Association of Healthy Lifestyle Factors and Obesity-Related Diseases in Adults in the UK

Importance: A healthy lifestyle is associated with a reduced risk of cardiovascular disease in adults with obesity. Little is known about the associations between a healthy lifestyle and the risk of other obesity-attributable diseases in this population. Objective: To examine the association between healthy lifestyle factors and the incidence of major obesity-related diseases in adults with obesity compared with those with normal weight. Design, Setting, and Participants: This cohort study evaluated UK Biobank participants aged 40 to 73 years and free of major obesity-attributable disease at baseline. Participants were enrolled from 2006 to 2010 and prospectively followed up for disease diagnosis. Exposures: A healthy lifestyle score was constructed using information on not smoking, exercising regularly, no or moderate alcohol consumption, and eating a healthy diet. For each lifestyle factor, participants scored 1 if they met the criterion for a healthy lifestyle and 0 otherwise. Main Outcomes and Measures: The risk of outcomes according to the healthy lifestyle score in adults with obesity compared with those with normal weight were examined using multivariable Cox proportional hazards models with Bonferroni correction for multiple testing. The data analysis was performed between December 1, 2021, and October 31, 2022. Results: A total of 438 583 adult participants in the UK Biobank were evaluated (female, 55.1%; male, 44.9%; mean [SD] age, 56.5 [8.1] years), of whom 107 041 (24.4%) had obesity. During a mean (SD) follow-up of 12.8 (1.7) years, 150 454 participants (34.3%) developed at least 1 of the studied diseases. Compared with adults with obesity and 0 healthy lifestyle factors, individuals with obesity who met all 4 healthy lifestyle factors were at lower risk of hypertension (HR, 0.84; 95% CI, 0.78-0.90), ischemic heart disease (HR, 0.72; 95% CI, 0.65-0.80), arrhythmias (HR, 0.71; 95% 0.61-0.81), heart failure (HR, 0.65; 95% CI, 0.53-0.80), arteriosclerosis (HR, 0.19; 95% CI, 0.07-0.56), kidney failure (HR, 0.73; 95% CI, 0.63-0.85), gout (HR, 0.51; 95% CI, 0.38-0.69), sleep disorders (HR, 0.68; 95% CI, 0.56-0.83), and mood disorders (HR, 0.66; 95% CI, 0.56-0.78). The lifestyle profiles associated with the lowest risks included a healthy diet and at least 1 of the 2 healthy behaviors of physical activity and never smoking. Compared with adults with normal weight, those with obesity were at higher risk of several outcomes, irrespective of the lifestyle score (adjusted HRs ranged from 1.41 [95% CI, 1.27-1.56] for arrhythmias to 7.16 [95% CI, 6.36-8.05] for diabetes for adults with obesity and 4 healthy lifestyle factors). Conclusion and Relevance: In this large cohort study, adherence to a healthy lifestyle was associated with reduced risk of a wide range of obesity-related diseases, but this association was modest in adults with obesity. The findings suggest that although a healthy lifestyle seems to be beneficial, it does not entirely offset the health risks associated with obesity

Long-term outcomes of patients with Takayasu arteritis and renal artery involvement: a cohort study.

OBJECTIVE: To describe the long-term outcomes of patients with Takayasu arteritis (TAK) and renal artery involvement (RAI). METHODS: A retrospective review of 122 patients with TAK at three tertiary centres in Canada, Sweden and the UK. Data on demographics, laboratory and clinical parameters, medications and angiography findings were collected. Non-renal and renal parameters were compared at baseline and follow-up. RESULTS: A total of 37 patients (30%) with RAI were identified: 18 (49%) with unilateral and 19 (51%) with bilateral RAI. Patients were predominantly female (89%). The median age at diagnosis was 27 years [interquartile range (IQR) 16-38]. The median follow-up time was 7 years (IQR 2-12). Hypertension was seen in 27 patients (73%) at presentation and 25 (68%) at follow-up. The median estimated glomerular filtration (eGFR) at presentation was 94 and 98 ml/min/1.73 m2 in those with unilateral and bilateral RAI, respectively. The corresponding median eGFR at follow-up was 101.5 and 104 ml/min/1.73 m2, respectively. Three patients at presentation and two at follow-up had an eGFR of <60 ml/min/1.73 m2. Five underwent endovascular intervention and three required surgical interventions. Among the 33 patients with radiologic follow-up, 23 (69%) had persistent RAI and 10 (30%) had resolution of RAI. One (6%) patient with unilateral RAI developed bilateral RAI and three (19%) with bilateral RAI regressed to unilateral RAI. Over time, 23 (62%) patients had stable renal function, 7 (19%) had improvement and 4 had a decline in renal function; no patient developed end-stage renal disease (ESRD). CONCLUSION: In this series of TAK patients with RAI, long-term non-renal and renal outcomes were favourable. No patient experienced ESRD or died

Identification de loci suppresseurs du phénotype diabétique lié à la déficience en Hnf1a chez la souris

Hnf1a-/- mice exhibit a severe diabetes mellitus due to a drastic defect in insulin secretion that closely resembles to the phenotype presented by MODY3 (Maturity Onset Diabetes of the Young type 3) patients. The molecular mechanisms responsible for the diabetes are still poorly understood. Here we show that congenic mice of different genetic backgrounds carrying the same Hnf1a deletion presented with drastically different phenotypes. Hnf1a-deficiency led to severe diabetes when introgressed into 129, B6, BALB/C or A/J genetic backgrounds (sensitive strains). Conversely, when the same null mutation was introgressed into CBA or C3H genetic backgrounds (resistant strains), the diabetic phenotype was suppressed. In sensitive strains, pancreatic islets did not increase in size compared to control animals and on the other hand average islet-size growth was normal in resistant strains. The genetic variations naturally present in these two resistant strains acted in a dominant way and a genome scan analysis led to the identification of a major suppressor locus on chromosome 3 that accounted for more than 60% of the variance of glycemia. The major locus contained 11 genes with non-synonymous SNPs changes and it interacted with 5 additional ancillary loci on chromosomes 4, 11 and 18. Our study demonstrated that the naturally occurring genetic variation present in distinct mouse laboratory strains is able to suppress the phenotype of a monogenic disorder.Les souris invalidées pour Hnf1a présentent un diabète sévère avec défaut d’insulino-sécrétion proche du phénotype observé chez les patients MODY3 (Maturity Onset Diabetes of te Young). Les mécanismes moléculaires responsables du diabète lié à la déficience en Hnf1a ne sont pas clairement compris. Dans ce travail, nous avons montré que des souris congéniques présentant la même délétion de Hnf1a dans des fonds génétiques différents présentent des phénotypes radicalement opposés. En effet, la déficience en Hnf1a conduit à un diabète sévère dans la plupart des lignées telles que 129, B6, BALB/c ou AJ (lignées sensibles). Mais à l’inverse, aucun diabète n’est observé chez les souris congéniques des lignées CBA et C3H malgré le défaut d’expression de Hnf1a (lignées résistantes). Les souris sensibles présentent une altération de leurs îlots de Langerhans avec notamment une diminution de taille de ces îlots. A l’inverse les souris résistantes présentent des îlots beta de taille normale malgré la déficience en Hnf1a. Nous avons pu montrer que le ou les variants génétiques présents dans les deux lignées résistantes agissent de façon dominante et, par un balayage du génome, nous avons identifié un locus majeur suppresseur du phénotype diabétique au niveau du chromosome 3. Ce locus majeur contient 11 gènes présentant des variations de SNP non synonymes et il interagit avec cinq autres loci ancillaires au niveau des chromosomes 4, 11 et 18. Notre travail montre finalement que les variations génétiques naturellement présentes dans les lignées de souris de laboratoire peuvent supprimer le phénotype diabétique lié à la déficience en Hnf1a

Diabetic phenotype linked to Hnf1a deficiency is suppressed by genetic background in mice

Les souris invalidées pour Hnf1a présentent un diabète sévère avec défaut d’insulino-sécrétion proche du phénotype observé chez les patients MODY3 (Maturity Onset Diabetes of te Young). Les mécanismes moléculaires responsables du diabète lié à la déficience en Hnf1a ne sont pas clairement compris. Dans ce travail, nous avons montré que des souris congéniques présentant la même délétion de Hnf1a dans des fonds génétiques différents présentent des phénotypes radicalement opposés. En effet, la déficience en Hnf1a conduit à un diabète sévère dans la plupart des lignées telles que 129, B6, BALB/c ou AJ (lignées sensibles). Mais à l’inverse, aucun diabète n’est observé chez les souris congéniques des lignées CBA et C3H malgré le défaut d’expression de Hnf1a (lignées résistantes). Les souris sensibles présentent une altération de leurs îlots de Langerhans avec notamment une diminution de taille de ces îlots. A l’inverse les souris résistantes présentent des îlots beta de taille normale malgré la déficience en Hnf1a. Nous avons pu montrer que le ou les variants génétiques présents dans les deux lignées résistantes agissent de façon dominante et, par un balayage du génome, nous avons identifié un locus majeur suppresseur du phénotype diabétique au niveau du chromosome 3. Ce locus majeur contient 11 gènes présentant des variations de SNP non synonymes et il interagit avec cinq autres loci ancillaires au niveau des chromosomes 4, 11 et 18. Notre travail montre finalement que les variations génétiques naturellement présentes dans les lignées de souris de laboratoire peuvent supprimer le phénotype diabétique lié à la déficience en Hnf1a.Hnf1a-/- mice exhibit a severe diabetes mellitus due to a drastic defect in insulin secretion that closely resembles to the phenotype presented by MODY3 (Maturity Onset Diabetes of the Young type 3) patients. The molecular mechanisms responsible for the diabetes are still poorly understood. Here we show that congenic mice of different genetic backgrounds carrying the same Hnf1a deletion presented with drastically different phenotypes. Hnf1a-deficiency led to severe diabetes when introgressed into 129, B6, BALB/C or A/J genetic backgrounds (sensitive strains). Conversely, when the same null mutation was introgressed into CBA or C3H genetic backgrounds (resistant strains), the diabetic phenotype was suppressed. In sensitive strains, pancreatic islets did not increase in size compared to control animals and on the other hand average islet-size growth was normal in resistant strains. The genetic variations naturally present in these two resistant strains acted in a dominant way and a genome scan analysis led to the identification of a major suppressor locus on chromosome 3 that accounted for more than 60% of the variance of glycemia. The major locus contained 11 genes with non-synonymous SNPs changes and it interacted with 5 additional ancillary loci on chromosomes 4, 11 and 18. Our study demonstrated that the naturally occurring genetic variation present in distinct mouse laboratory strains is able to suppress the phenotype of a monogenic disorder

Variations de l'expression des gènes de l'inflammation dans le tissu adipeux chez des sujets obèses soumis à une restriction calorique

PARIS-BIUM (751062103) / SudocCentre Technique Livre Ens. Sup. (774682301) / SudocSudocFranceF

Time of Bariatric Surgery and Hospitalization for SARS-CoV-2: a Nationwide Study

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For a better estimation of gamma heating in nuclear material-testing reactors and associated devices: status and work plan from calculation methods to nuclear data

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Impact Study on the Methodology used for Photon-Heating Calculations in Material-Testing Reactors

ANIMMA Conference, Lisbon, PORTUGAL, 2015International audienceDetermination of photon heating by calculation is an important issue for the Jules Horowitz Reactor (JHR), the next international Material-Testing Reactor (MTR) under construction in the south of France. Accurate knowledge of photon heating in structure materials and irradiation devices is necessary for JHR design and safety studies. In this paper, we quantify the impact of different photon-heating calculation routes by comparing absorbed dose and KERMA calculations (Kinetic Energy Released per MAss) from two different Monte Carlo codes, TRIPOLI-4.9 and MCNP (Monte Carlo N-Particle transport code). These calculations are carried out in JHR-representative geometries with the nuclear-data library JEFF3.1.1 and the photon-data library EPDL97. Discrepancies amounting to up to 18% between absorbed dose and KERMA are found in JHR irradiation devices and are linked to charged-particle transport effects taking place in heterogeneous materials of small dimensions. In a JHR-assembly cell, discrepancies of about 1% on photon KERMA and of about 3% on absorbed dose are highlighted between the two Monte Carlo codes. These latter discrepancies are small compared to typical sources of uncertainty for Monte Carlo calculation (for instance, nuclear data uncertainty) and are supposed to be due to differences in the processing of gamma-production data by neutron interactions and to differences in electromagnetic-shower models and implementation between the two codes

RYGB and Drug Disposition: How to Do Better? Analysis of Pharmacokinetic Studies and Recommendations for Clinical Practice

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Are aga-born obese adults more metabolically healhty than sga-born obese individuals?

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