulate matter, typical for smaller cities, are associated with acute systemic inflammation. Fifty-two elderly individuals with ischemic heart disease were followed for six months with biweekly clinical visits in the city of Kotka, Finland. Blood samples were collected for the determination of inflammatory markers interleukin (IL)-1β, IL-6, IL-8, IL-12, interferon (IFN)γ, C-reactive protein (CRP), fibrinogen, myeloperoxidase and white blood cell count. Particle number concentration and fine particle (particles with aerodynamic diameters <2.5 μm (PM(2.5))) as well as thoracic particle (particles with aerodynamic diameters <10 μm (PM(10))) mass concentration were measured daily at a fixed outdoor measurement site. Light-absorbance of PM(2.5) filter samples, an indicator of combustion derived particles, was measured with a smoke-stain reflectometer. In addition, personal exposure to PM(2.5) was measured with portable photometers. During the study period, wildfires in Eastern Europe led to a 12-day air pollution episode, which was excluded from the main analyses. Average ambient PM(2.5) concentration was 8.7 μg/m(3). Of the studied pollutants, PM(2.5) and absorbance were most strongly associated with increased levels of inflammatory markers; most notably with C-reactive protein and IL-12 within a few days of exposure. There was also some evidence of an effect of particulate air pollution on fibrinogen and myeloperoxidase. The concentration of IL-12 was considerably (227%) higher during than before the forest fire episode. These findings show that even low levels of particulate air pollution from urban sources are associated with acute systemic inflammation. Also particles from wildfires may exhibit pro-inflammatory effects., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Heterozygous mutations in the TCF2 gene encoding the transcription factor HNF-11 cause a dominantly inherited developmental disorder that may be associated with various dysplastic and cystic lesions of the kidneys and renal insufficiency, disorder of pancreatic development and insulin-deficient MODY diabetes, aberrant hepatic enzyme levels, gout and genital anomalies. Symptoms and findings vary in their degree of severity. When an isolated abnormality is detected, recognition of the syndrome is essential in order to diagnose the other organ manifestations. Since the mid-2000's, 10 to 20 patients have been diagnosed in Finland.

Objective: Although insulin resistance (IR) may underlie associations between depressive symptoms and diabetes, previous findings have been contradictory. We examined whether depressive symptoms associate with IR and insulin secretion, and, additionally, whether antidepressant medication use may modulate such associations., Research Design and Methods: A total of 4,419 individuals underwent an oral glucose tolerance test (OGTT). Participants with previously or newly diagnosed diabetes are excluded from this sample. The homeostasis model assessment of IR (HOMA-IR) and corrected insulin response (CIR) were calculated. Depressive symptoms and antidepressant medication use were self-reported., Results: After controlling for confounding factors, depressive symptoms were associated with higher fasting and 30-min insulin during the OGTT and higher HOMA-IR but not CIR. Antidepressant medication use failed to modify these associations., Conclusions: Depressive symptoms are associated with IR but not with changes in insulin response when corrected for IR in individuals without previously or newly diagnosed diabetes.

Aims/hypothesis: To study the heritability and familiality of type 2 diabetes and related quantitative traits in families from the Botnia Study in Finland., Methods: Heritability estimates for type 2 diabetes adjusted for sex, age and BMI are provided for different age groups of type 2 diabetes and for 34 clinical and metabolic traits in 5,810 individuals from 942 families using a variance component model (SOLAR). In addition, family means of these traits and their distribution across families are calculated., Results: The strongest heritability for type 2 diabetes was seen in patients with age at onset 35-60 years (h (2) = 0.69). However, including patients with onset up to 75 years dropped the h (2) estimates to 0.31. Among quantitative traits, the highest h (2) estimates in all individuals and in non-diabetic individuals were seen for lean body mass (h (2) = 0.53-0.65), HDL-cholesterol (0.52-0.61) and suppression of NEFA during OGTT (0.63-0.76) followed by measures of insulin secretion (insulinogenic index [IG(30)] = 0.41-0.50) and insulin action (insulin sensitivity index [ISI] = 0.37-0.40). In contrast, physical activity showed rather low heritability (0.16-0.18), whereas smoking showed strong heritability (0.57-0.59). Family means of these traits differed two- to fivefold between families belonging to the lowest and highest quartile of the trait (p < 0.00001)., Conclusions/interpretation: To detect stronger genetic effects in type 2 diabetes, it seems reasonable to restrict inclusion of patients to those with age at onset 35-60 years. Sequencing of families with extreme quantitative traits could be an important next step in the dissection of the genetics of type 2 diabetes.

Aims/hypothesis: We studied the impact of a family history of type 2 diabetes on physical fitness, lifestyle factors and diabetes-related metabolic factors., Methods: The Prevalence, Prediction and Prevention of Diabetes (PPP)-Botnia study is a population-based study in Western Finland, which includes a random sample of 5,208 individuals aged 18 to 75 years identified through the national Finnish Population Registry. Physical activity, dietary habits and family history of type 2 diabetes were assessed by questionnaires and physical fitness by a validated 2 km walking test. Insulin secretion and action were assessed based upon OGTT measurements of insulin and glucose., Results: A family history of type 2 diabetes was associated with a 2.4-fold risk of diabetes and lower physical fitness (maximal aerobic capacity 29.2 +/- 7.2 vs 32.1 +/- 7.0, p = 0.01) despite having similar reported physical activity to that of individuals with no family history. The same individuals also had reduced insulin secretion adjusted for insulin resistance, i.e. disposition index (p < 0.001) despite having higher BMI (27.4 +/- 4.6 vs 26.0 +/- 4.3 kg/m(2), p < 0.001)., Conclusions/interpretation: Individuals with a family history of type 2 diabetes are characterised by lower physical fitness, which cannot solely be explained by lower physical activity. They also have an impaired capacity of beta cells to compensate for an increase in insulin resistance imposed by an increase in BMI. These defects should be important targets for interventions aiming at preventing type 2 diabetes in individuals with inherited susceptibility to the disease.

Objective: To evaluate the significance of GAD antibodies (GADAs) and family history for type 1 diabetes (FH(T1)) or type 2 diabetes (FH(T2)) in nondiabetic subjects., Research Design and Methods: GADAs were analyzed in 4,976 nondiabetic relatives of type 2 diabetic patients or control subjects from Finland. Altogether, 289 (5.9%) were GADA(+)-a total of 253 GADA(+) and 2,511 GADA(-) subjects participated in repeated oral glucose tolerance tests during a median time of 8.1 years. The risk of progression to diabetes was assessed using Cox regression analysis., Results: Subjects within the highest quartile of GADA(+) (GADA(+)(high)) had more often first-degree FH(T1) (29.2 vs. 7.9%, P < 0.00001) and GADA(+) type 2 diabetic (21.3 vs. 13.7%, P = 0.002) or nondiabetic (26.4 vs. 13.3%, P = 0.010) relatives than GADA(-) subjects. During the follow-up, the GADA(+) subjects developed diabetes significantly more often than the GADA(-) subjects (36/253 [14.2%] vs. 134/2,511 [5.3%], P < 0.00001). GADA(+)(high) conferred a 4.9-fold increased risk of diabetes (95% CI 2.8-8.5) compared with GADA(-)-seroconversion to positive during the follow-up was associated with 6.5-fold (2.8-15.2) and first-degree FH(T1) with 2.2-fold (1.2-4.1) risk of diabetes. Only three subjects developed type 1 diabetes, and others had a non-insulin-dependent phenotype 1 year after diagnosis. GADA(+) and GADA(-) subjects did not clinically differ at baseline, but they were leaner and less insulin resistant after the diagnosis of diabetes., Conclusions: GADA positivity clusters in families with type 1 diabetes or latent autoimmune diabetes in adults. GADA positivity predicts diabetes independently of family history of diabetes, and this risk was further increased with high GADA concentrations.

Introduction: We have previously reported that outdoor levels of fine particles (PM(2.5), diameter <2.5 microm) are associated with urinary CC16, a marker for lung damage, in Helsinki, Finland, but not in the other two ULTRA cities (Amsterdam, The Netherlands, and Erfurt, Germany). We here evaluated whether PM(2.5) from specific source categories would be more strongly associated with CC16 than (total) PM(2.5). In addition, we compared two source apportionment methods., Methods: We collected biweekly spot urinary samples over 6 months from 121 subjects with coronary heart disease for the determination of CC16 (n = 1251). Principal component analysis (PCA) was used to apportion daily outdoor PM(2.5) between different source categories. In addition, the multilinear engine (ME) was used for the source apportionment in Amsterdam and Helsinki. We analyzed associations of source category-specific PM(2.5) and PM(2.5) absorbance, an indicator for combustion originating particles, with logarithmized values of CC16 adjusting for urinary creatinine using multivariate mixed models in STATA., Results: In the pooled analyses, CC16 was increased by 0.6% (standard error 0.3%) per 1 x 10(-5) m(-1) increase in the same-day levels of PM(2.5) absorbance. Source category-specific PM(2.5) concentrations were not consistently associated with the levels of CC16 in the three cities. Correlations between source category-specific PM(2.5) determined using either PCA or ME were in general high. Associations of source category-specific PM(2.5) with CC16 in Amsterdam and Helsinki were statistically less significant when ME was used., Conclusions: The present results suggest that PM(2.5) from combustion sources increases epithelial barrier permeability in lungs.

Objective: Two independent genome-wide association studies for type 2 diabetes in Japanese subjects have recently identified common variants in the KCNQ1 gene that are strongly associated with type 2 diabetes. Here we studied whether a common variant in KCNQ1 would influence BMI as well as insulin secretion and action and predict future type 2 diabetes in subjects from Sweden and Finland., Research Design and Methods: Risk of type 2 diabetes conferred by KCNQ1 rs2237895 was studied in 2,830 type 2 diabetic case subjects and 3,550 control subjects from Sweden (Malmö Case-Control) and prospectively in 16,061 individuals from the Malmö Preventive Project (MPP). Association between genotype and insulin secretion/action was assessed cross- sectionally in 3,298 nondiabetic subjects from the Prevalence, Prediction and Prevention of Diabetes (PPP)-Botnia Study and longitudinally in 2,328 nondiabetic subjects from the Botnia Prospective Study (BPS). KCNQ1 expression (n = 18) and glucose-stimulated insulin secretion (n = 19) were measured in human islets from nondiabetic cadaver donors., Results: The C-allele of KCNQ1 rs2237895 was associated with increased risk of type 2 diabetes in both the Malmö Case-Control (odds ratio 1.23 [95% CI 1.12-1.34]; P = 5.6 x 10(-6)) and the prospective (1.14 [1.06-1.22]; P = 4.8 x 10(-4)) studies. Furthermore, the C-allele was associated with decreased insulin secretion (corrected insulin response [CIR] P = 0.013; disposition index [DI] P = 0.013) in the PPP-Botnia Study and in the BPS at baseline (CIR P = 3.6 x 10(-4); DI P = 0.0058) and after follow-up (CIR P = 0.0018; DI P = 0.0030). C-allele carriers showed reduced glucose-stimulated insulin secretion in human islets (P = 2.5 x 10(-6))., Conclusions: A common variant in the KCNQ1 gene is associated with increased risk of future type 2 diabetes in Scandinavians, which partially can be explained by an effect on insulin secretion.

This study investigates commuter and driver exposure to aerosol particles in buses and trams in Helsinki, Finland. Particle number and PM(2.5) concentrations were determined in the cabin and the driver's compartment. In addition, the <2.5 microm black carbon concentration was measured in the driver's compartment and PM(2.5) was collected for elemental analysis in the cabin. The measurements were repeated on two generations of buses and trams including two measurement days in each vehicle type. Fine particle number and mass concentrations in the driver's compartments were only slightly increased compared to Helsinki background air. Daily average ratios of number and mass to the background varied in range 0.8-4.3 and 1.0-2.9, respectively, both being the highest in the older bus type. However, the drivers were exposed to elevated levels of black carbon, which some studies have addressed to be strongly correlated with adverse health effects. The daily average ratio of black carbon to the background varied between 2.4 and 11.4. Additionally, the black carbon concentration had spatial variation. The drivers were exposed to higher peak concentrations of black carbon in downtown area. Particle concentrations were smaller in the driver's compartment than in the cabin. The newer technology in the newer model of the tram and bus seemed to decrease driver exposure to aerosol particles.

This study's database comprised results of volatile organic compound (VOC) measurements from 176 office buildings. In 23 of the 176 buildings, formaldehyde measurements were also conducted. It was suspected that the buildings had indoor air problems, but a walk-through inspection did not reveal any clear, abnormal contaminant sources. The 50 most abundant VOCs and their concentrations in 520 air samples were analyzed. The irritation potency was estimated for 33 out of the 50 common VOCs and their mixtures, as well as for formaldehyde. This information was used to calculate the recommended indoor air levels (RILs) for the VOCs. The RILs were considerably higher than the measured mean indoor air concentrations in the buildings. However, the RIL for formaldehyde was exceeded in most of the 23 buildings studied. According to the evaluation of irritation potency, formaldehyde was a more likely cause of sensory irritation than the mixture of common nonreactive VOCs at the concentrations that occurred in the buildings without abnormal indoor sources. Furthermore, environmental symptoms of office workers were characterized in 20 office buildings (including the database of 176 office buildings) with the aid of an indoor air questionnaire. The most frequent symptoms related to the indoor environment were involved the upper respiratory tract. However, no relationship could be shown between the reported symptoms and the occurrence of VOC and formaldehyde concentrations in these buildings. Generally, the study results indicated that formaldehyde was the more likely agent causing sensory irritation than the mixture of the common nonreactive VOCs at the concentrations occurring in the buildings without abnormal indoor sources.

In Finland, the new limit values for maximal allowable heavy metal concentrations for materials used as an earth construction agent came into force in July 2006. These limit values are applied if ash is utilized, e.g. in roads, cycling paths, pavements, car parks, sport fields, etc. In this study we have determined the most important chemical and physical properties of the cyclone fly ash originating from the grate-fired boiler incinerating forest residues (i.e. wood chips, sawdust and bark) at a small municipal district heating plant (6 MW), Northern Finland. This study clearly shows that elements are enriched in cyclone fly ash, since the total element concentrations in the cyclone fly ash were within 0.2-10 times higher than those in the bottom ash. The total concentrations of Cd (25 mg kg(-1); d.w.), Zn (3630 mg kg(-1); d.w.), Ba (4260 mg kg(-1); d.w.) and Hg (1.7 mg kg(-1); d.w.) exceeded the limit values, and therefore the cyclone fly ash cannot be used as an earth construction agent. According to the leached amounts of Cr (38 mg kg(-1); d.w.), Zn (51 mg kg(-1); d.w.) and sulphate (50,000 mg kg(-1); d.w.), the cyclone fly ash is classified as a hazardous waste, and it has to be deposited in a hazardous waste landfill.

Objectives: Since there are few data on the effects of metalworking in populations representing a variety of metal companies or on dose-response relationships concerning metalworking, this study investigated the relationship between occupational exposures in machine shops and the occurrence of upper and lower respiratory symptoms, asthma, and chronic bronchitis., Methods: A cross-sectional study of 726 male machine workers and 84 male office workers from 64 companies was conducted in southern Finland. All of the participants filled out a questionnaire, and aerosol measurements were performed in 57 companies., Results: Exposure to metalworking fluids (MWF) showed a greater risk [odds ratio (OR)>or=2) for upper-airway symptoms, cough, breathlessness, and current asthma than exposures in office work did. Exposure to aerosol levels above the median (>or=0.17 mg/m3 in the general workshop air) was related to an increased risk (OR>or=2) of nasal and throat symptoms, cough, wheezing, breathlessness, chronic bronchitis, and current asthma. Machine workers with a job history of >or=15 years experienced increased throat symptoms, cough, and chronic bronchitis., Conclusions: This large study representing machine shops in southern Finland showed that machine workers experience increased nasal and throat symptoms, cough, wheezing, breathlessness, and asthma even in environments with exposure levels below the current occupational exposure limit for oil mists. The study suggests that improving machine shop environments could benefit the health of this workforce. It also suggests that it is time to consider reducing the current Finnish occupational exposure limit for oil mist or introducing the use of other health-relevant indicators of exposure.

Background: It is known that particulate air pollution affects cardiorespiratory health; however, it is unclear which particle size fractions and sources of particles are responsible for the health effects., Methods: Daily levels of nucleation (<0.03 microm), Aitken (0.03-0.1 microm), accumulation (0.1-0.29 microm), and coarse mode (2.5-10 microm) particles, particles with diameter <2.5 microm (PM2.5), and gaseous pollutants were measured at central outdoor measurement sites in Helsinki, Finland between 1998 and 2004. We determined the associations of particles with daily cardiorespiratory mortality and acute hospital admissions among the elderly (>or=65 years). For the analyses we used Poisson generalized additive models and for the source apportionment of PM2.5 we used the EPA positive matrix factorization method., Results: There was a suggestion of an association of hospital admissions for arrhythmia with Aitken mode particles and PM2.5 from traffic. Otherwise few associations were observed between various sizes and types of particles and either cardiovascular admissions or mortality. In contrast, most particle fractions had positive associations with admissions for pneumonia and asthma-chronic obstructive pulmonary disease (COPD). The strongest and most consistent associations were found for accumulation mode particles (3.1%; 95% confidence interval = 0.43-5.8 for pneumonia over the 5-day mean, and 3.8%; 1.3-6.3 for asthma-COPD at lag 0, for an interquartile increase in particles). We also found a positive association of respiratory mortality mainly with accumulation mode particles (5.1%; 1.2-9.0 at lag 0)., Conclusions: All particle fractions including Aitken, accumulation, and coarse mode had especially adverse respiratory health effects among the elderly. Overall associations were stronger for respiratory than for cardiovascular outcomes.

Background: Type 2 diabetes mellitus is thought to develop from an interaction between environmental and genetic factors. We examined whether clinical or genetic factors or both could predict progression to diabetes in two prospective cohorts., Methods: We genotyped 16 single-nucleotide polymorphisms (SNPs) and examined clinical factors in 16,061 Swedish and 2770 Finnish subjects. Type 2 diabetes developed in 2201 (11.7%) of these subjects during a median follow-up period of 23.5 years. We also studied the effect of genetic variants on changes in insulin secretion and action over time., Results: Strong predictors of diabetes were a family history of the disease, an increased body-mass index, elevated liver-enzyme levels, current smoking status, and reduced measures of insulin secretion and action. Variants in 11 genes (TCF7L2, PPARG, FTO, KCNJ11, NOTCH2, WFS1, CDKAL1, IGF2BP2, SLC30A8, JAZF1, and HHEX) were significantly associated with the risk of type 2 diabetes independently of clinical risk factors; variants in 8 of these genes were associated with impaired beta-cell function. The addition of specific genetic information to clinical factors slightly improved the prediction of future diabetes, with a slight increase in the area under the receiver-operating-characteristic curve from 0.74 to 0.75; however, the magnitude of the increase was significant (P=1.0x10(-4)). The discriminative power of genetic risk factors improved with an increasing duration of follow-up, whereas that of clinical risk factors decreased., Conclusions: As compared with clinical risk factors alone, common genetic variants associated with the risk of diabetes had a small effect on the ability to predict the future development of type 2 diabetes. The value of genetic factors increased with an increasing duration of follow-up., (2008 Massachusetts Medical Society)

Daily PM2.5 samples were repeatedly collected (1-8 times) in the homes of elderly nonsmoking individuals with coronary heart disease in Amsterdam, The Netherlands (33 individuals) and Helsinki, Finland (44 individuals). Sources of indoor PM2.5 were evaluated using a two-way multilinear engine model. Because the indoor elemental data lacked a traffic marker, separation of traffic related PM was attempted by combining the indoor data with fixed site outdoor data that also contained NO. Six outdoor sources, including long-range transport (LRT), urban mixture, oil combustion, traffic, sea-salt, and soil were identified, and three indoor sources were resolved: resuspension, potassium-rich and copper-rich sources. The average contribution of the indoor factors was 6% (1.1 microg m(-3)) and 22% (2.4 microg m(-3)) in Amsterdam and Helsinki, respectively. The highest longitudinal correlations between source-specific outdoor and indoor PM2.5 concentrations were found for LRT and urban mixture; the median R was above 0.6 for most sources. The longitudinal correlations were lower in Helsinki than in Amsterdam. Indoor-generated PM2.5 was not related to ambient concentrations. We conclude that using outdoor and indoor data together improved the source apportionment of indoor PM2.5. The results support the use of fixed site outdoor measurements in epidemiological time-series studies on outdoor air pollution.