Patterns of IgA Autoantibody Generation, Inflammatory Responses and Extracellular Matrix Metabolism in Patients with Alcohol Use Disorder.

Recent data have emphasized the role of inflammation and intestinal immunoglobulin A (IgA) responses in the pathogenesis of alcoholic liver disease (ALD). In order to further explore such associations, we compared IgA titers against antigens targeted to ethanol metabolites and tissue transglutaminase with pro- and anti-inflammatory mediators of inflammation, markers of liver status, transferrin protein desialylation and extracellular matrix metabolism in alcohol-dependent patients with or without liver disease and in healthy controls. Serum IgAs against protein adducts with acetaldehyde (HbAch-IgA), the first metabolite of ethanol, and tissue transglutaminase (tTG-IgA), desialylated transferrin (CDT), pro- and anti-inflammatory cytokines, markers of liver status (GT, ALP) and extracellular matrix metabolism (PIIINP, PINP, hyaluronic acid, ICTP and CTx) were measured in alcohol-dependent patients with (n = 83) or without (n = 105) liver disease and 88 healthy controls representing either moderate drinkers or abstainers. In ALD patients, both tTG-IgA and HbAch-IgA titers were significantly higher than those in the alcoholics without liver disease (p < 0.0005 for tTG-IgA, p = 0.006 for Hb-Ach-IgA) or in healthy controls (p < 0.0005 for both comparisons). The HbAch-IgA levels in the alcoholics without liver disease also exceeded those found in healthy controls (p = 0.0008). In ROC analyses, anti-tTG-antibodies showed an excellent discriminative value in differentiating between ALD patients and healthy controls (AUC = 0.95, p < 0.0005). Significant correlations emerged between tTG-IgAs and HbAch-IgAs (rs = 0.462, p < 0.0005), CDT (rs = 0.413, p < 0.0001), GT (rs = 0.487, p < 0.0001), alkaline phosphatase (rs = 0.466, p < 0.0001), serum markers of fibrogenesis: PIIINP (rs = 0.634, p < 0.0001), hyaluronic acid (rs = 0.575, p < 0.0001), ICTP (rs = 0.482, p < 0.0001), pro-inflammatory cytokines IL-6 (rs = 0.581, p < 0.0001), IL-8 (rs = 0.535, p < 0.0001) and TNF-α (rs = 0.591, p < 0.0001), whereas significant inverse correlations were observed with serum TGF-ß (rs = -0.366, p < 0.0001) and CTx, a marker of collagen degradation (rs = -0.495, p < 0.0001). The data indicate that the induction of IgA immune responses toward ethanol metabolites and tissue transglutaminaseis a characteristic feature of patients with AUD and coincides with the activation of inflammation, extracellular matrix remodeling and the generation of aberrantly glycosylated proteins. These processes appear to work in concert in the sequence of events leading from heavy drinking to ALD.

Associations between Liver Enzymes, Lifestyle Risk Factors and Pre-Existing Medical Conditions in a Population-Based Cross-Sectional Sample.

While alanine aminotransferase (ALT) and gamma-glutamyltransferase (GGT) enzymes are commonly used indicators of liver dysfunction recent studies have suggested that these may also serve as predictive biomarkers in the assessment of extrahepatic morbidity. In order to shed further light on the interactions between serum liver enzyme abnormalities, factors of lifestyle and health status we examined ALT and GGT activities in a population-based sample of 8743 adult individuals (4048 men, 4695 women from the National FINRISK 2002 Study, mean age 48.1 ± 13.1 years) with different levels of alcohol drinking, smoking, physical activity, body weight and the presence or absence of various pre-existing medical conditions. The assessments also included laboratory tests for inflammation, lipid status and fatty liver index (FLI), a proxy for fatty liver. The prevalence of ALT and GGT abnormalities were significantly influenced by alcohol use (ALT: p < 0.0005 for men; GGT: p <0.0005 for both genders), smoking (GGT: p <0.0005 for men, p =0.002 for women), adiposity (p < 0.0005 for all comparisons), physical inactivity (GGT: p <0.0005; ALT: p <0.0005 for men, p <0.05 for women) and coffee consumption (p <0.0005 for GGT in both genders; p <0.001 for ALT in men). The total sum of lifestyle risk factor scores (LRFS) influenced the occurrence of liver enzyme abnormalities in a rather linear manner. Significantly higher LRFS were observed in the subgroups of individuals with pre-existing medical conditions when compared with those having no morbidities (p <0.0005). In logistic regression analyses adjusted for the lifestyle factors, both ALT and GGT associated significantly with fatty liver, diabetes and hypertension. GGT levels also associated with coronary heart disease, angina pectoris, cardiac insufficiency, cerebrovascular disease, asthma and depression. Combinations of abnormal ALT and GGT activities significantly increased the odds for hypertension coinciding with abnormalities in biomarkers of inflammation, lipid status and FLI. The data indicates that ALT and GGT activities readily respond to unfavorable factors of lifestyle associating also with a wide array of pre-existing medical conditions. The data supports close links between both hepatic and extrahepatic morbidities and lifestyle risk factors and may open new insights on a more comprehensive use of liver enzymes in predictive algorithms for assessing mechanistically anchored disease conditions.

Blood Cell Responses Following Heavy Alcohol Consumption Coincide with Changes in Acute Phase Reactants of Inflammation, Indices of Hemolysis and Immune Responses to Ethanol Metabolites.

Aberrations in blood cells are common among heavy alcohol drinkers. In order to shed further light on such responses, we compared blood cell status with markers of hemolysis, mediators of inflammation and immune responses to ethanol metabolites in alcohol-dependent patients at the time of admission for detoxification and after abstinence. Blood cell counts, indices of hemolysis (LDH, haptoglobin, bilirubin), calprotectin (a marker of neutrophil activation), suPAR, CD163, pro- and anti-inflammatory cytokines and autoantibodies against protein adducts with acetaldehyde, the first metabolite of ethanol, were measured from alcohol-dependent patients (73 men, 26 women, mean age 43.8 ± 10.4 years) at baseline and after 8 ± 1 days of abstinence. The assessments also included information on the quantities of alcohol drinking and assays for biomarkers of alcohol consumption (CDT), liver function (AST, ALT, ALP, GGT) and acute phase reactants of inflammation. At baseline, the patients showed elevated values of CDT and biomarkers of liver status, which decreased significantly during abstinence. A significant decrease also occurred in LDH, bilirubin, CD163 and IgA and IgM antibodies against acetaldehyde adducts, whereas a significant increase was noted in blood leukocytes, platelets, MCV and suPAR levels. The changes in blood leukocytes correlated with those in serum calprotectin (p < 0.001), haptoglobin (p < 0.001), IL-6 (p < 0.02) and suPAR (p < 0.02). The changes in MCV correlated with those in LDH (p < 0.02), MCH (p < 0.01), bilirubin (p < 0.001) and anti-adduct IgG (p < 0.01). The data indicates that ethanol-induced changes in blood leukocytes are related with acute phase reactants of inflammation and release of neutrophil calprotectin. The studies also highlight the role of hemolysis and immune responses to ethanol metabolites underlying erythrocyte abnormalities in alcohol abusers.

Impact of Physical Activity on the Characteristics and Metabolic Consequences of Alcohol Consumption: A Cross-Sectional Population-Based Study.

Sedentary lifestyle and excessive alcohol drinking are major modifiable risk factors of health. In order to shed further light on the relationships between physical activity and health consequences of alcohol intake, we measured biomarkers of liver function, inflammation, lipid status and fatty liver index tests in a large population-based sample of individuals with different levels of physical activity, alcohol drinking and other lifestyle risk factors. The study included 21,050 adult participants (9940 men, 11,110 women) (mean age 48.2 ± 13.3 years) of the National FINRISK Study. Data on physical activity, alcohol drinking, smoking and body weight were recorded. The participants were classified to subgroups according to gender, levels of physical activity (sedentary, low, moderate, vigorous, extreme), alcohol drinking levels (abstainers, moderate drinkers, heavy drinkers) and patterns (regular or binge, types of beverages preferred in consumption). Serum liver enzymes (GGT, ALT), C-reactive protein (CRP) and lipid profiles were measured using standard laboratory techniques. Physical activity was linearly and inversely related with the amount of alcohol consumption, with the lowest alcohol drinking levels being observed in those with vigorous or extreme activity (p < 0.0005). Physically active individuals were less frequently binge-type drinkers, cigarette smokers or heavy coffee drinkers than those with sedentary activity (p < 0.0005 for linear trend in all comparisons). In the General Linear Model to assess the main and interaction effects of physical activity and alcohol consumption on biomarker status, as adjusted for anthropometric measures, smoking and coffee consumption, increasing levels of physical activity were found to be associated with more favorable findings on serum GGT (p < 0.0005), ALT (p < 0.0005 for men), cholesterol (p = 0.025 for men; p < 0.0005 for women), HDL-cholesterol (p < 0.0005 for men, p = 0.001 for women), LDL-cholesterol (p < 0.03 for men), triglycerides (p < 0.0005 for men, p < 0.03 for women), CRP (p < 0.0005 for men, p = 0.006 for women) and fatty liver index (p < 0.0005). The data support the view that regular moderate to vigorous physical activity may counteract adverse metabolic consequences of alcohol consumption on liver function, inflammation and lipid status. The role of physical activity should be further emphasized in interventions aimed at reducing health problems related to unfavorable risk factors of lifestyle.

Alcohol Drinking Patterns and Laboratory Indices of Health: Does Type of Alcohol Preferred Make a Difference?

Although excessive alcohol consumption is a highly prevalent public health problem the data on the associations between alcohol consumption and health outcomes in individuals preferring different types of alcoholic beverages has remained unclear. We examined the relationships between the amounts and patterns of drinking with the data on laboratory indices of liver function, lipid status and inflammation in a national population-based health survey (FINRISK). Data on health status, alcohol drinking, types of alcoholic beverages preferred, body weight, smoking, coffee consumption and physical activity were recorded from 22,432 subjects (10,626 men, 11,806 women), age range 25-74 years. The participants were divided to subgroups based on the amounts of regular alcohol intake (abstainers, moderate and heavy drinkers), patterns of drinking (binge or regular) and the type of alcoholic beverage preferred (wine, beer, cider or long drink, hard liquor or mixed). Regular drinking was found to be more typical in wine drinkers whereas the subjects preferring beer or hard liquor were more often binge-type drinkers and cigarette smokers. Alcohol use in all forms was associated with increased frequencies of abnormalities in the markers of liver function, lipid status and inflammation even at rather low levels of consumption. The highest rates of abnormalities occurred, however, in the subgroups of binge-type drinkers preferring beer or hard liquor. These results demonstrate that adverse consequences of alcohol occur even at moderate average drinking levels especially in individuals who engage in binge drinking and in those preferring beer or hard liquor. Further emphasis should be placed on such patterns of drinking in policies aimed at preventing alcohol-induced adverse health outcomes.

Elevated One-Hour Post-Load Glucose Is Independently Associated with Albuminuria: A Cross-Sectional Population Study.

The purpose of this study was to examine and compare the associations between albuminuria and fasting (FPG), 1 h post-load (1 h PG) and 2 h post-load plasma glucose (2 h PG) in an oral glucose tolerance test (OGTT). A total of 496 people free of known diabetes (mean age 72 years) participated in the examinations including the OGTT with plasma glucose measurements at 0, 1, and 2 h and levels of HbA1c. Albuminuria was determined by the urinary albumin-to-creatinine ratio and was defined as ≥3.0 mg/mmol. Compared with those without albuminuria, participants with albuminuria had significantly higher 1 h PG and 2 h PG levels, but not FPG or HbA1c levels. An elevated 1 h PG increased the estimated odds ratio of albuminuria more than three times in people with prediabetic 1 h PG (8.6-11.5 mmol/L: OR 3.60; 95% CI 1.70-7.64) and diabetic 1 h PG (≥11.6 mmol/L: OR 3.05; 95% CI 1.29-7.23). After adjusting for blood pressure and age, the association of elevated 1 h PG with albuminuria remained significant. Prediabetic or diabetic FPG, 2 h PG, or HbA1c did not have a statistically significant association with albuminuria. These findings suggest that 1 h PG seems to be the best glycemic parameter and is useful in recognizing persons with an elevated risk of early kidney disease due to hyperglycemia.

Long-term dysglycemia as a risk factor for faster cognitive decline during aging: A 12-year follow-up study.

AIMS: This longitudinal study evaluated associations between glucose metabolism and cognitive performance during a 12-year follow-up. METHODS: We included 714 subjects, which were followedfrom the age 55 to 70 years. Using oral glucose tolerance tests the population was classified as normoglycemic (NGT) and based on WHO diagnostic criteria for diabetes and prediabetes. Cognitive performance was assessed with a verbal fluency (category) test and wordlist learning tests of CERAD-nb, a verbal fluency (letter) test, and trail-making tests A and B. RESULTS: Compared to the normal group subjects with long-lasting prediabetes showed significantly greater decline (4.6 versus 2.9 words) on the verbal fluency (category) test (p = 0.041); subjects with long-lasting type 2 diabetes showed significantly greater decline (13 versus 6 s) on the trail making A test (p = 0.021) and on the wordlist learning test (3.3 versus 1.7 words) (p = 0.013); and a combined group of subjects with prediabetes or incident type 2 diabetes showed significantly greater cognitive decline (3.8 versus 2.9 words) in the verbal fluency (category) test (p = 0.039). CONCLUSION: Prediabetes was associated with cognitive decline during aging. This finding should be incorporated into prevention strategies, because both type 2 diabetes and dementia are increasing world-wide.

Comparison of serum calprotectin, a marker of neutrophil activation, and other mediators of inflammation in response to alcohol consumption.

AIMS: Previous studies have indicated that heavy alcohol intake stimulates inflammation and impairs the body's ability to regulate inflammation. The aim of this study was to compare changes in neutrophil calprotectin and a wide spectrum of other inflammatory mediators in response to heavy alcohol drinking. METHODS: Serum calprotectin (a marker of neutrophil activation), suPAR, CD163, and pro- (IL-6, IL-8, TNF-α) and anti-inflammatory (IL-10, TGF-ß) cytokines were measured from 61 alcohol-dependent subjects (46 men, 15 women, mean age 43.6 ± 11.0 years) at the time of admission for detoxification and after 8 ± 2 days of abstinence. These biomarkers were also measured from age- and sex-matched healthy controls representing abstainers or light drinkers. The clinical assessments included detailed clinical interviews on the amounts and patterns of alcohol consumption and assays for biomarkers of alcohol consumption (GGT, CDT, MCV, GGT-CDT) and liver function (AST, ALT). RESULTS: The subjects with alcohol use disorder showed significantly higher concentrations of serum calprotectin (p < 0.0005), suPAR (p < 0.01), CD163 (p < 0.01), IL-6 (p < 0.0005), IL-8 (p < 0.0005), TNF-α (p < 0.001), and IL-10 (p < 0.0005) than healthy controls. These inflammatory mediators, except for CD163, remained elevated after the 8 ± 2-day period of supervised abstinence, which resulted in significant decreases in the biomarkers of alcohol consumption and indices of liver status. The AUC (0.855) for serum calprotectin in differentiating between the heavy drinkers and healthy controls was equal or equivalent with those of the conventional biomarkers of alcohol consumption (GGT:0.835 or CDT:0.803). CONCLUSIONS: The data indicate that neutrophil calprotectin is released in response to heavy alcohol intake in a sensitive manner and may be associated with perpetuation of inflammation in patients with alcohol use disorder. Serum calprotectin may also prove to be a useful biomarker for inflammatory activity in alcohol-consuming patients.

Normal Gestational Weight Gain Protects From Large-for-Gestational-Age Birth Among Women With Obesity and Gestational Diabetes.

Background: Pre-pregnancy obesity, excess gestational weight gain (GWG), and gestational diabetes (GDM) increase fetal growth. Our aim was to assess whether normal GWG is associated with lower risk for a large-for-gestational-age (LGA; over the 90th percentile of birth weight for sex and gestational age) infant and lower birth weight standard deviation (SD) score in the presence of GDM and maternal obesity. Methods: This multicenter case-control study is part of the Finnish Gestational Diabetes (FinnGeDi) Study and includes singleton pregnancies of 1,055 women with GDM and 1,032 non-diabetic controls. Women were divided into 12 subgroups according to their GDM status, pre-pregnancy body mass index (BMI; kg/m2), and GWG. Non-diabetic women with normal BMI and normal GWG (according to Institute of Medicine recommendations) served as a reference group. Results: The prevalence of LGA birth was 12.2% among women with GDM and 6.2% among non-diabetic women (p < 0.001). Among all women, normal GWG was associated with lower odds of LGA [odds ratio (OR) 0.57, 95% CI: 0.41-0.78]. Among women with both obesity and GDM, the odds for giving birth to a LGA infant was 2.25-fold (95% CI: 1.04-4.85) among those with normal GWG and 7.63-fold (95% CI: 4.25-13.7) among those with excess GWG compared with the reference group. Compared with excess GWG, normal GWG was associated with 0.71 SD (95% CI: 0.47-0.97) lower birth weight SD score among women with GDM and obesity. Newborns of normal weight women with GDM and normal GWG had 0.28 SD (95% CI: 0.05-0.51) lower birth weight SD scores compared with their counterparts with excess GWG. In addition, in the group of normal weight non-diabetic women, normal GWG was associated with 0.46 SD (95% CI: 0.30-0.61) lower birth weight SD scores compared with excess GWG. Conclusion: GDM, obesity, and excess GWG are associated with higher risk for LGA infants. Interventions aiming at normal GWG have the potential to lower LGA rate and birth weight SD scores even when GDM and obesity are present.

One-hour post-load glucose improves the prediction of cardiovascular events in the OPERA study.

BACKGROUND: To estimate the ability of fasting, 1-h, and 2-h post-load glucose to predict cardiovascular outcomes. METHODS: We examined a population-based study consisting of 977 middle-aged subjects who underwent an oral glucose tolerance test with glucose values measured at 0, 60, and 120 min. Participants were followed up to 24 years, and cardiovascular outcomes were collected from national registers. Predictive abilities of fasting, 1-h, and 2-h glucose were evaluated alone and in the prediction models with traditional cardiovascular risk factors using Cox proportional hazard models, the likelihood-ratio test, Harrell's concordance index and integrated discrimination improvement. RESULTS: Cardiovascular endpoint occurred in 222 (22.7%) participants during a median follow-up of 19.8 years. In the prognostic models, 1-h glucose (HR 1.67, 95%CI 1.10-2.53), but not fasting or 2-h glucose, predicted cardiovascular events statistically significantly. In addition, when adding glucose parameters into the model including traditional cardiovascular risk factors, only 1-h glucose improved the predictive ability (LR-test p=.046). Finally, 1-h glucose found slightly over 50% more cardiovascular endpoints that were not recognized by fasting or 2-h glucose levels. CONCLUSIONS: Our findings support the earlier ones suggesting that 1-h glucose would be a better long-term predictor of cardiovascular morbidity and mortality than fasting or 2-h glucose.KEY MESSAGESIn addition to conventional CV risk factors,1-h but not fasting or 2-h post-load glucoses seems to be an independent predictor of cardiovascular events and seems to improve the predictive ability of the traditional cardiovascular risk model.Elevated 1-hpost-load glucose finds a large number (slightly over 50%)of cardiovascular endpoints that were not recognized by fasting or 2-h post-load glucose levels.One-hour glucose seems to be a better long-term predictor of cardiovascular morbidity and mortality than fasting or 2-h post-load glucose.

Accuracy of 1-Hour Plasma Glucose During the Oral Glucose Tolerance Test in Diagnosis of Type 2 Diabetes in Adults: A Meta-analysis.

OBJECTIVE: One-hour plasma glucose (1-h PG) during the oral glucose tolerance test (OGTT) is an accurate predictor of type 2 diabetes. We performed a meta-analysis to determine the optimum cutoff of 1-h PG for detection of type 2 diabetes using 2-h PG as the gold standard. RESEARCH DESIGN AND METHODS: We included 15 studies with 35,551 participants from multiple ethnic groups (53.8% Caucasian) and 2,705 newly detected cases of diabetes based on 2-h PG during OGTT. We excluded cases identified only by elevated fasting plasma glucose and/or HbA1c. We determined the optimal 1-h PG threshold and its accuracy at this cutoff for detection of diabetes (2-h PG ≥11.1 mmol/L) using a mixed linear effects regression model with different weights to sensitivity/specificity (2/3, 1/2, and 1/3). RESULTS: Three cutoffs of 1-h PG, at 10.6 mmol/L, 11.6 mmol/L, and 12.5 mmol/L, had sensitivities of 0.95, 0.92, and 0.87 and specificities of 0.86, 0.91, and 0.94 at weights 2/3, 1/2, and 1/3, respectively. The cutoff of 11.6 mmol/L (95% CI 10.6, 12.6) had a sensitivity of 0.92 (0.87, 0.95), specificity of 0.91 (0.88, 0.93), area under the curve 0.939 (95% confidence region for sensitivity at a given specificity: 0.904, 0.946), and a positive predictive value of 45%. CONCLUSIONS: The 1-h PG of ≥11.6 mmol/L during OGTT has a good sensitivity and specificity for detecting type 2 diabetes. Prescreening with a diabetes-specific risk calculator to identify high-risk individuals is suggested to decrease the proportion of false-positive cases. Studies including other ethnic groups and assessing complication risk are warranted.

Association of Self-Reported Polycystic Ovary Syndrome, Obesity, and Weight Gain From Adolescence to Adulthood With Hypertensive Disorders of Pregnancy: A Community-Based Approach.

The purpose of this prospective, population-based cohort study was to evaluate the roles of polycystic ovary syndrome (PCOS), obesity, weight gain, and hyperandrogenemia in the development of hypertensive disorders of pregnancy (HDP) through fertile age both in PCOS and in non-PCOS women. The study population-NFBC1966 (Northern Finland Birth Cohort 1966)-allowed a long-term follow-up of women from age 14 until 46 years who developed HDP (n=408) or did not (n=3373). HDP diagnosis was confirmed by combining hospital discharge records, data from Finnish Medical Birth Registers, and the questionnaire data at age 46. Women with self-reported PCOS (srPCOS; n=279), defined by both oligo-amenorrhea and hirsutism at age 31 or with PCOS diagnosis by age 46, were compared with women without reported PCOS (n=1577). Women with srPCOS had an increased HDP risk (odds ratio, 1.56 [95% CI, 1.03-2.37]), but the association disappeared after adjustment for body mass index. In women with srPCOS and HDP, body mass index increased from age 14 to 46 significantly more than in srPCOS women without HDP (median [interquartile range], 9.82 [6.23-14.6] and 7.21 [4.16-10.5] kg/m2, respectively; P<0.001). Also, in non-PCOS women, the increase was higher in women with (7.54 [5.32-11.62] kg/m2; P<0.001) than without HDP (6.33 [3.90-9.33] kg/m2; P<0.001). Increase in waist circumference between ages 31 and 46 years was associated with HDP but not with PCOS. Hyperandrogenemia at 31 or 46 years did not associate with HDP (1.44 [0.98-2.11]). In conclusion, obesity, especially abdominal obesity, and weight gain from adolescence to age 46, but not srPCOS or hyperandrogenemia, were associated with an increased risk of HDP.

Fear of childbirth after medical vs surgical abortion. Population-based register study from Finland.

INTRODUCTION: To evaluate the effect of method of induced abortion and other abortion-associated variables on the incidence of fear of childbirth in subsequent pregnancy. MATERIAL AND METHODS: This population-based register study cohort includes all nulliparous women with their first pregnancy ending in an induced abortion in 2000-2015 and subsequent pregnancy with live singleton delivery between 2000 and 2017 (n = 21 479). Data were derived from three national registers maintained by the Finnish Institute for Health and Welfare. We divided the study population in three cohorts: (a) medical and (b) surgical abortion during first trimester (≤84 days of gestation), and (c) medical abortion during second trimester (85-168 days of gestation). Primary outcome measures were the incidence of registry-identified fear of childbirth and cesarean delivery related to it. RESULTS: The overall incidence of fear of childbirth was 5.6% (n = 1209). Altogether, 19.2% (n = 4121) of women underwent cesarean delivery. The odds were elevated especially for elective cesarean delivery (odds ratio [OR] 9.30, 95% CI 7.95-10.88, P < .001) in women with fear of childbirth. In multivariable analysis, the odds for fear of childbirth (adjusted OR [aOR] 0.80, 95% CI 0.68-0.94) and cesarean delivery (aOR 0.66, 95% CI 0.84-0.90) were decreased in women with a history of first-trimester medical abortion compared with those with first-trimester surgical abortion. Second-trimester medical abortion had no effect on the odds for fear of childbirth (aOR 1.04, 95% CI 0.71-1.50). Maternal age of 30-39 years and interpregnancy interval over 2 years were additional risk factors for both fear of childbirth and cesarean delivery, but surgical evacuation of uterus after the abortion was not. CONCLUSIONS: One first- or second-trimester medical abortion does not increase the odds for fear of childbirth, and cesarean delivery related to it in subsequent pregnancy when compared with first-trimester surgical abortion. Older maternal age and longer interpregnancy interval emerged as risk factors for fear of childbirth.

Serum Calprotectin, a Marker of Neutrophil Activation, and Other Mediators of Inflammation in Response to Various Types of Extreme Physical Exertion in Healthy Volunteers.

PURPOSE: While extreme physical exertion is known to induce changes in the status of inflammation comparisons of the responses for various mediators of inflammation after acute bouts of high-intensity exercise have been limited. SUBJECTS AND METHODS: We examined the responses in serum levels of novel inflammatory proteins, calprotectin, suPAR, CD163, and pro- and anti-inflammatory cytokines in 12 physically active volunteers (10 men, 2 women, mean age 37±14 years) before and after completing various types of extreme physical exertion (marathon run, half-marathon run or 24-h cross-country skiing). For comparisons, the levels of the biomarkers were also measured at rest in 30 healthy controls (25 men, 5 women, mean age 42 ± 12 years) with low or sedentary activity. RESULTS: Extreme physical exertion induced significant increases in serum calprotectin (p < 0.0005), suPAR (p < 0.01), CD163 (p < 0.05), IL-6 (p < 0.0005), IL-8 (p < 0.01) and IL-10 (p < 0.0005) (pre- vs 3h-post-exercise). These responses were found to normalize within 48 hours. While the increases in blood leukocytes were of similar magnitude following the different types of exercise, markedly more pronounced responses occurred in serum TNF-α (p < 0.01), IL-8 (p < 0.01) and CD163 (p < 0.05) in those with more intense activity. In 3-h post-exercise samples significant correlations were observed between serum calprotectin and IL-6 (rs = 0.720, p < 0.01), IL-10 (rs = 0.615, p < 0.05), TNF-α (rs = 0.594, p < 0.05), suPAR (rs = 0.587, p < 0.05) and blood leukocytes (rs = 0.762, p < 0.01). CONCLUSION: The present results suggest distinct exercise-intensity dependent changes in mediators of inflammation (including calprotectin, suPAR and CD163) following extreme physical exertion. Our findings indicate that there is a major reversible impact of high-intensity physical exertion on the status of inflammation.

Combined effects of lifestyle risk factors on fatty liver index.

BACKGROUND: Factors of lifestyle may have a major impact on liver-related morbidity and mortality. We examined independent and joint effects of lifestyle risk factors on fatty liver index (FLI), a biomarker of hepatic steatosis, in a population-based cross-sectional national health survey. METHODS: The study included 12,368 participants (5784 men, 6584 women) aged 25-74 years. Quantitative estimates of alcohol use, smoking, adiposity and physical activity were used to establish a total score of risk factors, with higher scores indicating an unhealthier lifestyle. FLI was calculated based on an algorithm including body mass index, waist circumference, serum gamma-glutamyltransferase and triglycerides. RESULTS: The occurrence of FLI ≥ 60% indicating fatty liver increased from 2.4% in men with zero risk factors to 81.9% in those with a total risk score of 7-8 (p <  0.0005 for linear trend) and in women from 0 to 73.5% (p <  0.0005). The most striking individual impacts on the likelihood for FLI above 60% were observed for physical inactivity (p <  0.0005 for both genders) and alcohol consumption (p <  0.0005 for men). Interestingly, coffee consumption was also found to increase with increasing risk factor scores (p <  0.0005 for linear trend in both genders). CONCLUSIONS: The data indicates that unfavorable combinations of lifestyle risk factors lead to a high likelihood of hepatic steatosis. Use of FLI as a diagnostic tool may benefit the assessment of interventions aimed at maintaining a healthy lifestyle and prevention of liver-related morbidity.

Evaluating the 1-h post-load glucose level to predict future type 2 diabetes.

AIMS: To evaluate the predictive ability of 2-h post-load glucose level in addition to fasting and 1-h glucose levels in predicting the risk of type 2 diabetes. METHODS: We examined a prospective population-based cohort study of 654 subjects without type 2 diabetes at baseline. All subjects underwent an oral glucose tolerance test (OGTT), with measurement of glucose at 0, 60, and 120 min at baseline, and after 12 years in a follow-up survey. We evaluated the predictive properties of fasting, 1- and 2-h post-load glucose levels by comparing the areas under the receiver-operating characteristic (ROC) curve. RESULTS: We found that 2-h glucose concentration in the prediction model with fasting and 1-h glucose levels did not significantly increase the predictability of type 2 diabetes compared to a model only including fasting and 1-h glucose levels (AUC 0.83 vs. AUC 0.82, respectively; p = 0.23). The area under the ROC curve was the largest for 1-h glucose level (AUC 0.81), compared to fasting (AUC 0.71; p < 0.01) and 2-h glucose levels (AUC 0.72; p = 0.01). CONCLUSIONS: Adding 2-h glucose to the model with fasting and 1-h glucose levels did not improve the predictability of new onset type 2 diabetes.

Induced abortion and future use of IVF treatment; A nationwide register study.

OBJECTIVE: In this nationwide study we assessed the use and factors associated with future in vitro fertilization (IVF) treatment after induced abortion. MATERIALS AND METHODS: The study population was collected by means of record linkage between Finnish national registers. All women who underwent induced abortion between 2000 and 2009 in Finland were identified through the Register of Induced Abortions (n = 88 522). The study group consisted of women who underwent induced abortion and subsequently had an IVF treatment (n = 379); the comparison group were all women who had a spontaneous pregnancy and delivery 12-24 months after the index abortion (n = 7434). Demographic characteristics at the time of index abortion, and factors associated with the abortion (gestational age at abortion, indication and method of abortion, complications after abortion) were compared between the study groups. Logistic regression was used to assess whether some of the demographic characteristics or abortion associated factors increased the use of IVF treatment in the future. RESULTS: The proportion of women with IVF treatment after induced abortion in the whole cohort was 0.4%. Women needing IVF treatment were older, of a higher socioeconomic status, and had fewer previous induced abortions and deliveries compared to women in the comparison group. No statistically significant differences were observed in the gestational age (≤ 12 weeks or >12 weeks of gestation) at abortion, method or complications of abortion. In multivariable analysis higher age increased, and history of previous deliveries or one or two abortions decreased the use of IVF. CONCLUSIONS: Infertility necessitating the use of IVF treatment after induced abortion is uncommon. The factors associated with use of IVF after abortion are those generally recognized as risk factors of infertility. Abortion-related outcomes are not associated with an increased need of future IVF-treatment.

Impacts of unfavourable lifestyle factors on biomarkers of liver function, inflammation and lipid status.

BACKGROUND: Adopting a healthy lifestyle is associated with prolonged life expectancy. The main modifiable lifestyle-related risk factors are hazardous alcohol drinking, smoking, excess body weight and lack of physical activity. Our aim was to estimate the impact of unfavourable lifestyle factors on abnormalities in laboratory tests reflecting liver status, inflammation and lipid metabolism in a population-based cross-sectional study. METHODS: The study included 22,273 participants (10,561 men, 11,712 women) aged 25-74 years from the National FINRISK Study. Data on alcohol use, smoking, body weight, and physical activity were recorded from structured interviews. The risk scores for the various life style factors were established on a 0-8 scale and used to stratify the population in classes to allow estimates of their joint effects. Serum liver enzymes (GGT, ALT), C-reactive protein (CRP) and lipid profiles were measured using standard laboratory techniques. RESULTS: Consistent dose-response relationships were observed between the number of unfavourable risk factors and serum levels of GGT, ALT, CRP, cholesterol, HDL, LDL and triglycerides (p < 0.0005 for linear trend in all comparisons). When compared with those with zero risk factors, the multivariable-adjusted odds ratios (ORs) for abnormalities in all biomarkers were significantly higher in those with a sum of risk score two or more. The most striking increases in ORs in the group with the highest numbers of risk factors were observed among men in serum GGT: 26.6 (12.4-57.0), ALT: 40.3 (5.3-307.8), CRP: 16.2 (7.8-33.7) and serum triglycerides: 14.4 (8.6-24.0). CONCLUSIONS: The data support the view that the presence of unfavourable life style risk factors is associated with distinct abnormalities in laboratory tests for liver function, inflammation and lipid status. Such biomarkers may prove to be of value in the assessment of interventions aimed at reducing unfavourable risk factors and in helping individuals in long-term maintenance of lifestyle modifications.

Liver enzymes in alcohol consumers with or without binge drinking.

BACKGROUND: While alcohol use is linked with a wide variety of health problems, the question of whether differences in drinking patterns could yield different outcomes has remained unclear. PATIENTS AND METHODS: We measured liver enzymes (ALT, GGT) from alcohol consumers with or without binge drinking from a population-based sample in Finland, where binge-type drinking is common. Data on alcohol use, diet, body weight, lifestyle (smoking, coffee consumption, physical activity), and health status were collected from 19225 subjects (9492 men, 9733 women), aged 25-74 years. The participants were subsequently classified to subgroups, both according to the frequencies of binge drinking and the amounts of regular alcohol intake (low-, medium-, and high-risk drinking). RESULTS: The quantity of regular alcohol use was roughly linearly related with GGT and ALT activities. ANOVA analyses of the trends according to the frequency of binge drinking showed a significant GGT increase in both men (p < 0.0005) and women (p < 0.0005), and a significant increase of ALT in men (p < 0.0005). In those with low-risk overall consumption, markedly higher GGT (p < 0.0005) and ALT (p < 0.0005) occurred in those with binge drinking more than once a month, compared with those with no such occasions. Binge drinking occurring ≤1/month also resulted in higher GGT (p < 0.0005) and ALT (p < 0.05) activities. CONCLUSIONS: These results emphasize possible adverse consequences of binge drinking on hepatic function even in those with low-risk overall consumption. The pattern of drinking should be more systematically implicated in clinical recommendations for drinking reduction.