Physiopathology, Metabolism, Nutrition

The Institute of Physiopathology, Metabolism, Nutrition covers a broad research spectrum in physiology, experimental medicine and diseases. Cardiovascular diseases, diabetes and obesity are some of its priorities.

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(Directory of research teams ITMO PMN 2015 coming)

Scientific challenges

Diseases of the heart and blood vessels, lungs, endocrine tissues, liver, kidneys, digestive tract, skin, bones, joints are specific to the organs affected. But they can be understood and treated without taking account the numerous interactions between the body and its environment.

Cross-disciplinary aspects of physiology and pathology are therefore a major issue for the Institute. This is all the more true given the various diseases involved arising from essentially common mechanisms. They are often diseases arising against a background of genetic predisposition, but interacting closely with the environment and its sometimes sudden upsets. We often know little about the triggering mechanisms due to:

  • still insufficient knowledge of the genetic polymorphism involved in their aetiology, genes and proteins functionally expressed in the tissues involved and their interaction with the environment;
  • incomplete modelling of physiopathological mechanisms leading to the initiation and then the advance of the disease in the tissues.

The consequence of it is often inadequacy of available treatments, rarely appropriate to the origin of these common diseases. Knowledge of the mechanisms of diseases is also likely to lead to defining new biomarkers, which we can hope will improve the diagnosis, prognosis and choice of treatment for these diseases.

Several opportunities for progress are therefore identified. Genomics and proteomics are a major issue for better understanding of normal function of the tissues and their interactions with the environment. This means developing functional genomics, characterising the tissues in which the newly discovered genes are expressed, but also using comparative genomics and proteomics to understand the development of tissues (from gene to organ), ageing mechanisms, and signalling routes that enable the tissues to function. Epigenetics and metagenomics are new fields, and it is thought they will be drivers in the study of gene-environment interactions. The diseases covered by the Institute are generally multifactorial, so their models should include their three triggering levels and their progression: genetic predisposition (these are multi-genetic diseases involving genes that are normal but not exactly the same in different individuals), cellular circuit implicated by each gene identified, and environmental factors. Work on targeted cohorts allow the clinical phenotypes of different diseases to be analysed and the causes of their frequent variability to be researched.

A major issue in these diseases is to implement appropriate treatment. Currently available treatments often remain unsatisfactory, for various reasons. Some are only palliative or symptomatic (hormonal substitutes for endocrine diseases, dialysis in the final phase of kidney diseases, organ transplants, etc.). Others are non-specific and led to side effects (immunosuppressive treatments in inflammatory or auto-immune diseases). We are also missing treatments to eliminate the after-effects of ischemia on the organs affected. And yet opportunities are identified to improve and individualise treatments: molecules specifically targeting inflammatory pathways, purification and injection of monoclonal antibodies, cellular biotherapies intended to produce tissues and organs from the patient's stem cells... But today these biotherapies remain the field of research, already rarely of clinical investigation. Advances in the knowledge of risk factors also allow the development of individualised predictive medicine and better targeting of preventive messages addressed to the population.

 

The 2nd International Encounters of Biomedical Research, jointly organized by the International Research Laboratories (LIR), French Pharmaceutical Companies Association (LEEM) and Circulation, Metabolism and Nutrition thematic multi-organization institute, focused on cardiovascular and metabolic diseases
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Interview of Christian Boitard, Director of the thematic multi-organization institute Physiopathology, Metabolism, Nutrition

Medical challenges

Heart, blood vessels, lungs, endocrine glands, liver, kidneys, digestive tract, skin, bones, joints... not a single family today is spared the great many diseases affecting these organs. And in the space of two generations, obesity has become a plague in our affluent societies. 

Cardiovascular, respiratory, metabolic and nutritional diseases are very common and have devastating complications, and they therefore represent a major public health issue. Diabetes, hyperlipidaemia, obesity, kidney failure and atherosclerosis lead to cardiovascular diseases that are, alongside cancer, the main cause of death in industrialised societies.

Coronary disease, strokes and chronic heart failure account for 75% of cerebrovascular diseases and are alone responsible for 29% of deaths annually. Thrombotic diseases are very prevalent, arterial thrombosis (ischaemic diseases) and venous thrombosis (thrombo-embolic disease) are the world's leading cause of death. The prevalence of constitutional haemorrhagic diseases is limited, but their social and economic impact is significant, as in the case of haemophilia.

Respiratory diseases (asthma, chronic obstructive pulmonary disease, COPD; pulmonary fibroses) affect millions of people in France and their incidence is increasing. COPD alone already represents the third-largest cause of death in Europe (sixth in the world).

The prevalence of diabetes and glucose intolerance has now reached 7.1% and 5.6%, respectively, in France, affecting nearly 4 million people.

This prevalence follows a steadily rising trend, galloping in certain countries, parallel to that for obesity, that affects more than 15% of the adult population, but also the child and teenage populations. Hyperlipidaemia, obesity and diabetes are the cause of serious complications: vision disorders and blindness, strokes and heart attacks, neurological disorders, amputations, respiratory, liver and kidney problems.

These diseases, all cardiovascular risk factors, are all the more severe in their medical impact as they are often combined in the same patient. There has even been talk of a truemetabolic syndrome in patients presenting visceral (abdominal) obesity, dyslipidaemia (increased level of triglycerides and/or low level of HDL-cholesterol), high blood pressure, diabetes, blood clotting problems and kidney disorders (microalbuminuria). These are often associated with non-vascular complications such as hepatic steatoses, which generally lead to cirrhosis or arthrosis, for which obesity is itself a considerable aggravating factor. Very diverse populations are affected. In particular, several epidemiological studies suggest that people of non-European origins are most exposed to the risk.

Paradoxically, our societies are also facing the problem of malnutrition. It is estimated that nutritional deficiencies are still causing the deaths of 3 million children annually, essentially in developing countries. But malnutrition also affects 40% of patients suffering from chronic diseases, 30% to 50% of patients admitted to hospital (taking all illnesses combined), aggravating both the morbidity and mortality of patients. Normal ageing is also accompanied by frequent disruption to food intake leading to various deficiencies.

Diseases of the bones and joints are also a concern for the French, particularly due to ageing of the population. On their own they represent half of chronic diseases in people over 65 and are a major cause of invalidity (arthrosis is the second largest handicap factor in men, the fourth in women). Among the over 50s, one women in four and one man in eight will be affected by osteoporosis during their lives.

Skin diseases include a proportion of allergic complaints (atopic dermatitis, contact eczema, occupational dermatoses, photo-allergies, urticaria and skin accidents due to oral administration of a drug (toxicodermatitis)) and a proportion of chronic inflammatory disorders (psoriasis, atopic dermatitis, pelada, etc.). Among this latter group, psoriasis, affects between two and three million people in France and is associated with a significant change in the quality of life, often leading to a severe social handicap. The impact of this dermatosis on the quality of life is as significant as that caused by asthma, diabetes or chronic cardiac ischaemic diseases. The social cost of psoriasis is therefore considerable. Ageing of the population is accompanied is increasingly frequently accompanied by chronic vascular complaints of the lower limbs. Their treatment is complex and should be multi-disciplinary, ideally as part of a care network led by dermatologists specialised in the field of cicatrisation.


Director : Christian Boitard

Deputy Director: Christine Cherbut

Policy Officers: Nathalie Grivel, Raymond Bazin

Contact: itmoPMN@aviesan.fr

Experts Committee: Jean-François Arnal (PU-PH), Francis Berenbaum (PU-PH), Chantal Boulanger (DR, Inserm), Nadine Cerf-Bensussan (DR, Inserm), Jean Dallongeville (DR, Inra), Barbara Demeneix (PR, MNHN), Chloé Féral (DR2, Inserm), Marc Humbert (PU-PH), Christophe Junot (Chercheur, CEA), Armelle Leturque (DR, CNRS), Michael Lukasiewicz (Directeur médical, ARIIS), Roger Marthan (PU-PH), Renato Monteiro (PU-PH), Richard Moreau (DR, Inserm), Luc Pénicaud (DR, CNRS), Mickaël Tanter (DR, Inserm)
 

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