History of the EGIR Group

EGIR has been in existence for around 14 years, so this is a good time to recall its origins, particularly for newer members encouraged to participate in the group because of interest in the RISC project and the EGIR publications.

The first meeting of the group was entitled an ‘Informal Meeting’ and was held during the EASD meeting in Prague in September 1992. The meeting was supported by Lipha (which became Lipha Santé, and now Merck Santé), and Christophe Pasik from Lipha wrote the Minutes. Present at the meeting were Stefano del Prato, Johan Eriksson, Eveline Eschwège, Ele Ferrannini, Annick Fontbonne, Leif Groop, Rury Holman, Hans Janka, Markku Laakso, Hans Lithell, André Scheen, Marja Riitta Taskinen, Robert Turner, Ivana Zavaroni as well as participants from Lipha: Philippe André, Françoise Isnard and Christophe Pasik. Others invited but who were not able to attend were Luc Van Gaal, Paul McKeigh, Stephan Jacob and Peter Nilsson.

The meeting lasted almost three hours, with the interest in pre-diabetes, insulin resistance and the metabolic syndrome at that time, the participants considered that there was an urgent need to define ‘insulin resistance’. The agreed objectives of the group were to discuss hypotheses, experience and clinical ideas. It was decided to convene a formal meeting to be held at the end of March in the following year.

Annick Fontbonne, along with Leif Groop and Christophe Pasik, organised the first formal meeting, at Le Château de Maffliers near Paris, in France. Lipha sponsored the meeting and provided the administrative support. There were 34 participants, and 16 abstracts were presented. The plenary sessions involved Ele Ferrannini, Paul McKeigh and Ulf Smith on the ‘metabolic syndrome’ (and we still don’t know what it is), Stefano del Prato, Robert Turner and André Scheen on ‘how to measure insulin resistance’, and Leif Groop, Robert Turner and Philippe Froguel on ‘what predicts NIDDM’.

Since that first meeting EGIR has held a conference annually, with ad hoc committee meetings in between to discuss possible projects  in which different research groups could participate. Lipha has consistently provided the financial support for these meetings and until 1998 the administrative support. The idea of a common project crystallized in part, with the proposal by Ele Ferrannini in 1995 to combine data on measures of insulin resistance using the hyperinsulinaemic euglycaemic clamp. This was the start of the EGIR clamp data set, in which observations were pooled from 21 different European centres on 1308 subjects, and has produced 12 published papers (EGIR publications page). This research work has provided a lot of visibility for the EGIR group within the scientific community.             

Following discussions on the definition of the ‘metabolic syndrome’, otherwise known as the ‘insulin resistance syndrome’ or in its original guise as given by Reaven, ‘syndrome X’, the EGIR group criticized the syndrome definition published in 1998 by the WHO Expert Committee on the “diagnosis and classification of diabetes”. EGIR proposed a more practical definition, following along the lines of the WHO definition, and this has become known as the ‘EGIR’ definition of the metabolic syndrome. Subsequently there was a second data-pooling project, where various members of the group calculated the prevalence of the syndrome in their study cohorts, according to a written protocol. The wide variations in prevalence, not only of the syndrome but of its component abnormalities, over European countries, and even within a given country, was surprising.

The success of these data-pooling projects, which created the beginnings of a research network, and because Sarah Hills (originally working on the journal Diabetologia) had remained in Pisa, meant that it was feasible to plan a European project with a uniform protocol. Support for a secretariat office was negotiated in 1998 with Lipha (Merck Santé). An official constitution was then drawn up and accepted by the membership at the meeting in Paris, along with the election of a Steering Committee. Organization of annual meetings could then be streamlined and initiatives to coordinate the group and disseminate information (e.g. Newsletter) could be carried out. During 1998 and 1999 Christophe Hubert assumed responsibility for liaising between the EGIR group and Lipha Santé in Lyon, this continued until 2001 when Harry Howlett took over and has provided collaboration from Merck Santé in the UK ever since. The membership list was originally printed but has now gone online with the possibility to also register for meetings online. Membership is informal since there is no fee to join but new members are generally introduced by existing members, in this way the membership grows steadily. Members are encouraged to submit abstracts for presentation. The meetings have a reputation for excellent presentations of state-of-the-art research in an informal atmosphere.

Because one of the main reasons to form a more official group was to carry out a collaborative project, a Project Committee was also elected (the origins of the present RISC Project Management Board). This committee worked intensively between 1999 and 2002 on preparation for the RISC project, holding meetings and contributing to an extensive on-line debate about the different procedures, calling on the help of experts outside the group when necessary. The membership of the committee has evolved over the years, the original members were Beverley Balkau as Chairperson and Jacqueline Dekker who prepared the original draft proposal for the group project. Also involved in the project group at its inception were Knut Borch-Johnson, Simon Coppack, and Mina Mitrakou. Mark Walker later joined the group when Knut Borch-Johnson left along with Andrea Mari, who proposed the mathematical modelling.

In January 1999 a number of potential RISC project investigators met in London at the Whittington Hospital centre of Simon Coppack. The euglycaemic clamp technique (as agreed upon by the EGIR group) was demonstrated by Andrea Natali and Stephanie Baldeweg, and this was filmed to provide a visual record (on CD-ROM) of the clamp procedure that is used in the RISC project.

Following an initial unsuccessful attempt to be financed by the European Commission in 1999, the comments from the referees were considered and a visit by Beverley Balkau, Jacqueline Dekker and Sarah Hills, was made to the research directorate of the Commission in Brussels. The protocol was extensively rewritten following advice from an expert on the EU research frameworks from London University. A more complete version of the project was submitted in October 2000. This was successful and the project was financed, with about 50% of the funding necessary to do 1500 clamps in 20 centres across Europe, fortunately additional financial support was agreed with the European pharmaceutical company AstraZeneca. The RISC project completed recruitment on late 2004 and is in process of completing year 3 follow up (December 2007).

The RISC coordinating office is located at the EGIR secretariat with two staff (Lucrecia Mota recently joined the team) and there is a data management centre in Villejuif ( Beverley Balkau). The format of the EGIR meetings was adapted in Amsterdam in 2004 to include the RISC project, which was well received and shall continue in a similar fashion.

For the members of the RISC project, this is history and we hope that this project will be followed by other projects where those who do not have access to clinical facilities may participate. The establishment of the EGIR network means that there are now communication pathways, both traditional and using website technology, for development of ideas and creation of new research collaborations particularly relevant in the light of recent controversy over definitions of the metabolic syndrome.

Article by Beverley Balkau and Sarah Hills (July 2004)

1998 Paris – France

- I. Juhan-Vague (France) Fibrinolytic factors involved in insulin resistance

- M. Marre (France) Microalbuminuria and insulin resistance

- J.-P. Després (Canada) The atherogenic lipoprotein phenotype of insulin resistance: are small density LDL particles an independent IHD risk factor?

- M. Bots (NL) Measuring inter-media thickness

- M. Pugeat (France) Insulin sensitizing agents in the polycystic ovarian syndrome

The programme in 1998 included Jacqueline Dekker who presented a proposal for the group project and first suggested the RISC acronym. EGIR became ‘official’ and a Steering Committee and Project Committee were elected.

1999 Forte dei Marmi - Italy

                                                                                                                                                        - M. Laville (France) Molecular biology of insulin resistance

- P. Arner (Sweden) Adipose tissue metabolism and insulin resistance

- D. Phillips (UK) Birth weight as a marker of disease

- O. Hother-Nielsen (DK) Hepatic insulin resistance: sites and mechanisms

- H. Galbo (DK) Insulin and physical activity

- J. Pickup (UK) Insulin, inflammation and atherosclerosis

2001 Göteborg - Sweden

- U. Smith (Sweden) PPAR-gamma agonists: mechanisms and effects

- M. Walker (UK) PPAR-gamma and IGT

- J. Nolan (Ireland) Current and future clinical indications for TZD

- O. Wiklund (Sweden) Inflammation markers of atherosclerosis

- L Groop (Sweden) Genetic variation in the PPAR-gamma gene

2002 Santorini - Greece

- M. Kambouris (USA) Genetics of insulin resistance.

- M. Roden (Austria) Free fatty acids and pathogenesis of insulin resistance.

- R.A. De Fronzo (USA) Treatment of insulin resistance: metabolic and cardiovascular implications.

- H. Vlassara (USA) AGEs in insulin resistance.

- Stefanadis (Greece) Are diabetic vessels hot?

2003 Dublin - Ireland

- J. Zierath (Sweden) Validation of novel targets for insulin resistance in type 2 diabetes patients

- D. O’Gorman (Ireland) Mechanisms of improved insulin sensitivity in obesity and type 2 diabetes with acute exercise and training

- R. Wilson (Scotland) Genetics of human obesity/ response to physical activity

- M. Byrne (Germany) MODY, clinical and mechanistic aspects

- S. McQuaid (Ireland) Early onset type 2 diabetes in Europe

- A. Natali (Italy) Insulin resistance and endothelial dysfunction

2004 Amsterdam - Netherlands

- P. Grant (UK) Insulin resistance and the atherothrombotic syndrome

- C.D.A. Stehouwer (Netherlands) Can microcirculatory dysfunction cause insulin resistance?

- J.A. Romijn (Netherlands) Modulation of insulin sensitivity

Also included were some talks on the RISC project preliminary data analyses

2005 Belgrade - Serbia and Montenegro

-M. Laakso ( Finland) Genetic determinants of atherosclerotic vascular disease: an overview

-M. Walker ( UK) Genetic determinants of the features of the insulin resistance syndrome: heritability estimates from family studies

-J. Petrie ( Scotland) Can proteomics identify the key determinents of atherosclerosis progression?

-A. Fyvbjerg ( Denmark) Adiponectin in insulin resistance, diabetes and cardiovascular diseases

-M. Ostojic (Serbia ) Progression of coronary artery disease: a cardiologist view

-A. Mari ( Italy) In praise of the ogtt: a fair method for assessing insulin sensitivity and beta-cell function

-J. Nolan ( Ireland) Insulin resistance and diabesity in youth

-V.S. Kostic ( Serbia ) Metabolic diseases of the brain: a neurologist view

Debate: Overlap between hypertension and diabetes treatment: myth or reality? Between Peter Nilsson and Andrea Natali

2006 Parma - Italy

-G. Reaven (USA) Insulin resistance, the link between obesity and CVD: not all obese persons are created equal

-MR Taskinen (Finland) Clinical strategies to treat lipid abnormalities

-A. Avogaro (Padova) Oxidative stress

-J. Petrie (UK) Vascular reactivity

-M.Trovati ((Italy) Vascular cells

-S. Del Prato (Italy) Beta cell a site of insulin resistance

-P. Marchetti (Italy) Beta cell function in type 2 diabetes

2007 Edinburgh - Scotland

-C.Sutherland (UK) Studying Insulin signalling in human muscle to identify new treatment targets

-J. Gill (UK)Exercise, Metabolism amd insulin sensitivity

-B. Walker ( UK) Glucocorticoids and insulin resistance

-N. Sattar ( UK) Insulin resistance/metabolic syndrome in type 1 diabetes

-G. Hardie ( UK ) AMPK, metformin and isulin sensitivity