Dietary n-6 to n-3 fatty acid ratio is related to liver fat content independent of genetic effects : Evidence from the monozygotic co-twin control design

Background & aim: Lifestyle changes focusing on diet and exercise remain the cornerstone of the treatment of non-alcoholic fatty liver disease (NAFLD). The present co-twin control study of monozygotic (MZ) twin pairs was designed to identify nutritional factors potentially involved in the pathogenesis of NAFLD. Methods: Cross-sectional study of 50 MZ twin pairs (age range: 23-36 years), of which ten pairs were discordant for liver fat (liver fat percentage of one twin 5% and a difference between co-twins of >5%) as determined by magnetic resonance spectroscopy. Nutrient intake was calculated from 3-day food records. Results: Among the ten liver fat-discordant twin pairs, the n-6: n-3 ratio was significantly higher in the twins with higher liver as compared to their co-twins with lower liver fat (6.6:1 vs. 3.2:1, p-value = 0.005). In multiple regression analysis of within-pair differences including all 50 twin pairs, a higher n-6: n-3 ratio was significantly associated with a higher liver fat percentage within MZ twin pairs after adjustment for body mass index, energy intake and other covariates (standardized beta = 0.43, p-value = 0.001). Conclusions: Our findings suggest that the n-6: n-3 ratio is a promising dietary agent for the prevention and treatment of NAFLD. Clinical trials are required to better understand causal relationships and required doses. (C) 2019 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.Peer reviewe

Is preoperative gastroscopy necessary before sleeve gastrectomy and Roux-en-Y gastric bypass?

Background: Consensus on the necessity of esophagogastroduodenoscopy (EGD) before bariatric surgery is lacking. Recommendations and practices vary by country and unit. Several reports have expressed concerns on gastroesophageal reflux disease (GERD) and its consequences after sleeve gastrectomy (SG) and the risk of leaving a premalignant lesion in the excluded stomach after Roux en -Y gastric bypass (RYGB). Objectives: We explored the number and types of clinically significant findings in preoperative EGDs and how they associate with preexisting GERD-symptoms (SG) and premalignant lesions (RYGB). We also studied how many reoperations were performed due to postoperative GERD in SG-patients. Setting: University hospital. Methods: We investigated preoperative EGD-findings and gastrointestinal symptoms before bariatric surgery in all patients with a primary bariatric operation in our unit between December 2007 and May 2016. Results: We performed 1474 operations: 1047 (71.0%) RYGB, 407 (27.6%) SG, and 20 (1.4%) others. One thousand two hundred seventy-five (86.5%) preoperative EGD reports were analyzed: 647 (50.7%) EGDs were completely normal. Altogether, 294 patients (23.0% of total) had a clinically significant finding that was relevant for SG (hiatal hernia, esophagitis, Barrett's esophagus, esophageal dysplasia), 144 (49.0%) of whom reported gastrointestinal symptoms. Twenty patients (1.6%) had a significant finding relevant for RYGB (peptic ulcer, atrophic gastritis, gastrointestinal stromal tumor), and 6 (30%) reported gastrointestinal symptoms. Thirteen (3.2%) SGs were converted into RYGB due to GERD. Conclusions: Preoperative EGD is indicated before SG but not before RYGB for asymptomatic patients without a risk for gastric pathology. (C) American Society for Metabolic and Bariatric Surgery. All rights reserved.Peer reviewe

Prospective randomized controlled trial comparing the efficacy and safety of Roux-en-Y gastric bypass and one-anastomosis gastric bypass (the RYSA trial): trial protocol and interim analysis

INTRODUCTION: There is a lack of prospective studies comparing Roux-en-Y gastric bypass (RYGB) and one-anastomosis gastric bypass (OAGB). Also, the effects of bariatric surgery and weight loss need a deeper understanding through metabolic studies. We describe the trial protocol and interim analysis of a prospective randomized controlled study comparing RYGB and OAGB: the RYSA trial. MATERIALS AND METHODS: In total, 120 bariatric patients will be randomized between RYGB and OAGB in two academic centers. All patients will be followed up for 10 years with analysis and measurements of weight, comorbidities, blood tests, body composition and questionnaires. Extensive metabolic analyses (mixed meal tests, energy expenditure, biopsies of muscle and subcutaneous fat, urine, saliva and fecal samples) will be carried out in the Obesity Research Unit, University of Helsinki, for all patients treated at the Helsinki University Hospital (80 patients) at baseline, 6 months and 12 months. Bile reflux will be studied for the OAGB group at the Helsinki University Hospital at 6 months with gastroscopy and scintigraphy. RESULTS: At an interim analysis at 3 months (half-way) through recruitment (30 RYGB and 30 OAGB patients) there have been no deaths and no intensive care unit admittances. One patient in both groups required additional gastroscopy, with anastomosis dilatation in the RYGB group but with no additional intervention in the OAGB group. CONCLUSION: The trial can be safely carried out. Recruitment is estimated to be complete by the end of 2019. TRIAL REGISTRATION: Clinical Trials Identifier NCT02882685. Registered on August 30th 2016.Peer reviewe

Kaksosten hankinnainen lihavuus

Vertaisarvioitu. English summary.Vertailemalla harvinaisia identtisiä mutta eripainoisia kaksosia voidaan selvittää lihavuuden vaikutusta aineenvaihduntaan DNA-sekvenssin samankaltaisuudesta riippumatta. Hankinnainen lihavuus vaikuttaa epäedullisesti veren rasvoihin, hyytymistekijöiden pitoisuuksiin ja tulehdusvälittäjäaineisiin sekä huonontaa endoteelitoimintaa ja altistaa ateroskleroosille. Tutkimusten perusteella rasvakudos on keskeisessä asemassa siinä, miten lihavuuden havaitut haitalliset aineenvaihdunnan muutokset syntyvät. Hankinnainen lihavuus liittyy rasvakudoksessa mitokondriotoiminnan heikentymiseen ja lievään tulehdukseen sekä insuliiniresistenssiin. Nämä muutokset heikentävät rasvakudoksen laajenemiskapasiteettia, jolloin ylimääräinen rasva alkaa varastoitua muihin kudoksiin, kuten maksaan, haimaan ja lihakseen, ja aiheuttaa aineenvaihdunnan laaja-alaisen häiriötilan. Erityisesti maksaan kertyvä rasva näyttää määrittävän lihavuuden haitallista metaboliaa.Peer reviewe

Errors-in-Variables Modeling of Personalized Treatment-Response Trajectories

Estimating the impact of a treatment on a given response is needed in many biomedical applications. However, methodology is lacking for the case when the response is a continuous temporal curve, treatment covariates suffer extensively from measurement error, and even the exact timing of the treatments is unknown. We introduce a novel method for this challenging scenario. We model personalized treatment-response curves as a combination of parametric response functions, hierarchically sharing information across individuals, and a sparse Gaussian process for the baseline trend. Importantly, our model accounts for errors not only in treatment covariates, but also in treatment timings, a problem arising in practice for example when data on treatments are based on user self-reporting. We validate our model with simulated and real patient data, and show that in a challenging application of estimating the impact of diet on continuous blood glucose measurements, accounting for measurement error significantly improves estimation and prediction accuracy.Peer reviewe

Potential direct secondary care cost benefits of HealthyWeightHub - Virtual Hospital 2.0 digital lifestyle intervention

Peer reviewe

Mechanisms of early glucose regulation disturbance after out-of-hospital cardiopulmonary resuscitation : An explorative prospective study

Background Hyperglycemia is common and associated with increased mortality after out-of-hospital cardiac arrest (OHCA) and return of spontaneous circulation (ROSC). Mechanisms behind ultra-acute hyperglycemia are not well known. We performed an explorative study to describe the changes in glucose metabolism mediators during the prehospital postresuscitation phase. Methods We included patients who were successfully resuscitated from out-of-hospital cardiac arrest in two physician-staffed units. Insulin, glucagon, and glucagon-like peptide 1 (GLP-1) were measured in prehospital and hospital admission samples. Additionally, interleukin-6 (IL-6), cortisol, and HbA1c were measured at hospital admission. Results Thirty patients participated in the study. Of those, 28 cases (71% without diabetes) had sufficient data for analysis. The median time interval between prehospital samples and hospital admission samples was 96 minutes (IQR 85-119). At the time of ROSC, the patients were hyperglycemic (11.2 mmol/l, IQR 8.8-15.7), with insulin and glucagon concentrations varying considerably, although mostly corresponding to fasting levels (10.1 mU/l, IQR 4.2-25.2 and 141 ng/l, IQR 105-240, respectively). GLP-1 increased 2- to 8-fold with elevation of IL-6. The median glucose change from prehospital to hospital admission was -2.2 mmol/l (IQR -3.6 to -0.2). No significant correlations between the change in plasma glucose levels and the changes in insulin (r = 0.30, p = 0.13), glucagon (r = 0.29, p = 0.17), or GLP-1 levels (r = 0.32, p = 0.15) or with IL-6 (r = (-0.07), p = 0.75), cortisol (r = 0.13, p = 0.52) or HbA1c levels (r = 0.34, p = 0.08) were observed. However, in patients who did not receive exogenous epinephrine during resuscitation, changes in blood glucose correlated with changes in insulin (r = 0.59, p = 0.04) and glucagon (r = 0.65, p = 0.05) levels, demonstrating that lowering glucose values was associated with a simultaneous lowering of insulin and glucagon levels. Conclusions Hyperglycemia is common immediately after OHCA and cardiopulmonary resuscitation. No clear hormonal mechanisms were observed to be linked to changes in glucose levels during the postresuscitation phase in the whole cohort. However, in patients without exogenous epinephrine treatment, the correlations between glycemic and hormonal changes were more obvious. These results call for future studies examining the mechanisms of postresuscitation hyperglycemia and the metabolic effects of the global ischemic insult and medical treatment.Peer reviewe

Evaluation of the effect of donor weight on adipose stromal/stem cell characteristics by using weight-discordant monozygotic twin pairs

Background Adipose stromal/stem cells (ASCs) are promising candidates for future clinical applications. ASCs have regenerative capacity, low immunogenicity, and immunomodulatory ability. The success of future cell-based therapies depends on the appropriate selection of donors. Several factors, including age, sex, and body mass index (BMI), may influence ASC characteristics. Our aim was to investigate the effect of acquired weight on ASC characteristics under the same genetic background using ASCs derived from monozygotic (MZ) twin pairs. Methods ASCs were isolated from subcutaneous adipose tissue from five weight-discordant (WD, within-pair difference in BMI > 3 kg/m(2)) MZ twin pairs, with measured BMI and metabolic status. The ASC immunophenotype, proliferation and osteogenic and adipogenic differentiation capacity were studied. ASC immunogenicity, immunosuppression capacity and the expression of inflammation markers were investigated. ASC angiogenic potential was assessed in cocultures with endothelial cells. Results ASCs showed low immunogenicity, proliferation, and osteogenic differentiation capacity independent of weight among all donors. ASCs showed a mesenchymal stem cell-like immunophenotype; however, the expression of CD146 was significantly higher in leaner WD twins than in heavier cotwins. ASCs from heavier twins from WD pairs showed significantly greater adipogenic differentiation capacity and higher expression of TNF and lower angiogenic potential compared with their leaner cotwins. ASCs showed immunosuppressive capacity in direct cocultures; however, heavier WD twins showed stronger immunosuppressive capacity than leaner cotwins. Conclusions Our genetically matched data suggest that a higher weight of the donor may have some effect on ASC characteristics, especially on angiogenic and adipogenic potential, which should be considered when ASCs are used clinically.Peer reviewe