26 results on '"Matthias Hepprich"'
Search Results
2. Review for 'Once‐weekly semaglutide use in patients with type 2 diabetes: real‐world data from the <scp>SURE</scp> Italy observational study'
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Matthias Hepprich
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- 2023
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3. Predictors of Postprandial Hypoglycemia After Gastric Bypass Surgery: a Retrospective Case-Control Study
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Marc Y. Donath, Matthias Hepprich, and Elric Zweck
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Blood Glucose ,medicine.medical_specialty ,Complications ,endocrine system diseases ,Original Contributions ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Gastric Bypass ,030209 endocrinology & metabolism ,Relative weight ,Hypoglycemia ,medicine.disease_cause ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Weight loss ,Mixed-meal test ,Internal medicine ,medicine ,Humans ,Insulin ,030212 general & internal medicine ,Retrospective Studies ,Bariatric surgery ,Nutrition and Dietetics ,Receiver operating characteristic ,Gastric bypass surgery ,business.industry ,Case-control study ,nutritional and metabolic diseases ,Postprandial Period ,medicine.disease ,Late-dumping ,Obesity, Morbid ,Case-Control Studies ,Quality of Life ,Postprandial hypoglycemia ,Surgery ,medicine.symptom ,business ,Postprandial Hypoglycemia - Abstract
Background Postprandial hypoglycemia after bariatric surgery is an exigent disorder, often impacting the quality of life. Distinguishing clinically relevant hypoglycemic episodes from symptoms of other origin can be challenging. Diagnosis is demanding and often requires an extensive testing such as prolonged glucose tolerance or mixed-meal test. Therefore, we investigated whether baseline parameters of patients after gastric bypass with suspected hypoglycemia can predict the diagnosis. Methods We analyzed data from 35 patients after gastric bypass with suspected postprandial hypoglycemia and performed a standardized mixed-meal test. Hypoglycemia was defined by the appearance of typical symptoms, low plasma glucose, and relief of symptoms following glucose administration. Parameters that differed in patients with and without hypoglycemia during MMT were identified and evaluated for predictive precision using receiver operating characteristic (ROC) areas under the curve (AUC). Results Out of 35 patients, 19 (54%) developed symptomatic hypoglycemia as a result of exaggerated insulin and C-peptide release in response to the mixed-meal. Hypoglycemic patients exhibited lower glycosylated hemoglobin A1c (HbA1c) and higher absolute and relative weight loss from pre-surgery to study date. HbA1c and absolute weight loss alone could achieve acceptable AUCs in ROC analyses (0.76 and 0.72, respectively) but a combined score of absolute weight loss divided by HbA1c (0.78) achieved the best AUC. Conclusions HbA1c and weight loss differed in patients with and without symptomatic hypoglycemia during mixed-meal test. These baseline parameters could be used for screening of postprandial hypoglycemia in patients after gastric bypass and may facilitate the selection of patients requiring further evaluation. Graphical abstract
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- 2021
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4. Switch-to-Semaglutide Study (STS-Study): a Retrospective Cohort Study
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Marc Y. Donath, Gottfried Rudofsky, Matthias Hepprich, Daniela Zillig, and Manuel A. Florian-Reynoso
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medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,030209 endocrinology & metabolism ,Type 2 diabetes ,030204 cardiovascular system & hematology ,Antidiabetic drug ,03 medical and health sciences ,0302 clinical medicine ,Observational study ,Internal medicine ,Diabetes mellitus ,Internal Medicine ,medicine ,Clinical endpoint ,Adverse effect ,Original Research ,GLP-1 analogue ,business.industry ,Semaglutide ,Retrospective cohort study ,medicine.disease ,Median body ,business ,Body mass index - Abstract
Introduction Despite expert consensus guidelines, data is scarce on how to switch patients with type 2 diabetes when treatment with glucagon-like peptide 1 (GLP-1) receptor agonists is not effective and whether a switch to semaglutide brings any benefit on glucose and weight control for patients with type 2 diabetes. Methods Retrospective cohort analysis of patients with type 2 diabetes who were switched from any GLP-1 agonist in a stable dose to subcutaneously administered semaglutide. Primary endpoint was change of glycated haemoglobin (HbA1c) at 6 months. Secondary endpoints were weight, body mass index (BMI), heart rate, blood pressure and adverse events. Results In total, 77 patients (median age 65 years) with long-standing type 2 diabetes (median 15 years, median HbA1c 8.4%/68 mmol/l, median BMI 33 kg/m2) were included. HbA1c was significantly lower 6 months after switching to semaglutide (7.3%; 56 mmol/l). Median body weight was significantly lower at 3 months (94 kg) and 6 months (93 kg) compared to baseline (98 kg). An equipotential dose switch of semaglutide was used in 61 patients (79%) and a stepwise initiation approach was used in 16 patients (21%). Both treatment regimens improved glucose control and weight. Side effects occurred in 28 patients (36%). Conclusion Switching to semaglutide from established GLP-1 analogue therapy improved HbA1c and body weight. Both equipotential and stepwise dosing initiation appear to be effective and well tolerated. Supplementary Information The online version contains supplementary material available at 10.1007/s13300-021-01016-y.
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- 2021
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5. Canakinumabin patients with COVID-19 and type 2 diabetes (CanCovDia) - a multicentric, randomised, double-blind, placebo-controlled phase 3 trial
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Matthias Hepprich, Jonathan Mudry, Claudia Gregoriano, Francois R Jornayvaz, Sebastian Carballo, Anne Wojtusciszyn, Pierre-Alexandre Bart, Jean-Daniel Chiche, Stefan Fischli, Thomas Baumgartner, Claudia Cavelti-Weder, Felix Beuschlein, Dominque L Braun, Huldrych F Gunthard, Emily West, Anna Conen, Egon Isenring, Gabriela Bucklar, Yoann Aubry, Ludovic Dey, Beat Muller, Philipp Schutz, Marco Cattaneo, Patrick Hunziker, and Marc Y Donath
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- 2022
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6. Knowledge about Diabetic Ketoacidosis in Patients with Type 1 Diabetes mellitus - Data of a Patient-centered Questionnaire
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Matthias Hepprich, Sebastian Stiebitz, Bernd Schultes, Daniela Schmitz, Barbara Felix, Jonas Rutishauser, Sabine Schubert, Pia Roser, Jens Aberle, and Gottfried Rudofsky
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- 2022
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7. Glucagon-like peptide-1 receptor PET/CT in patients with and without post gastric bypass hypoglycemia – a prospective, matched case-control study
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Matthias Hepprich, Kwadwo Antwi, Patricia Wiesner, Claudia Cavelti-Weder, Marc Y. Donath, Emanuel R. Christ, and Damian Wild
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Purpose The aim of this pilot study is to prospectively compare in vivo glucagon-like peptide-1 (GLP-1) receptor expression in the duodenum and pancreas of patients with and without postprandial hypoglycemia after gastric bypass using GLP-1 receptor imaging with 68Ga-DOTA-exendin-4 PET/CT.MethodsFive patients after Roux-Y-gastric bypass (RYGB) surgery with postprandial hypoglycemia (PGBH) and five patients after RYGB without PGBH matched for sex, age, operative procedure and postoperative interval underwent 68Ga-DOTA-exendin-4 PET/CT. Total 68Ga-DOTA-exendin-4 uptake in the duodenum and pancreas, defined as the sum of the standard uptake value (SUVsum) for each voxel in the volume of interest (VOI) was measured by two independent readers who were blinded for the clinical information. Additionally, three further patients with PGBH who received 68Ga-DOTA-exendin-4 PET/CT at our center were added to the analysis. Clinical follow-up data was collected for all patients with PGBH.Results68Ga-DOTA-exendin-4 PET/CT exhibited a greater range of total duodenal and pancreatic uptake (SUVsum) for matched hypoglycemic patients (2144-7802, median 3022) than for matched normoglycemic patients (5104-7507, median 7072), with no statistical significant difference of total uptake = total in vivo GLP-1 receptor expression (p-value of 0.187). In one patient with PGBH a focal tracer uptake in the pancreatic tail was identified. Four patients with PGBH required ultimately a reversal of their gastric bypass surgery due to insufficient dietary and medical therapy of their hypoglycemic episodes.Conclusion68Ga-DOTA-exendin-4 uptake appears not to be significantly different in patients with PGBH compared to matched normoglycemic patients but may reflect varying stages of the complex pathophysiology of postbariatric hypoglycemia.
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- 2022
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8. Effects of a single 10mg dose of empagliflozin on postprandial insulin kinetics in patients with postbariatric hypoglycaemia
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Lia Bally, Chiara Dalla Man, Matthias Hepprich, David Herzig, Michele Schiavon, and Marc Y. Donath
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medicine.medical_specialty ,business.industry ,Insulin ,medicine.medical_treatment ,Gastric bypass ,Placebo ,Insulin kinetics ,Endocrinology ,Postprandial ,Basal (medicine) ,Internal medicine ,Empagliflozin ,Medicine ,In patient ,business - Abstract
IntroductionPostbariatric hypoglycaemia (PBH) is an increasingly recognized late metabolic complication of Roux-en-Y gastric bypass (GB) surgery. PBH typically manifests with a fact occurring post-meal hyperglycaemic peak, followed by a disproportionately exaggerated insulin response leading to low glucose levels. On this basis, we evaluated the effect of a single dose of empagliflozin 10mg vs. placebo on parameters of insulin kinetics.Materials and methodsInsulin secretion, hepatic insulin extraction and total insulin clearance were evaluated after a single of empagliflozin 10mg vs. placebo followed by a standardized liquid mixed meal were evaluated in 11 subjects with confirmed PBH after GB over 3h. Parameters of interest were calculated using established mathematical models. Indices were compared between the groups using the Wilcoxon signed-rank test.ResultsTotal beta-cell responsiveness tends to be lower with empagliflozin vs. placebo (24.83±11.00 vs. 27.15±9.68 [10−9 min-1], p=0.150). Total first-pass hepatic insulin extraction increased after empagliflozin compared to placebo (49.6±14.2 vs. 39.7±12.1 %, p=0.006), while no significant effect of empaglizflozin on basal first-pass hepatic insulin extraction was observed (79.7±7.1 vs. 81.1±6.6 %, p=0.521). Total insulin clearance resulted to be significantly lower after empagliflozin compared to placebo (3.91±1.58 vs. 3.00±1.27 l/min, p=0.002).ConclusionThe present analysis suggests that the hypoglycaemia-attenuating effect of SGLT2-inhibition in patients with PBH is mainly mediated by an increment in insulin clearance, with also a tendency to a reduction in insulin secretion.
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- 2021
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9. Regular intake of energy drinks and multivitamin supplements is associated with elevated plasma vitamin B6 levels in post-bariatric patients
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Matthias Hepprich, Katharina Timper, and Martina Tynes
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Adult ,Male ,medicine.medical_specialty ,Science ,Bariatric Surgery ,Gastroenterology ,Article ,Young Adult ,Internal medicine ,medicine ,Energy Drinks ,Humans ,Outpatient clinic ,Endocrine system ,In patient ,Postoperative Period ,Obesity ,Aged ,Retrospective Studies ,Multidisciplinary ,business.industry ,Metabolic diseases ,Vitamins ,Plasma levels ,Middle Aged ,University hospital ,Normal limit ,Vitamin B 6 ,Obesity, Morbid ,Dietary Supplements ,Medicine ,Female ,Vitamin b6 ,Multivitamin ,business - Abstract
The aim of the present survey was to analyze plasma vitamin B6 levels in post-bariatric patients and to elucidate the causal factors associated with elevated plasma vitamin B6 levels. This is a retrospective analysis of electronic patient data of all post-bariatric patients evaluated at the endocrine outpatient clinic of the University Hospital Basel in 2017, for which plasma vitamin B6 values were assessed during regular follow-up visits. In total, 205 patients were included in the study, whereof a minority of 43% had vitamin B6 levels in the normal range. 50% of the patients had vitamin B6 levels up to fourfold higher than the upper normal limit and 7% had levels more than fourfold above the upper normal limit. Vitamin B6 deficiency was not observed in any patient. While multivitamin supplementation in general was associated with elevated plasma vitamin B6 levels, the highest vitamin B6 levels were found after biliopancreatic diversion (BPD) and in patients who reported daily energy drink intake. Elevated plasma vitamin B6 levels up to fourfold above the upper normal limit are common in postbariatric patients and are associated with regular multivitamin supplementation, while highly elevated plasma vitamin B6 levels were seen primarily upon regular energy drink intake. Thus, a regular follow-up of vitamin B6 plasma levels and critical evaluation of vitamin B6 supplementation, either as part of the multivitamin preparation or related to regular energy drink intake, is highly warranted and should be an integral part of the routine post-bariatric follow-up.
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- 2021
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10. Patient involvement to inform the design of a clinical trial in postbariatric hypoglycaemia
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Matthias Hepprich, Marc Y Donath, and Lars G Hemkens
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Bariatric surgery ,lcsh:R5-920 ,Postprandial hypoglycaemia ,Patient involvement ,Outcome finding ,lcsh:Medicine (General) ,Late-dumping - Abstract
Background: Bariatric surgery may lead to symptomatic postprandial hypoglycaemia as a major side effect without established therapy so far. We aimed to develop an evidence-based study design of a clinical trial that tests treatment options and can provide useful patient-relevant evidence.Methods: We searched systematically for guidance of core outcome sets to determine the most relevant types of outcomes and duration of such a trial. Our search comprised literature databases, a database of core outcome sets and self-help organizations. We then developed a simple online questionnaire based on interviews with German-speaking patients with postprandial hypoglycaemia after bariatric surgery. We recruited participants by reaching out to all German speaking endocrinologists in Switzerland and large Swiss bariatric centres. We asked for preferences regarding outcome types and acceptable duration of being included in a corresponding clinical trial.Results: The literature search did not identify evidence-based guidance for informing our study design. Experience of clinical and research routine as well as patient interviews helped in identifying potential outcomes and the design of an online questionnaire. Therein, a total of 29 persons started the questionnaire and 22 answered questions related to the primary outcome. Of these, 17 (77.3%) deemed quality of life more relevant as primary outcome than the rate of hypoglycaemic episodes. A trial length of four weeks or longer was regarded as acceptable for 19 of 21 respondents to this question (91.4 %) and of six months or longer for 12 respondents (56 %). Conclusions: In situations with no other guidance, a simple questionnaire may help to inform trial design decisions. This study identifies a patient preference for “quality of life” as a primary outcome and supports the evidence-based conception of a patient-centred clinical trial in postbariatric hypoglycaemia.
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- 2021
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11. Model-Based Assessment of C-Peptide Secretion and Kinetics in Post Gastric Bypass Individuals Experiencing Postprandial Hyperinsulinemic Hypoglycemia
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Marc Y. Donath, Michele Schiavon, Matthias Hepprich, Lia Bally, Chiara Dalla Man, and David Herzig
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0301 basic medicine ,Blood Glucose ,Male ,obesity ,insulin secretion ,Endocrinology, Diabetes and Metabolism ,medicine.disease_cause ,lcsh:Diseases of the endocrine glands. Clinical endocrinology ,Gastroenterology ,Cohort Studies ,chemistry.chemical_compound ,0302 clinical medicine ,Postoperative Complications ,Endocrinology ,model identification ,Insulin ,Postoperative Period ,610 Medicine & health ,mixed meal ,Original Research ,education.field_of_study ,C-Peptide ,C-peptide ,Middle Aged ,Obesity, Morbid ,Postprandial ,Female ,Bolus (digestion) ,parameter estimation ,Switzerland ,Adult ,medicine.medical_specialty ,Kinetics ,Gastric bypass ,Population ,Gastric Bypass ,030209 endocrinology & metabolism ,Models, Biological ,03 medical and health sciences ,Internal medicine ,Hyperinsulinism ,medicine ,OGTT ,Humans ,Hyperinsulinemic hypoglycemia ,Insulin secretion ,education ,lcsh:RC648-665 ,business.industry ,Glucose Tolerance Test ,Hypoglycemia ,030104 developmental biology ,oral minimal model ,chemistry ,business - Abstract
Assessment of insulin secretion is key to diagnose postprandial hyperinsulinemic hypoglycemia (PHH), an increasingly recognized complication following bariatric surgery. To this end, the Oral C-peptide Minimal Model (OCMM) can be used. This usually requires fixing C-peptide (CP) kinetics to the ones derived from the Van Cauter population model (VCPM), which has never been validated in PHH individuals. The objective of this work was to test the validity of the OCMM coupled with the VCPM in PHH subjects and propose a method to overcome the observed limitations. Two cohorts of adults with PHH after gastric bypass (GB) underwent either a 75 g oral glucose (9F/3M; age=42±9 y; BMI=28.3±6.9 kg/m2) or a 60 g mixed-meal (7F/3M; age = 43 ± 11 y; BMI=27.5±4.2 kg/m2) tolerance test. The OCMM was identified on CP concentration data with CP kinetics fixed to VCPM (VC approach). In both groups, the VC approach underestimated CP-peak and overestimated CP-tail suggesting CP kinetics predicted by VCPM to be inaccurate in this population. Thus, the OCMM was identified using CP kinetics estimated from the data (DB approach) using a Bayesian Maximum a Posteriori estimator. CP data were well predicted in all the subjects using the DB approach, highlighting a significantly faster CP kinetics in patients with PHH compared to the one predicted by VCPM. Finally, a simulation study was used to validate the proposed approach. The present findings question the applicability of the VCPM in patients with PHH after GB and call for CP bolus experiments to develop a reliable CP kinetic model in this population.
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- 2020
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12. Patient Involvement to Inform the Design of a Clinical Trial in Postbariatric Hypoglycemia
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Matthias Hepprich, Marc Y Donath, and Lars G Hemkens
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Background: Bariatric surgery may lead to symptomatic postprandial hypoglycemia as a major side effect without established therapy so far. We aimed to develop an evidence-based study design of a clinical trial that tests treatment options and can provide useful patient-relevant evidence.Methods: We searched systematically for guidance of core outcome sets to determine the most relevant types of outcomes and duration of such a trial. Our search comprised literature databases, a database of core outcome sets and self-help organizations. We then developed a simple online questionnaire based on interviews with German-speaking patients with postprandial hypoglycemia after bariatric surgery. We recruited participants by reaching out to all German speaking endocrinologists in Switzerland and large Swiss bariatric centers. We asked for preferences regarding outcome types and acceptable duration of being included in a corresponding clinical trial.Results: The systematic search did not identify evidence-based guidance for informing our study design. Experience of clinical and research routine as well as patient interviews helped in identifying potential outcomes and the design of an online questionnaire. Therein, a total of 29 persons started the questionnaire and 22 answered questions related to the primary outcome. Of these, 17 (77.3%) deemed quality of life more relevant as primary outcome than the rate of hypoglycemic episodes. A trial length of four weeks or longer was regarded as acceptable for 19 of 21 respondents to this question (91.4 %) and of six months or longer for 12 respondents (56 %). Conclusions: In situations with no other guidance, a simple questionnaire may help to inform trial design decisions. This study identifies a patient preference for “quality of life” as a primary outcome and supports the evidence-based conception of a patient-centered clinical trial in postbariatric hypoglycemia.
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- 2020
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13. Patient involvement to inform the design of a clinical trial in postbariatric hypoglycaemia
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Matthias, Hepprich, Marc Y, Donath, and Lars G, Hemkens
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Bariatric surgery ,Quality of Life ,Humans ,Insulin ,Patient Participation ,Postprandial hypoglycaemia ,Patient involvement ,Outcome finding ,Late-dumping ,Hypoglycemia ,Switzerland ,Research Article - Abstract
Background Bariatric surgery may lead to symptomatic postprandial hypoglycaemia as a major side effect without established therapy so far. We aimed to develop an evidence-based study design of a clinical trial that tests treatment options and can provide useful patient-relevant evidence. Methods We searched systematically for guidance of core outcome sets to determine the most relevant types of outcomes and duration of such a trial. Our search comprised literature databases, a database of core outcome sets and self-help organizations. We then developed a simple online questionnaire based on interviews with German-speaking patients with postprandial hypoglycaemia after bariatric surgery. We recruited participants by reaching out to all German speaking endocrinologists in Switzerland and large Swiss bariatric centres. We asked for preferences regarding outcome types and acceptable duration of being included in a corresponding clinical trial. Results The literature search did not identify evidence-based guidance for informing our study design. Experience of clinical and research routine as well as patient interviews helped in identifying potential outcomes and the design of an online questionnaire. Therein, a total of 29 persons started the questionnaire and 22 answered questions related to the primary outcome. Of these, 17 (77.3%) deemed quality of life more relevant as primary outcome than the rate of hypoglycaemic episodes. A trial length of four weeks or longer was regarded as acceptable for 19 of 21 respondents to this question (91.4%) and of six months or longer for 12 respondents (56%). Conclusions In situations with no other guidance, a simple questionnaire may help to inform trial design decisions. This study identifies a patient preference for “quality of life” as a primary outcome and supports the evidence-based conception of a patient-centred clinical trial in postbariatric hypoglycaemia. Supplementary Information Supplementary information accompanies this paper at 10.1186/s12874-020-01171-z.
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- 2020
14. 1793-P: C-Peptide Kinetics: The Van Cauter Population Model May Not Be Applicable to Post–Gastric Bypass Adults with Postprandial Hyperinsulinemic Hypoglycemia
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Christoph Stettler, Marc Y. Donath, Chiara Dalla Man, Michele Schiavon, David Herzig, Lia Bally, and Matthias Hepprich
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education.field_of_study ,medicine.medical_specialty ,Kinetic model ,C-peptide ,business.industry ,Endocrinology, Diabetes and Metabolism ,Gastric bypass ,Population ,medicine.disease ,medicine.disease_cause ,Gastroenterology ,chemistry.chemical_compound ,Postprandial ,chemistry ,Diabetes mellitus ,Internal medicine ,Internal Medicine ,Medicine ,Bolus (digestion) ,business ,education ,Hyperinsulinemic hypoglycemia - Abstract
Insulin secretion is key to understand postprandial hyperinsulinemic hypoglycemia (PHH), an increasingly recognized and potentially debilitating complication of gastric bypass (GB) surgery. To assess it noninvasively, the Oral C-peptide Minimal Model (OCMM) can be used. This requires to know C-peptide (CP) metabolic clearance rate (MCR) usually fixed to the values predicted by the Van Cauter (VC) population model, but this has never been assessed in PHH individuals. Here, the aim is to fill this gap. Two groups of post-GB adults with PHH underwent either a 75g oral glucose (11F/5M; age=43±8 y; BMI=28.2±7.1kg/m2) or a 60g mixed-meal (9F/3M; age=44±10y; BMI=27.4±3.9kg/m2) tolerance test with sampling for plasma glucose and CP over 3.5 and 3h, respectively. The OCMM was used to describe CP concentration with CP kinetics fixed to VC or estimated based on data (DB). Model performance was assessed by its ability to predict CP data. In both groups, the VC approach underestimated CP-peak and overestimated CP-tail, while the DB one well predicted CP data in all subjects (Figure 1A). As a consequence, MCR resulted significantly higher with DB than VC approach (Figure 1B). The present findings question the validity of the VC population model to predict CP kinetics in PHH patients and call for CP bolus experiments to develop a reliable kinetic model in this population. Disclosure M. Schiavon: None. D. Herzig: None. M. Hepprich: None. M.Y. Donath: Advisory Panel; Self; AstraZeneca, Bayer Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Lilly Diabetes, Merck Sharp & Dohme Corp., Novo Nordisk Inc., Roche Pharma, Sanofi-Aventis. C. Stettler: None. L. Bally: None. C. Dalla Man: Research Support; Self; Sanofi-Aventis Deutschland GmbH. Funding Italian Ministry of Education (232/2016); Swiss National Science Foundation (PCEGP3_186978); University of Padova
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- 2020
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15. The role of IL-1 in postprandial fatigue
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Emma Dorph, Matthias Hepprich, Judith Siegenthaler, Marc Y. Donath, Louise Lang Lehrskov, Katharina Timper, and Andrea Widmer
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Adult ,Male ,0301 basic medicine ,lcsh:Internal medicine ,medicine.medical_specialty ,Postprandial fatigue ,Sleepiness ,Calorie ,Adolescent ,medicine.drug_class ,Brief Communication ,Diet, High-Fat ,Placebo ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,Ingestion ,Obesity ,lcsh:RC31-1245 ,Molecular Biology ,Fatigue ,Meal ,Anakinra ,business.industry ,Cell Biology ,Middle Aged ,Anakinra and obesity ,Postprandial Period ,Receptor antagonist ,Crossover study ,Interleukin 1 Receptor Antagonist Protein ,030104 developmental biology ,Endocrinology ,Postprandial ,Diet, Carbohydrate Loading ,business ,030217 neurology & neurosurgery ,Interleukin-1 ,medicine.drug - Abstract
Objectives Cytokines such as IL-1 seems to play a role in the pathogenesis of fatigue associated with some chronic diseases and anti-inflammatory treatment has been shown to reduce these symptoms. Ingestion of a calorie rich meal leads to postprandial fatigue, and is associated with increased systemic concentrations of cytokines, which is more pronounced in obese than lean subjects. We investigated whether postprandial fatigue is regulated by IL-1, and therefore reduced by IL-1 antagonism, in lean and obese subjects. Methods In a double-blind, crossover study in 8 lean and 8 obese male subjects, randomized to receive either saline (placebo) or the IL-1 receptor antagonist anakinra, we investigated whether postprandial fatigue was regulated by IL-1. To promote postprandial fatigue, subjects ran 30 min prior to a high-fat, high-carbohydrate meal. Fatigue was determined using the Stanford Sleepiness Scale and blood samples were drawn at baseline and after the intervention. Results IL-1 antagonism led to a reduction in postprandial fatigue and this effect was more pronounced in obese than lean individuals. Conclusions We conclude that IL-1 is involved in the regulation of postprandial fatigue under physiologic conditions in lean and obese individuals. It remains to be shown whether this effect translates into clinical relevant effects., Graphical abstract, Highlights • Ingestion of a calorie rich meal leads to postprandial fatigue • IL-1 contributes to postprandial fatigue in lean and obese individuals. • IL-1 antagonism may decrease postprandial fatigue in humans.
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- 2018
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16. Cétoacidose diabétique sous empagliflozine
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Gianmarco M. Balestra, Matthias Hepprich, Anne Leuppi-Taegtmeyer, Stephan Krähenbühl, Matthias J. Betz, Florian Pfefferkorn, and Alexandra E. Rätz Bravo
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- 2019
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17. Diabetische Ketoazidose unter Empagliflozin
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Alexandra E. Rätz Bravo, Gianmarco M. Balestra, Anne Leuppi-Taegtmeyer, Stephan Krähenbühl, Florian Pfefferkorn, Matthias Hepprich, and Matthias J. Betz
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business.industry ,Medicine ,business - Published
- 2019
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18. Hypothyroidism manifesting as multiple cranial neuropathies: a case report
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Nils Peters, Matthias J. Betz, Matthias Hepprich, and Johannes Lorscheider
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Adult ,Male ,Thyroid Hormones ,medicine.medical_specialty ,Hormone Replacement Therapy ,Myopathy ,Levothyroxine ,Thyrotropin ,lcsh:Medicine ,Renal function ,Case Report ,Cranial neuropathy ,Thyroid Function Tests ,Hashimoto ,030204 cardiovascular system & hematology ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Cerebrospinal fluid ,Hypothyroidism ,Internal medicine ,Myxedema ,medicine ,Humans ,Creatine Kinase ,medicine.diagnostic_test ,Lumbar puncture ,business.industry ,lcsh:R ,Brain ,General Medicine ,medicine.disease ,Magnetic Resonance Imaging ,Cranial Nerve Diseases ,Thyroxine ,Treatment Outcome ,Elevated serum creatinine ,Creatinine ,030220 oncology & carcinogenesis ,Differential diagnosis ,business ,medicine.drug ,Kidney disease - Abstract
Introduction The clinical picture of hypothyroidism, including neurological symptoms, can be multiform, which may delay or hamper the correct diagnosis. Case presentation We present an uncommon clinical presentation of a 38-year-old Caucasian man with mild facial palsy on the left side, uvular deviation to the left with preserved gag reflex, tongue deviation to the left, lingual dysarthria, and xerosis by severe hypothyroidism. Blood tests on admission showed elevated serum creatinine of 151 μmol/L (glomerular filtration rate 47 ml/min/1.7 CKD-EPI [Chronic Kidney Disease Epidemiology Collaboration equation]), increased creatinine phosphokinase activity (1243 U/L), markedly elevated thyroid-stimulating hormone (292.2 mIU/L), low free thyroxine level (1.1 pmol/L), and free triiodothyronine level below the limit of detection (
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- 2019
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19. 1830-P: Empagliflozin as Well as Anakinra Reduces Symptomatic Postprandial Hypoglycemia after Gastric Bypass
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Beckey Trinh, Marc Y. Donath, Marianne Böni-Schnetzler, Benjamin Schelker, Matthias Hepprich, and Sophia J. Wiedemann
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0301 basic medicine ,Anakinra ,medicine.medical_specialty ,business.industry ,Endocrinology, Diabetes and Metabolism ,Insulin ,medicine.medical_treatment ,030209 endocrinology & metabolism ,medicine.disease ,Placebo ,Gastroenterology ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Postprandial ,Diabetes mellitus ,Internal medicine ,Internal Medicine ,medicine ,Empagliflozin ,business ,Complication ,medicine.drug ,Postprandial Hypoglycemia - Abstract
Background: Postprandial hypoglycemia (PPH) is a debilitating complication after bariatric surgery, due to an exaggerated hyperinsulinemic response after carbohydrate ingestion. Recent studies have shown that IL-1β contributes to the postprandial stimulation of insulin. Similarly, lowering hyperglycemic peak by SGLT2-inhibition may reduce insulin secretion. We investigated whether the IL-1 receptor antagonist anakinra or empagliflozin influence PPH in patients after gastric bypass. Methods: We included 12 subjects with PPH after gastric bypass in a placebo controlled, double-blind, randomized, cross-over proof-of-concept study. Subjects received on each of the 3 study days either empagliflozin, anakinra or the respective placebos followed by a mixed-meal-test (MMT) with assessment of hypoglycaemia. Results: Treatment with empagliflozin reduced glycaemia at 30 (11.2 vs. 10.1 mmol/l), 60 (9.1 vs. 6.9 mmol/l) and 90 (4.5 vs. 3.5 mmol/l) minutes of the MMT compared to placebo and was followed by a significant reduction of hypoglycemic events (n = 2, 16.6%) compared to placebo (n = 8, 61.5%). Treatment with anakinra showed a similar glucose curve as placebo, but was also followed by a significantly reduced rate of hypoglycemic events (n = 2, 16.6%). Both treatment interventions showed lowered insulin and c-peptide levels compared to placebo (p Conclusion: Empagliflozin as well as Anakinra significantly reduced hypoglycemic episodes in patients after gastric bypass by decreased insulin secretion. Therefore, empagliflozin and IL-1 antagonism, could be promising novel therapeutic options for patients with refractory PPH after gastric bypass. Disclosure M. Hepprich: None. B. Schelker: None. S.J. Wiedemann: None. B. Trinh: None. M. Böni-Schnetzler: None. M.Y. Donath: Consultant; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Lilly Diabetes, Merck & Co., Inc., Novartis AG, Novo Nordisk A/S, Sanofi. Funding University of Basel
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- 2019
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20. Empagliflozin as well as Anakinra reduce symptomatic hypoglycemia in patients after Roux-Y-gastric bypass by lowered insulin secretion
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Marianne Böni-Schnetzler, Gottfried Rudofsky, Alessandra Starkle, Sophia J. Wiedemann, Marc Y. Donath, Matthias Hepprich, Beckey Trinh, and Benjamin Schelker
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medicine.medical_specialty ,Anakinra ,business.industry ,Hypoglycemia ,medicine.disease ,Gastroenterology ,Internal medicine ,medicine ,Empagliflozin ,In patient ,Insulin secretion ,business ,Roux y gastric bypass ,medicine.drug - Published
- 2019
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21. Treatment of Primary Aldosteronism with mTORC1 Inhibitors
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Michael N. Hall, Claudia Cavelti-Weder, Martin Reincke, Fabian Meienberg, Thilo Burkard, Felix Beuschlein, Denise V. Kratschmar, Marta M. Swierczynska, Matthias Hepprich, Beckey Trinh, Eleonora Seelig, Alex Odermatt, Marc Y. Donath, Matthias J. Betz, University of Zurich, and Trinh, Beckey
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Male ,0301 basic medicine ,1303 Biochemistry ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Clinical Biochemistry ,10265 Clinic for Endocrinology and Diabetology ,Secondary hypertension ,Blood Pressure ,Pilot Projects ,1308 Clinical Biochemistry ,Biochemistry ,Plasma renin activity ,Mice ,chemistry.chemical_compound ,Mineralocorticoid receptor ,0302 clinical medicine ,Endocrinology ,Primary aldosteronism ,Corticosterone ,Renin ,Aldosterone ,Mice, Inbred BALB C ,Adrenal cortex ,Angiotensin II ,Middle Aged ,1310 Endocrinology ,2712 Endocrinology, Diabetes and Metabolism ,medicine.anatomical_structure ,Female ,biological phenomena, cell phenomena, and immunity ,medicine.drug ,Adult ,medicine.medical_specialty ,Mice, 129 Strain ,610 Medicine & health ,030209 endocrinology & metabolism ,Mechanistic Target of Rapamycin Complex 1 ,2704 Biochemistry (medical) ,Proof of Concept Study ,03 medical and health sciences ,Internal medicine ,Hyperaldosteronism ,Renin–angiotensin system ,medicine ,Animals ,Humans ,Everolimus ,Sirolimus ,business.industry ,Biochemistry (medical) ,Hemodynamics ,medicine.disease ,Mice, Inbred C57BL ,Clinical trial ,Steroid hormone ,030104 developmental biology ,chemistry ,business - Abstract
Context Mammalian target of rapamycin complex 1 (mTORC1) activity is often increased in the adrenal cortex of patients with primary aldosteronism (PA), and mTORC1 inhibition decreases aldosterone production in adrenocortical cells, suggesting the mTORC1 pathway as a target for treatment of PA. Objective To investigate the effect of mTORC1 inhibition on adrenal steroid hormones and hemodynamic parameters in mice and in patients with PA. Design (i) Plasma aldosterone, corticosterone, and angiotensin II (Ang II) were measured in mice treated for 24 hours with vehicle or rapamycin. (ii) Plasma aldosterone levels after a saline infusion test, plasma renin, and 24-hour urine steroid hormone metabolome and hemodynamic parameters were measured during an open-label study in 12 patients with PA, before and after 2 weeks of treatment with everolimus and after a 2-week washout. Main Outcome Measures (i) Change in plasma aldosterone levels. (ii) Change in other steroid hormones, renin, Ang II, and hemodynamic parameters. Results Treatment of mice with rapamycin significantly decreased plasma aldosterone levels (P = 0.007). Overall, treatment of PA patients with everolimus significantly decreased blood pressure (P < 0.05) and increased renin levels (P = 0.001) but did not decrease aldosterone levels significantly. However, prominent reduction of aldosterone levels upon everolimus treatment was observed in four patients. Conclusion In mice, mTORC1 inhibition was associated with reduced plasma aldosterone levels. In patients with PA, mTORC1 inhibition was associated with improved blood pressure and renin suppression. In addition, mTORC1 inhibition appeared to reduce plasma aldosterone in a subset of patients.
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- 2019
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22. Postprandial Hypoglycemia in Patients after Bariatric Surgery is Mediated by Glucose-Induced Il-1β
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Alessandra Staerkle, Matthias Hepprich, Marianne Böni-Schnetzler, Marco Geigges, Beckey Trinh, Gottfried Rudofsky, Sophia J. Wiedemann, Benjamin Luca Schelker, Marc Y. Donath, and Jordan Löliger
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medicine.medical_specialty ,Anakinra ,medicine.drug_class ,business.industry ,Insulin ,medicine.medical_treatment ,Hypoglycemia ,Receptor antagonist ,medicine.disease ,Surgery ,Postprandial ,medicine ,Empagliflozin ,Complication ,business ,Postprandial Hypoglycemia ,medicine.drug - Abstract
Postprandial hypoglycemia is a disabling complication of the treatment of obesity by bariatric surgery. So far, no therapy exists, and the underlying mechanisms remain unclear. Here, we hypothesized that glucose-induced IL-1β leads to an exaggerated insulin response in this condition. Therefore, we conducted a placebo-controlled, randomized, double-blind, cross-over study with the SGLT2-inhibitor empagliflozin and the IL-1 receptor antagonist anakinra. Both drugs reduced postprandial insulin release and prevented hypoglycemia. Moreover, analysis of monocytes ex vivo revealed a hyper-reactive inflammatory state that resembles an exaggerated response to a meal. Our study proposes a role for glucose-induced IL-1β in postprandial hypoglycemia after bariatric surgery and suggests that SGLT2-inhibitors and IL-1 antagonism may improve this condition.
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- 2019
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23. Association of Convalescent Plasma Treatment With Clinical Outcomes in Patients With COVID-19
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Cathrine Axfors, David Moher, Matthias Hepprich, Viktoria Gloy, Fahim Ebrahimi, John P. A. Ioannidis, Noah Haber, Perrine Janiaud, Emily R. Smith, Andreas M. Schmitt, Steven N. Goodman, Lars G. Hemkens, and Nina Khanna
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Mechanical ventilation ,medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,010102 general mathematics ,Hazard ratio ,Absolute risk reduction ,General Medicine ,Placebo ,01 natural sciences ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Randomized controlled trial ,law ,Internal medicine ,Meta-analysis ,Relative risk ,medicine ,030212 general & internal medicine ,0101 mathematics ,business ,Adverse effect - Abstract
Importance: Convalescent plasma is a proposed treatment for COVID-19. Objective: To assess clinical outcomes with convalescent plasma treatment vs placebo or standard of care in peer-reviewed and preprint publications or press releases of randomized clinical trials (RCTs). Data Sources: PubMed, the Cochrane COVID-19 trial registry, and the Living Overview of Evidence platform were searched until January 29, 2021. Study Selection: The RCTs selected compared any type of convalescent plasma vs placebo or standard of care for patients with confirmed or suspected COVID-19 in any treatment setting. Data Extraction and Synthesis: Two reviewers independently extracted data on relevant clinical outcomes, trial characteristics, and patient characteristics and used the Cochrane Risk of Bias Assessment Tool. The primary analysis included peer-reviewed publications of RCTs only, whereas the secondary analysis included all publicly available RCT data (peer-reviewed publications, preprints, and press releases). Inverse variance-weighted meta-analyses were conducted to summarize the treatment effects. The certainty of the evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation. Main Outcomes and Measures: All-cause mortality, length of hospital stay, clinical improvement, clinical deterioration, mechanical ventilation use, and serious adverse events. Results: A total of 1060 patients from 4 peer-reviewed RCTs and 10â¯722 patients from 6 other publicly available RCTs were included. The summary risk ratio (RR) for all-cause mortality with convalescent plasma in the 4 peer-reviewed RCTs was 0.93 (95% CI, 0.63 to 1.38), the absolute risk difference was -1.21% (95% CI, -5.29% to 2.88%), and there was low certainty of the evidence due to imprecision. Across all 10 RCTs, the summary RR was 1.02 (95% CI, 0.92 to 1.12) and there was moderate certainty of the evidence due to inclusion of unpublished data. Among the peer-reviewed RCTs, the summary hazard ratio was 1.17 (95% CI, 0.07 to 20.34) for length of hospital stay, the summary RR was 0.76 (95% CI, 0.20 to 2.87) for mechanical ventilation use (the absolute risk difference for mechanical ventilation use was -2.56% [95% CI, -13.16% to 8.05%]), and there was low certainty of the evidence due to imprecision for both outcomes. Limited data on clinical improvement, clinical deterioration, and serious adverse events showed no significant differences. Conclusions and Relevance: Treatment with convalescent plasma compared with placebo or standard of care was not significantly associated with a decrease in all-cause mortality or with any benefit for other clinical outcomes. The certainty of the evidence was low to moderate for all-cause mortality and low for other outcomes.
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- 2021
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24. Postprandial Hypoglycemia in Patients after Gastric Bypass Surgery Is Mediated by Glucose-Induced IL-1β
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Marc Y. Donath, Alessandra Starkle, Gottfried Rudofsky, Matthias Hepprich, Marco Geigges, Marianne Böni-Schnetzler, Sophia J. Wiedemann, Beckey Trinh, Jordan Löliger, and Benjamin Schelker
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Adult ,Male ,0301 basic medicine ,medicine.medical_specialty ,Physiology ,medicine.medical_treatment ,Interleukin-1beta ,Gastric Bypass ,Hypoglycemia ,medicine.disease_cause ,Proof of Concept Study ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Double-Blind Method ,Glucosides ,Internal medicine ,medicine ,Empagliflozin ,Humans ,Benzhydryl Compounds ,Sodium-Glucose Transporter 2 Inhibitors ,Molecular Biology ,Anakinra ,Cross-Over Studies ,Gastric bypass surgery ,business.industry ,Insulin ,Cell Biology ,Middle Aged ,Postprandial Period ,medicine.disease ,Crossover study ,Interleukin 1 Receptor Antagonist Protein ,Glucose ,030104 developmental biology ,Postprandial ,Female ,business ,030217 neurology & neurosurgery ,medicine.drug ,Postprandial Hypoglycemia - Abstract
Summary Postprandial hypoglycemia is a disabling complication of the treatment of obesity by gastric bypass surgery. So far, no therapy exists, and the underlying mechanisms remain unclear. Here, we hypothesized that glucose-induced IL-1β leads to an exaggerated insulin response in this condition. Therefore, we conducted a placebo-controlled, randomized, double-blind, crossover study with the SGLT2-inhibitor empagliflozin and the IL-1 receptor antagonist anakinra ( clinicaltrials.gov NCT03200782 ; n = 12). Both drugs reduced postprandial insulin release and prevented hypoglycemia (symptomatic events requiring rescue glucose: placebo = 7/12, empagliflozin = 2/12, and anakinra = 2/12, pvallikelihood ratio test (LRT) = 0.013; nadir blood glucose for placebo = 2.4 mmol/L, 95% CI 2.18–2.62, empagliflozin = 2.69 mmol/L, 95% CI 2.31–3.08, and anakinra = 2.99 mmol/L, 95% CI 2.43–3.55, pvalLRT = 0.048). Moreover, analysis of monocytes ex vivo revealed a hyper-reactive inflammatory state that has features of an exaggerated response to a meal. Our study proposes a role for glucose-induced IL-1β in postprandial hypoglycemia after gastric bypass surgery and suggests that SGLT2-inhibitors and IL-1 antagonism may improve this condition.
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- 2020
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25. Anticoagulation orale et prophylaxie des thromboses chez les patients obèses et bariatriques
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Dimitrios A. Tsakiris, Matthias Hepprich, Tarik Delko, and Julie Refardt
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macromolecular substances - Abstract
La prophylaxie des thromboses et l’anticoagulation orale chez les patients presentant une obesite severe et ayant subi une operation bariatrique n’ont ete que peu etudiees et s’averent critiques a de nombreux egards.
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- 2018
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26. Orale Antikoagulation und Thromboseprophylaxe bei adipösen und bariatrischen Patienten
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Julie Refardt, Matthias Hepprich, Dimitrios A. Tsakiris, and Tarik Delko
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Die Thromboseprophylaxe bei schwer adiposen und bariatrisch operierten Patienten wie auch eine orale Antikoagulation sind nur wenig untersucht und in mehrfacher Hinsicht kritisch.
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- 2018
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