Insomnia symptoms and risk for atrial fibrillation - The HUNT study.

Studies on the effect of insomnia on atrial fibrillation risk in the general population are limited, therefore we investigated the association between insomnia and the risk of atrial fibrillation in a large-scale population-based study with valid atrial fibrillation measure. A total of 33,983 participants (55% women) reported their insomnia symptoms in the third wave of the HUNT study (between 2006 and 2008) in Norway, and they were followed for their first atrial fibrillation diagnosis until 2020 using hospital registers. Atrial fibrillation diagnoses were validated by physicians based on medical records and electrocardiograms. Insomnia symptoms were assessed by four questions, and analysed both individually and as cumulative symptoms. Cox regression, adjusted for age, sex, social and marital status, working in shiftwork, alcohol consumption, smoking, physical activity, body mass index, systolic blood pressure, and symptoms of anxiety and depression, was conducted. Overall, 1592 atrial fibrillation cases were identified during the follow-up and 31.6% of individuals reported at least one insomnia symptom. In our analysis, we did not detect meaningful associations between insomnia symptoms and the risk of atrial fibrillation. In conclusion, in this population there was no evidence for an association between insomnia symptoms and the risk of subsequent atrial fibrillation.

Preconception diet in adolescence and its association with hypertensive disorders of pregnancy and preterm birth. Results from the HUNT study.

Our aim was to estimate associations of adolescent dietary patterns and meal habits with hypertensive disorders of pregnancy (HDP) and preterm birth. We used data from a prospective cohort study (Norwegian Young-HUNT1) where dietary information was collected during adolescence and pregnancy outcomes were obtained through record linkage to the Norwegian national birth registry. The outcomes were HDP, hypertension, pre-eclampsia/eclampsia, and preterm birth in the first pregnancy and in any pregnancy. Diet was self-reported from validated questionnaires, and exposures were dietary indexes (healthy; unhealthy; fruit and vegetable; fibre index) and meal habits. Recruitment took place in schools. Eligible participants were females aged 13-19 years at the time of dietary assessment with a subsequent singleton pregnancy (n 3622). Women who reported a higher fibre intake in adolescence had a lower risk of pre-eclampsia in the first pregnancy (Relative Risk: 0·84; 95 % CI 0·7, 1·0), although this was weaker in sensitivity analyses. Regular meal habits in mid-adolescence (aged 13-15 years), particularly breakfast and lunch, were weakly associated with a lower risk of hypertension in pregnancy. Our results are the first to indicate an association between aspects of diet and dietary behaviour in mid-adolescence and subsequent HDP. More evidence is needed from larger studies to replicate the results and from alternative study designs to disentangle causality.

Loneliness increases the risk of type 2 diabetes: a 20 year follow-up - results from the HUNT study.

AIMS/HYPOTHESIS: Type 2 diabetes is one of the leading causes of death globally and its incidence has increased dramatically over the last two decades. Recent research suggests that loneliness is a possible risk factor for type 2 diabetes. This 20 year follow-up study examined whether loneliness is associated with an increased risk of type 2 diabetes. As both loneliness and type 2 diabetes have been linked to depression and sleep problems, we also investigated whether any association between loneliness and type 2 diabetes is mediated by symptoms of depression and insomnia. METHODS: We used data from the Trøndelag Health Study (HUNT study), a large longitudinal health study based on a population from central Norway (n=24,024). Self-reports of loneliness (HUNT2 survey, 1995-1997) and data on HbA1c levels (HUNT4 survey, 2017-2019) were analysed to evaluate the associations between loneliness and incidence of type 2 diabetes. Associations were reported as ORs with 95% CIs, adjusted for sex, age and education. We further investigated the role of depression and insomnia as potential mediating factors. RESULTS: During the 20 year follow-up period, 4.9% of the study participants developed type 2 diabetes. Various degrees of feeling lonely were reported by 12.6% of the participants. Individuals who felt most lonely had a twofold higher risk of developing type 2 diabetes relative to those who did not feel lonely (adjusted OR 2.19 [95% CI 1.16, 4.15]). The effect of loneliness on type 2 diabetes was weakly mediated by one subtype of insomnia but not by symptoms of depression. CONCLUSIONS/INTERPRETATION: This study suggests that loneliness may be one factor that increases the risk of type 2 diabetes; however, there is no strong support that the effect of loneliness on type 2 diabetes is mediated by depression or insomnia. We recommend that loneliness should be included in clinical guidelines on consultations and interventions related to type 2 diabetes.

The causal role of C-reactive protein and interleukin-6 on anxiety and depression symptoms and life satisfaction: Mendelian randomisation analyses in the HUNT study.

BACKGROUND: Serum levels of C-reactive protein (CRP) and interleukin-6 (IL-6) have been associated with anxiety and depression in cross-sectional and Mendelian randomisation studies, but results regarding the effect size and direction have been mixed. A recent Mendelian Randomisation (MR) study suggested that CRP may decrease and IL-6 may increase anxiety and depression symptoms. METHODS: Among 68 769 participants of the population-based Trøndelag Health Study (HUNT), we performed cross-sectional observational and one-sample MR analyses of serum CRP and two-sample MR analysis of serum IL-6. The main outcomes were symptoms of anxiety and depression assessed using the Hospital Anxiety and Depression Scale (HADS) and life satisfaction assessed using a seven-level ordinal questionnaire where higher scores indicate lower life satisfaction. RESULTS: In cross-sectional observational analyses, a doubling in serum CRP level was associated with 0.27% (95% CI -0.20 to 0.75) difference in HADS depression score (HADS-D), -0.77% (95% CI -1.24 to -0.29) difference in HADS anxiety score (HADS-A) and -0.10% (95% CI -0.41 to 0.21) difference in life satisfaction score. In one-sample MR analyses, a doubling in serum CRP was associated with 2.43% (95% CI -0.11 to 5.03) higher HADS-D, 1.94% (95% CI -0.58 to 4.52) higher HADS-A, and 2.00% (95% CI 0.45 to 3.59) higher life satisfaction score. For IL-6, causal point estimates were in the opposite direction, but imprecise and far from conventional criteria for statistical significance. CONCLUSIONS: Our results do not support a major causal role of serum CRP on anxiety and depression symptoms and life satisfaction, but provides weak evidence that serum CRP may modestly increase anxiety and depression symptoms and reduce life satisfaction. Our findings do not support the recent suggestion that serum CRP may lower anxiety and depression symptoms.

Insomnia and risk of dementia in a large population-based study with 11-year follow-up: The HUNT study.

Despite evidence suggesting that insomnia is associated with the risk of dementia and cognitive dysfunction, studies have shown mixed results. Dementia has a long prodromal phase, and studies with long follow-up are required to avoid reverse causality. In our 11-year follow-up study, we assessed whether probable insomnia disorder (PID) based on diagnostic criteria, and insomnia symptoms were associated with risk of all-cause dementia, Alzheimer's disease (AD) and cognition, measured with the Montreal Cognitive Assessment scale. We also examined if Apolipoprotein E genotype modified any associations with dementia through interaction. We analysed data from 7492 participants in the Norwegian Trøndelag Health Study. PID was not associated with all-cause dementia (odds ratio = 1.03, 95% confidence interval = 0.74-1.43), AD (odds ratio = 1.07, 95% confidence interval = 0.71-1.60) or Montreal Cognitive Assessment score (regression coefficient = 0.37, 95% confidence interval = -0.06 to 0.80). The insomnia symptom "difficulties maintaining sleep" was associated with a lower risk of all-cause dementia (odds ratio = 0.81, 95% confidence interval = 0.67-0.98), AD (odds ratio = 0.73, 95% confidence interval = 0.57-0.93), and better Montreal Cognitive Assessment score, mean 0.40 units (95% confidence interval = 0.15-0.64). No interaction with Apolipoprotein E genotype was found. PID and insomnia symptoms did not increase the risk of dementia in our study. More research with longer follow-up is needed, and future studies should explore if the associations to dementia risk vary across insomnia subtypes.

Trends in social inequality and how mental wellbeing vary and covary among Norwegian adolescents and their families: the Young-HUNT Study.

BACKGROUND: The study had two aims: first, to investigate trends in socioeconomic inequalities in psychological distress and loneliness among Norwegian adolescents, and second, to study variation and covariation of psychological distress and loneliness within adolescents and between siblings within families. METHODS: Multivariate mixed models were used to investigate trends in socioeconomic inequality in psychological distress and loneliness using three separate cohorts of Norwegian adolescents from the Young-HUNT study conducted in 1995-1997 (Young-HUNT1, n = 8980), 2006-2008 (Young-HUNT3, n = 8199) and 2017-2019 (Young-HUNT4, n = 8066). Register data on parental education level was used as a marker of socioeconomic position (SEP), and a unique family number was used to identify adolescents belonging to the same family. A three-level multivariate mixed model was created, consisting of the outcomes at level 1, adolescents at level 2 and families at level 3. RESULTS: No statistically significant difference in scores on loneliness and psychological distress was observed between low and high parental education level in Young-HUNT1, whereas in Young-HUNT4, low parental education level was associated with a higher score on both psychological distress (ß = 0.09; 95% confidence interval (CI), 0.03-0.14) and loneliness (ß = 0.12; 95% CI 0.07-0.17). Analyses of covariation between psychological distress and loneliness showed that they were correlated within adolescents and strongly correlated within families across all timepoints. CONCLUSIONS: Increasing socioeconomic inequalities in psychological distress and loneliness among Norwegian adolescents is worrisome. Further, the family seems to be an important arena for potential prevention of psychological distress and loneliness among adolescents, regardless of parental education level.

Body mass index and incidence of lung cancer in the HUNT study: using observational and Mendelian randomization approaches.

BACKGROUND: Traditional observational studies have shown an inverse association between body mass index (BMI) and lung cancer risk. Mendelian randomization (MR) analysis using genetic variants as instruments for BMI may clarify the nature of the association. AIMS: We studied the causal association between BMI and lung cancer incidence using observational and MR approaches. METHODS: We followed up 62,453 cancer-free Norwegian adults from 1995-97 (HUNT2) until 2017. BMI at baseline in HUNT2 was classified as < 25.0, 25.0-29.9 and ≥ 30.0 kg/m2. BMI change over ten years between HUNT1 (1984-86) and HUNT2 was calculated and classified into quartiles. Seventy-five genetic variants were included as instruments for BMI (among which 14 also associated with smoking behavior). Incident lung cancer cases were ascertained from the Cancer Registry of Norway. Cox regression models were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). Multivariable MR was used to examine the effect of BMI after genetically controlling for smoking. RESULTS: During a median follow-up of 21.1 years, 1009 participants developed lung cancer including 327 with lung adenocarcinoma. The HRs and 95% CIs for incidence of adenocarcinoma were 0.73 (0.58-0.92) for BMI 25.0-29.9 kg/m2 and 0.53 (0.37-0.76) for BMI ≥ 30 kg/m2 compared with BMI < 25.0 kg/m2 in HUNT2 (P for trend < 0.001). However, there was little evidence of a dose-response relationship between the BMI change from HUNT1 to HUNT2 in quartiles and the incidence of adenocarcinoma (P for trend = 0.08). Furthermore, multivariable MR approach suggested a positive association between genetically determined 1 kg/m2 increase in BMI and the incidence of adenocarcinoma (HR 1.25, 95% CI 1.02-1.53). No associations were found with other lung cancer histologic types. CONCLUSIONS: Our study suggests that the inverse association between baseline BMI and lung adenocarcinoma in observational analysis may not be causal. More MR studies are needed to confirm our finding of a positive association between BMI and lung adenocarcinoma.

Is intracranial volume a risk factor for IDH-mutant low-grade glioma? A case-control study.

PURPOSE: Risk of cancer has been associated with body or organ size in several studies. We sought to investigate the relationship between intracranial volume (ICV) (as a proxy for lifetime maximum brain size) and risk of IDH-mutant low-grade glioma. METHODS: In a multicenter case-control study based on population-based data, we included 154 patients with IDH-mutant WHO grade 2 glioma and 995 healthy controls. ICV in both groups was calculated from 3D MRI brain scans using an automated reverse brain mask method, and then compared using a binomial logistic regression model. RESULTS: We found a non-linear association between ICV and risk of glioma with increasing risk above and below a threshold of 1394 ml (p < 0.001). After adjusting for ICV, sex was not a risk factor for glioma. CONCLUSION: Intracranial volume may be a risk factor for IDH-mutant low-grade glioma, but the relationship seems to be non-linear with increased risk both above and below a threshold in intracranial volume.

The HUNT study: Association of comorbidity clusters with long-term survival and incidence of exacerbation in a population-based Norwegian COPD cohort.

BACKGROUND AND OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease often viewed as part of a multimorbidity complex. There is a need for better phenotyping of the disease, characterization of its interplay with other comorbidities and its association with long-term outcomes. This study aims to examine how clusters of comorbidities are associated with severe exacerbations and mortality in COPD. METHODS: Participants with potential COPD were recruited from the second (1995-1997) and third (2006-2008) survey of the HUNT Study and followed up until April 2020. Ten objectively identified comorbidities were clustered using self-organizing maps. Severe COPD exacerbations requiring hospitalization were assessed using hospital data. All-cause mortality was collected from national registries. Multivariable Cox regression was used to calculate hazard ratios (HRs) with 95% CIs for the association between comorbidity clusters and all-cause mortality. Poisson regression was used to calculate incidence rate ratios (IRRs) with 95% CI for the cumulative number of severe exacerbations for each cluster. RESULTS: Five distinct clusters were identified, including 'less comorbidity', 'psychological', 'cardiovascular', 'metabolic' and 'cachectic' clusters. Using the less comorbidity cluster as reference, the psychological and cachectic clusters were associated with all-cause mortality (HR 1.23 [1.04-1.45] and HR 1.83 [1.52-2.20], adjusted for age and sex). The same clusters also had increased risk of exacerbations (unadjusted IRR of 1.24 [95% CI 1.04-1.48] and 1.50 [95% CI 1.23-1.83], respectively). CONCLUSION: During 25 years of follow-up, individuals in the psychological and cachectic clusters had increased mortality. Furthermore, these clusters were associated with increased risk of severe COPD exacerbations.

Long-term changes in self-reported sleep quality and risk of chronic musculoskeletal pain: The HUNT Study.

We examined the association between long-term (~10 years) changes in self-reported sleep quality and risk of any chronic musculoskeletal pain and chronic widespread pain. The study comprised data on 6,033 people who participated in three consecutive surveys in the Norwegian HUNT Study (1995-1997, 2006-2008 and 2017-2019) and who were without chronic musculoskeletal pain at the first two surveys. We used a modified Poisson regression model to calculate adjusted risk ratios for chronic pain at follow-up (2017-2019) associated with categories of poor and good sleep quality reported in 1995-1997 and 2006-2008. Compared with people who reported good sleep at both surveys (crude absolute risk: 32.4%), the risk ratios of any chronic pain were 1.20 (95% confidence interval: 1.02-1.41) for those who changed from poor to good sleep; 1.25 (95% confidence interval: 1.12-1.39) for those who changed from good to poor sleep; and 1.41 (95% confidence interval: 1.21-1.63) for those who reported long-term poor sleep. The corresponding risk ratios for chronic widespread pain were 1.35 (95% confidence interval: 0.82-2.23), 1.55 (95% confidence interval: 1.14-2.12) and 2.09 (95% confidence interval: 1.38-3.17), respectively. In conclusion, these findings indicate that people with long-term poor sleep quality have a markedly higher risk of chronic musculoskeletal pain and chronic widespread pain, compared with people who remain good sleep quality.

Physical activity, sugar-sweetened beverages, whole grain bread and insomnia among adolescents and psychological distress in adulthood: prospective data from the population-based HUNT study.

BACKGROUND: In this study, we examined the relationship between low levels of physical activity, high consumption of sugar-sweetened beverages and low consumption of whole grain bread and experiencing insomnia in adolescence and psychological distress in young adults. METHODS: This prospective study was based on information retrieved from the Trøndelag Health Study (HUNT) in Norway and included adolescents (age 13-19) participating in Young-HUNT3 (2006-2008) and in HUNT4 (2017-2019) 11 years later (age 23-31). The study sample consisted of 2,230 participants (1,287 females and 943 males). The exposure variables collected in adolescence included self-reported physical activity, consumption of sugar-sweetened beverages and whole grain bread and insomnia, and psychological distress in young adulthood was used as an outcome variable. The relationship between lifestyle behaviours in adolescence and psychological distress in young adulthood was examined using multivariable logistic regression, adjusted for gender, age and psychological distress in adolescence and educational level in young adulthood. RESULTS: An increased odds of psychological distress was shown among young adults who reported low levels of physical activity (OR: 1.44, 95 % CI: 1.10-2.89), high consumption of sugar-sweetened beverages (OR: 1.49, 95 % CI: 1.12-1.98), low consumption of whole grain bread (OR: 1.35, 95 % CI: 1.04-1.77) and insomnia (OR: 1.69, 95 % CI: 1.23-2.33) in adolescence. In terms of absolute differences, unhealthy lifestyle behaviours increased the risk of psychological distress in young adulthood between 3.18 (95 % CI: 0.29-6.07) (low whole grain bread consumption) and 6.01 (95 % CI: 1.95-10.07) (insomnia) percentage points. CONCLUSIONS: Low levels of physical activity, high consumption of sugar-sweetened beverages and low consumption of whole grain bread and insomnia during adolescence were associated with psychological distress in young adulthood.

Associations between complex multimorbidity, activities of daily living and mortality among older Norwegians. A prospective cohort study: the HUNT Study, Norway.

BACKGROUND: With increasing age, having multiple chronic conditions is the norm. It is of importance to study how co-existence of diseases affects functioning and mortality among older persons. Complex multimorbidity may be defined as three or more conditions affecting at least three different organ systems. The aim of this study was to investigate how complex multimorbidity affects activities of daily living and mortality amongst older Norwegians. METHODS: Participants were 60-69-year-olds at baseline in the Nord-Trøndelag Health Study 1995-1997 (HUNT2) n = 9058. Multinomial logistic regression models were used to investigate the association between complex multimorbidity in HUNT2, basic and instrumental activities of daily living in HUNT3 (2006-2008) and mortality during follow-up (n = 5819/5836). Risk ratios (RR) and risk differences (RD) in percentage points (pp) with 95% confidence intervals (CI) were reported. RESULTS: 47.8% of 60-69-year-olds met the criteria of complex multimorbidity at baseline (HUNT2). Having complex multimorbidity was strongly associated with the need for assistance in IADL in HUNT3 11 years later (RR = 1.80 (1.58-2.04) and RD = 8.7 (6.8-10.5) pp) and moderately associated with mortality during the follow-up time (RR = 1.22 (1.12-1.33) and RD = 5.1 (2.9-7.3) pp). Complex multimorbidity was to a lesser extent associated with basic activities of daily living 11 years later (RR = 1.24 (0.85-1.83) and RD = 0.4 (- 0.3-1.1) pp). CONCLUSIONS: This is the first study to show an association between complex multimorbidity and activities of daily living. Complex multimorbidity should receive more attention in order to prevent future disability amongst older persons.

Genetic polymorphisms associated with sleep-related phenotypes; relationships with individual nocturnal symptoms of insomnia in the HUNT study.

BACKGROUND: In recent years, several GWAS (genome wide association studies) of sleep-related traits have identified a number of SNPs (single nucleotides polymorphism) but their relationships with symptoms of insomnia are not known. The aim of this study was to investigate whether SNPs, previously reported in association with sleep-related phenotypes, are associated with individual symptoms of insomnia. METHODS: We selected participants from the HUNT study (Norway) who reported at least one symptom of insomnia consisting of sleep onset, maintenance or early morning awakening difficulties, (cases, N = 2563) compared to participants who presented no symptoms at all (controls, N = 3665). Cases were further divided in seven subgroups according to different combinations of these three symptoms. We used multinomial logistic regressions to test the association among different patterns of symptoms and 59 SNPs identified in past GWAS studies. RESULTS: Although 16 SNPS were significantly associated (p < 0.05) with at least one symptom subgroup, none of the investigated SNPs remained significant after correction for multiple testing using the false discovery rate (FDR) method. CONCLUSIONS: SNPs associated with sleep-related traits do not replicate on any pattern of insomnia symptoms after multiple tests correction. However, correction in this case may be overly conservative.

Female sex hormones and risk of incident abdominal aortic aneurysm in Norwegian women in the HUNT study.

OBJECTIVE: The delayed development of abdominal aortic aneurysm (AAA) in women compared with men might be secondary to a protective effect from endogenous estrogens. The role of postmenopausal hormone therapy remains unclear. The aim of the present study was to evaluate the effect of female sex hormones compared with other risk factors associated with AAA through a long-term study of a large female cohort. METHODS: The present prospective cohort study included 20,024 postmenopausal women from the Norwegian Nord-Trøndelag Health Study. A total of 201 cases of AAA were identified during a median follow-up period of 18 years (295,554 person-years; 1995-2014). The data were recorded from questionnaires, physical measurements, medical records, blood sample test results, and the Norwegian Cause of Death Registry. The effect of risk factors was evaluated in a multiple Cox regression analysis. Multiple imputation was performed for missing data (n = 50 data sets). The serum estradiol concentrations in women with and without incidental AAAs were compared. The median interval from blood sample collection to the AAA diagnosis was 7 years. RESULTS: Current smokers had >10-fold increased risk of incident AAA during the follow-up period (hazard ratio [HR], 10.9; 95% confidence interval [CI], 7.4-16.1). Positive associations were found for hypertension (HR, 2.0; 95% CI, 1.4-3.0) and coronary heart disease (HR, 2.2; 95% CI, 1.6-3.2). The HR associated with the current use of postmenopausal hormone therapy was 0.58 (95% CI, 0.6-1.5). No substantial difference in estradiol concentrations was found between women with and without AAA (P = .075). CONCLUSIONS: The effect of female sex hormones on the risk of incident AAAs in women, as evaluated by the serum concentrations of estradiol and the use of postmenopausal hormone therapy, is clinically less important than the strong associations found with smoking, hypertension, and coronary heart disease.

Long-term changes in body weight and physical activity in relation to all-cause and cardiovascular mortality: the HUNT study.

BACKGROUND: Most previous studies have relied on single measurements of body weight and physical activity and have not considered the interplay between long-term changes in body weight and physical activity in relation to mortality. The aim of the current study was therefore to examine the joint effect of changes in body weight and leisure-time physical activity over a period of ~ 10 years on all-cause and cardiovascular mortality. METHODS: The study population comprised 34,257 individuals who participated in the first (1984-86) and second (1995-97) waves of the HUNT Study, and were followed up through the Norwegian Cause of Death Registry until December 31st, 2013. We used Cox regression to estimate hazard ratios (HR) with 95% confidence intervals (CI) of death associated with changes in body weight and leisure-time physical activity. RESULTS: Compared to the reference group with stable weight who were long-term physically active, people who gained ≥5% of their weight had a HR for all-cause mortality of 1.54 (95% CI: 1.28-1.85) if they were long-term physically inactive; a HR of 1.23 (1.09-1.40) if they became physically active, and a HR of 1.00 (95% CI 0.94-1.06) if they were long-term physically active. The corresponding HRs for cardiovascular mortality were 1.57 (95% CI 1.17-2.12), 1.28 (95% CI 1.04-1.58) and 1.06 (95% CI 0.96-1.16), respectively. Long-term physical inactivity was associated with increased all-cause (HR 1.29; 95% CI 1.08-1.53) and cardiovascular (HR 1.37; 95% CI 1.05-1.79) mortality among those who were weight stable. CONCLUSIONS: The risk of all-cause and cardiovascular mortality is particularly evident among people who gain weight while remaining inactive during a ~ 10 year period. However, participants who remained physically active had the lowest risk of premature mortality, regardless of maintenance or increase in weight. These findings suggest that there is an interplay between long-term changes in body weight and physical activity that should receive particular attention in the prevention of premature mortality.

Time trends (1995-2008) in dietary habits among adolescents in relation to the Norwegian school fruit scheme: the HUNT study.

INTRODUCTION: The importance of healthy eating in adolescence is well established. The present study examined possible effects of the free Norwegian School Fruit Scheme (NSFS), changes in dietary habits between 1995 and 2008, and whether secular changes in dietary habits differed among schools who implemented the NSFS during September 2007. METHOD: We used data from the Young-HUNT1 survey conducted from 1995 to 1997 and the Young-HUNT3 survey conducted from 2006 to 2008, which are part of the Nord-Trøndelag Health Study (HUNT), a longitudinal population health study. To evaluate the NSFS, the date Young-HUNT3 participants answered the questionnaire was used to identify affiliation to the intervention group (post-September 2007, n = 1892) or control group (pre-September 2007, n = 2855). To explore dietary habits over time, adolescents attending the same schools in Young-HUNT1 (n = 4137) and Young-HUNT3 (n = 4113) were included. Further, we investigated secular changes in dietary habits according to school type (intervention schools vs control schools). In all analysis, we explored possible differential effects according to socioeconomic status (SES) and gender. A questionnaire measured adolescents' consumption of fruit, vegetables, candy, potato chips, sugar-sweetened beverages (SSB) and artificially sweetened beverages (ASB). Educational intention was used as a proxy for SES. Multilevel logistic regression was used. RESULTS: Within Young-HUNT3, the intervention group showed increased odds of daily consumption of fruit (aOR 1.7, 95% CI = 1.3-2.4) compared to the control group. Over time, adolescents were more likely to consume fruit (aOR = 1.48, 95% CI = 1.28-1.71), vegetables (OR = 1.41, 95% CI = 1.28-1.53), potato chips (aOR = 1.60, 95% CI = 1.26-2.04) and SSB (OR = 2.02, 95% CI = 1.66-2.45). Secular changes for fruit differed by school type: adolescents in intervention schools had higher odds of daily consumption (aOR = 1.82, 95% CI = 1.38-2.38) than those in control schools (aOR 1.26, 95% CI = 1.07-1.47). CONCLUSION: The results indicated that the NSFS increased adolescents' fruit consumption. In the period assessed, the study identified positive and negative changes in adolescents' dietary habits.

Overweight, obesity and the risk of LADA: results from a Swedish case-control study and the Norwegian HUNT Study.

AIMS/HYPOTHESIS: Excessive weight is a risk factor for type 2 diabetes, but its role in the promotion of autoimmune diabetes is not clear. We investigated the risk of latent autoimmune diabetes in adults (LADA) in relation to overweight/obesity in two large population-based studies. METHODS: Analyses were based on incident cases of LADA (n = 425) and type 2 diabetes (n = 1420), and 1704 randomly selected control participants from a Swedish case-control study and prospective data from the Norwegian HUNT Study including 147 people with LADA and 1,012,957 person-years of follow-up (1984-2008). We present adjusted ORs and HRs with 95% CI. RESULTS: In the Swedish data, obesity was associated with an increased risk of LADA (OR 2.93, 95% CI 2.17, 3.97), which was even stronger for type 2 diabetes (OR 18.88, 95% CI 14.29, 24.94). The association was stronger in LADA with low GAD antibody (GADA;

Powerful extreme phenotype sampling designs and score tests for genetic association studies.

We consider cross-sectional genetic association studies (common and rare variants) where non-genetic information is available or feasible to obtain for N individuals, but where it is infeasible to genotype all N individuals. We consider continuously measurable Gaussian traits (phenotypes). Genotyping n < N extreme phenotype individuals can yield better power to detect phenotype-genotype associations, as compared to randomly selecting n individuals. We define a person as having an extreme phenotype if the observed phenotype is above a specified threshold or below a specified threshold. We consider a model where these thresholds can be tailored to each individual. The classical extreme sampling design is to set equal thresholds for all individuals. We introduce a design (z-extreme sampling) where personalized thresholds are defined based on the residuals of a regression model including only non-genetic (fully available) information. We derive score tests for the situation where only n extremes are analyzed (complete case analysis) and for the situation where the non-genetic information on N - n non-extremes is included in the analysis (all case analysis). For the classical design, all case analysis is generally more powerful than complete case analysis. For the z-extreme sample, we show that all case and complete case tests are equally powerful. Simulations and data analysis also show that z-extreme sampling is at least as powerful as the classical extreme sampling design and the classical design is shown to be at times less powerful than random sampling. The method of dichotomizing extreme phenotypes is also discussed.

Has life satisfaction in Norway increased over a 20-year period? Exploring age and gender differences in a prospective longitudinal study, HUNT.

AIM: The aim of the present study was to investigate the change in overall life satisfaction for different age groups and between genders over a 20-year period. METHODS: Data from 1984 to 2008 were extracted from a large prospective longitudinal health study of Nord-Trøndelag (HUNT), Norway. The study included more than 176,000 participants ranging from 20 to 70+ years of age. Data were analysed using logistic regression and adjusted for gender. RESULTS: The analyses revealed an increase in life satisfaction for all age groups from 1984-1986 (HUNT 1) to 1995-1997 (HUNT 2), with the highest levels being reached at 2006-2008 (HUNT 3). For all age groups, the data showed an increase of about 20% for the period from 1984-1986 (HUNT 1) to 1995-1997 (HUNT 2). From 1995-1997 (HUNT 2) to 2006-2008 (HUNT 3), the increase in overall life satisfaction was 16% for the younger age groups, and about 32% for the older age groups (40-69 and 70+ years). Women's scores for overall life satisfaction were higher for nearly all age groups when compared to men using HUNT 3 as a reference. CONCLUSIONS: These findings suggest an increase in life satisfaction for all age groups from 1984 to 2008, especially for the older age group (40-69 and 70+ years). The data indicate that women score higher on life satisfaction for most age groups as compared to men.

Self-reported visual impairment, physical activity and all-cause mortality: The HUNT Study.

AIMS: To examine the associations of self-reported visual impairment and physical activity (PA) with all-cause mortality. METHODS: This prospective cohort study included 65,236 Norwegians aged ⩾20 years who had participated in the Nord-Trøndelag Health Study (HUNT2, 1995-1997). Of these participants, 11,074 (17.0%) had self-reported visual impairment (SRVI). The participants' data were linked to Norway's Cause of Death Registry and followed throughout 2012. Hazard ratios and 95% confidence intervals (CI) were assessed using Cox regression analyses with age as the time-scale. The Cox models were fitted for restricted age groups (<60, 60-84, ⩾85 years). RESULTS: After a mean follow-up of 14.5 years, 13,549 deaths were identified. Compared with adults with self-reported no visual impairment, the multivariable hazard ratios among adults with SRVI were 2.47 (95% CI 1.94-3.13) in those aged <60 years, 1.22 (95% CI 1.13-1.33) in those aged 60-84 years and 1.05 (95% CI 0.96-1.15) in those aged ⩾85 years. The strength of the associations remained similar or stronger after additionally controlling for PA. When examining the joint associations, the all-cause mortality risk of SRVI was higher for those who reported no PA than for those who reported weekly hours of PA. We found a large, positive departure from additivity in adults aged <60 years, whereas the departure from additivity was small for the other age groups. CONCLUSIONS: Adults with SRVI reporting no PA were associated with an increased all-cause mortality risk. The associations attenuated with age.