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  • 1
    In: BMJ Open Diabetes Research & Care, BMJ, Vol. 9, No. 1 ( 2021-01), p. e001948-
    Abstract: 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.
    Type of Medium: Online Resource
    ISSN: 2052-4897
    Language: English
    Publisher: BMJ
    Publication Date: 2021
    detail.hit.zdb_id: 2732918-5
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  • 2
    In: Thorax, BMJ, Vol. 75, No. 3 ( 2020-03), p. 202-208
    Abstract: We aimed to investigate the potential causal associations of adiposity with asthma overall, asthma by atopic status or by levels of symptom control in a large adult population and stratified by sex. We also investigated the potential for reverse causation between asthma and risk of adiposity. Methods We performed a bidirectional one-sample Mendelian randomisation (MR) study using the Norwegian Nord-Trøndelag Health Study population including 56 105 adults. 73 and 47 genetic variants were included as instrumental variables for body mass index (BMI) and waist-to-hip ratio (WHR), respectively. Asthma was defined as ever asthma, doctor-diagnosed asthma and doctor-diagnosed active asthma, and was further classified by atopic status or levels of symptom control. Causal OR was calculated with the Wald method. Results The ORs per 1 SD (4.1 kg/m 2 ) increase in genetically determined BMI were ranged from 1.36 to 1.49 for the three asthma definitions and similar for women and men. The corresponding ORs for non-atopic asthma (range 1.42–1.72) appeared stronger than those for the atopic asthma (range 1.18–1.26), but they were similar for controlled versus partly controlled doctor-diagnosed active asthma (1.43 vs 1.44). There was no clear association between genetically predicted WHR and asthma risk or between genetically predicted asthma and the adiposity markers. Conclusions Our MR study provided evidence of a causal association of BMI with asthma in adults, particularly with non-atopic asthma. There was no clear evidence of a causal link between WHR and asthma or of reverse causation.
    Type of Medium: Online Resource
    ISSN: 0040-6376 , 1468-3296
    Language: English
    Publisher: BMJ
    Publication Date: 2020
    detail.hit.zdb_id: 1481491-2
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  • 3
    In: BMJ Open, BMJ, Vol. 7, No. 6 ( 2017-06), p. e017256-
    Type of Medium: Online Resource
    ISSN: 2044-6055 , 2044-6055
    Language: English
    Publisher: BMJ
    Publication Date: 2017
    detail.hit.zdb_id: 2599832-8
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  • 4
    In: BMJ Open, BMJ, Vol. 10, No. 9 ( 2020-09), p. e039192-
    Abstract: 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/m 2 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.
    Type of Medium: Online Resource
    ISSN: 2044-6055 , 2044-6055
    Language: English
    Publisher: BMJ
    Publication Date: 2020
    detail.hit.zdb_id: 2599832-8
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  • 5
    In: BMJ, BMJ
    Abstract: To investigate the shape of the causal relation between body mass index (BMI) and mortality. Design Linear and non-linear mendelian randomisation analyses. Setting Nord-Trøndelag Health (HUNT) Study (Norway) and UK Biobank (United Kingdom). Participants Middle to early late aged participants of European descent: 56 150 from the HUNT Study and 366 385 from UK Biobank. Main outcome measures All cause and cause specific (cardiovascular, cancer, and non-cardiovascular non-cancer) mortality. Results 12 015 and 10 344 participants died during a median of 18.5 and 7.0 years of follow-up in the HUNT Study and UK Biobank, respectively. Linear mendelian randomisation analyses indicated an overall positive association between genetically predicted BMI and the risk of all cause mortality. An increase of 1 unit in genetically predicted BMI led to a 5% (95% confidence interval 1% to 8%) higher risk of mortality in overweight participants (BMI 25.0-29.9) and a 9% (4% to 14%) higher risk of mortality in obese participants (BMI ≥30.0) but a 34% (16% to 48%) lower risk in underweight (BMI 〈 18.5) and a 14% (−1% to 27%) lower risk in low normal weight participants (BMI 18.5-19.9). Non-linear mendelian randomisation indicated a J shaped relation between genetically predicted BMI and the risk of all cause mortality, with the lowest risk at a BMI of around 22-25 for the overall sample. Subgroup analyses by smoking status, however, suggested an always-increasing relation of BMI with mortality in never smokers and a J shaped relation in ever smokers. Conclusions The previously observed J shaped relation between BMI and risk of all cause mortality appears to have a causal basis, but subgroup analyses by smoking status revealed that the BMI-mortality relation is likely comprised of at least two distinct curves, rather than one J shaped relation. An increased risk of mortality for being underweight was only evident in ever smokers.
    Type of Medium: Online Resource
    ISSN: 0959-8138 , 1756-1833
    Language: English
    Publisher: BMJ
    Publication Date: 2019
    detail.hit.zdb_id: 1479799-9
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