Attribution of diabetes to the development of severe liver disease in the general population

Background and Aims: Diabetes is associated with advanced liver disease and predicts mortality regardless of the primary aetiology of the liver disease. Even a family history of diabetes has been linked to advanced liver fibrosis in non-alcoholic fatty liver disease (NAFLD). However, the fraction of liver-related outcomes in the general population that are attributable to diabetes remains unclear. Methods: The population attributable fraction (PAF) of diabetes for liver disease as a time-dependent exposure was estimated in the Finnish FINRISK study (n = 28 787) and the British Whitehall II study (n = 7855). We also assessed the predictive ability of a family history of diabetes for liver-related outcomes. Incident diabetes data were from drug purchase/reimbursement and healthcare registries (FINRISK) or follow-up examinations (Whitehall II). Incident severe liver outcomes were identified through linkage with national healthcare registries. Results: Diabetes was associated with a two-fold risk of liver-related outcomes in both the FINRISK (HR, 1.92; p <.001) and Whitehall II (HR, 2.37; p <.001) cohorts, and this remained significant after adjusting for multiple confounders. PAF analyses demonstrated that diabetes explained 12–14% of the risk for severe liver-related outcomes after 10 and 20 years of follow-up. Also, maternal diabetes increased the risk of liver-related outcomes in the FINRISK (HR, 1.43; p =.044) and Whitehall II (HR, 2.04; p =.051) cohorts. Conclusion: Approximately 12%–14% of severe liver-related outcomes are attributable to diabetes at the population level. The association between maternal diabetes and liver disease might suggest a mitochondrial genetic mechanism

Small spatial variability in methane emission measured from a wet patterned boreal bog

We measured methane fluxes of a patterned bog situated in Siikaneva in southern Finland from six different plant community types in three growing seasons (2012-2014) using the static chamber method with chamber exposure of 35 min. A mixed-effects model was applied to quantify the effect of the controlling factors on the methane flux. The plant community types differed from each other in their water level, species composition, total leaf area (LAI(TOT)) and leaf area of aerenchymatous plant species (LAI(AER)). Methane emissions ranged from -309 to 1254 mg m(-2) d(-1). Although methane fluxes increased with increasing peat temperature, LAI(TOT) and LAI(AER), they had no correlation with water table or with plant community type. The only exception was higher fluxes from hummocks and high lawns than from high hummocks and bare peat surfaces in 2013 and from bare peat surfaces than from high hummocks in 2014. Chamber fluxes upscaled to ecosystem level for the peak season were of the same magnitude as the fluxes measured with the eddy covariance (EC) technique. In 2012 and in August 2014 there was a good agreement between the two methods; in 2013 and in July 2014, the chamber fluxes were higher than the EC fluxes. Net fluxes to soil, indicating higher methane oxidation than production, were detected every year and in all community types. Our results underline the importance of both LAI(AER) and LAI(TOT) in controlling methane fluxes and indicate the need for automatized chambers to reliably capture localized events to support the more robust EC method.Peer reviewe

Effect of maternal chronic disease on obstetric complications in twin pregnancies in a United States cohort

To evaluate the effect of maternal chronic disease on obstetric complications among twin pregnancies

Role of inflammation markers in the prediction of weight gain and development of obesity in adults – a prospective study

BACKGROUND AND AIMS There is a growing body of literature confirming the association between inflammation and obesity. Recent research suggests that inflammation may play a role in weight gain. The aim of the study was to analyse whether serum inflammatory markers predict weight gain or development of obesity in a prospective study design. METHODS AND RESULTS The baseline study (DILGOM 2007) consists of a population-based sample of 5024 Finnish men and women aged 25-75 years, of whom 3735 participated in the follow-up study in 2014. Baseline data collection included a questionnaire on health behaviour, physical examinations and blood samples including serum high-sensitivity C-Reactive Protein (hs-CRP), Interleukin-1 receptor antagonist (IL-1Ra), Interleukin-6 (IL-6), Tumor Necrosis Factor Alpha (TNF-alpha) and high molecular weight adiponectin (HMW adiponectin). Indicators of obesity were weight, body mass index (BMI), waist circumference and body fat percentage (% body fat). At baseline hs-CRP, IL-1Ra, IL-6, TNF-alpha and HMW adiponectin associated strongly (pPeer reviewe

An overview of the European health examination survey pilot joint action

Background Health Examination Surveys (HESs) can provide essential information on the health and health determinants of a population, which is not available from other data sources. Nevertheless, only some European countries have systems of national HESs. A study conducted in 2006-2008 concluded that it is feasible to organize national HESs using standardized measurement procedures in nearly all EU countries. The feasibility study also outlined a structure for a European Health Examination Survey (EHES), which is a collaboration to organize standardized HESs in countries across Europe. To facilitate setting up national surveys and to gain experience in applying the EHES methods in different cultures, EHES Joint Action (2010-2011) planned and piloted standardized HESs in the working age population in 12 countries. This included countries with earlier national HESs and countries which were planning their first national HES. The core measurements included in all surveys were weight, height, waist circumference and blood pressure, and blood samples were taken to measure lipid profiles and glucose or glycated haemoglobin (HbA1c). These are modifiable determinants of major chronic diseases not identified in health interview surveys. There was a questionnaire to complement the data on the examination measurements. Methods Evaluation of the pilot surveys was based on review of national manuals and evaluation reports of survey organizers; observations and discussions of survey procedures during site visits and training seminars; and other communication with the survey organizers. Results Despite unavoidable differences in the ways HESs are organized in the various countries, high quality and comparability of the data seems achievable. The biggest challenge in each country was obtaining high participation rate. Most of the pilot countries are now ready to start their full-size national HES, and six of them have already started. Conclusions The EHES Pilot Project has set up the structure for obtaining comparable high quality health indicators on health and important modifiable risk factors of major non-communicable diseases from the European countries. The European Union is now in a key position to make this structure sustainable. The EHES core survey can be expanded to cover other measurements

Elevated serum alpha-1 antitrypsin is a major component of GlycA-associated risk for future morbidity and mortality

Background GlycA is a nuclear magnetic resonance (NMR) spectroscopy biomarker that predicts risk of disease from myriad causes. It is heterogeneous; arising from five circulating glycoproteins with dynamic concentrations: alpha-1 antitrypsin (AAT), alpha-1-acid glycoprotein (AGP), haptoglobin (HP), transferrin (TF), and alpha-1-antichymotrypsin (AACT). The contributions of each glycoprotein to the disease and mortality risks predicted by GlycA remain unknown. Methods We trained imputation models for AAT, AGP, HP, and TF from NMR metabolite measurements in 626 adults from a population cohort with matched NMR and immunoassay data. Levels of AAT, AGP, and HP were estimated in 11,861 adults from two population cohorts with eight years of follow-up, then each biomarker was tested for association with all common endpoints. Whole blood gene expression data was used to identify cellular processes associated with elevated AAT. Results Accurate imputation models were obtained for AAT, AGP, and HP but not for TF. While AGP had the strongest correlation with GlycA, our analysis revealed variation in imputed AAT levels was the most predictive of morbidity and mortality for the widest range of diseases over the eight year follow-up period, including heart failure (meta-analysis hazard ratio = 1.60 per standard deviation increase of AAT, P-value = 1×10−10), influenza and pneumonia (HR = 1.37, P = 6×10−10), and liver diseases (HR = 1.81, P = 1×10−6). Transcriptional analyses revealed association of elevated AAT with diverse inflammatory immune pathways. Conclusions This study clarifies the molecular underpinnings of the GlycA biomarker’s associated disease risk, and indicates a previously unrecognised association between elevated AAT and severe disease onset and mortality.Peer reviewe

Joint effects of alcohol use, smoking and body mass index as an explanation for the alcohol harm paradox : causal mediation analysis of eight cohort studies

Background and aims Lower socio-economic status (SES) is associated with higher alcohol-related harm despite lower levels of alcohol use. Differential vulnerability due to joint effects of behavioural risk factors is one potential explanation for this 'alcohol harm paradox'. We analysed to what extent socio-economic inequalities in alcohol-mortality are mediated by alcohol, smoking and body mass index (BMI), and their joint effects with each other and with SES. DesignCohort study of eight health examination surveys (1978-2007) linked to mortality data. Setting Finland.ParticipantsA total of 53 632 Finnish residents aged 25+ years.MeasurementsThe primary outcome was alcohol-attributable mortality. We used income as an indicator of SES. We assessed the joint effects between income and mediators (alcohol use, smoking and BMI) and between the mediators, adjusting for socio-demographic indicators. We used causal mediation analysis to calculate the total, direct, indirect and mediated interactive effects using Aalen's additive hazards models. Findings During 1 085 839 person-years of follow-up, we identified 865 alcohol-attributable deaths. We found joint effects for income and alcohol use and income and smoking, resulting in 46.8 and 11.4 extra deaths due to the interaction per 10 000 person-years. No interactions were observed for income and BMI or between alcohol and other mediators. The lowest compared with the highest income quintile was associated with 5.5 additional alcohol deaths per 10 000 person-years (95% confidence interval = 3.7, 7.3) after adjusting for confounders. The proportion mediated by alcohol use was negative (-69.3%), consistent with the alcohol harm paradox. The proportion mediated by smoking and BMI and their additive interactions with income explained 18.1% of the total effect of income on alcohol-attributable mortality. Conclusions People of lower socio-economic status appear to be more vulnerable to the effects of alcohol use and smoking on alcohol-attributable mortality. Behavioural risk factors and their joint effects with income may explain part of the alcohol harm paradox.Peer reviewe

Substantial fat mass loss reduces low-grade inflammation and induces positive alteration in cardiometabolic factors in normal-weight individuals

( )The accumulation of fat, especially in visceral sites, is a significant risk factor for several chronic diseases with altered cardiometabolic homeostasis. We studied how intensive long-term weight loss and subsequent weight regain affect physiological changes, by longitudinally interrogating the lipid metabolism and white blood cell transcriptomic markers in healthy, normal-weight individuals. The current study examined 42 healthy, young (age: 27.5 +/- 4.0 years), normal-weight (body mass index, BMI: 23.4 +/- 1.7 kg/m(2)) female athletes, of which 25 belong to the weight loss and regain group (diet group), and 17 to the control group. Participants were evaluated, and fasting blood samples were drawn at three time points: at baseline (PRE); at the end of the weight loss period (MID: 21.1 +/- 3.1 weeks after PRE); and at the end of the weight regain period (POST: 18.4 +/- 2.9 weeks after MID). Following the weight loss period, the diet group experienced a similar to 73% reduction (similar to 0.69 kg) in visceral fat mass (false discovery rate, FDR <2.0 x 10(-16)), accompanied by anti-atherogenic effects on transcriptomic markers, decreased low-grade inflammation (e.g., as alpha(1)-acid glycoprotein (FDR = 3.08 x 10(-13)) and hs-CRP (FDR = 2.44 x 10(-3))), and an increase in functionally important anti-atherogenic high-density lipoprotein -associated metabolites (FDR <0.05). This occurred even though these values were already at favorable levels in these participants, who follow a fitness-lifestyle compared to age- and BMI-matched females from the general population (n = 58). Following the weight regain period, most of the observed beneficial changes in visceral fat mass, and meta bolomic and transcriptomic profiles dissipated. Overall, the beneficial anti-atherogenic effects of weight loss can be observed even in previously healthy, normal-weight individuals.Peer reviewe

Childhood socioeconomic status and lifetime health behaviors : The Young Finns Study

Background: Differences in health behaviors partly explain the socioeconomic gap in cardiovascular health. We prospectively examined the association between childhood socioeconomic status (SES) and lifestyle factors in adulthood, and the difference of lifestyle factors according to childhood SES in multiple time points from childhood to adulthood. Methods and results: The sample comprised 3453 participants aged 3-18 years at baseline (1980) from the longitudinal Young Finns Study. The participants were followed up for 31 years (N = 1675-1930). SES in childhood was characterized as reported annual family income and classified on an 8-point scale. Diet, smoking, alcohol intake and physical activity were used as adult and life course lifestyle factors. Higher childhood SES predicted a healthier diet in adulthood in terms of lower consumption of meat (beta +/- SE -3.6 +/- 0.99, p <0.001), higher consumption of fish (1.1 +/- 0.5, p = 0.04) and higher diet score (0.14 +/- 0.044, p = 0.01). Childhood SES was also directly associated with physical activity index (0.059 +/- 0.023, p = 0.009) and inversely with the risk of being a smoker (RR 0.90 95%CI 0.85-0.95, p <0.001) and the amount of pack years (-0.47 +/- 0.18, p = 0.01). Life course level of smoking was significantly higher and physical activity index lower among those below the median childhood SES when compared with those above the median SES. Conclusions: These results show that childhood SES associates with several lifestyle factors 31 years later in adulthood. Therefore, attention could be paid to lifestyle behaviors of children of low SES families to promote cardiovascular health. (C) 2017 Elsevier B.V. All rights reserved.Peer reviewe

Application of non-HDL cholesterol for population-based cardiovascular risk stratification: results from the Multinational Cardiovascular Risk Consortium.

BACKGROUND: The relevance of blood lipid concentrations to long-term incidence of cardiovascular disease and the relevance of lipid-lowering therapy for cardiovascular disease outcomes is unclear. We investigated the cardiovascular disease risk associated with the full spectrum of bloodstream non-HDL cholesterol concentrations. We also created an easy-to-use tool to estimate the long-term probabilities for a cardiovascular disease event associated with non-HDL cholesterol and modelled its risk reduction by lipid-lowering treatment. METHODS: In this risk-evaluation and risk-modelling study, we used Multinational Cardiovascular Risk Consortium data from 19 countries across Europe, Australia, and North America. Individuals without prevalent cardiovascular disease at baseline and with robust available data on cardiovascular disease outcomes were included. The primary composite endpoint of atherosclerotic cardiovascular disease was defined as the occurrence of the coronary heart disease event or ischaemic stroke. Sex-specific multivariable analyses were computed using non-HDL cholesterol categories according to the European guideline thresholds, adjusted for age, sex, cohort, and classical modifiable cardiovascular risk factors. In a derivation and validation design, we created a tool to estimate the probabilities of a cardiovascular disease event by the age of 75 years, dependent on age, sex, and risk factors, and the associated modelled risk reduction, assuming a 50% reduction of non-HDL cholesterol. FINDINGS: Of the 524 444 individuals in the 44 cohorts in the Consortium database, we identified 398 846 individuals belonging to 38 cohorts (184 055 [48·7%] women; median age 51·0 years [IQR 40·7-59·7]). 199 415 individuals were included in the derivation cohort (91 786 [48·4%] women) and 199 431 (92 269 [49·1%] women) in the validation cohort. During a maximum follow-up of 43·6 years (median 13·5 years, IQR 7·0-20·1), 54 542 cardiovascular endpoints occurred. Incidence curve analyses showed progressively higher 30-year cardiovascular disease event-rates for increasing non-HDL cholesterol categories (from 7·7% for non-HDL cholesterol <2·6 mmol/L to 33·7% for ≥5·7 mmol/L in women and from 12·8% to 43·6% in men; p<0·0001). Multivariable adjusted Cox models with non-HDL cholesterol lower than 2·6 mmol/L as reference showed an increase in the association between non-HDL cholesterol concentration and cardiovascular disease for both sexes (from hazard ratio 1·1, 95% CI 1·0-1·3 for non-HDL cholesterol 2·6 to <3·7 mmol/L to 1·9, 1·6-2·2 for ≥5·7 mmol/L in women and from 1·1, 1·0-1·3 to 2·3, 2·0-2·5 in men). The derived tool allowed the estimation of cardiovascular disease event probabilities specific for non-HDL cholesterol with high comparability between the derivation and validation cohorts as reflected by smooth calibration curves analyses and a root mean square error lower than 1% for the estimated probabilities of cardiovascular disease. A 50% reduction of non-HDL cholesterol concentrations was associated with reduced risk of a cardiovascular disease event by the age of 75 years, and this risk reduction was greater the earlier cholesterol concentrations were reduced. INTERPRETATION: Non-HDL cholesterol concentrations in blood are strongly associated with long-term risk of atherosclerotic cardiovascular disease. We provide a simple tool for individual long-term risk assessment and the potential benefit of early lipid-lowering intervention. These data could be useful for physician-patient communication about primary prevention strategies. FUNDING: EU Framework Programme, UK Medical Research Council, and German Centre for Cardiovascular Research