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Background: Observed associations of high-protein diets with changes in insulin resistance are inconclusive.Objectives: We aimed to assess associations of changes in both reported and estimated protein (PRep; PEst) and energy intake (EIRep; EIEst) with changes in HOMA-IR, glycated hemoglobin (HbA1c), and BMI (in kg/m2), in 1822 decreasing to 833 adults (week 156) with overweight and prediabetes, during the 3-y PREVIEW (PREVention of diabetes through lifestyle intervention and population studies In Europe and around the World) study on weight-loss maintenance. Eating behavior and measurement errors (MEs) of dietary intake were assessed. Thus, observational post hoc analyses were applied.Methods: Associations of changes in EIEst, EIRep, PEst, and PRep with changes in HOMA-IR, HbA1c, and BMI were determined by linear mixed-model analysis in 2 arms [high-protein-low-glycemic-index (GI) diet and moderate-protein-moderate-GI diet] of the PREVIEW study. EIEst was derived from energy requirement: total energy expenditure = basal metabolic rate × physical activity level; PEst from urinary nitrogen, and urea. MEs were calculated as [(EIEst - EIRep)/EIEst] × 100% and [(PRep - PEst)/PEst] × 100%. Eating behavior was determined using the Three Factor Eating Questionnaire, examining cognitive dietary restraint, disinhibition, and hunger.Results: Increases in PEst and PRep and decreases in EIEst and EIRep were associated with decreases in BMI, but not independently with decreases in HOMA-IR. Increases in PEst and PRep were associated with decreases in HbA1c. PRep and EIRep showed larger changes and stronger associations than PEst and EIEst. Mean ± SD MEs of EIRep and PRep were 38% ± 9% and 14% ± 4%, respectively; ME changes in EIRep and En% PRep were positively associated with changes in BMI and cognitive dietary restraint and inversely with disinhibition and hunger.Conclusions: During weight-loss maintenance in adults with prediabetes, increase in protein intake and decrease in energy intake were not associated with decrease in HOMA-IR beyond associations with decrease in BMI. Increases in PEst and PRep were associated with decrease in HbA1c.This trial was registered at clinicaltrials.gov as NCT01777893.

Aims/hypothesis Lifestyle interventions are the first-line treatment option for body weight and cardiometabolic health management. However, whether age groups or women and men respond differently to lifestyle interventions is under debate. We aimed to examine age- and sex-specific effects of a low-energy diet (LED) followed by a long-term lifestyle intervention on body weight, body composition and cardiometabolic health markers in adults with prediabetes (i.e. impaired fasting glucose and/or impaired glucose tolerance). Methods This observational study used longitudinal data from 2223 overweight participants with prediabetes in the multicentre diabetes prevention study PREVIEW. The participants underwent a LED-induced rapid weight loss (WL) period followed by a 3 year lifestyle-based weight maintenance (WM) intervention. Changes in outcomes of interest in prespecified age (younger: 25–45 years; middle-aged: 46–54 years; older: 55–70 years) or sex (women and men) groups were compared. Results In total, 783 younger, 319 middle-aged and 1121 older adults and 1503 women and 720 men were included in the analysis. In the available case and complete case analyses, multivariable-adjusted linear mixed models showed that younger and older adults had similar weight loss after the LED, whereas older adults had greater sustained weight loss after the WM intervention (adjusted difference for older vs younger adults −1.25% [95% CI −1.92, −0.58], ppp1c and systolic blood pressure after the WM intervention than middle-aged adults. In the complete case analysis, the above-mentioned differences between middle-aged and older adults disappeared, but the direction of the effect size did not change. After the WL period, compared with men, women had less weight loss (adjusted difference for women vs men 1.78% [95% CI 1.12, 2.43], p1c, LDL-cholesterol and diastolic blood pressure. After the WM intervention, women had greater fat-free mass and bone mass loss and smaller improvements in HbA1c and LDL-cholesterol, while they had greater improvements in fasting glucose, triacylglycerol (adjusted difference for women vs men −0.08 mmol/l [−0.11, −0.04], p Conclusions/interpretation Older adults benefited less from a lifestyle intervention in relation to body composition and cardiometabolic health markers than younger adults, despite greater sustained weight loss. Women benefited less from a LED followed by a lifestyle intervention in relation to body weight and body composition than men. Future interventions targeting older adults or women should take prevention of fat-free mass and bone mass loss into consideration. Clinical trial registration number ClinicalTrials.gov NCT01777893. Graphical abstract

Low-energy diet replacement is an effective tool to induce large and rapid weight loss and improve metabolic health, but in the long-term individuals often experience significant weight regain. Little is known about the role of animal-based foods in weight maintenance and metabolic health. We aimed to examine longitudinal associations of animal-based foods with weight maintenance and glycaemic and cardiometabolic risk factors. We also modelled replacement of processed meat with other high-protein foods.In this secondary analysis, longitudinal data were analysed from 688 adults (26-70 years) with overweight and prediabetes after 8-week low-energy diet-induced weight loss (≥8% of initial body weight) in a 3-year, multi-centre, diabetes prevention study (PREVIEW). Animal-based food consumption, including unprocessed red meat, processed red meat, poultry, dairy products, fish and seafood, and eggs, was repeatedly assessed using 4-day food records. Multi-adjusted linear mixed models and isoenergetic substitution models were used to examine the potential associations.The available-case analysis showed that each 10-g increment in processed meat, but not total meat, unprocessed red meat, poultry, dairy products, or eggs, was positively associated with weight regain (0.17 kg⋅yearHigher intake of processed meat, but not total or unprocessed red meat, poultry, dairy products, or eggs may be associated with greater weight regain and more adverse glycaemic and cardiometabolic risk factors. Replacing processed meat with a wide variety of high-protein foods, including unprocessed red meat, poultry, dairy products, fish, eggs, grains, and nuts, could improve weight maintenance and metabolic health after rapid weight loss. This study was registered as ClinicalTrials.gov, NCT01777893.

Background & Aims Non-alcoholic fatty liver disease (NAFLD) increases morbidity and mortality. However, patients in biopsy-based cohorts are highly selected and the absolute risks of liver- and non-liver outcomes in NAFLD in population remains undefined. We analysed both liver-related and non-liver-related outcomes in Finnish population cohorts of NAFLD. Methods We included 10 993 individuals (6707 men, mean age 53.3 +/- 12.6 years) with NAFLD (fatty liver index >= 60) from the Finnish population-based FINRISK and Health 2000 studies. Liver fibrosis was assessed by the dAAR score, and genetic risk by a recent polygenic risk score (PRS-5). Incident liver-related outcomes, cardiovascular disease (CVD), cancer and chronic kidney disease (CKD) were identified through linkage with national registries. Results Mean follow-up was 12.1 years (1128 069 person-years). The crude incidence rate of liver-related outcomes in NAFLD was 0.97/1000 person-years. The cumulative incidence increased with age, being respectively 2.4% and 1.5% at 20 years in men and women aged 60 years at baseline, while the relative risks for CVD and cancer were 9-16 times higher. The risk of CKD exceeded that of liver outcomes at a baseline age around 50 years. 20-year cumulative incidence of liver-related outcomes was 4.3% in the high, and 1.5% in the low PRS-5 group. The dAAR score associated with liver outcomes, but not with extra-hepatic outcomes. Conclusion The absolute risk of liver-related outcomes in NAFLD is low, with much higher risk of CVD and cancer, emphasizing the need for more individualized and holistic risk-stratification in NAFLD.

OBJECTIVE To examine longitudinal and dose-dependent associations of dietary glycemic index (GI), glycemic load (GL), and fiber with body weight and glycemic status during 3-year weight loss maintenance (WLM) in adults at high risk of type 2 diabetes. RESEARCH DESIGN AND METHODS In this secondary analysis we used pooled data from the PREVention of diabetes through lifestyle Intervention and population studies in Europe and around the World (PREVIEW) randomized controlled trial, which was designed to test the effects of four diet and physical activity interventions. A total of 1,279 participants with overweight or obesity (age 25–70 years and BMI ≥25 kg ⋅ m−2) and prediabetes at baseline were included. We used multiadjusted linear mixed models with repeated measurements to assess longitudinal and dose-dependent associations by merging the participants into one group and dividing them into GI, GL, and fiber tertiles, respectively. RESULTS In the available-case analysis, each 10-unit increment in GI was associated with a greater regain of weight (0.46 kg ⋅ year−1; 95% CI 0.23, 0.68; P < 0.001) and increase in HbA1c. Each 20-unit increment in GL was associated with a greater regain of weight (0.49 kg ⋅ year−1; 0.24, 0.75; P < 0.001) and increase in HbA1c. The associations of GI and GL with HbA1c were independent of weight change. Compared with those in the lowest tertiles, participants in the highest GI and GL tertiles had significantly greater weight regain and increases in HbA1c. Fiber was inversely associated with increases in waist circumference, but the associations with weight regain and glycemic status did not remain robust in different analyses. CONCLUSIONS Dietary GI and GL were positively associated with weight regain and deteriorating glycemic status. Stronger evidence on the role of fiber is needed.

Aims: The PREVIEW lifestyle intervention study (ClinicalTrials.gov Identifier: NCT01777893) is, to date, the largest, multinational study concerning prevention of type-2 diabetes. We hypothesized that the initial, fixed low-energy diet (LED) would induce different metabolic outcomes in men vs women.Materials and methods: All participants followed a LED (3.4 MJ/810 kcal/daily) for 8 weeks (Cambridge Weight Plan). Participants were recruited from 8 sites in Europe, Australia and New Zealand. Those eligible for inclusion were overweight (BMI ≥ 25 kg/m2 ) individuals with pre-diabetes according to ADA-criteria. Outcomes of interest included changes in insulin resistance, fat mass (FM), fat-free mass (FFM) and metabolic syndrome Z-score.Results: In total, 2224 individuals (1504 women, 720 men) attended the baseline visit and 2020 (90.8%) completed the follow-up visit. Following the LED, weight loss was 16% greater in men than in women (11.8% vs 10.3%, respectively) but improvements in insulin resistance were similar. HOMA-IR decreased by 1.50 ± 0.15 in men and by 1.35 ± 0.15 in women (ns). After adjusting for differences in weight loss, men had larger reductions in metabolic syndrome Z-score, C-peptide, FM and heart rate, while women had larger reductions in HDL cholesterol, FFM, hip circumference and pulse pressure. Following the LED, 35% of participants of both genders had reverted to normo-glycaemia.Conclusions: An 8-week LED induced different effects in women than in men. These findings are clinically important and suggest gender-specific changes after weight loss. It is important to investigate whether the greater decreases in FFM, hip circumference and HDL cholesterol in women after rapid weight loss compromise weight loss maintenance and future cardiovascular health.

Psychosis is associated with low-grade inflammation as measured by high-sensitivity C-reactive protein (hs-CRP), a risk factor for cardiovascular events and mortality in the general population. We investigated the relationship between hs-CRP and anthropometric and metabolic changes in first-episode psychosis (FEP) during the first treatment year. We recruited 95 FEP patients and 62 controls, and measured longitudinal changes in hs-CRP, weight, waist circumference, insulin resistance, and lipids. We used linear mixed models to analyze the longitudinal relationship between hs-CRP and clinical, anthropometric and metabolic measures. At baseline, patients with FEP had higher levels of insulin resistance, total and low-density lipoprotein cholesterol, apolipoprotein B, and triglycerides. Baseline weight, waist circumference, hs-CRP, fasting glucose, and high-density lipoprotein cholesterol were similar between patients and controls. Marked increases in anthropometric measures and hs-CRP were observed in FEP during the 12-month follow-up. However, glucose and lipid parameters did not change significantly. In the mixed models, waist circumference and female sex were significant predictors of hs-CRP levels in FEP. Prevention of the early development of abdominal obesity in FEP is crucial, as abdominal obesity is accompanied by chronic low-grade inflammation, which increases further the cardiovascular risk in this vulnerable population.

OBJECTIVE Stress, sleep, eating behavior, and physical activity are associated with weight change and insulin resistance (IR). The aim of this analysis was the assessment of the overall and sex-specific associations of psychobehavioral variables throughout the 3-year PREVIEW intervention using the homeostatic model assessment of IR (HOMA-IR), BMI, and length of time in the study. RESEARCH DESIGN AND METHODS Associations of psychobehavioral variables, including stress, mood, eating behavior, physical activity (PA), and sleep, with BMI, HOMA-IR, and time spent in the study were assessed in 2,184 participants with prediabetes and overweight/obesity (n = 706 men; n = 1,478 women) during a 3-year lifestyle intervention using linear mixed modeling and general linear modeling. The study was a randomized multicenter trial using a 2 × 2 diet-by-PA design. RESULTS Overall, cognitive restraint and PA increased during the intervention compared with baseline, whereas BMI, HOMA-IR, disinhibition, hunger, and sleepiness decreased (all P < 0.05). Cognitive restraint and PA were negatively, whereas disinhibition, hunger, stress, and total mood disturbance were positively, associated with both BMI and HOMA-IR. Sleep duration, low sleep quality, total mood disturbance, disinhibition, and hunger scores were positively associated with HOMA-IR for men only. Participants who dropped out at 6 months had higher stress and total mood disturbance scores at baseline and throughout their time spent in the study compared with study completers. CONCLUSIONS Eating behavior and PA, control of stress, mood disturbance, and sleep characteristics were associated with BMI, HOMA-IR, and time spent in the study, with different effects in men and women during the PREVIEW lifestyle intervention study.

The aspartate-to-alanine aminotransferase ratio (AAR) is associated with liver fibrosis, but its predictive performance is suboptimal. We hypothesized that the association between AAR and liver disease depends on absolute transaminase levels and developed and validated a model to predict liver-related outcomes in the general population. A Cox regression model based on age, AAR, and alanine aminotransferase (ALT) level (dynamic AAR [dAAR]) using restricted cubic splines was developed in Finnish population-based health-examination surveys (FINRISK, 2002-2012; n = 18,067) with linked registry data for incident liver-related hospitalizations, hepatocellular carcinoma, or liver death. The model was externally validated for liver-related outcomes in a Swedish population cohort (Swedish Apolipoprotein Mortality Risk [AMORIS] subcohort; n = 126,941) and for predicting outcomes and/or prevalent fibrosis/cirrhosis in biopsied patients with nonalcoholic fatty liver disease (NAFLD), chronic hepatitis C, or alcohol-related liver disease (ALD). The dynamic AAR model predicted liver-related outcomes both overall (optimism-corrected C-statistic, 0.81) and in subgroup analyses of the FINRISK cohort and identified persons with >10% risk for liver-related outcomes within 10 years. In independent cohorts, the C-statistic for predicting liver-related outcomes up to a 10-year follow-up was 0.72 in the AMORIS cohort, 0.81 in NAFLD, and 0.75 in ALD. Area-under-the-curve (AUC) for detecting prevalent cirrhosis was 0.80-0.83 in NAFLD, 0.80 in hepatitis C, but only 0.71 in ALD. In ALD, model performance improved when using aspartate aminotransferase instead of ALT in the model (C-statistic, 0.84 for outcome; AUC, 0.82 for prevalent cirrhosis). Conclusion: A dAAR score provides prospective predictions for the risk of incident severe liver outcomes in the general population and helps detect advanced liver fibrosis/cirrhosis. The dAAR score could potentially be used for screening the unselected general population and as a trigger for further liver evaluations. Funding Agencies|Mary and Georg Ehrnrooth Foundation; Medicinska Understodsforeningen Liv och Halsa; Finska Lakaresallskapet; Finnish Foundation for Cardiovascular Research; National Institute of Diabetes, Digestive and Kidney DiseasesUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) [K08DK115883]; Innovation Fund Denmark; European UnionEuropean Commission [668031]; Novo Nordisk FoundationNovo Nordisk Foundation [NNF15OC0016692]; Region of Southern Denmark [K2017--4579]; Center for Innovative Medicine [20180889]

BackgroundReliable data on clinical biomarkers are necessary in order to assess the health risks of populations and especially in assessing long-term trends related to disease incidence.MethodsTen European laboratories participated in a two-phase quality control exercise of total cholesterol (TC) and high-density lipoprotein-cholesterol (HDL-C) analysis. The European Health Examination Survey Reference Laboratory prepared plasma batches for analysis, and provided target values for them. Two criteria were set for the precision and the systematic error (bias). Three plasma samples were analysed in duplicate on separate days (n=12).ResultsIn Round 1, all laboratories met the acceptable criterion (3%) for precision of TC. The mean bias of all laboratories was 0.99% (95% CI 0.03% to 1.95%). Six laboratories measured samples from Round 2. Five laboratories met the goal criterion of 3%; one failed to meet the acceptable criterion of 5%. The mean bias for HDL-C of the three batches of six laboratories was within goal limits (±5% from target) and that of all 10 within acceptable (±10%). The mean bias of all laboratories was 1.1% (95% CI −0.18 to 2.32). In Round 2 four laboratories met the goal criterion and one the acceptable criterion.ConclusionThe quality control exercise demonstrated that although the majority of the laboratories met the strict criteria for systematic error for TC and HDL-C, standardisation of methods is still needed to improve the accuracy of biomarker measurements of laboratories engaged in population health surveys. A protocol is recommended for obtaining reliable and comparable biomarker data between countries.

We examined the association between plasma 25-hydroxyvitamin D [25(OH)D] concentration and islet autoimmunity (IA) and whether vitamin D gene polymorphisms modify the effect of 25(OH)D on IA risk. We followed 8,676 children at increased genetic risk of type 1 diabetes at six sites in the U.S. and Europe. We defined IA as positivity for at least one autoantibody (GADA, IAA, or IA-2A) on two or more visits. We conducted a risk set sampled nested case-control study of 376 IA case subjects and up to 3 control subjects per case subject. 25(OH)D concentration was measured on all samples prior to, and including, the first IA positive visit. Nine polymorphisms in VDR, CYP24A, CYP27B1, GC, and RXRA were analyzed as effect modifiers of 25(OH)D. Adjusting for HLA-DR-DQ and ancestry, higher childhood 25(OH)D was associated with lower IA risk (odds ratio = 0.93 for a 5 nmol/L difference; 95% CI 0.89, 0.97). Moreover, this association was modified by VDR rs7975232 (interaction P = 0.0072), where increased childhood 25(OH)D was associated with a decreasing IA risk based upon number of minor alleles: 0 (1.00; 0.93, 1.07), 1 (0.92; 0.89, 0.96), and 2 (0.86; 0.80, 0.92). Vitamin D and VDR may have a combined role in IA development in children at increased genetic risk for type 1 diabetes.

Background: Vitamin D insufficiency might be associated with biased T-cell responses resulting in inflammatory conditions such as atopy and asthma. Little is known about the role of vitamin D in low-grade systemic inflammation and airway hyperresponsiveness (AHR) in young children. Objective: To evaluate whether vitamin D insufficiency and increased serum high-sensitivity C-reactive protein (hs-CRP) are linked to AHR in symptomatic infants. Methods: Seventy-nine infants with recurrent or persistent lower respiratory tract symptoms underwent comprehensive lung function testing and a bronchial methacholine challenge test. In addition, skin prick tests were performed and serum 25-hydroxyvitamin D (S-25-OHD), hs-CRP, total immunoglobulin E, and blood eosinophil levels were determined. Results: S-25-OHD was lowest in infants with blood eosinophilia and AHR (n = 10) compared with those with eosinophilia only (n = 6) or AHR only (n = 50) or those with neither (n = 13; P = .035). Moreover, vitamin D insufficiency (S-25-OHD

Background Systematic monitoring of cardiovascular disease (CVD) risk factors started in eastern Finland already in the 1970s as part of the North Karelia Project. Later on risk factor monitoring was extended to other parts of the country. Purpose In this study we report the trends of main CVD risk factors in Finland from 1992 to 2017. Methods Study population consists of a population-based random sample of 31 402 men and women aged 25–64 years who participated in the FINRISK Studies from 1992 to 2012, and in the FinHealth Study in 2017. Data collection was done every five years. Participation rate decreased from 76% in 1992 to 56% in 2017. Study protocol included self-reported questionnaire data on smoking and other health behavior, measurements of height, weight and blood pressure, and venous blood sample for laboratory analysis. Blood pressure was measured two times, and the average of the measurements was calculated, total serum cholesterol was analyzed using enzymatic method, and LDL cholesterol was calculated using Friedewald formula. Results Smoking prevalence, mean blood pressure and total and LDL cholesterol levels declined markedly during the 25 year follow up but BMI, waist circumference and prevalence of obesity increased (table). CVD risk factor change from 1992 to 2017 Risk factor Men 1992 Men 2017 p value Women 1992 Women 2017 p value Smoking (%) 36.7 20.6 Conclusions The levels of main traditional CVD risk factors have markedly decreased among the Finnish population during the last 25 years but in the same time, obesity has become a major public health challenge.

The insulin-like growth factor (IGF) axis may be involved in the development of type 2 diabetes. We examined the associations of IGF-I and IGF binding proteins (IGFBP)-1 and -3 with diabetes risk and evaluated macronutrient intakes related to the observed associations. In a nested case–control study of the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study of Finnish male smokers aged 50–69 years, the IGF variables were measured from baseline serum samples for a random sample of 310 men with diabetes diagnosed during a 12-year follow-up and for 310 controls matched by age, recruitment day and intervention group. Diet at baseline was assessed using a validated FFQ. The associations of IGF proteins with diabetes risk were estimated using conditional logistic regression and the associations with macronutrient intakes using linear regression. IGF-I and IGFBP-3 were not associated with the incidence of diabetes. Higher IGFBP-1 was associated with lower diabetes risk in an unadjusted crude model (OR 0·25; 95 % CI 0·15, 0·42 in the highest quartile compared with the lowest), but not after adjustment for BMI (corresponding OR 0·76; 95 % CI 0·41, 1·40). Intakes of carbohydrates, plant protein and milk protein associated positively and intake of meat protein and fat negatively with IGFBP-1 (P

Context: Maternal gestational diabetes mellitus (GDM) and prepregnancy overweight/obesity [body mass index (BMI) ≥25 kg/m²] might adversely affect offspring cardiometabolic health. Objective: To assess the associations between maternal GDM and prepregnancy overweight/obesity with adult offspring cardiometabolic risk factors. Design: Longitudinal cohort study (ESTER Maternal Pregnancy Disorders Study and the Arvo Ylppö Longitudinal Study). Setting: Province of Uusimaa and Northern Finland. Participants: At a mean age of 24.1 ± 1.3 years, we classified offspring as offspring of mothers with GDM regardless of the prepregnancy BMI (OGDM; n = 193); normoglycemic mothers with prepregnancy overweight/obesity (ONO; n = 157); and normoglycemic mothers with prepregnancy BMI

SummaryBackground The results of longitudinal studies on the association between thyroid function and blood pressure (BP) are divided. This study aimed to investigate this association in cross-sectional and longitudinal settings in a nationwide, random sample representative of the Finnish adult population aged 30 and over. Methods The study sample was randomly drawn from the population register. A total of 5655 participants were included in the baseline analyses and 3453 in the 11-year prospective analyses. The associations between baseline TSH and (i) BP and BP change over time; and (ii) prevalent and incident hypertension were assessed using linear and logistic models, adjusted for age, gender, smoking and body mass index. Results A positive association (β ± standard error) was observed between TSH and diastolic (0·36 ± 0·12, P = 0·003) but not systolic BP (0·16 ± 0·21, P = 0·45) at baseline. TSH was negatively associated with 11-year BP change in men (systolic: −0·92 ± 0·41, P = 0·03; diastolic: −0·66 ± 0·26, P = 0·01) but not in women (P ≥ 0·09 for systolic and diastolic BP change). Participants in the highest TSH tertile within the TSH reference interval (0·4–3·4 mU/L), as compared with the lowest, had increased odds of prevalent (odds ratio 1·22, 95% confidence interval 1·05–1·43, P = 0·01) but not incident hypertension (odds ratio 0·93, 95% confidence interval 0·73–1·19, P = 0·58). Conclusions A modest association was found between increasing TSH and prevalent but not incident hypertension. TSH was inversely associated with BP change in men in our study. These findings contest an independent role of thyroid function at normal to near-normal levels in the pathogenesis of hypertension.

First-episode psychosis (FEP) is associated with weight gain during the first year of treatment, and risk of abdominal obesity is particularly increased. To identify early risk markers of weight gain and abdominal obesity, we investigated baseline metabolic differences in 60 FEP patients and 27 controls, and longitudinal changes during the first year of treatment in patients. Compared to controls at baseline, patients had higher low-density lipoprotein, triglyceride and apolipoprotein B levels, and lower levels of high-density lipoprotein and apolipoprotein A-I but no difference in body mass index or waist circumference. At 12-month follow-up, 60.6% of patients were overweight or obese and 58.8% had abdominal obesity. No significant increase during follow-up was seen in markers of glucose and lipid metabolism or blood pressure, but increase in C-reactive protein between baseline and 12-month follow-up was statistically significant. Weight increase was predicted by baseline insulin resistance and olanzapine use, while increase in waist circumference was predicted by baseline insulin resistance only. In conclusion, insulin resistance may be an early marker of increased vulnerability to weight gain and abdominal obesity in young adults with FEP. Olanzapine should be avoided as a first-line treatment in FEP due to the substantial weight increase it causes. In addition, the increase in the prevalence of overweight and abdominal obesity was accompanied by the emergence of low-grade systemic inflammation.

Introduction Periodontitis is associated with increased serum lipopolysaccharide (LPS) activity, which may be one mechanism linking periodontitis with the risk of cardiovascular diseases. As LPS-carrying proteins including lipoproteins modify LPS-activity, we investigated the determinants of serum LPS-neutralizing capacity (LPS-NC) in ischemic stroke. The association of LPS-NC and Aggregatibacter actinomycetemcomitans, a major microbial biomarker in periodontitis, was also investigated. Materials and methods The assay to measure LPS-NC was set up by spiking serum samples with E. coli LPS. The LPS-NC, LPS-binding protein (LBP), soluble CD14 (sCD14), lipoprotein profiles, apo(lipoprotein) A-I, apoB, and phospholipid transfer protein (PLTP) activity, were determined in 98 ischemic stroke patients and 100 age- and sex-matched controls. Serum and saliva immune response to A. actinomycetemcomitans, its concentration in saliva, and serotype-distribution were examined. Results LPS-NC values ranged between 51–83% in the whole population. Although several of the LPS-NC determinants differed significantly between cases and controls (PLTP, sCD14, apoA-I, HDL-cholesterol), the levels did not (p = 0.056). The main determinants of LPS-NC were i) triglycerides (β = -0.68, p

Adults who were born preterm with a very low birth weight have higher blood pressure and impaired glucose regulation later in life compared with those born at term. We investigated cardiometabolic risk factors in young adults who were born at any degree of prematurity in the Preterm Birth and Early Life Programming of Adult Health and Disease (ESTER) Study, a population-based cohort study of individuals born in 1985–1989 in Northern Finland. In 2009–2011, 3 groups underwent clinical examination: 134 participants born at less than 34 gestational weeks (early preterm), 242 born at 34–36 weeks (late preterm), and 344 born at 37 weeks or later (controls). Compared with controls, adults who were born preterm had higher body fat percentages (after adjustment for sex, age, and cohort (1985–1986 or 1987–1989), for those born early preterm, difference = 6.2%, 95% confidence interval (CI): 0.4, 13.2; for those born late preterm, difference = 8.0%, 95% CI: 2.4, 13.8), waist circumferences, blood pressure (for those born early preterm, difference = 3.0 mm Hg, 95% CI: 0.9, 5.1; for those born late preterm, difference = 1.7, 95% CI: −0.1, 3.4), plasma uric acid levels (for those born early preterm, difference = 20.1%, 95% CI: 7.9, 32.3; for those born late preterm, difference = 20.2%, 95% CI: 10.7, 30.5), alanine aminotransferase levels, and aspartate transaminase levels. They were also more likely to have metabolic syndrome (for those born early preterm, odds ratio = 3.7, 95% CI: 1.6, 8.2; for those born late preterm, odds ratio = 2.5, 95% CI: 1.2, 5.3). Elevated levels of conventional and emerging risk factors suggest a higher risk of cardiometabolic disease later in life. These risk factors are also present in the large group of adults born late preterm.

Elite-class athletes have longer life expectancy and lower risk for chronic noncommunicable diseases possibly because of physically active and healthier lifestyle. In this study, we assessed former male Finnish elite-class athletes' (n = 392) and their matched controls' (n = 207) body composition, and risk for the metabolic syndrome (MS) and nonalcoholic fatty liver disease (NAFLD) in later life. Compared with the controls, the former athletes had lower body fat percentage (24.8% vs 26.0%, P = 0.021), lower risk for MS [odds ratio (OR) 0.57, 95% confidence interval (CI) 0.40-0.81], and NAFLD (OR 0.61, 95% CI 0.42-0.88). High volume of current leisure-time physical activity (LTPA) was associated with lower body fat percentage (P for trend < 0.001). When current volume of LTPA increased 1 MET h/week, the risk of MS and NAFLD decreased (OR 0.99, 95% CI 0.98-0.99 and OR 0.97, 95% CI 0.96-0.98, respectively). Although a career as an elite-class athlete during young adulthood may help to protect from developing metabolic syndrome, present exercise levels and volume of LTPA seem equally important as well.

Type-2 diabetes (T2D) is one of the fastest growing chronic diseases worldwide. The PREVIEW project has been initiated to find the most effective lifestyle (diet and physical activity) for the prevention of T2D, in overweight and obese participants with increased risk for T2D. The study is a three-year multi-centre, 2 × 2 factorial, randomised controlled trial. The impact of a high-protein, low-glycaemic index (GI) vs. moderate protein, moderate-GI diet in combination with moderate or high-intensity physical activity on the incidence of T2D and the related clinical end-points are investigated. The intervention started with a two-month weight reduction using a low-calorie diet, followed by a randomised 34-month weight maintenance phase comprising four treatment arms. Eight intervention centres are participating (Denmark, Finland, United Kingdom, The Netherlands, Spain, Bulgaria, Australia, and New Zealand). Data from blood specimens, urine, faeces, questionnaires, diaries, body composition assessments, and accelerometers are collected at months 0, 2, 6, 12, 18, 24, and 36. In total, 2326 adults were recruited. The mean age was 51.6 (SD 11.6) years, 67% were women. PREVIEW is, to date, the largest multinational trial to address the prevention of T2D in pre-diabetic adults through diet and exercise intervention. Participants will complete the final intervention in March, 2018.

Background Previous data on the association of thyroid function with total mortality, cardiovascular disease (CVD) outcomes and sudden cardiac death (SCD) are conflicting or limited. We investigated associations of TSH with these outcomes in a nationwide population-based prospective cohort study. Methods We examined 5211 participants representative of the Finnish population aged ≥30 years in 2000–2001 and followed them for a median of 13.2 years. Using Cox proportional hazards regression models adjusted for baseline age, gender, smoking, diabetes, systolic blood pressure and total and high-density lipoprotein cholesterol, we assessed the associations of continuous baseline TSH and TSH categories (low [ 3.4 mU/L]) with incident total mortality, SCD, coronary heart disease events, stroke, CVD, major adverse cardiac events and atrial fibrillation. Results High TSH at baseline was related to a greater risk of total mortality (HR 1.34, 95% CI 1.02–1.76) and SCD (HR 2.28, 95% CI 1.13–4.60) compared with TSH within the reference range. High TSH was not associated with the other outcomes (P≥0.51) whereas low TSH was not associated with any of the outcomes (P≥0.09). TSH at baseline over the full range did not have a linear relation with any of the outcomes (P≥0.17). TSH showed a U-shaped association with total mortality after a restricted cubic spline transformation (P=0.01). Conclusions Thyroid function abnormalities could be linked with higher risks of total mortality and SCD. Large-scale randomised studies are needed for evidence-based recommendations regarding treatment of mild thyroid failure. This article is protected by copyright. All rights reserved.

Measurement of serum 25-hydroxyvitamin D [25(OH)D] is considered the best indicator of vitamin D status. Two minor vitamin D metabolites are common interferences encountered in 25(OH)D assays. The first is 3-epi-25-hydroxyvitamin D3 [3-epi-25(OH)D3], which if not chromatographically resolved from 25-hydroxyvitamin D3 [25(OH)D3], can overestimate 25(OH)D concentrations. The second is 24R,25-dihydroxyvitamin D3 [24R,25(OH)2D3], which can cross-react with the antibodies in 25(OH)D immunoassays. Our aim was to develop an LCâ MS/MS method capable of detecting both 3-epi-25(OH)D3 and 24R,25(OH)2D3 in serum without the use of a derivatization agent. We report an isotope dilution LCâ MS/MS method, with electrospray ionization in the positive mode, that can simultaneously detect 24R,25(OH)2D3, 25(OH)D3, 3-epi-25(OH)D3, and 25-hydroxyvitamin D2. The method employs a cost-effective liquidâ liquid extraction using only 150 μL of sera and a total run time of 10 min. Method performance was assessed by using quality controls made from pooled sera as an alternative to sera spiked with analytes. Biobanked samples, originally analyzed by chemiluminescent microparticle immunoassay (CMIA), were re-analyzed with this method to determine the contribution of 24R,25(OH)2D3 cross-reactivity to 25(OH)D measurement bias. The CMIA over-estimation of 25(OH)D measurements relative to LCâ MS/MS was found to depend on both 25(OH)D and 24R,25(OH)2D3 concentrations.

From whole organisms to individual cells, responses to environmental conditions are influenced by genetic makeup, where the effect of genetic variation on a trait depends on the environmental context. RNA-sequencing quantifies gene expression as a molecular trait, and is capable of capturing both genetic and environmental effects. In this study, we explore opportunities of using allele-specific expression (ASE) to discovercisacting genotype-environment interactions (GxE) - genetic effects on gene expression that depend on an environmental condition. Treating 17 common, clinical traits as approximations of the cellular environment of 267 skeletal muscle biopsies, we identify 10 candidate interaction quantitative trait loci (iQTLs) across 6 traits (12 unique gene-environment trait pairs; 10% FDR per trait) including sex, systolic blood pressure, and low-density lipoprotein cholesterol. Although using ASE is in principle a promising approach to detect GxE effects, replication of such signals can be challenging as validation requires harmonization of environmental traits across cohorts and a sufficient sampling of heterozygotes for a transcribed SNP. Comprehensive discovery and replication will require large human transcriptome datasets, or the integration of multiple transcribed SNPs, coupled with standardized clinical phenotyping.

BACKGROUND Scant data exist on the longitudinal association between thyroid function and lipid concentrations. We investigated associations of TSH and lipid concentrations cross-sectionally and longitudinally in a nationwide population sample. METHODS A total of 5205 randomly sampled participants representative of Finns aged ≥30 years were examined in 2000-2001 and included in cross-sectional analyses. A total of 2486 were re-examined 11 years later and included in longitudinal analyses. With linear regression models adjusted for age, gender, smoking and body mass index, we assessed the associations of baseline TSH and TSH categories (low, reference range and high) with total, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol; apolipoprotein A1 and B; and triglycerides at baseline and follow-up. RESULTS At baseline, higher TSH associated with higher total cholesterol (β = 0·025, standard error [SE] = 0·007, P < 0·001), LDL cholesterol (β = 0·020, SE = 0·007, P = 0·002), apolipoprotein B (β = 0·006, SE = 0·002, P < 0·001) and log triglycerides (β = 0·008, SE = 0·003, P = 0·004), but not with other lipid outcomes. Higher baseline TSH associated with higher total cholesterol (β = 0·056, SE = 0·026, P = 0·033), LDL cholesterol (β = 0·057, SE = 0·023, P = 0·015) and apolipoprotein B (β = 0·012, SE = 0·006, P = 0·028) at follow-up in women, but not with any lipid outcomes in men. Participants with high TSH at baseline had a 0·22 mmol/l (95% confidence interval 0·02-0·41 mmol/l) higher LDL cholesterol at follow-up (P = 0·028) than participants with TSH in the reference range (0·4-3·4 mU/l). However, exclusion of participants with high-risk baseline lipid values rendered these positive longitudinal associations nonsignificant (P ≥ 0·098). CONCLUSIONS We could confirm a modest association between higher TSH and an adverse lipid profile cross-sectionally but not indisputably longitudinally.

Background: Finland has experienced remarkable changes in population levels of coronary heart disease risk factors and mortality over the past decades. The National FINRISK studies have monitored risk factors in major non-communicable diseases from 1972 to 2012. The 40-year changes in those risk factors are presented. Methods: Study population included participants aged 30–59 years in the series on independent random population samples. Data were collected in 5-year intervals in 1972–2012. FINRISK studies so far comprised 53 589 men and women who participated in a health examination, gave a venous blood sample and filled in questionnaires. Serum total cholesterol, systolic and diastolic blood pressure, and body mass index (BMI) were measured using standardized protocol, and smoking status was recorded. Results: Total serum cholesterol decreased remarkably until 2007, but after that has increased. Systolic blood pressure has continued to decline over time since 1972, while decrease in diastolic blood pressure has levelled off during the last 10 years. Smoking prevalence has markedly decreased. BMI has increased in the population, but most significantly in the earlier survey years, not the past 10 years. Conclusions: After three decades of favourable development, the population risk factor levels showed some increase in total cholesterol and diastolic blood pressure. This emphasizes the need for continued efforts towards national disease prevention and health promotion.

Dyslipidaemia, hypertension and low-grade inflammation increase the risk of CVD. In the present meta-analysis, we examined whether adherence to a healthy Nordic diet, also called the Baltic Sea diet, may associate with a lower risk of these cardiometabolic risk factors. In 2001–2007, three cross-sectional Finnish studies were conducted: the Dietary, Lifestyle and Genetic Determinants of Obesity and Metabolic Syndrome study (n4776); Health 2000 Survey (n5180); Helsinki Birth Cohort Study (n1972). The following parameters were assessed in these three studies: blood pressure, total, HDL- and LDL-cholesterol, TAG and high-sensitivity C-reactive protein (hs-CRP); a validated FFQ was used to assess the participants' dietary intakes. The Baltic Sea Diet Score (BSDS) was developed based on the healthy Nordic diet. All studies assessed confounding variables, such as physical activity and BMI, based on standardised questionnaires and measurements. The random-effects meta-analysis provided summary estimates for OR and 95 % CI by the BSDS quintiles. In the meta-analysis, the risk of elevated hs-CRP concentration was lower among men (OR 0·58, 95 % CI 0·43, 0·78) and women (OR 0·73, 95 % CI 0·58, 0·91) in the highest BSDS quintile than among those in the lowest BSDS quintile. In contrast, the risk of lowered HDL-cholesterol concentration was higher among women (OR 1·67, 95 % CI 1·12, 2·48) in the highest BSDS quintile than among those in the lowest BSDS quintile. However, no other associations were found. In conclusion, the associations between the adherence to the healthy Nordic diet and cardiometabolic risk factors are equivocal. Longitudinal studies are needed to further examine this hypothesis.

Microalbuminuria, defined as urine albumin-to-creatinine ratio (UACR)>3.0 mg/mmol and ≤ 30 mg/mmol, is an early marker of endothelial damage of the renal glomeruli. Recent research suggests an association among microalbuminuria, albuminuria (UACR > 3.0 mg/mmol), and cognitive impairment. Previous studies on microalbuminuria, albuminuria, and cognition in the middle-aged have not provided repeated cognitive testing at different time-points. We hypothesized that albuminuria (micro- plus macroalbuminuria) and microalbuminuria would predict cognitive decline independently of previously reported risk factors for cognitive decline, including cardiovascular risk factors. In addition, we hypothesized that UACR levels even below the cut-off for microalbuminuria might be associated with cognitive functioning. These hypotheses were tested in the Finnish nationwide, population-based Health 2000 Survey (n = 5,921, mean age 52.6, 55.0% women), and its follow-up, Health 2011 (n = 3,687, mean age at baseline 49.3, 55.6% women). Linear regression analysis was used to determine the associations between measures of albuminuria and cognitive performance. Cognitive functions were assessed with verbal fluency, word-list learning, word-list delayed recall (at baseline and at follow-up), and with simple and visual choice reaction time tests (at baseline only). Here, we show that micro- plus macroalbuminuria associated with poorer word-list learning and a slower reaction time at baseline, with poorer word-list learning at follow-up, and with a steeper decline in word-list learning during 11 years after multivariate adjustments. Also, higher continuous UACR consistently associated with poorer verbal fluency at levels below microalbuminuria. These results suggest that UACR might have value in evaluating the risk for cognitive decline.

Background Secreted frizzled-related protein 5 (Sfrp5) has been described as novel adipokine in mice with insulin-sensitising and anti-inflammatory properties similar to adiponectin. The aim of this study was to compare serum concentrations and determinants of Sfrp5, its pro-inflammatory antagonist wingless-type MMTV integration site family member (Wnt)5a and adiponectin in humans and their regulation by coffee. Material and methods Serum concentrations of Sfrp5, Wnt5a and adiponectin were measured in 47 individuals who participated in a coffee intervention study. Associations with demographic, metabolic and immunological variables and regulation of serum levels by different amounts of daily coffee intake were analysed. Results At baseline, fasting serum Sfrp5 levels ranged between 96 and 4056 ng/mL. Sfrp5 was directly correlated with a surrogate of insulin resistance (homeostasis model assessment of insulin resistance/HOMA-IR; r = 0·32, P

Objective Apolipoproteins B (apoB) and A1 (apoA1) may be better markers of atherosclerosis than serum lipids. We used computational methods to estimate apoB and apoA1 from serum total cholesterol, HDL-cholesterol and triglycerides and tested their clinical value in comparison to measured apoB and apoA1 values. Methods ApoB and apoA1 were measured with standard methods and estimated based on neural network regression models in 2166 young adult with data on carotid artery intima-media thickness (cIMT). Results Correlations between estimated and measured apoB and apoA1 were r = 0.98 and r = 0.95, respectively. ApoB/apoA1-ratio (both measured and estimated) associated with cIMT in multivariable models, and predicted cIMT at all levels of LDL-cholesterol concentration. Strong correlations between the estimated apolipoproteins and those measured from fasting samples were replicated in over 15,000 Caucasian subjects ( r = 0.93–0.96 for apoB and r = 0.91–0.92 for apoA1). Correlations with cIMT were replicated in over 2000 individuals. Estimated apoB/apoA1-ratio calculated from non-fasting lipids in over 20,000 individuals in the INTERHEART study was better than any of the cholesterol measures for estimation of the myocardial risk. Conclusions Serum cholesterol, HDL-cholesterol and triglycerides can be used to compute clinically useful estimates of apoB and apoA1. Using this methodology, estimates of apolipoproteins could be routinely added to laboratory reports to complement lipoprotein lipids in risk assessment.

High-density lipoprotein cholesterol (HDL-C) is important in risk assessment for cardiovascular disease or metabolic syndrome; however, different direct HDL-C assays may lead to erroneous risk estimates and potentially misclassify people.Data for 30-year HDL-C trends in Finland were obtained from the national FINRISK surveys during 1982-2012 (n=45766) taking into account biases from three external quality assessment programs (EQA). We also compared two different direct HDL-C and turbidimetric apolipoprotein A-I methods using 413 fresh serum samples.HDL-C concentrations in the Finnish population were on average 1.33 (±0.04) mmol/l for men and 1.62 (±0.05) mmol/l for women after bias-correction. Positive HDL-C trends were observed for both sexes with original data, but trends disappeared after bias-correction. Comparison of two direct HDL-C methods demonstrated concentration-dependent difference. When HDL-C concentrations were1.0 mmol/l, the mean bias was -12.0% (95% CI -13.5 to -10.0) whereas HDL-C concentrations1.55 mmol/l showed mean bias of 9.0% (95% CI 7.0-10.5).Accurate reporting of HDL-C concentrations at the population level requires proper and regular attendance to reliable EQA programs. We found evidence for a concentration-dependent difference between some direct HDL-C methods, which may cause misclassification of people in cardiovascular risk assessment.

Measurement of serum 25-hydroxyvitamin D [25(OH)D] is considered the best indicator of vitamin D status. Two minor vitamin D metabolites are common interferences encountered in 25(OH)D assays. The first is 3-epi-25-hydroxyvitamin D

Blood low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and triglyceride levels are risk factors for cardiovascular disease. To dissect the polygenic basis of these traits, we conducted genome-wide association screens in 19,840 individuals and replication in up to 20,623 individuals. We identified 30 distinct loci associated with lipoprotein concentrations (each with P < 5 x 10(-8)), including 11 loci that reached genome-wide significance for the first time. The 11 newly defined loci include common variants associated with LDL cholesterol near ABCG8, MAFB, HNF1A and TIMD4; with HDL cholesterol near ANGPTL4, FADS1-FADS2-FADS3, HNF4A, LCAT, PLTP and TTC39B; and with triglycerides near AMAC1L2, FADS1-FADS2-FADS3 and PLTP. The proportion of individuals exceeding clinical cut points for high LDL cholesterol, low HDL cholesterol and high triglycerides varied according to an allelic dosage score (P < 10(-15) for each trend). These results suggest that the cumulative effect of multiple common variants contributes to polygenic dyslipidemia.

Data on associations of apolipoproteins A-I and B (apo A-I, apo B) and HDL cholesterol (HDL-C) with dementia and Alzheimer’s disease (AD) are conflicting. Our aim was to examine, whether apo B, apoA-I, their ratio, or HDL-C are significant, independent predictors of incident dementia and AD in the general population free of dementia at baseline. We analyzed the results from two Finnish prospective population-based cohort studies in a total of 13,275 subjects aged 25 to 74 years with mainly Caucasian ethnicity. The follow-up time for both cohorts was 10 years. We used Cox proportional hazards regression to evaluate hazard ratios (HR) for incident dementia (including AD) (n = 220) and for AD (n = 154). Cumulative incidence function (CIF) analysis was also performed to adjust the results for competing risks of death. Adjusted for multiple dementia and AD risk factors, log-transformed apo A-I, log HDL-C, log apo B, and log apo B/A-I ratio were not associated with incident dementia or AD. HDL-C was inversely associated with AD risk when adjusted for competing risks but no other statistically significant associations were observed in the CIF analyses. Apo A-I, HDL-C, apo B, or apo B/A-I ratio were not associated with future dementia or AD. HDL-C was inversely associated with incident AD risk when adjusted for competing risks of death, but the finding is unlikely to be of clinical relevance. Our study does not support the use of these risk markers to predict incident dementia or AD.

OBJECTIVE We investigated the effect of early-phase insulin secretion on the incidence of type 2 diabetes in individuals with impaired glucose tolerance (IGT) participating in the Finnish Diabetes Prevention Study (DPS). We examined how a lifestyle intervention affected early-phase insulin secretion (ratio of total insulin area under the curve [AUC] and total glucose AUC [AIGR] from 0 to 30 min) during a 4-year follow-up intervention trial and whether AIGR0–30 response was modified by insulin sensitivity (IS) and obesity. RESEARCH DESIGN AND METHODS A total of 443 participants with IGT originally randomized to a lifestyle intervention or control group were studied. IS and AIGR0–30 were estimated from an oral tolerance glucose test administered annually during the 4-year follow-up trial and were related to the risk of diabetes onset over a 6-year follow-up. RESULTS Lifestyle intervention resulted in higher IS (P = 0.02) and lower unadjusted AIGR0–30 (P = 0.08) during the 4-year follow-up. A higher IS and a lower BMI during the follow-up were associated with a lower unadjusted AIGR0–30 during the follow-up, independently of study group (P < 0.001). A greater increase in IS on the median cutoff point of a 0.69 increase was associated with higher IS-adjusted AIGR0–30 during the follow-up (P = 0.002). In multivariate models, IS and IS-adjusted AIGR0–30 were both inversely associated with diabetes incidence (P < 0.001). Participants who progressed to type 2 diabetes were more obese and had lower IS and Matsuda IS index-AIGR0–30 than nonprogressors. CONCLUSIONS Our results indicate that the reduction in the risk of developing type 2 diabetes after lifestyle intervention is related to the improvement of IS along with weight loss. Improved IS may also have beneficial effects on preservation of β-cell function.

To evaluate the single and joint associations of serum high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol with coronary heart disease (CHD) risk.Study cohorts included 21,375 Finnish participants who were 25-74 years of age and free of CHD and stroke at baseline.During a median follow-up period of 10.8 years, 437 participants developed CHD. The sex- and multivariable-adjusted hazard ratios (HRs) of CHD at different levels of HDL cholesterol [40 (reference), 40-49, 50-59, 60-69, and ≥ 70 mg/dL] were 1.00, 1.00, 0.74, 0.58, and 0.69 (p (trend) = 0.006), respectively. The sex- and multivariable-adjusted HRs of CHD at different levels of LDL cholesterol [100 (reference), 100-129, 130-159, and ≥ 160 mg/dL] were 1.00, 1.25, 1.92, and 2.65 (p (trend)0.001), respectively. In joint analyses, a decreased trend in the incidence rate of CHD with an increasing HDL cholesterol level was consistent in people with any level of LDL cholesterol. Likewise, an increasing trend in incidence of CHD with an increase in the LDL cholesterol level was consistent in subjects with any level of HDL cholesterol.These results suggest an inverse association between HDL cholesterol and CHD risk and a direct association between LDL cholesterol and CHD risk, independent of other risk factors. The protective effect of HDL cholesterol on CHD risk is observed at all levels of LDL cholesterol.

In this FIN-D2D cross-sectional survey the relationship of age with HbA(1c) and fasting and 2h glucose in the oral glucose tolerance test (OGTT) was explored in apparently randomly selected healthy population.The glycaemic parameters were measured in 1344 men and 1482 women (aged 45-74 years), and among them we excluded all subjects with known diabetes, hypertension or dyslipidaemia. The final analyses for HbA(1c) and the ratios of fasting glucose/HbA(1c) and 2h glucose/HbA(1c) included 649 men and 804 women.Mean age was 57 years and BMI 26.1kg/m(2) for both genders. HbA(1c) increased in both genders with age (p0.001). For a particular fasting glucose level HbA(1c) level was higher in older age groups (p0.001 for linearity). By contrast, a particular 2h plasma glucose value in OGTT implied significantly lower HbA(1c) in the elderly (p0.001 for linearity).In apparently healthy population, screened with OGTT, in older individuals compared with younger ones a particular HbA(1c) value implies slightly lower fasting glucose, but relatively higher 2h glucose. These results need to be verified in different populations. The effects of age on relation between HbA(1c) and plasma glucose should be taken into account in classifying people into different dysglycaemia categories.

BackgroundThe aim of this cross-sectional study was to examine the association between serum calcium and the components of metabolic syndrome (MetS).MethodsAs a part of the national prevention program of diabetes in Finland (FIN-D2D), a randomly selected study population of 4500 middle-aged men and women were recruited from three central hospital district areas. Anthropometric measurements were performed by a trained nurse. An oral glucose tolerance test was performed and serum calcium and lipids were measured. We assessed current medications, physical activity, smoking, alcohol consumption, calcium intake, and vitamin D intake. The MetS was defined according to the criteria of the updated National Education Program. The study population consisted of 2896 individuals: 1396 men (62% of invited individuals) and 1500 women (66.7% of invited individuals).ResultsThe mean age was 60.3±8.3 years in men and 59.8±8.5 years in women. The prevalence of MetS was 50.7% in women and 55.8% in men. The prevalence of MetS and its components, except high-density lipoprotein (HDL)-cholesterol, increased linearly with increasing serum calcium (PConclusionsSerum calcium level is associated with MetS and its components, except HDL-cholesterol.

Background In addition to traditional measurements of serum lipid levels, apolipoprotein A-I (apoA-I), apolipoprotein B (apoB), and apoB/apoA-I ratio may add more value to risk assessment guidelines for cardiovascular disease. Methods We calculated reference intervals for apoA-I, apoB, and apoB/apoA-I ratio using a reference sample (n = 2828) from the FINRISK 2007 study. Results The reference intervals for apoA-I were 1.1–2.0 g/l for men and 1.2–2.3 g/l for women. The corresponding reference intervals for apoB were 0.6–1.5 g/l and 0.6–1.3 g/l. The reference intervals for apoB/apoA-I ratio were 0.3–1.0 for men and 0.3–0.8 for women. Compared with the healthy reference group, obese men had the lowest ApoA-I, the highest apoB, and the highest apoB/apoA-I ratio. Men with CVD and cholesterol-lowering medication, or diabetes had lower apoB levels and apoB/apoA-1 ratio than the reference group but the opposite was true for women. The therapeutic goal for low-risk individuals for apoB was 0.9 g/l coinciding with LDL-C concentration of 3.0 mmol/l. Conclusions Reference intervals for apoA-I, apoB, and the apoB/apoA-I ratio and their cutoff values may be useful for the risk evaluation and follow-up of treatment among individuals having CVD or other metabolic disorders.