29 May 2007

Dundee scientists in European Diabetes research initiative

60 of Europe’s leading diabetes researchers will meet this week at the Royal College of Physicians in Edinburgh to plan joint working to develop effective methods of targeting the complications of maturity-onset (type 2) diabetes.

The European Group for the study of Insulin Resistance (EGIR) meeting will be hosted by Dr John Petrie, Reader in Diabetic Medicine at the University of Dundee. Leading the discussions will be Professor Ele Ferrannini, current President of the European Association for the Study of Diabetes.

Invited lecturers include several of Dundee’s world-leading diabetes researchers including Professor Grahame Hardie and Dr Calum Sutherland (www.diabetes.dundee.ac.uk). The meeting will run from the evening of Wednesday May 30th until the afternoon of Friday June 1st.

The European Group for the study of Insulin Resistance originated in 1992 (see www.egir.org). Insulin resistance was already well known to play a key role in causing type 2 diabetes but collaborating EGIR researchers were keen to focus on the role of insulin insensitivity in causing heart attacks and strokes - and not just in people with full-blown diabetes.

In 2001, the collaboration secured funding from the European Commission to conduct a follow-up study ("RISC", Relationship between Insulin Sensitivity and Cardiovascular disease) in 20 participating European centres. The RISC cohort is now established and involves 1400 healthy middle-aged people being followed up to determine the importance of insulin resistance in the development of blood vessel (vascular) disease.

RISC is the only large international cohort in which insulin sensitivity has been measured using a "gold standard" technique and in which all methodologies have been shared and standardized. Dr John Petrie is on the Steering Committee of EGIR and leads a workpackage aimed at developing novel "biomarkers" of insulin sensitivity which is being conducted in collaboration with Dundee colleagues including Professor Nick Morrice (Life Sciences), Dr Calum Sutherland (Pharmacology and Neuroscience), and Dr Fiona Paulin (Surgery and Molecular Oncology), as well as colleagues from the University of Glasgow.

The RISC study will complete three year follow-ups by the end of this year. Interim findings will be presented in September at a special session of the large European Association for the Study of Diabetes meeting in Amsterdam. However, the researchers believe that much longer term follow up of the cohort will lead to significant advances in the understanding of vascular disease. As well as including state-of-the-art lectures and the presentation of late-breaking abstracts, this week’s meeting will therefore provide a forum for discussion of plans for a "phase two" follow-up of the cohort.

Dr John Petrie, who is Lead Clinician of the Scottish Diabetes Research Network, said: "Understanding and targeting the causes of blood vessel disease requires careful study over time of human volunteers in numbers which are not possible in a single city or country. Under the leadership of Professor Ferrannini, the European Group for the Study of Insulin Resistance has created a unique collaborative network. Together we are now brimming with ideas for building upon the platform we have created to identify targets for prevention and therapy of common human diseases."

NOTES TO EDITORS

Background:

1) The present EGIR Steering Committee consists of:

Professor Alain Golay (2005-2009) Chair
Division of Therapeutic Teaching for Chronic Diseases, University Hospital Geneva, CH-1211 Geneva 14, Switzerland

Prof Nebojsa Lalic (2004-2007)
Institute for Endocrinology, Diabetes Centre, Dr Subotica 13, 11000 Belgrade, Serbia and Montenegro

Dr John Petrie (2005-2008)
Dept of Medicine, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, Scotland

Dr Ivana Zavaroni (2004-2007)
Dept of Internal Medicine and Biolmedical Sciences, University of Parma, Via Gramsci 14, I-43100 Parma, Italy

Prof Ele Ferrannini (remains until 2008 as RISC Principal Investigator)
Dept of Internal Medicine, Metabolism Division, University of Pisa, Via Roma 67, 56126 Pisa, Italy

2) The EGIR Group
The EGIR group was formed several years ago by a group of investigators from different research backgrounds - epidemiology, endocrinology, basic science, public health - interested in insulin resistance. The first combined activity of the group was a data pooling project from euglycaemic hyperinsulinaemic clamp experiments performed in 20 centres across Europe. This unique database has now produced 11 publications.

EGIR is managed by a Steering Committee and its scientific activities are managed by a separate committee.

EGIR holds annual meetings, hosted by one of its members, in a different European city each year. Presentations are given by members of the group, and by invited speakers, in the area of insulin resistance.

In 2001 the EGIR project Relationship between Insulin Sensitivity and Cardiovascular Disease (RISC) was awarded funding by the EU 5th Framework (EU contract QLG1-CT-2001-01252) to carry out a project examining the effects of insulin resistance in healthy (non-diabetic, non-hypertensive) people. The project started on 1 February 2002 and will continue until the end of December 2007.

3) Research activity of the EGIR Group
The main activity of the European Group for the study of Insulin Resistance (EGIR) is continuous collaboration between members in various forms. The annual meetings act as the focus for the EGIR network and allow an exchange of views and presentation of state-of-the-art research by experts in the field of insulin resistance.

The ‘EGIR’ database
The first scientific endeavor of EGIR was a data-pooling project started in the mid-1990s when 21 clinical research centres from across Europe pooled their data on in vivo insulin action obtained in non-diabetic, normotensive subjects of any age and body mass index with the use of the hyperinsulinaemic euglycaemic clamp technique, the "gold standard" for the measurement of insulin resistance. The result of this first project was the creation of the largest clamp database in the world. From this data collection, it was possible to analyse the relation of insulin resistance to age [1, 2], lipolysis [3], arterial blood pressure [4], obesity [5], and thermogenesis [6]. Additional information was extracted with respect to the influence of family history of diabetes on insulin sensitivity [7], the impact of insulin resistance on serum lipid levels [8], and the relationship between peripheral insulin action and hepatic glucose production [9].

The ‘EGIR definition’ of the metabolic syndrome
Members of EGIR have been productive in contributing to the literature on the metabolic syndrome (10-13) (or the ‘insulin resistance’ syndrome or in its original guise as given by Reaven ‘syndrome X’). Following discussions on the definition of the ‘metabolic syndrome’, 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, this widely quoted publication has become known as the EGIR definition of the metabolic syndrome (14).

The RISC Study
Today EGIR is highly active in research into insulin resistance and has created a task force aimed at testing whether the presence of insulin resistance in healthy individuals confers an enhanced risk for the development of atherosclerotic cardiovascular disease. In 2001 the EGIR project Relationship between Insulin Sensitivity and Cardiovascular Disease (RISC) was awarded funding by the EU 5th Framework Program (EU contract QLG1-CT-2001-01252) to resolve the question of whether insulin resistance is a risk factor for progression of carotid artery intima-media thickness (an index of cardiovascular disease) independently of other risk factors (lipids, body weight, haemostatic and inflammatory factors etc). The RISC Project started in February 2002.

4) Selected EGIR Publications

1. Ferrannini E, Vichi S, Beck-Nielsen H, Laakso M, Paolisso G, Smith U on behalf of EGIR (1996) Insulin action and age. Diabetes 45:947-953
2. Iozzo P, Beck-Nielsen H, Laakso M, Smith U, Yki-Jarvinen H, Ferrannini E on behalf of EGIR (1999) Independent influence of age on basal insulin secretion in nondiabetic humans. Journal of Clinical Endocrinology and Metabolism 84:863-868
3. Ferrannini E, Natali A, Capaldo B, Lehtovirta M, Jacob S, Yki-Jrvinen H on behalf of EGIR (1997) Insulin resistance, hyperinsulinemia, and blood pressure. Role of age and obesity. Hypertension 30:1144-1149
4. Ferrannini E, Natali A, Bell P, Cavallo-Perin P, Lalic N, Mingrone G on behalf of EGIR (1997) Insulin resistance and hypersecretion in obesity. Journal of Clinical Investigation 100:1166-1173
5. Vaag A, Lehtovirta M, Thye-Ronn P, Groop L (2001) Metabolic impact of a family history of type 2 diabetes. Results of a European multicentre study (EGIR). Diabetic Medicine 18:533-540
6. Natali A, Toschi E, Camastra S, Gastaldelli A, Groop L, Ferrannini E, on behalf of EGIR (2000) Determinants of post-absorptive endogenous glucose output in non-diabetic subjects. Diabetologia 43:1266-1272
7. Balkau B et al (2002) Frequency of the WHO metabolic syndrome in European cohorts, and an alternative definition of an insulin resistance syndrome. Diabetes Metabolism (Paris) 20: 364-376
8. Hills S, Balkau B, Coppack SW, Dekker JM, Mari A, Natali A, Walker M, Natali A, Ferrannini E, The EGIR-RISC STUDY (The European group for the study of insulin resistance: relationship between insulin sensitivity and cardiovascular disease risk): I. Methodology and objectives. Diabetologia. 2004 Mar; 47(3):566-70.
9. Ferrannini E, Balkau B, Coppack SW, Dekker JM, Mari A, Nolan J, Walker M, Natali A, Beck-Nielsen H and the RISC Investigators. Insulin resistance, insulin response, and obesity as indicators of metabolic risk. J Clin Endocrin Metab (First published ahead of print May 15, 2007 as doi:10.1210/jc.2007-0334).

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