Subclinical markers of diabetes and obesity
Diabetes is a chronic disease most often linked to a family history including obesity and gestational diabetes. Understanding obesity requires the discovery of molecular markers of pre-diabetes specific to each situation, from an early age. The validation of these markers should allow the implementation of targeted preventive interventions in people with a clearly identified risk profile.
Prediction of the incidence of T2DM in families from the DESCENDENCE cohort
The heritability of type 2 diabetes (T2DM) is estimated to be between 40 and 75%. To effectively prevent this disease, it is necessary to identify as early as possible future diabetic patients who are, in most cases, descendants of diabetic patients.
The objective is to genetically and metabolically characterize these families to identify risk profiles of subclinical development of a future T2DM so as to put in place more effective preventive strategies. From the data and samples from the DESCENDANCE cohort, we wish to combine genetic, metabolomic and phenotypic biomarkers, we intend to establish an equation allowing better prevention of T2DM.
Understanding the fetal epigenic risk in T2DM
Prematurity affects 6% of newborns, with adverse consequences on the subsequent development of these children, in particular an increased risk of T2DM in adulthood. Knowing the nature of the biological biomarkers associated with prematurity would help prevent its early and distant consequences.
This project proposes to identify the epigenetic factors caused by prematurity through the study of the cord blood of premature children, to better understand the mechanisms of accelerated aging in these subjects and to set in motion effective preventive strategies for these chronic diseases. age-related.
Prediction of the incidence of obesity and prediabetes
Obesity in children and adolescents, if not managed, is the main risk factor for the development of chronic obesity in adults and then type 2 diabetes. is therefore important for reducing the incidence of new cases of diabetes and more generally of metabolic diseases.
Our goal is to identify from childhood, thanks to genetics and microbiome analysis, people with a high risk profile so as to put in place monitoring and prevention measures and if necessary to implement a personalized support.
Risk markers for complications
Study of the links between diabetes and cancer risks
Diabetic complications are very difficult to predict and lead to an increase in early mortality. At present, there is no relevant marker for the risk of complications, especially for patients in stressful life situations (eg: unstabilized insulin-dependent patient).
Our goal is to make new discoveries in the assessment of the risk of complications and comorbidities associated with diabetes in order to allow more effective management of patients in potentially critical situations, particularly in cases of association between diabetes and cancer.
Indeed, the prevalence of breast and colorectal cancers is higher in people with diabetes and also leads to higher mortality. It is therefore essential to develop tools to assess the risk of cancer in diabetic patients at an early stage, notably through the use of genetics, epigenetics and microbiome analysis in patients with T2D.
Genomic medicine for diabetes and obesity
10% of early diabetes are atypical (not classified DT1 or DT2). However, 80% of these diabetes have a monogenic origin for which effective personalized treatments are possible. These monogenic forms are also present in 5% of T2DMs and 5% of childhood obesity.
The development of Next Generation Sequencing (NGS) methods reveals the possibility of a targeted molecular diagnosis allowing personalized genomic medicine.
Médecine génomique des diabètes
T2D is indeed considered a complex genetic disease : most T2D is considered to be “polygenic forms” which depend on multiple common genetic variants acting in combination with environmental risk factors. However, there are also rarer and generally more severe forms known as “monogenic forms”, in which a single constitutional genetic mutation is sufficient to cause diabetes most often at an early age. Genetic investigations of these monogenic forms have revealed crucial players involved in the development and function of pancreatic β cells, leading to the discovery of real “case studies” of personalized genomic medicine.
In this project, we wish to sequence the genes involved in monogenic forms of diabetes and associated diseases in patients with T2D in order to launch an interventional study on the adaptation of treatment and / or the specific clinical investigation of organs. The aim is to assess the effectiveness of these interventions for patients and the gains in terms of public health.
Genomic medicine for obesity
In some countries, up to 25% of children are obese, suggesting a reduction in their life expectancy of 5 to 10 years. Childhood obesity is the dominant risk factor for persistent adult obesity and is associated with delayed schooling and harmful social isolation. Often overlooked, obesity puts many patients at a diagnostic and therapeutic level.
Common obesity is a multifactorial disease. However, there is a monogenic component of obesity (phenotypically isolated or syndromic) with disruption of the hypothalamic appetite control circuits. We estimate that in France at least 10,000 children have a monogenic form of obesity, most of them neither being diagnosed nor cared for properly. We were pioneers and world leaders in identifying the various obesity genes. Recently, a medicament (setmelanotide – MC4R agonist) has been shown to reduce hunger for a long time and allow significant weight reduction in carriers of pathogenic mutations in the melanocortin pathway.
Here we will analyze the genome of children and adults with suspected monogenic obesity undiagnosed to date, and through this project we intend to unlock the diagnostic locks of severe monogenic obesity paving the way for efficient precision medicine.
Nutrition, environment and metabolic diseases
Nutrition, environment and metabolic diseases
Metabolic disorders and cardiovascular complications are multifactorial diseases resulting from the strong interaction between lifestyle factors such as nutrition, drug treatments or physical activity, the microbiome and the human host genome.
From the metabolomic, metagenomic and epigenomic data generated by the clinical studies of PreciDIAB and the partner studies, our objective to assess the impact of nutrition, medication and lifestyle on (cardio) metabolic diseases, in particular of particular interest to the role played by the microbiome and its metabolites as mediators.
We thus wish to provide new hypotheses on the spectrum of cardiometabolic diseases that we will validate in the PreciDIAB cohorts by a holistic approach of the links between lifestyle, microbiome and cardiometabolic risk.