Body mass index and all-cause mortality in HUNT and UK biobank studies: revised non-linear Mendelian randomisation analyses.

OBJECTIVES: To estimate the shape of the causal relationship between body mass index (BMI) and mortality risk in a Mendelian randomisation framework. DESIGN: Mendelian randomisation analyses of two prospective population-based cohorts. SETTING: Individuals of European ancestries living in Norway or the UK. PARTICIPANTS: 56 150 participants from the Trøndelag Health Study (HUNT) in Norway and 366 385 participants from UK Biobank recruited by postal invitation. OUTCOMES: All-cause mortality and cause-specific mortality (cardiovascular, cancer, non-cardiovascular non-cancer). RESULTS: A previously published non-linear Mendelian randomisation analysis of these data using the residual stratification method suggested a J-shaped association between genetically predicted BMI and mortality outcomes with the lowest mortality risk at a BMI of around 25 kg/m2. However, the 'constant genetic effect' assumption required by this method is violated. The reanalysis of these data using the more reliable doubly-ranked stratification method provided some indication of a J-shaped relationship, but with much less certainty as there was less precision in estimates at the lower end of the BMI distribution. Evidence for a harmful effect of reducing BMI at low BMI levels was only present in some analyses, and where present, only below 20 kg/m2. A harmful effect of increasing BMI for all-cause mortality was evident above 25 kg/m2, for cardiovascular mortality above 24 kg/m2, for cancer mortality above 30 kg/m2 and for non-cardiovascular non-cancer mortality above 26 kg/m2. In UK Biobank, the association between genetically predicted BMI and mortality at high BMI levels was stronger in women than in men. CONCLUSION: This research challenges findings from previous conventional observational epidemiology and Mendelian randomisation investigations that the lowest level of mortality risk is at a BMI level of around 25 kg/m2. Our results provide some evidence that reductions in BMI will increase mortality risk for a small proportion of the population, and clear evidence that increases in BMI will increase mortality risk for those with BMI above 25 kg/m2.

Associations of Serum Vitamin D With Dental Caries and Periodontitis: The HUNT Study.

OBJECTIVE: To study the relationships of serum 25-hydroxyvitamin D [25(OH)D] with dental caries and periodontitis in a general Norwegian adult population. METHODS: We analysed a subsample of 1605 participants from the Trøndelag Health Study (HUNT) in Norway that had serum 25(OH)D levels measured in HUNT3 (2006-08) and oral health assessed in the HUNT4 Oral Health Study (2017-19). Negative binomial and Poisson regression models were used to estimate the ratios of means (RMs; for count oral outcomes) and prevalence ratios (PRs; for dichotomous oral outcomes). RESULTS: Serum 25(OH)D was inversely associated with the number of decayed teeth in a dose-response gradient (<30.0 nmol/L: RM 1.41, 95% CI 1.07-1.85; 30.0-49.9 nmol/L: 1.14, 0.98-1.32 and ≥75.0 nmol/L: 0.84, 0.67-1.04, as compared to the 50.0-74.9 nmol/L group, P for trend <.001). Each 25 nmol/L decrease in 25(OH)D level was associated with a 15% (RM 1.15, 95% CI 1.05-1.26) increase in the mean number of decayed teeth. Serum 25(OH)D <30.0 nmol/L was associated with a 35% higher prevalence of severe periodontitis (PR 1.35, 95% CI 1.00-1.83). No association was observed between 25(OH)D and the number of natural teeth. CONCLUSION: The present study suggested that serum 25(OH)D level had an inverse and dose-response association with the number of decayed teeth, and serum 25(OH)D <30 nmol/L was associated with a higher prevalence of severe periodontitis in this Norwegian adult population.

Sex hormones and risk of lung and colorectal cancers in women: a Mendelian randomization study.

The roles of sex hormones such as estradiol, testosterone, and sex hormone-binding globulin (SHBG) in the etiology of lung and colorectal cancers in women, among the most common cancers after breast cancer, are unclear. This Mendelian randomization (MR) study evaluated such potential causal associations in women of European ancestry. We used summary statistics data from genome-wide association studies (GWASs) on sex hormones and from the Trøndelag Health (HUNT) Study and large consortia on cancers. There was suggestive evidence of genetically predicted 1-standard deviation increase in total testosterone levels being associated with a lower risk of lung non-adenocarcinoma (hazard ratio (HR) 0.60, 95% CI 0.37-0.98) in the HUNT Study. However, this was not confirmed by using data from a larger consortium. In general, we did not find convincing evidence to support a causal role of sex hormones on risk of lung and colorectal cancers in women of European ancestry.

The association between serum vitamin D status and dental caries or molar incisor hypomineralisation in 7-9-year-old Norwegian children: a cross-sectional study.

BACKGROUND: Research focusing on the association between serum vitamin D and oral health outcomes in children, such as dental caries and molar incisor hypomineralisation (MIH), shows inconsistent results. Previous studies have predominantly investigated dental caries and MIH as dichotomized outcomes, which limits the information on their distribution. In addition, the methods used for analysing serum vitamin D have varied. The present study aimed to investigate potential associations between serum vitamin D status measured by Liquid Chromatography with Tandem Mass Spectrometry (LC-MS/MS) and the prevalence, as well as the number of teeth, affected by dental caries or MIH among 7-9-year-old Norwegian children. METHODS: The study had a cross-sectional design and included 101 children aged 7-9 years. Serum 25-hydroxyvitamin D (25(OH)D) was measured and included as continuous (per 25 nmol/l) and categorised (insufficient (< 50 nmol/l) and sufficient (≥50 nmol/l)) exposure variables. Adjusted negative binomial hurdle models were used to investigate the potential associations between serum vitamin D and the oral health outcomes (dental caries and MIH) adjusted for sex, age, body mass index, season of blood draw, and mother's educational level. RESULTS: Of the 101 children in the total sample, 27% had insufficient vitamin D levels (< 50 nmol/l). The descriptive analysis indicated that the children with insufficient vitamin D levels had a higher prevalence (33.3%) and a higher number of teeth affected by dental caries (mean (SD) = 0.7 (1.4)), compared to children with sufficient levels of vitamin D (21.6% and mean (SD) = 0.4 (0.8), respectively). The same holds for MIH, with a higher prevalence (38.5%) and a higher number of teeth affected (mean (SD) = 1.2 (2.3)), compared to children with sufficient levels of vitamin D (30.1% and mean (SD) = 0.8 (1.6), respectively). However, in the adjusted hurdle model analysis, neither the prevalence or number of teeth affected by caries or MIH showed statistically significant associations with having insufficient or lower vitamin D levels. CONCLUSIONS: Vitamin D status was not significantly associated with the prevalence and number of teeth affected by caries and MIH among the participating children. Large prospective studies with multiple serum vitamin D measurements and oral examinations throughout childhood are warranted to elucidate the relationship.

Increased expression of individual genes in whole blood is associated with late-stage lung cancer at and close to diagnosis.

Lung cancer (LC) mortality rates are still increasing globally. As survival is linked to stage, there is a need to identify markers for earlier LC diagnosis and individualized treatment. The whole blood transcriptome of LC patients represents a source of potential LC biomarkers. We compared expression of > 60,000 genes in whole blood specimens taken from LC cases at diagnosis (n = 128) and controls (n = 62) using genome-wide RNA sequencing, and identified 14 candidate genes associated with LC. High expression of ANXA3, ARG1 and HP was strongly associated with lower survival in late-stage LC cases (hazard ratios (HRs) = 2.81, 2.16 and 2.54, respectively). We validated these markers in two independent population-based studies with pre-diagnostic whole blood specimens taken up to eight years prior to LC diagnosis (n = 163 cases, 184 matched controls). ANXA3 and ARG1 expression was strongly associated with LC in these specimens, especially with late-stage LC within two years of diagnosis (odds ratios (ORs) = 3.47 and 5.00, respectively). Additionally, blood CD4 T cells, NK cells and neutrophils were associated with LC at diagnosis and improved LC discriminative ability beyond candidate genes. Our results indicate that in whole blood, increased expression levels of ANXA3, ARG1 and HP are diagnostic and prognostic markers of late-stage LC.

Prevalence of malnutrition among older adults in a population-based study - the HUNT Study.

BACKGROUND: Malnutrition is common in older adults and is associated with increased morbidity and mortality rates. AIM: The aim of the study is to describe the prevalence of malnutrition based on low BMI, involuntary weight loss, and reduced food intake, in a Norwegian population of community-dwelling older adults and older adults living in nursing homes. METHODS: This population-based study is part of the fourth wave of the Trøndelag Health Study (HUNT4) and includes participants ≥70 years from the HUNT4 70+ cohort. The HUNT4 70+ cohort consist of 9930 (response rate 51.2%) participants. In the current study 8127 older people had complete dataset for inclusion in the analyses. Participants completed a self-report questionnaire and standardised interviews and clinical assessments at field stations, in participants' homes or at nursing homes. Malnutrition was defined using the following criteria: low BMI, involuntary weight loss and severely reduced food intake. The standardised prevalence of malnutrition was estimated using inverse probability weighting (IPW) with weights for sex, age and education of the total population in the catchment area of HUNT. RESULTS: Of the 8127 included participants, 7671 (94.4%) met at field stations, 356 (4.4%) were examined in their home, and 100 (1.2%) in nursing homes. In total, 14.3% of the population were malnourished based on either low BMI, weight loss, or reduced food intake, of which low BMI was the most frequently fulfilled criterion. The prevalence of malnutrition was less common among men than among women (10.1 vs 18.0%, p < 0.001), also after adjustment for age (OR 0.53, 95% confidence interval (CI) 0.46-0.61). The prevalence increased gradually with increasing age and the regression analysis adjusted for sex showed that for each year increase in age the prevalence of malnutrition increased with 4.0% (OR 1.04, 95% CI 1.03-1.05). The prevalence was higher both among older adults examined in their homes (26.4%) and residents in nursing home (23.6%), as compared to community-dwelling older adults who met at field stations (13.5%). CONCLUSION: The prevalence of malnutrition is high in the older population. Special attention on prevention and treatment of malnutrition should be given to older women, the oldest age groups, and care-dependent community-dwelling older adults and nursing home residents.

Age at Menarche, age at Natural Menopause, and Risk of Lung and Colorectal Cancers: A Mendelian Randomization Study.

Background: The roles of age at menarche and age at menopause in the etiology of lung and colorectal cancers are unclear. Objective: We aimed to investigate potential causal associations between age at menarche, age at natural menopause, and risk of lung and colorectal cancers using a Mendelian randomization (MR) approach. Methods: From the Trøndelag Health Study in Norway, we defined two cohorts of 35 477 and 17 118 women to study the effects of age at menarche and age at natural menopause, respectively. We ran univariable MR to evaluate the potential causal associations. We performed multivariable MR adjusting for genetic variants of adult body mass index (BMI) to estimate the direct effect of age at menarche. Results: Genetically predicted 1-year increase in age at menarche was associated with a lower risk of lung cancer overall (hazard ratio [HR, 0.64; 95% CI, 0.48-0.86), lung adenocarcinoma (HR, 0.61; 95% CI, 0.38-0.99), and lung non-adenocarcinoma (HR, 0.66; 95% CI, 0.45-0.95). After adjusting for adult BMI using a multivariable MR model, the direct effect estimates reduced to HR 0.72 (95% CI, 0.54-0.95) for lung cancer overall, HR 0.67 (95% CI, 0.43-1.03) for lung adenocarcinoma, and HR 0.77 (95% CI, 0.54-1.09) for lung non-adenocarcinoma. Age at menarche was not associated with colorectal cancer. Moreover, genetically predicted age at natural menopause was not associated with lung and colorectal cancers. Conclusion: Our MR study suggested that later age at menarche was causally associated with a decreased risk of lung cancer overall and its subtypes, and adult BMI might be a mediator.

Estimated cardiorespiratory fitness in relation to overall, breast and prostate cancer incidence: the Norwegian HUNT study.

PURPOSE: To investigate the relationships between the estimated cardiorespiratory fitness (eCRF) and the incidence of overall, breast, and prostate cancer in a large prospective cohort study. METHODS: We included 46,968 cancer-free adults who participated in the second survey of the Trøndelag Health Study in Norway. Sex-specific non-exercise algorithms were used to estimate CRF. eCRF was classified into sex and age-specific tertiles, that is, into low, medium and high levels. Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: Over a median of 22.1 years' follow-up, there were 7752 overall, 858 breast and 1376 prostate cancer cases. Medium and high levels of eCRF were associated with a reduced incidence of overall cancer in a dose-response manner in all participants (HR 0.96; 95% CI, 0.90-1.01 and HR 0.85; 95% CI, 0.79-0.91, respectively, and P-value for trend <.001). No association was observed between eCRF and breast cancer incidence in women. Only the high level of eCRF seemed to be associated with a reduced incidence of prostate cancer in men (HR 0.85; 95% CI, 0.72-1.02). CONCLUSIONS: eCRF may be a practical and cost-effective means of investigating the association between the CRF and cancer incidence.

Reproductive Factors in Relation to Incidence of Lung and Colorectal Cancers in a Cohort of Norwegian Women: The HUNT Study.

Context: The roles of reproductive factors in the etiology of lung and colorectal cancers, among the most common cancers in women, are unclear. Objective: We aimed to explore whether female reproductive factors were associated with the incidence of lung and colorectal cancers. Methods: We followed up 33 314 cancer-free women who participated in the HUNT Study in Norway from 1995-1997 to 2018. A large panel of reproductive factors were self-reported at baseline. Incident lung and colorectal cancer cases were ascertained from the Cancer Registry of Norway. Cox regression models were used to estimate hazard ratios (HRs) with 95% CIs after adjustment for important confounders. Results: During a median follow-up interval of 22.2 years, 467 women developed lung cancer (including 169 lung adenocarcinoma), 660 developed colon cancer, and 211 had rectal cancer. Early menarche (≤12 years) was associated with an increased incidence of lung adenocarcinoma (HR 1.43; 95% CI, 1.02-2.03). Women with one or no child had an increased colon cancer incidence (HR 1.26; 95% CI, 1.03-1.54). Hormone therapy appeared to be associated with a decreased incidence of rectal cancer (HR 0.68; 95% CI, 0.44-1.04). Results in the subgroup of postmenopausal women were similar or strengthened. Other reproductive factors were not related to the risk of lung, colon, and rectal cancers. Conclusion: Certain reproductive factors might play a role in the etiology of lung and colorectal cancers. Further investigations are warranted to study if they are causal associations.

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.

Oral health history in children referred to a child advocacy center in Norway.

BACKGROUND: Some suspected child victims of physical or sexual abuse undergo dental forensic examinations at child advocacy centers (CACs) in Norway. Their oral health history has not previously been studied. OBJECTIVE: This study aimed to compare oral health history of CAC children to matched children. Additionally, the oral health history of children exposed to sexual abuse was compared to children exposed to physical abuse. PARTICIPANTS AND SETTING: The CAC cohort included 100 children, 3-16 years. The matched cohort, with no known history of abuse, included 63 children. METHODS: The retrospective study analyzed registered data in the children's dental records. RESULTS: CAC children were more likely than matched children to have caries experience in both primary and permanent teeth, with incidence rate ratio (IRR) 1.50 (95 % CI 1.01-2.25) and 1.92 (1.11-3.30). "Was Not Brought" to dental appointments was more than twice as likely, IRR 2.25 (1.31-3.86), in the CAC cohort. There were no significant differences in reports to the Child Protection Services or dental traumas. Suspected victims of sexual abuse had more caries, IRR 4.28 (2.36-7.77), and fillings, IRR 4.83 (2.55-9.16), in permanent teeth compared to suspected victims of physical abuse. CONCLUSIONS: CAC children were more likely to have caries experience and not show up for dental appointments than the matched children. Sexual abuse suspected had four times more caries experience than physical abuse suspected. This study supports the need for addressing oral health in risk evaluations concerning child abuse, and provides valuable information to dental professionals and prosecuting authorities.

The validity of self-reported number of teeth and edentulousness among Norwegian older adults, the HUNT Study.

BACKGROUND: Number of teeth is an established indicator of oral health and is commonly self-reported in epidemiological studies due to the costly and labor-intensive nature of clinical examinations. Although previous studies have found self-reported number of teeth to be a reasonably accurate measure, its accuracy among older adults ≥ 70 years is less explored. The aim of this study was to assess the validity of self-reported number of teeth and edentulousness in older adults and to investigate factors that may affect the accuracy of self-reports. METHODS: This study included two different samples of older adults ≥ 70 years drawn from the fourth wave of the Trøndelag Health Study (the HUNT Study), Norway. Sample 1 (n = 586) was used to evaluate the validity of self-reported number of teeth and sample 2 (n = 518) was used to evaluate self-reported edentulousness. Information on number of teeth and background variables (education, smoking, cognitive function, and self-perceived general and oral health) were self-reported in questionnaires, while clinical oral health examinations assessed number of teeth, number of teeth restored or replaced by fixed prosthodontics and edentulousness. Spearman and Pearson correlation coefficients, Bland-Altman plot, chi-square test and kappa statistics were used to assess the agreement between self-reported and clinically recorded number of teeth. RESULTS: The mean difference between self-reported and clinically recorded number of teeth was low (- 0.22 teeth), and more than 70% of the participants reported their number of teeth within an error of two teeth. Correlations between self-reports and clinical examinations were high for the total sample (0.86 (Spearman) and 0.91 (Pearson)). However, a lower correlation was found among participants with dementia (0.74 (Spearman) and 0.85 (Pearson)), participants having ≥ 20 teeth (0.76 (Spearman) and 0.67 (Pearson)), and participants with ≥ 5 teeth restored or replaced by fixed prosthodontics (0.75 (Spearman) and 0.77 (Pearson)). Self-reports of having teeth or being edentulous were correct in 96.3% of the cases (kappa value 0.93, p value < 0.001). CONCLUSIONS: Among older Norwegian adults, self-reported number of teeth agreed closely with clinical tooth counts and nearly all the edentulous participants correctly reported having no teeth.

Coupling of the engineered DNA "mutator" to a biosensor as a new paradigm for activation of silent biosynthetic gene clusters in Streptomyces.

DNA replication fidelity in Streptomyces bacteria, prolific producers of many medically important secondary metabolites, is understudied, while in Escherichia coli it is controlled by DnaQ, the ϵ subunit of DNA polymerase III (DNA PolIII). Manipulation of dnaQ paralogues in Streptomyces lividans TK24, did not lead to increased spontaneous mutagenesis in this bacterium suggesting that S. lividans DNA PolIII uses an alternative exonuclease activity for proofreading. In Mycobacterium tuberculosis, such activity is attributed to the DnaE protein representing α subunit of DNA PolIII. Eight DnaE mutants designed based on the literature data were overexpressed in S. lividans, and recombinant strains overexpressing two of these mutants displayed markedly increased frequency of spontaneous mutagenesis (up to 1000-fold higher compared to the control). One of these 'mutators' was combined in S. lividans with a biosensor specific for antibiotic coelimycin, which biosynthetic gene cluster is present but not expressed in this strain. Colonies giving a positive biosensor signal appeared at a frequency of ca 10-5, and all of them were found to produce coelimycin congeners. This result confirmed that our approach can be applied for chemical- and radiation-free mutagenesis in Streptomyces leading to activation of orphan biosynthetic gene clusters and discovery of novel bioactive secondary metabolites.

Corrigendum to "Health-Related Quality of Life and Sleep Quality after 12 Months of Treatment in Nonsevere Obstructive Sleep Apnea: A Randomized Clinical Trial with Continuous Positive Airway Pressure and Mandibular Advancement Splints".

[This corrects the article DOI: 10.1155/2020/2856460.].

Assessing the role of genome-wide DNA methylation between smoking and risk of lung cancer using repeated measurements: the HUNT study.

BACKGROUND: It is unclear if smoking-related DNA methylation represents a causal pathway between smoking and risk of lung cancer. We sought to identify novel smoking-related DNA methylation sites in blood, with repeated measurements, and to appraise the putative role of DNA methylation in the pathway between smoking and lung cancer development. METHODS: We derived a nested case-control study from the Trøndelag Health Study (HUNT), including 140 incident patients who developed lung cancer during 2009-13 and 140 controls. We profiled 850 K DNA methylation sites (Illumina Infinium EPIC array) in DNA extracted from blood that was collected in HUNT2 (1995-97) and HUNT3 (2006-08) for the same individuals. Epigenome-wide association studies (EWAS) were performed for a detailed smoking phenotype and for lung cancer. Two-step Mendelian randomization (MR) analyses were performed to assess the potential causal effect of smoking on DNA methylation as well as of DNA methylation (13 sites as putative mediators) on risk of lung cancer. RESULTS: The EWAS for smoking in HUNT2 identified associations at 76 DNA methylation sites (P < 5 × 10-8), including 16 novel sites. Smoking was associated with DNA hypomethylation in a dose-response relationship among 83% of the 76 sites, which was confirmed by analyses using repeated measurements from blood that was collected at 11 years apart for the same individuals. Two-step MR analyses showed evidence for a causal effect of smoking on DNA methylation but no evidence for a causal link between DNA methylation and the risk of lung cancer. CONCLUSIONS: DNA methylation modifications in blood did not seem to represent a causal pathway linking smoking and the lung cancer risk.

Asthma and asthma symptom control in relation to incidence of lung cancer in the HUNT study.

Large prospective studies on asthma, especially asthma symptom control, as a potential risk factor for lung cancer are limited. We followed up 62,791 cancer-free Norwegian adults from 1995-1997 to 2017. Self-reported doctor-diagnosed asthma was categorized into active and non-active asthma. Levels of asthma symptom control were classified into controlled and partially controlled (including partly controlled and uncontrolled) according to the Global Initiative for Asthma guidelines. 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) for possible associations. Totally, 984 participants developed lung cancer during a median follow-up of 21.1 years. After adjustment for smoking and other potential confounders, an increased incidence of lung cancer was found for adults with partially controlled asthma (HR 1.39, 95% CI 1.00-1.92) compared with those without asthma at baseline. Adults with active asthma had a tendency of increased lung cancer incidence (HR 1.29, 95% CI 0.95-1.75). Sensitivity analyses indicated that the observed associations were less likely resulted from reverse causation or residual confounding by smoking. Our findings suggested that proper control of asthma symptoms might contribute to a reduced incidence of lung cancer.

Vitamin D status and risk of type 2 diabetes in the Norwegian HUNT cohort study: does family history or genetic predisposition modify the association?

INTRODUCTION: We sought to investigate the relationship between serum 25-hydroxyvitamin D (25(OH)D) level and the risk of type 2 diabetes mellitus (T2DM) in adults who participated in the Trøndelag Health Study (HUNT), and the possible effect modification by family history and genetic predisposition. RESEARCH DESIGN AND METHODS: This prospective study included 3574 diabetes-free adults at baseline who participated in the HUNT2 (1995-1997) and HUNT3 (2006-2008) surveys. Serum 25(OH)D levels were determined at baseline and classified as <50 and ≥50 nmol/L. Family history of diabetes was defined as self-reported diabetes among parents and siblings. A Polygenic Risk Score (PRS) for T2DM based on 166 single-nucleotide polymorphisms was generated. Incident T2DM was defined by self-report and/or non-fasting glucose levels greater than 11 mmol/L and serum glutamic acid decarboxylase antibody level of <0.08 antibody index at the follow-up. Multivariable logistic regression models were applied to calculate adjusted ORs with 95% CIs. Effect modification by family history or PRS was assessed by likelihood ratio test (LRT). RESULTS: Over 11 years of follow-up, 92 (2.6%) participants developed T2DM. A higher risk of incident T2DM was observed in participants with serum 25(OH)D level of<50 nmol/L compared with those of ≥50 nmol/L (OR 1.72, 95% CI 1.03 to 2.86). Level of 25(OH)D<50 nmol/L was associated with an increased risk of T2DM in adults without family history of diabetes (OR 3.87, 95% CI 1.62 to 9.24) but not in those with a family history (OR 0.72, 95% CI 0.32 to 1.62, p value for LRT=0.003). There was no effect modification by PRS (p value for LRT>0.23). CONCLUSION: Serum 25(OH)D<50 nmol/L was associated with an increased risk of T2DM in Norwegian adults. The inverse association was modified by family history of diabetes but not by genetic predisposition to T2DM.

Serum 25-hydroxyvitamin D level in relation to weight change and the risk of weight gain in adults of normal weight at baseline: the Norwegian HUNT cohort study.

OBJECTIVE: We sought to investigate the relationship of serum 25-hydroxyvitamin D (25(OH)D) level with weight change and the risk of weight gain in an adult population who had normal weight at baseline and were followed up for 11 years. DESIGN: A population-based prospective cohort study. SETTING: Nord-Trøndelag, Norway. PARTICIPANTS: The study included 1501 adults who participated in the second and third surveys of the Nord-Trøndelag Health Study (HUNT2 (1995-1997) and HUNT3 (2006-2008)) and had a normal body mass index ≥18.5 and <25.0 kg/m2 at baseline. PRIMARY AND SECONDARY OUTCOME MEASURES: Relative weight change (%) was calculated as ((HUNT3 weight-HUNT2 weight)/HUNT2 weight×100). Relative annual weight change (%) was calculated as (relative weight change/follow-up years×100). Clinical weight gain was defined as relative weight change ≥5% over the 11 years, while annual weight gain was defined as relative annual weight change >1.25%. METHODS: Multiple regression models were used to estimate adjusted coefficients for the relative annual weight change and risk ratios (RRs) for the risk of clinical weight gain and of annual weight gain. RESULTS: Each 25 nmol/L increase in season-standardised serum 25(OH)D level at baseline was associated with a reduction of 0.05% (95% CI -0.11 to 0.01) for relative annual weight change, a 10% (RR 0.90, 95% CI 0.82 to 0.97) reduced risk of clinical weight gain, and a 19% (RR 0.81, 95% CI 0.65 to 1.00) reduced risk of annual weight gain. A statistically significant trend was evident for the risk of clinical weight gain when 25(OH)D levels were treated as a categorical variable (p=0.006). CONCLUSIONS: The findings suggested an inverse association of serum 25(OH)D level with the risk of clinical weight gain in adults who had normal weight at baseline over 11 years' follow-up.

Health-Related Quality of Life and Sleep Quality after 12 Months of Treatment in Nonsevere Obstructive Sleep Apnea: A Randomized Clinical Trial with Continuous Positive Airway Pressure and Mandibular Advancement Splints.

In this randomized controlled trial, patients with nonsevere obstructive sleep apnea (OSA) were treated with continuous positive airway pressure (CPAP) or a twin block mandibular advancement splint (MAS). The primary objective was to compare how CPAP and MAS treatments change the health-related quality of life (HRQoL) and self-reported sleep quality of patients after 12 months of treatment. In total, 104 patients were recruited: 55 were allocated to the CPAP treatment group and 49 to the MAS treatment group. We used the SF36 questionnaire to evaluate HRQoL and the Pittsburgh Sleep Quality Index (PSQI) to evaluate sleep quality. All patients were included in the intention-to-treat analyses. These analyses showed improvements in the SF36 physical component score (from 48.8 ± 7.6 at baseline to 50.5 ± 8.0 at follow-up, p=0.03) in the CPAP treatment group and in the mental component score (from 44.9 ± 12.1 to 49.3 ± 9.2, p=0.009) in the MAS treatment group. The PSQI global score improved in both the CPAP (from 7.7 ± 3.5 to 6.6 ± 2.9, p=0.006) and the MAS (8.0 ± 3.1 to 6.1 ± 2.6, p < 0.001) treatment groups. No difference was found between the treatment groups in any of the SF36 scores or PSQI global score at the final follow-up (p > 0.05) in any analysis. The improvement in the SF36 vitality domain moderately correlated to the improvement in the PSQI global score in both groups (CPAP: |r|=0.47, p < 0.001; MAS: |r|=0.36, p=0.01). In the MAS treatment group, we also found a weak correlation between improvements in the SF36 mental component score and PSQI global score (|r|=0.28, p=0.05). In conclusion, CPAP and MAS treatments lead to similar improvements in the HRQoL and self-reported sleep quality in nonsevere OSA. Improvements in aspects of HRQoL seem to be moderately correlated to the self-reported sleep quality in both CPAP and MAS treatments.

Friedman Score in Relation to Compliance and Treatment Response in Nonsevere Obstructive Sleep Apnea.

Nonsevere obstructive sleep apnea (OSA) is most often treated with a continuous positive airway pressure (CPAP) device or a mandibular advancement splint (MAS). However, patient compliance with these treatments is difficult to predict. Improvement in apnea-hypopnea index (AHI) is also somewhat unpredictable in MAS treatment. In this study, we investigated the association between Friedman tongue position score (Friedman score) and both treatment compliance and AHI improvement in patients with nonsevere OSA receiving CPAP or MAS treatment. 104 patients with nonsevere OSA were randomly allocated to CPAP or MAS treatment and followed for 12 months. Data were collected through a medical examination, questionnaires, sleep recordings from ambulatory type 3 polygraphic sleep recording devices, and CPAP recordings. Associations between Friedman score, treatment compliance, and AHI improvement were analysed with logistic regression analyses. Friedman score was not associated with treatment compliance (odds ratio [OR]: 0.85, 95% confidence interval [CI]: 0.59-1.23), or AHI improvement (OR: 1.05, 95% CI: 0.62-1.76) in the overall study sample, the CPAP treatment group, or the MAS treatment group. Adjustment for socioeconomic factors, body mass index, and tonsil size did not significantly impact the results. Although Friedman score may predict OSA severity and contribute to the prediction of success in uvulopalatopharyngoplasty, we found no association between Friedman score and treatment compliance in patients with nonsevere OSA receiving CPAP or MAS treatment, nor did we find any association between Friedman score and AHI improvement. Factors other than Friedman score should be considered when deciding whether a patient with nonsevere OSA should be treated with CPAP or MAS.