Violeta Raverdy

• Doctor of Medicine
• University of Lille

Type 2 diabetes (T2D) is a common comorbidity in kidney transplant recipients, representing a significant proportion of the candidate pool. Post-kidney transplantation management of T2D remains challenging, leading to inferior long-term outcomes compared to non-diabetic recipients. This study aimed to assess the association between Homeostatic Mode...

Metabolic dysfunction-associated steatotic liver disease (MASLD) exhibits considerable variability in clinical outcomes. Identifying specific phenotypic profiles within MASLD is essential for developing targeted therapeutic strategies. Here we investigated the heterogeneity of MASLD using partitioning around medoids clustering based on six simple c...

Objective Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterised by lipid accumulation in the liver and is often associated with obesity and type 2 diabetes. The gut microbiome recently emerged as a significant player in liver metabolism and health. Hippurate, a host-microbial co-metabolite has been associated with human...

Plasma growth differentiation factor-15 (GDF-15) levels increase with obesity and metabolic dysfunction-associated steatotic liver disease (MASLD) but the underlying mechanism remains poorly defined. Using male mouse models of obesity and MASLD, and biopsies from carefully-characterized patients regarding obesity, type 2 diabetes (T2D) and MASLD st...

Objective Help public health decision-making requires a better understanding of the dynamics of obesity and type 2 diabetes and an assessement of different strategies to decrease their burdens. Methods Based on 97,848 individual data, collected in the French Health, Health Care and Insurance Survey over 1998–2014, a Markov model was developed to d...

The postprandial glucose response is an independent risk factor for type 2 diabetes. Observationally, early glucose response after an oral glucose challenge has been linked to intestinal glucose absorption, largely influenced by the expression of sodium–glucose cotransporter 1 (SGLT1). This study uses Mendelian randomization (MR) to estimate the ca...

Type 2 Diabetes (T2D) is one of the main epidemics of this century. One of the hypothesis of medical research is that an important cause of T2D may be the abnormal regulation of intestinal glucose absorption (IGA). Early detection of IGA disorders, and, more generally, precision medicine, may help to prevent the risk of T2D. This could be achieved...

Obesity is considered by many as a lifestyle choice rather than a chronic progressive disease. The Innovative Medicines Initiative (IMI) SOPHIA (Stratification of Obesity Phenotypes to Optimize Future Obesity Therapy) project is part of a momentum shift aiming to provide better tools for the stratification of people with obesity according to diseas...

Type 2 diabetes (T2D) is a common comorbidity in kidney transplant recipients, representing a significant proportion of the candidate pool. Post-kidney transplantation management of T2D remains challenging, leading to inferior long-term outcomes compared to non-diabetic recipients. This study aimed to assess the association between Homeostatic Mode...

In islet transplantation (ITx), primary graft function (PGF) or beta cell function measured early after last infusion is closely associated with long term clinical outcomes. We investigated the association between PGF and 5 year insulin independence rate in ITx and pancreas transplantation (PTx) recipients. This retrospective multicenter study incl...

Objective Steatotic liver disease (SLD) is frequent in individuals with obesity. In this study, type 2 diabetes (T2D), sex, and menopausal status were combined to refine the stratification of obesity regarding the risk of advanced SLD and gain further insight into disease physiopathology. Methods This study enrolled 1446 participants with obesity...

Background & Aims Liver homeostasis is ensured in part by time-of-day-dependent processes, many of them being paced by the molecular circadian clock. Liver functions are compromised in metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH), and clock disruption increases suscepti...

Background 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. Methods In this multinational retrospecti...

We evaluate the shared genetic regulation of mRNA molecules, proteins and metabolites derived from whole blood from 3029 human donors. We find abundant allelic heterogeneity, where multiple variants regulate a particular molecular phenotype, and pleiotropy, where a single variant associates with multiple molecular phenotypes over multiple genomic r...

Background: 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. Methods: In this multinational retros...

Liver homeostasis is ensured in part by time-of-day-dependent processes, many of them being paced by the molecular circadian clock. Liver functions are compromised in non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH), and clock disruption increases susceptibility to non-alcoholic fatty liver disease (NAFLD) progression in ro...

Metformin (MET) is the most prescribed antidiabetic drug, but its mechanisms of action remain elusive. Recent data point to the gut as MET's primary target. Here, we explored the effect of MET on the gut glucose transport machinery. Using human enterocytes (Caco-2/TC7 cells) in vitro, we showed that MET transiently reduced the apical density of sod...

Background: Allogeneic islet transplantation is a validated therapy in type 1 diabetes; however, there is decline of transplanted islet graft function over time and the mechanisms underlying this decline are unclear. We evaluated the distinct association between primary graft function (PGF) and 5-year islet transplantation outcomes. Methods: In...

The application of multiple omics technologies in biomedical cohorts has the potential to reveal patient-level disease characteristics and individualized response to treatment. However, the scale and heterogeneous nature of multi-modal data makes integration and inference a non-trivial task. We developed a deep-learning-based framework, multi-omics...

Tissue injury triggers activation of mesenchymal lineage cells into wound-repairing myofibroblasts, whose unrestrained activity leads to fibrosis. Although this process is largely controlled at the transcriptional level, whether the main transcription factors involved have all been identified has remained elusive. Here, we report multi-omics analys...

Background and Aim: Increasing evidences suggest that intestinal glucose absorption (IGA) plays a distinct role in pathophysiology of type 2 diabetes (T2D) . However, state of the art IGA measurement with multiple tracers techniques are demanding and . We propose D-xylose, a non metabolized pentose, as a proxy to quantify IGA levels to study IGA in...

Background: Non-alcoholic fatty liver disease (NAFLD) affects nearly 25% of the global population. Cardiovascular disease (CVD) is the most common cause of death among patients with NAFLD, in line with highly prevalent dyslipidemia in this population. Increased plasma triglyceride (TG)-rich lipoprotein (TRL) concentrations, an important risk facto...

Objective: Maternal glycemic dysregulation during pregnancy increases the risk of adverse health outcomes in her offspring, a risk thought to be linearly related to maternal hyperglycemia. It is hypothesized that changes in offspring DNA methylation (DNAm) underline these associations. Research design and methods: To address this hypothesis, we...

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 p...

Fatty liver disease (FLD) is a growing health issue with burdening unmet clinical needs. FLD has a genetic component but, despite the common variants already identified, there is still a missing heritability component. Using a candidate gene approach, we identify a locus (rs71519934) at the Pleckstrin and Sec7 domain-containing 3 ( PSD3 ) gene resu...

To liberate fatty acids (FAs) from intracellular stores, lipolysis is regulated by the activity of the lipases adipose triglyceride lipase (ATGL), hormone-sensitive lipase and monoacylglycerol lipase. Excessive FA release as a result of uncontrolled lipolysis results in lipotoxicity, which can in turn promote the progression of metabolic disorders....

Background/objectives Innate lymphoid cells (ILCs) play an important role in the maintenance of immune and metabolic homeostasis in adipose tissue (AT). The crosstalk between AT ILCs and adipocytes and other immune cells coordinates adipocyte differentiation, beiging, glucose metabolism and inflammation. Although the metabolic and homeostatic funct...

Background Knowledge of age‐related DNA methylation changes in skeletal muscle is limited, yet this tissue is severely affected by ageing in humans. Methods We conducted a large‐scale epigenome‐wide association study meta‐analysis of age in human skeletal muscle from 10 studies (total n = 908 muscle methylomes from men and women aged 18–89 years o...

Background Previous studies unveiled a relation between the severity of COVID‐19 pneumonia and obesity. The aims of this multicenter retrospective cohort study were to disentangle the association of BMI and associated metabolic risk factors (diabetes, hypertension, hyperlipidemia, current smoking) in critically ill patients with COVID‐19. Methods...

Genetic variants identified by genome-wide association studies can contribute to disease risk by altering the production and abundance of mRNA, proteins and other molecules. However, the interplay between molecular intermediaries that define the pathway from genetic variation to disease is not well understood. Here, we evaluated the shared genetic...

Background/objectives: The alimentary limb has been proposed to be a key driver of the weight-loss-independent metabolic improvements that occur upon bariatric surgery. However, the One Anastomosis Gastric Bypass (OAGB) procedure, consisting of one long biliary limb and a short common limb, induces stronger beneficial metabolic effects compared to...

Background & aims: Fatty liver disease (FLD) is a growing epidemic that is expected to be the leading cause of end-stage liver disease within the next decade. Both environmental and genetic factors contribute to the susceptibility of FLD. Several genetic variants contributing to FLD have been identified in exome-wide association studies. However,...

Introduction Plasma bile acids (BA) have been extensively studied as pathophysiological actors in Non-Alcoholic Steatohepatitis (NASH). However, results from clinical studies are often complicated by the association of NASH with type 2 diabetes (T2D), obesity and insulin resistance (IR). Here, we sought to dissect the relationship between NASH, T2D...

In addition to their well-known role in the control of cellular proliferation and cancer, cell cycle regulators are increasingly identified as important metabolic modulators. Several GWAS have identified SNPs near CDKN2A, the locus encoding for p16INK4a (p16), associated with elevated risk for cardiovascular diseases and type-2 diabetes development...

Objective: The aim of this study was to compare the efficacy and safety of 12-month implantation of a duodeno-jejunal bypass liner (DJBL) with conventional medical care in patients with metabolic syndrome (MS). Summary background data: DJBL is an endoscopic device for treating obesity and related disorders. The persistence of favorable results a...

Background&Aims Severely obese patients are a growing population at risk of non‐alcoholic fatty liver disease (NAFLD). Considering the increasing burden, a predictive tool of NAFLD progression would be of interest. Our objective is to provide a tool allowing general practitioners to identify and refer the patients most at risk , and specialists to...

Background Non-alcoholic fatty liver disease (NAFLD) is highly prevalent and causes serious health complications in individuals with and without type 2 diabetes (T2D). Early diagnosis of NAFLD is important, as this can help prevent irreversible damage to the liver and, ultimately, hepatocellular carcinomas. We sought to expand etiological understan...

Background & Aims Studies are needed to determine the long-term effects of bariatric surgery for patients with nonalcoholic steatohepatitis (NASH). We evaluated sequential liver biopsies, collected the time of bariatric surgery and 1 and 5 years later, to assess the long-term effects of bariatric surgery in patients with NASH. Methods We performed...

Roux-en-Y gastric bypass surgery (RYGB) has been effective for inducing weight-loss and remission of diabetes in obese persons. Nonetheless, the response to RYGB and resulting improvements in glycemic control are heterogeneous and not well understood. To gain molecular insights into how individuals respond to RYGB, we monitored the longitudinal eff...

Background and aims: Non-Alcoholic SteatoHepatitis (NASH) is considered as a pivotal stage in Non-Alcoholic Fatty Liver Disease (NAFLD) progression, as it paves the way for severe liver injuries such as fibrosis and cirrhosis. The etiology of human NASH is multi-factorial and identifying reliable molecular players and/or biomarkers has proven diff...

Objective The Covid‐19 pandemic is rapidly spreading worldwide, notably in Europe and North America, where obesity is highly prevalent. The relation between obesity and severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) has not been fully documented. Methods In this retrospective cohort study we analyzed the relationship between clinical...

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AimsNot all people with obesity become glucose intolerant, suggesting differential activation of cellular pathways. The unfolded protein response (UPR) may contribute to the development of insulin resistance in several organs, but its role in skeletal muscle remains debated. Therefore, we explored the UPR activation in muscle from non-diabetic gluc...

Background: Non-alcoholic fatty liver disease (NAFLD) is highly prevalent and causes serious health complications in type 2 diabetes (T2D) and beyond. Early diagnosis of NAFLD is important, as this can help prevent irreversible damage to the liver and ultimately hepatocellular carcinomas. Methods and Findings: Utilizing the baseline data from the I...

Autophagy facilitates the adaptation to nutritional stress. Here, we show that short-term starvation of cultured cells or mice caused the autophagy-dependent cellular release of acyl-CoA-binding protein (ACBP, also known as diazepam-binding inhibitor, DBI) and consequent ACBP-mediated feedback inhibition of autophagy. Importantly, ACBP levels were...

Objective: The long-term outcome of allogenic islet transplantation is unknown. The aim of this study was to evaluate the 10-year outcome of islet transplantation in patients with type 1 diabetes and hypoglycemia unawareness and/or a functioning kidney graft. Research design and methods: We enrolled in this prospective parallel-arm cohort study...

Autophagy facilitates the adaptation to nutritional stress. Here, we show that short-term starvation of cultured cells or mice caused the autophagy-dependent cellular release of acyl-CoA-binding protein (ACBP, also known as diazepam-binding inhibitor, DBI) and consequent ACBP-mediated feedback inhibition of autophagy. Importantly, ACBP levels were...

Background: Clinical data identified an association between the use of HMG-CoA reductase inhibitors (statins) and incident diabetes in patients with underlying diabetes risk factors such as obesity, hypertension and dyslipidemia. The molecular mechanisms however are unknown. Methods: An observational cross-sectional study included 910 severely o...

Introduction: Different factors, such as age, gender, preoperative weight but also the patient's motivation, are known to impact outcomes after Roux-en-Y gastric bypass (RYGBP). Weight loss prediction is helpful to define realistic expectations and maintain motivation during follow-up, but also to select good candidates for surgery and limit failu...

RÉSUMÉ Le diabète de Type 2 (DT2) se caractérise par un défaut combiné de la sécrétion et de l’action de l’insuline. La chirurgie bariatrique et notamment le Roux-en-Y Gastric Bypass (RYGB) ont montré des effets bénéfiques spectaculaires sur le contrôle glycémique remettant en perspective la prise en charge médicale du DT2. L’exclusion gastroduodén...

Aberrant histone methylation profile is reported to correlate with the development and progression of NAFLD during obesity. However, the identification of specific epigenetic modifiers involved in this process remains poorly understood. Here, we identify the histone demethylase Plant Homeodomain Finger 2 (Phf2) as a new transcriptional co-activator...

Background: Islet transplantation is indicated for patients with type 1 diabetes with severe hypoglycaemia or after kidney transplantation. We did a randomised trial to assess the efficacy and safety of islet transplantation compared with insulin therapy in these patients. Methods: In this multicentre, open-label, randomised controlled trial, we...

Epidemiological studies identify tobacco as an independent risk factor for T2D, however, the mechanisms involved remains unclear. Clinical studies incriminate an increase of insulin resistance but a direct effect on pancreatic islet mass is suggested by some animal studies. The aim of this study was to document the association between tobacco smoki...

Type 2 diabetes (T2D) is closely linked with non-alcoholic fatty liver disease (NAFLD) and hepatic insulin resistance, but the involved mechanisms are still elusive. Using DNA methylome and transcriptome analyses of livers from obese individuals, we found that both hypomethylation at a CpG site in PDGFA (encoding platelet derived growth factor alph...

Type 2 diabetes (T2D) is closely linked with non-alcoholic fatty liver disease (NAFLD) and hepatic insulin resistance, but the involved mechanisms are still elusive. Using DNA methylome and transcriptome analyses of livers from obese individuals, we found that both hypomethylation at a CpG site in PDGFA (encoding platelet derived growth factor alph...

Background and study aims Endoscopic techniques have demonstrated their effectiveness in metabolic surgery, notably through a gastrointestinal (GI) liner, with a less invasive approach than conventional surgery. Our study evaluates the safety and efficacy of endoscopic GI anastomosis (EGIA) using a lumen-apposing stent to secure the anastomosis. Ma...

Résumé Les maladies métaboliques comme l’obésité, l’hypertension artérielle et le diabète de type 2 ont vu leur prévalence augmenter de façon vertigineuse dans le monde. En parallèle, les habitudes alimentaires se sont profondément modifiées ces dernières décennies avec l’augmentation de la consommation d’aliments riches en sel et en sucre. Des étu...

In allogenic islet transplantation (IT), high purity of islet preparations and low contamination by non-islet cells are generally favored. The aim of the present study was to analyze the relation between the purity of transplanted preparations, and graft function during 5 years post-IT. Twenty-four type 1 diabetic patients, followed-up 5 years afte...

PurposeThis study examines the effect of Roux-en-Y gastric bypass (RYGB) and laparoscopic adjustable gastric banding (LAGB) on renal function for at least 5 years 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, blo...

Background Salivary (AMY1) and pancreatic (AMY2) amylases hydrolyze starch. Copy number of AMY1A (encoding AMY1) was reported to be higher in populations with a high-starch diet and reduced in obese people. These results based on quantitative PCR have been challenged recently. We aimed to re-assess the relationship between amylase and adiposity usi...

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 of metabolic disease is not known. We therefore studied the transcriptional regulation of hepatic Dpp4 in young mice prone to diet-induced obe...

Background: Postprandial hyperinsulinemic hypoglycemia (PHH) is often reported after Roux-en-Y gastric bypass (RYGB). In the absence of a prospective study, the clinical and biological determinants of PHH remain unclear. Objective: To determine the incidence and predictive factors of PHH after RYGB. Methods: Participants were 957 RYGB patients...

Background: An increase of plasma kynurenine concentrations, potentially bioactive metabolites of tryptophan, was found in subjects with obesity, resulting from low-grade inflammation of the white adipose tissue. Bariatric surgery decreases low-grade inflammation associated with obesity and improves glucose control. Objective: Our goal was to de...

Active sodium glucose transporters (SGLTs) contribute to glucose homeostasis and represent novels targets for the management of type 2 diabetes (T2D). SGLT1 is essential for intestinal glucose absorption from the lumen into enterocytes, while glucose reabsorption by the kidney is mediated predominantly by sodium glucose co-transporter 2 (SGLT2). SG...

Background: Roux-en-Y gastric bypass (RYGBP) is the most widely used bariatric surgery procedure, which induces profound metabolic and physiological effects, such as substantial improvements in obesity, type 2 diabetes and their comorbidities. Increasing evidence identifies bile acids (BAs) as signaling molecules that contribute to the metabolic i...

Introduction Le foie joue un role majeur mais encore mal connu dans le risque de diabete de type 2 (DT2) dont l'heritabilite est en partie expliquee par des facteurs genetiques et epigenetiques. Notre projet a pour but d'identifier des variations de la methylation de l'ADN associees au DT2 dans le tissu hepatique. Patients et Methodes Nous avons an...

Rationnel Le Roux-en-Y gastric bypass (RYGB) est une chirurgie de l'obésité morbide qui induit des effets métaboliques bénéfiques indépendants de la perte de poids (en particulier amélioration du diabète de type 2) dont les mécanismes ne sont pas identifiés. Les acides biliaires (ABs) sont de bons candidats puisque ce sont des molécules de signalis...

Introduction Objective : La chirurgie métabolique (MSurg) se révèle très efficace contre les pathologies liées à l'obésité. La compréhension de ses mécanismes est cruciale. L'objectif de la biobanque ABOS est d'identifier les mécanismes expliquant l'efficacité de la MSurg afin de proposer de solutions innovantes susceptibles d'optimiser les résulta...

Objectif Notre étude décrit le profil glycémique des femmes enceintes après chirurgie bariatrique, alors que peu de données existent dans la littérature. Patients et Méthodes 12 femmes enceintes opérées d'une chirurgie bariatrique (8 procédures malabsorptives et 4 restrictives) ont bénéficié entre 24 et 28 semaines d'aménorrhées, de la pose d'un h...

Introduction La chirurgie bariatrique améliore l'homéostasie glycémique et réduit l'inflammation chronique associée à l'obésité. Conséquence de cette inflammation, une augmentation des kynurénines circulantes provenant de la dégradation du tryptophane a été démontrée chez les sujets obèses. Certaines kynurénines sont neurotoxiques et pourraient êtr...

Introduction Le diabete de type 2 (DT2) est caracterise par une resistance a l'insuline (RI), qui est associee a l'expansion des cellules beta et une augmentation de la secretion insulinique, et une incapacite a repondre a la demande metabolique. Les etudes chez la souris suggerent que la proteine circulante ANGPTL8 (gene C19orf80) est impliquee da...

Introduction Le diabete de type 2 (DT2) s'ameliore chez la majorite des patients beneficiant d'une chirurgie bariatrique. Cependant chez une proportion importante d'entre eux, le DT2 progresse a nouveau apres sa remission initiale. L'objectif de cette etude est d'evaluer la progression du controle glycemique a long terme chez des patients DT2 obese...