| 1. |
- Baumeier, Christian, et al.
(författare)
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Hepatic DPP4 DNA methylation associates with fatty liver
- 2017
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 66:1, s. 25-35
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Tidskriftsartikel (refereegranskat)abstract
- Hepatic DPP4 expression is elevated in subjects with ectopic fat accumulation in the liver. However, whether increased dipeptidyl peptidase 4 (DPP4) is involved in the pathogenesis or is rather a consequence ofmetabolic disease is not known. We therefore studied the transcriptional regulation of hepatic Dpp4 in young mice prone to diet-induced obesity. Already at 6 weeks of age, expression of hepatic Dpp4 was increased in mice with high weight gain, independent of liver fat content. In the same animals, methylation of four intronic CpG sites was decreased, amplifying glucose-induced transcription of hepatic Dpp4. In older mice, hepatic triglyceride content was increased only in animals with elevated Dpp4 expression. Expression and release of DPP4 were markedly higher in the liver compared with adipose depots. Analysis of human liver biopsy specimens revealed a correlation of DPP4 expression and DNA methylation to stages of hepatosteatosis and nonalcoholic steatohepatitis. In summary, our results indicate a crucial role of the liver in participation to systemic DPP4 levels. Furthermore, the data show that glucoseinduced expression of Dpp4 in the liver is facilitated by demethylation of the Dpp4 gene early in life. This might contribute to early deteriorations in hepatic function, which in turn result in metabolic disease such as hepatosteatosis later in life.
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| 2. |
- Saux, Patrick, et al.
(författare)
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Development and validation of an interpretable machine learning-based calculator for predicting 5-year weight trajectories after bariatric surgery: a multinational retrospective cohort SOPHIA study.
- 2023
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Ingår i: The Lancet. Digital health. - 2589-7500. ; 5:10
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Tidskriftsartikel (refereegranskat)abstract
- Weight loss trajectories after bariatric surgery vary widely between individuals, and predicting weight loss before the operation remains challenging. We aimed to develop a model using machine learning to provide individual preoperative prediction of 5-year weight loss trajectories after surgery.In this multinational retrospective observational study we enrolled adult participants (aged ≥18 years) from ten prospective cohorts (including ABOS [NCT01129297], BAREVAL [NCT02310178], the Swedish Obese Subjects study, and a large cohort from the Dutch Obesity Clinic [Nederlandse Obesitas Kliniek]) and two randomised trials (SleevePass [NCT00793143] and SM-BOSS [NCT00356213]) in Europe, the Americas, and Asia, with a 5 year follow-up after Roux-en-Y gastric bypass, sleeve gastrectomy, or gastric band. Patients with a previous history of bariatric surgery or large delays between scheduled and actual visits were excluded. The training cohort comprised patients from two centres in France (ABOS and BAREVAL). The primary outcome was BMI at 5 years. A model was developed using least absolute shrinkage and selection operator to select variables and the classification and regression trees algorithm to build interpretable regression trees. The performances of the model were assessed through the median absolute deviation (MAD) and root mean squared error (RMSE) of BMI.10231 patients from 12 centres in ten countries were included in the analysis, corresponding to 30602 patient-years. Among participants in all 12 cohorts, 7701 (75·3%) were female, 2530 (24·7%) were male. Among 434 baseline attributes available in the training cohort, seven variables were selected: height, weight, intervention type, age, diabetes status, diabetes duration, and smoking status. At 5 years, across external testing cohorts the overall mean MAD BMI was 2·8 kg/m2 (95% CI 2·6-3·0) and mean RMSE BMI was 4·7 kg/m2 (4·4-5·0), and the mean difference between predicted and observed BMI was -0·3 kg/m2 (SD 4·7). This model is incorporated in an easy to use and interpretable web-based prediction tool to help inform clinical decision before surgery.We developed a machine learning-based model, which is internationally validated, for predicting individual 5-year weight loss trajectories after three common bariatric interventions.SOPHIA Innovative Medicines Initiative 2 Joint Undertaking, supported by the EU's Horizon 2020 research and innovation programme, the European Federation of Pharmaceutical Industries and Associations, Type 1 Diabetes Exchange, and the Juvenile Diabetes Research Foundation and Obesity Action Coalition; Métropole Européenne de Lille; Agence Nationale de la Recherche; Institut national de recherche en sciences et technologies du numérique through the Artificial Intelligence chair Apprenf; Université de Lille Nord Europe's I-SITE EXPAND as part of the Bandits For Health project; Laboratoire d'excellence European Genomic Institute for Diabetes; Soutien aux Travaux Interdisciplinaires, Multi-établissements et Exploratoires programme by Conseil Régional Hauts-de-France (volet partenarial phase 2, project PERSO-SURG).
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| 3. |
- Burdge, Kevin B., et al.
(författare)
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A 62-minute orbital period black widow binary in a wide hierarchical triple
- 2022
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 605:7908, s. 41-45
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Tidskriftsartikel (refereegranskat)abstract
- Over a dozen millisecond pulsars are ablating low-mass companions in close binary systems. In the original 'black widow', the eight-hour orbital period eclipsing pulsar PSR J1959+2048 (PSR B1957+20)(1), high-energy emission originating from the pulsar2 is irradiating and may eventually destroy(3) a low-mass companion. These systems are not only physical laboratories that reveal the interesting results of exposing a close companion star to the relativistic energy output of a pulsar, but are also believed to harbour some of the most massive neutron stars(4), allowing for robust tests of the neutron star equation of state. Here we report observations of ZTF J1406+1222, a wide hierarchical triple hosting a 62-minute orbital period black widow candidate, the optical flux of which varies by a factor of more than ten. ZTF J1406+1222 pushes the boundaries of evolutionary models(5), falling below the 80-minute minimum orbital period of hydrogen-rich systems. The wide tertiary companion is a rare low-metallicity cool subdwarf star, and the system has a Galactic halo orbit consistent with passing near the Galactic Centre, making it a probe of formation channels, neutron star kick physics(6) and binary evolution.
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| 4. |
- Neff, Karl J., et al.
(författare)
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Renal Function and Remission of Hypertension After Bariatric Surgery: a 5-Year Prospective Cohort Study
- 2017
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Ingår i: Obesity Surgery. - : Springer Science and Business Media LLC. - 0960-8923 .- 1708-0428. ; 27, s. 613-619
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Tidskriftsartikel (refereegranskat)abstract
- © 2016, Springer Science+Business Media New York. Purpose: This study examines the effect of Roux-en-Y gastric bypass (RYGB) and laparoscopic adjustable gastric banding (LAGB) on renal function for at least 5years post-operatively in a tertiary referral center for bariatric surgery. Materials and Methods: This prospective cohort study of patients undergoing RYGB and LAGB measured renal function, blood pressure, and diabetes status pre-operatively and then 1 and 5years post-operatively. Renal function was assessed using the Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), and Cockcroft-Gault formulae. Hypertension and diabetes were defined by the European Society of Hypertension and European Society of Cardiology joint guidelines and American Diabetes Association guidelines, respectively. A sub-group who had completed 10years post-operative follow-up was also included. Results: Estimated glomerular filtration rate (eGFR) increased over 5years after RYGB (N = 190; 94 ± 2mL/min/1.73m2 to 102 ± 22mL/min/1.73m2, p = 0.01) and LAGB (N = 271; 88 ± 1 to 93 ± 22mL/min/1.73m2, p = 0.02). In a sub-group with up to 10years post-operative date, this trend was maintained. In patients with renal impairment, eGFR improved over 5years (52 ± 2 to 68 ± 7mL/min/1.73m2, p = 0.01). Remission of hypertension was greater after RYGB than LAGB at 1year (32 vs. 16%, p = 0.008) and at 5years post-operatively (23 vs. 11%, p = 0.02). Conclusions: Bariatric surgery stabilizes eGFR post-operatively for at least 5years. In a sub-group with renal impairment, eGFR is increased in the first post-operative year and this is maintained for up to 5years. RYGB is an effective procedure in achieving blood pressure control.
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| 5. |
- Raverdy, Violeta, et al.
(författare)
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Data-driven subgroups of type 2 diabetes, metabolic response, and renal risk profile after bariatric surgery : a retrospective cohort study
- 2022
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Ingår i: The Lancet Diabetes and Endocrinology. - 2213-8587. ; 10:3, s. 167-176
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Tidskriftsartikel (refereegranskat)abstract
- Background: A novel data-driven classification of type 2 diabetes has been proposed to personalise anti-diabetic treatment according to phenotype. One subgroup, severe insulin-resistant diabetes (SIRD), is characterised by mild hyperglycaemia but marked hyperinsulinaemia, and presents an increased risk of diabetic nephropathy. We hypothesised that patients with SIRD could particularly benefit from metabolic surgery. Methods: We retrospectively related the newly defined clusters with the response to metabolic surgery in participants with type 2 diabetes from independent cohorts in France (the Atlas Biologique de l'Obésite Sévère [ABOS] cohort, n=368; participants underwent Roux-en-Y gastric bypass or sleeve gastrectomy between Jan 1, 2006, and Dec 12, 2017) and Brazil (the metabolic surgery cohort of the German Hospital of San Paulo, n=121; participants underwent Roux-en-Y gastric bypass between April 1, 2008, and March 20, 2016). The study outcomes were type 2 diabetes remission and improvement of estimated glomerular filtration rate (eGFR). Findings: At baseline, 34 (9%) of 368 patients, 314 (85%) of 368 patients, and 17 (5%) of 368 patients were classified as having SIRD, mild obesity-related diabetes (MOD), and severe insulin deficient diabetes (SIDD) in the ABOS cohort, respectively, and in the São Paulo cohort, ten (8%) of 121 patients, 83 (69%) of 121 patients, and 25 (21%) of 121 patients were classified as having SIRD, MOD, and SIDD, respectively. At 1 year, type 2 diabetes remission was reported in 26 (81%) of 32 and nine (90%) of ten patients with SIRD, 167 (55%) of 306 and 42 (51%) of 83 patients with MOD, and two (13%) of 16 and nine (36%) of 25 patients with SIDD, in the ABOS and São Paulo cohorts, respectively. The mean eGFR was lower in patients with SIRD at baseline and increased postoperatively in these patients in both cohorts. In multivariable analysis, SIRD was associated with more frequent type 2 diabetes remission (odds ratio 4·3, 95% CI 1·8–11·2; p=0·0015), and an increase in eGFR (mean effect size 13·1 ml/min per 1·73 m2, 95% CI 3·6–22·7; p=0·0070). Interpretation: Patients in the SIRD subgroup had better outcomes after metabolic surgery, both in terms of type 2 diabetes remission and renal function, with no additional surgical risk. Data-driven classification might help to refine the indications for metabolic surgery.
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| 6. |
- Raverdy, Violeta, et al.
(författare)
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Performance of non-invasive tests for liver fibrosis and resolution after bariatric surgery.
- 2024
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Ingår i: Metabolism: clinical and experimental. - 1532-8600. ; 153
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Tidskriftsartikel (refereegranskat)abstract
- The value of non-invasive tests for monitoring the resolution of significant liver fibrosis after treatment is poorly investigated. We compared the performances of six non-invasive tests to predict the resolution of significant fibrosis after bariatric surgery.Participants were individuals with obesity submitted to needle liver biopsy at the time of bariatric surgery, and 12 and/or 60months after surgery. We calculated the fibrosis-4 index (FIB-4), NAFLD fibrosis score (NFS), AST to platelet ratio index (APRI), Hepatic fibrosis score (HFS), Fibrosis NAFLD index (FNI), and Liver risk score (LRS) at each time point, and compared their performances for predicting significant fibrosis (F≥2) and its resolution following surgery.At baseline, 2436 patients had liver biopsy, including 261 (10.7%) with significant fibrosis. Overall, 672 patients had pre- and post-operative biopsies (564 at M12 and 328 at M60). The fibrosis stage decreased at M12 and M60 (p<0.001 vs M0). Resolution of significant fibrosis occurred in 58/121 (47.9%) at M12 and 32/50 (64%) at M60. The mean value of all tests decreased after surgery, except for FIB-4. Performances for predicting fibrosis resolution was higher at M60 than at M12 for all tests, and maximal at M60 for FNI and LRS: area under the curve 0.843 (95%CI 0.71-0.95) and 0.92 (95%CI 0.84-1.00); positive likelihood ratio 3.75 (95% CI 1.33-10.59) and 4.58 (95% CI 1.65-12.70), respectively.Results showed the value and limits of non-invasive tests for monitoring the evolution of liver fibrosis after an intervention. Following bariatric surgery, the best performances to predict the resolution of significant fibrosis were observed at M60 with tests combining liver and metabolic traits, namely FNI and LRS.
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