Abstract: AIMS/HYPOTHESIS: We examined the association between sitting time and diabetes incidence, overall and by strata of leisure-time physical activity and BMI. METHODS: We followed 28,051 adult participants of the Nord-Trondelag Health Study (the HUNT Study), a population-based study, for diabetes incidence from 1995-1997 to 2006-2008 and estimated HRs of any diabetes by categories of self-reported total daily sitting time at baseline. RESULTS: Of 28,051 participants, 1253 (4.5%) developed diabetes during 11 years of follow-up. Overall, sitting >/=8 h/day was associated with a 17% (95% CI 2, 34) higher risk of developing diabetes compared with sitting </=4 h/day, adjusted for age, sex and education. However, the association was attenuated to a non-significant 9% (95% CI -5, 26) increase in risk after adjustment for leisure-time physical activity and BMI. The association between sitting time and diabetes risk differed by leisure-time physical activity (p Interaction = 0.01). Among participants with low leisure-time physical activity (</=2 h light activity per week and no vigorous activity), sitting 5-7 h/day and >/=8 h/day were associated with a 26% (95% CI 2, 57) and 30% (95% CI 5, 61) higher risk of diabetes, respectively, compared with sitting </=4 h/day. There was no corresponding association among participants with high leisure-time physical activity (>/=3 h light activity or >0 h vigorous activity per week). There was no statistical evidence that the association between sitting time and diabetes risk differed by obesity (p Interaction = 0.65). CONCLUSIONS/INTERPRETATION: Our findings suggest that total sitting time has little association with diabetes risk in the population as a whole, but prolonged sitting may contribute to an increased diabetes risk among physically inactive people.

Abstract: BACKGROUND: Cigarette smoking is strongly associated with mental illness but the causal direction of the association is uncertain. We investigated the causal relationship between smoking and symptoms of anxiety and depression in the Norwegian HUNT study using the rs1051730 single nucleotide polymorphism (SNP) variant located in the nicotine acetylcholine receptor gene cluster on chromosome 15 as an instrumental variable for smoking phenotypes. Among smokers, this SNP is robustly associated with smoking quantity and nicotine dependence. Method In total, 53 601 participants were genotyped for the rs1051730 SNP and provided information on smoking habits and symptoms of anxiety and depression using the Hospital Anxiety and Depression Scale (HADS). RESULTS: Self-reported smoking was positively associated with the prevalence of both anxiety and depression, and the measured polymorphism was positively associated with being a current smoker and the number of cigarettes smoked in current smokers. In the sample as a whole, risk of anxiety increased with each affected T allele [odds ratio (OR) 1.06, 95% confidence interval (CI) 1.02-1.09, p = 0.002] but there was no association with depression (p = 0.31). However, we found no clear association of the polymorphism with either anxiety (OR 1.03, 95% CI 0.97-1.09, p = 0.34) or depression (OR 1.02, 95% CI 0.95-1.09, p = 0.62) among smokers. CONCLUSIONS: As there was no association of the smoking-related rs1051730 SNP with anxiety and depression among smokers, the results suggest that smoking is not a cause of anxiety and depression.

Abstract: Measures of body mass index (BMI) and waist circumference define general obesity and abdominal obesity respectively. While high BMI has been established as a risk factor for asthma in adults, waist circumference has seldom been investigated. To determine the association between BMI, waist circumference and incident asthma in adults, we conducted a prospective study (n=23,245) in a population living in Nord-Trondelag, Norway in 1995-2008. Baseline BMI and waist circumference were measured and categorised as general obesity (BMI >/=30.0 kg.m(2)) and abdominal obesity (waist circumference >/=88 cm in females and >/=102 cm in males). Incident asthma was self-reported new-onset cases during an 11-yr follow-up period. Odds ratios for asthma associated with obesity were calculated using multivariable logistic regression. General obesity was a risk factor for asthma in females (OR 1.96, 95% CI 1.52-2.52) and males (OR 1.84, 95% CI 1.30-2.59). In females, after additional adjustment for BMI, abdominal obesity remained a risk factor for asthma development (OR 1.46, 95% CI 1.04-2.05). Abdominal obesity seems to increase the risk of incident asthma in females in addition to BMI, indicating that using both measures of BMI and waist circumference in females may be a superior clinical assessment for asthma risk than any measure alone.

Abstract: OBJECTIVES: To examine associations of total sitting time, TV-viewing and leisure-time computer use with cardiometabolic risk biomarkers in adults. DESIGN: Population based cross-sectional study. METHODS: Waist circumference, BMI, total cholesterol, HDL cholesterol, blood pressure, non-fasting glucose, gamma glutamyltransferase (GGT) and triglycerides were measured in 48,882 adults aged 20 years or older from the Nord-Trondelag Health Study 2006-2008 (HUNT3). Adjusted multiple regression models were used to test for associations between these biomarkers and self-reported total sitting time, TV-viewing and leisure-time computer use in the whole sample and by cardiometabolic disease status sub-groups. RESULTS: In the whole sample, reporting total sitting time >/=10 h/day was associated with poorer BMI, waist circumference, total cholesterol, HDL cholesterol, diastolic blood pressure, systolic blood pressure, non-fasting glucose, GGT and triglyceride levels compared to those reporting total sitting time <4h/day (all p<0.05). TV-viewing >/=4 h/day was associated with poorer BMI, waist circumference, total cholesterol, HDL cholesterol, systolic blood pressure, GGT and triglycerides compared to TV-viewing <1h/day (all p<0.05). Leisure-time computer use >/=1 h/day was associated with poorer BMI, total cholesterol, diastolic blood pressure, GGT and triglycerides compared with those reporting no leisure-time computing. Sub-group analyses by cardiometabolic disease status showed similar patterns in participants free of cardiometabolic disease, while similar albeit non-significant patterns were observed in those with cardiometabolic disease. CONCLUSIONS: Total sitting time, TV-viewing and leisure-time computer use are associated with poorer cardiometabolic risk profiles in adults. Reducing sedentary behaviour throughout the day and limiting TV-viewing and leisure-time computer use may have health benefits.

Abstract: AIM: The aim of this analysis was to examine the association between asthma and general and abdominal weight status, defined by age- and sex-specific cut-offs for body mass index (BMI) and waist circumference (WC) in adolescents. METHODS: Participants aged 12-19 years in the Young-HUNT (YH) Study (YH1 1995-1997: n = 8222; YH3 2006-2008: n = 7403) completed self-administered questionnaires in school as part of a series of cross-sectional, population-based studies conducted in Nord-Trondelag, Norway. Weight, height and WC were measured. Adjusted odds ratios (ORs) and 95% Confidence Intervals (CI) for asthma, defined by self-reported physician diagnosis, were calculated. Potential effect modifiers evaluated included sex and pubertal development status (PDS). RESULTS: Asthma was reported by 11.8% of the adolescents in YH1 and 17.0% in YH3. Asthma odds significantly increased for adolescents with general (OR = 1.33; 95%CI: 1.13, 1.56), but not abdominal, overweight and increased for adolescents with general (OR = 1.34; 95%CI: 1.02, 1.75) or abdominal obesity (OR = 1.36; 95%CI: 1.16, 1.60). Underweight had no association with asthma regardless of weight assessment type, and PDS did not meaningfully influence the associations between asthma and weight. CONCLUSION: Overweight and obesity both increased the odds of asthma in 12-19 year-old Norwegians. WC did not add further information to that already provided by BMI to improve our understanding of the association between asthma and weight.

Abstract: OBJECTIVE: The purpose of the present paper was to examine the association between prospectively and cross-sectionally assessed cardiovascular risk factors and hearing loss. DESIGN: Hearing was assessed by pure-tone average thresholds at low (0.25-0.5 kHz), middle (1-2 kHz), and high (3-8 kHz) frequencies. Self-reported or measured cardiovascular risk factors were assessed both 11 years before and simultaneously with the audiometric assessment. Cardiovascular risk factors were smoking, alcohol use, physical inactivity, waist circumference, body mass index, resting heart rate, blood pressure, triglycerides, total serum cholesterol, LDL cholesterol, HDL cholesterol, and diabetes. STUDY SAMPLE: A population-based cohort of 31 547 subjects. RESULTS: After adjustment for age, sex, level of education, income, recurrent ear infections, and noise exposure, risk factors associated with poorer hearing sensitivity were smoking, diabetes, physical inactivity, resting heart rate, and waist circumference. Smoking was only associated with hearing loss at high frequencies. The effects were very small, in combination explaining only 0.2-0.4% of the variance in addition to the component explained by age and the other cofactors. CONCLUSION: This cohort study indicates that, although many cardiovascular risk factors are associated with hearing loss, the effects are small and of doubtful clinical relevance.

Abstract: Physical activity (PA) may modify the genetic effects that give rise to increased risk of obesity. To identify adiposity loci whose effects are modified by PA, we performed genome-wide interaction meta-analyses of BMI and BMI-adjusted waist circumference and waist-hip ratio from up to 200,452 adults of European (n = 180,423) or other ancestry (n = 20,029). We standardized PA by categorizing it into a dichotomous variable where, on average, 23% of participants were categorized as inactive and 77% as physically active. While we replicate the interaction with PA for the strongest known obesity-risk locus in the FTO gene, of which the effect is attenuated by ~30% in physically active individuals compared to inactive individuals, we do not identify additional loci that are sensitive to PA. In additional genome-wide meta-analyses adjusting for PA and interaction with PA, we identify 11 novel adiposity loci, suggesting that accounting for PA or other environmental factors that contribute to variation in adiposity may facilitate gene discovery.

Abstract: Lung cancer has the highest mortality of all cancers. Patients with early stage disease have the best cure rates and that emphasizes the importance of early detection. About half of all non-small cell lung cancers (NSCLC) are estrogen receptor positive. The impact of estrogen and its receptors for NSCLC carcinogenesis has been studied but is still unclear. Low estrogen levels are associated with osteoporosis. We hypothesize that low bone mineral density (BMD), a positive history of fracture or self-reported osteoporosis, used as a proxy variable for life time estrogen exposure, are associated with a low incidence of NSCLC. We analyzed data from a cohort study, the Nord-Trondelag Health Study 2 (1995-1997) linked to the Norwegian Cancer Registry. Using the logistic regression model we calculated the odds ratio (OR) with a 95% confidence interval (CI) for the risk of NSCLC for the three proxy variables, stratified by sex. Participants older than 50 years of age, having measured bone density (N = 18,156), having answered the questions on self-reported fracture (N = 37,883) and osteoporosis (N = 25,701) and known body mass index (BMI) (N = 29,291), were evaluated for inclusion. In 6996 participants all these information was available in addition to tobacco use, and in women also hormonal replacement therapy (HRT). Lung function (FEV1 percent of predicted) was included in a sensitivity analysis. We identified 132 (1.9%) cases of NSCLC, 59 (1.2%) and 73 (3.3%) cases in women and men, respectively. Low BMD was associated with a higher risk of NSCLC, OR: 2.38, 95% CI: 1.09-5.18 and OR: 2.67, 95% CI: 1.39-5.16 in women and men, respectively. No association was found between the two other proxy variables and the risk of NSCLC. Inclusion of lung function in the model did not change the results. Contrary to our hypothesis, women and men with low BMD had a higher risk for NSCLC. In addition the study demonstrates that the risk depends on which proxy variable was chosen, and we may ask: are proxy variables reliable?

Abstract: BACKGROUND: Physical activity may counteract the adverse effects of adiposity on cardiovascular mortality; however, the evidence of a similar effect on diabetes is sparse. This study examines whether physical activity may compensate for the adverse effect of adiposity on diabetes risk. METHODS: The study population consisted of 38 231 individuals aged 20 years or more who participated in two consecutive waves of the prospective longitudinal Nord-Trondelag Health Study in Norway: in 1984-1986 and in 1995-1997. A Poisson regression model with SEs derived from robust variance was used to estimate adjusted risk ratios of diabetes between categories of body mass index and physical activity. RESULTS: Risk of diabetes increased both with increasing body mass (Ptrend <0.001) and with decreasing physical activity level (Ptrend <0.001 in men and 0.01 in women). Combined analyses showed that men who were both obese and had low activity levels had a risk ratio of 17 (95% CI 9.52 to 30) compared to men who were normal weight and highly active, whereas obese men who reported high activity had a risk ratio of 13 (95% CI 6.92 to 26). Corresponding analysis in obese women produced risk ratios of 15 (95% CI 9.18 to 25) and 13 (95% CI 7.42 to 21) among women reporting low and high activity levels, respectively. CONCLUSIONS: This study shows that overweight and obesity are associated with a substantially increased risk of diabetes, particularly among those who also reported being physically inactive. High levels of physical activity were associated with a lower risk of diabetes within all categories of body mass index, but there was no clear evidence that being physically active could entirely compensate for the adverse effect of adiposity on diabetes risk.

Abstract: INTRODUCTION: The complexity of obesity and onset and susceptibility of cardio-metabolic disorders are still poorly understood and is addressed here through studies of genetic influence on weight gain and increased metabolic risk longitudinally. SUBJECTS/METHODS: Twenty seven previously identified obesity, eating disorder or metabolic risk susceptibility SNPs were tested for association with weight or metabolically related traits longitudinally in 3999 adults participating both in the HUNT2 (1995-97) and HUNT3 (2006-08) surveys. Regression analyses were performed with changes from normal weight to overweight/obesity or from metabolically healthy to adverse developments with regards to blood pressure, glucose, HDL cholesterol, triglycerides or metabolic syndrome as outcomes. Additionally, a sub-sample of 1380 adolescents was included for testing association of nine SNPs with longitudinal weight gain into young adulthood. RESULTS: The most substantial effect on BMI-based weight gain from normal to overweight/obesity in adults was observed for the DRD2 variant (rs6277)(OR: 0.79, 95% CI: 0.69-0.90, P = 3.9x10-4, adj. P = 0.015). DRD2 was not associated with BMI on a cross-sectional level. In the adolescent sample, FTO (rs1121980) was associated with change to overweight at adulthood in the combined male-female sample (OR: 1.27, 95% CI: 1.09-1.49, P = 3.0x10-3, adj. P = 0.019) and in females (OR: 1.53, 95% CI: 1.23-1.91, P = 1.8x10-4, adj. P = 0.003). When testing for association to longitudinal adverse developments with regard to blood pressure, blood lipids and glucose, only rs964184 (ZNF259/APOA5) was significantly associated to unfavourable triglyceride changes (OR: 1.66, 95% CI: 1.36-2.03, P = 5.7x10-7, adj. P = 0.001). Pleiotropic effects on metabolic traits, however, were observed for several genetic loci cross-sectionally, ZNF259/APOA5, LPL and GRB14 being the most important. CONCLUSIONS: DRD2 exhibits effects on weight gain from normal weight to overweight/obesity in adults, while, FTO is associated to weight gain from adolescence to young adulthood. Unhealthy longitudinal triglyceride development is strongly affected by ZNF259/APOA. Our main finding, linking the DRD2 variant directly to the longitudinal weight gain observed, has not previously been identified. It suggests a genetic pre-disposition involving the dopaminergic signalling pathways known to play a role in food reward and satiety linked mechanisms.

Abstract: BACKGROUND: The association of high-sensitivity C-reactive protein (hsCRP) with metabolic syndrome in younger age groups has not been studied extensively and few population-based studies have included both sexes. Therefore we estimated the association of high-sensitivity C-reactive protein (hsCRP) with the metabolic factors at different ages in men and women in a large population-based study. METHODS AND OBJECTIVES: In this cross-sectional study, clinical information and non-fasting blood samples including measurement of hsCRP from 4587 men and 5408 women 20 years and older in the HUNT study in Norway were used to study the association of components of the metabolic syndrome with levels of hsCRP, by sex and age group. RESULTS: All measured metabolic factors were associated with hsCRP. Among these factors, body mass index appeared to be the most strongly associated, and the strong positive association persisted also after adjustment for the other metabolic factors, with similar associations in women and men. The associations were generally somewhat stronger in younger than in older age groups. CONCLUSION: Metabolic factors, especially body mass index, have a relatively strong association with high-sensitivity C-reactive protein at all ages both in men and women.

Abstract: Experimental studies suggest that vitamin D modulates the activity of adipocytes. The authors examined baseline serum 25-hydroxyvitamin D (25(OH)D) level in relation to prevalent and cumulative incident obesity in Norway. A cohort of 25,616 adults aged 19-55 years participated in both the second and third surveys of the Nord-Trondelag Health Study (HUNT 2 (1995-1997) and HUNT 3 (2006-2008)). Serum 25(OH)D levels measured at baseline and anthropometric measurements taken at both baseline and follow-up were available for a random sample of 2,460 subjects. Overall, 40% of the 2,460 subjects had a serum 25(OH)D level less than 50.0 nmol/L, and 37% had a level of 50.0-74.9 nmol/L. The prevalence and cumulative incidence of obesity, defined as body mass index (weight (kg)/height (m)(2)) >/=30, were 12% and 15%, respectively. Lower serum 25(OH)D level was associated with a higher prevalence of obesity. In the 2,165 subjects with baseline BMI less than 30, a serum 25(OH)D level less than 50.0 nmol/L was associated with a significantly increased odds ratio for incident obesity during follow-up (adjusted odds ratio = 1.73, 95% confidence interval: 1.24, 2.41). When prevalent and incident obesity were classified according to waist circumference (>/=88 cm for women, >/=102 cm for men), similar results were obtained. In addition to prevalent obesity, a serum 25(OH)D level less than 50.0 nmol/L was significantly associated with new-onset obesity in adults.