RHAPSODY

Assessing risk and progression of prediabetes and type 2 diabetes to enable disease modification

Summary

The number of people living with diabetes rose from 200 million in 1990 to 830 million in 2022. If poorly managed or undiagnosed, diabetes can cause blindness, kidney failure, heart attacks, stroke and lower limb amputation.

But diabetes does not affect everyone in the same way. There’s a lot of variation in what causes type 2 diabetes (T2D), rates of progression, and responses to treatment. Traditional “one-size-fits-all” approaches to diagnosis, clinical trials, and therapy do not take this into account, limiting the effectiveness of these treatments and increasing the risk of complications.

The RHAPSODY project sought to make significant advances in precision medicine for type 2 diabetes (T2D). Towards that end, the project identified and refined five clinically and biologically distinct T2D subgroups, each characterised by specific metabolic and molecular features and differing risks of complications. This classification can help clinicians to tailor treatment more accurately and enable patients to access the correct treatment sooner.

RHAPSODY also established a secure, EU-wide federated database comprising fully harmonised clinical, genetic, and multi-omics data from more than 68,000 individuals across 12 cohorts, enabling cross-cohort analyses while preserving patient anonymity. The federated database is part of a platform that also includes physiological and multi-omics datasets from preclinical models of prediabetes and T2D. This source of information has allowed for an unprecedented comparative analysis of the mechanisms underlying T2D progression and for the identification of prognostic and diagnostic biomarkers.

Through integrated analyses of human cohorts, isolated pancreatic islets, and preclinical models, RHAPSODY identified biomarkers of beta-cell dysfunction and disease progression and generated key mechanistic insights into beta-cell failure, insulin resistance, lipid metabolism, and multi-organ dysfunction. RHAPSODY also uncovered a liver–beta-cell axis in which circulating triglycerides act as biomarkers of beta-cell function.

In addition, the consortium developed novel bioinformatics tools and open-access software which will help to support biomarker prioritisation, validation, and regulatory discussions with authorities such as the European Medicines Agency (EMA). For instance, the project established a diabetes biomarker prioritisation matrix and a web-based prioritisation tool that can help researchers to evaluate potential biomarker candidates on the basis of RHAPSODY’s data as well as external data sources.

Health and economic impact modelling further demonstrated the potential cost-effectiveness and public health benefits of using RHAPSODY-derived biomarkers to guide preventive and therapeutic strategies.

Achievements & News

Diabetes treatments set to get personal, thanks to new IT tool

Building on ground-breaking results from IMI diabetes projects, scientists are now working on a software tool that would identify what subtype of diabetes a patient has, and suggest which treatment would work best for them.###

For many years, the medical world has recognised two main types of diabetes: type 1 and type 2. However, research funded in part by IMI through the BEAt-DKD and RHAPSODY projects paints a different picture, suggesting that there are not two subtypes of diabetes, but five. The scientists have since validated these initial findings in additional patient populations, and several studies are currently ongoing to test the effects of different treatments on the different diabetes subtypes.

Meanwhile, investigators have developed a software tool, which is currently used for research purposes and is soon to be implemented in the clinic, to allow doctors to identify which diabetes subtype the patient has. The researchers have received funding from other sources beyond IMI to carry out these additional studies. All in all, this story shows how IMI projects can deliver ground-breaking results, validate them, and turn them into a tool that can hopefully assist in providing the right treatment for the right patient at the right time.

Find out more

Taking a tailored approach to type 2 diabetes

Diabetes is a chronic and incurable illness linked to blood sugar that has traditionally been divided into type 1 and type 2. Type 2 accounts for the vast majority of cases – some 285 million – and its prevalence is expected to soar over the coming decade. Amid this backdrop, IMI's RHAPSODY project set out to look more closely at type 2 in a bid to develop targeted treatments for the condition, which can vary significantly and cause serious complications such as kidney failure. ###In a major development, RHAPSODY – in conjunction with others including IMI's BEAT-DKD project – has broken type 2 diabetes down into five subgroups which need different treatments and have different progressions. And this, the researchers believe, has the potential to revolutionise how doctors deal with diabetics. ‘What RHAPSODY is really about is individualising diabetes treatment,’ says vice project coordinator Leif Groop of Lund University in Sweden. ‘For too long, we have had the situation that one size fits all.’  The subgroups grew out of a Swedish study known as ANDIS involving more than 13 000 diabetics and initiated by Groop. It monitored not only patients' blood sugar but also factors such as insulin resistance and secretion, as well as age. The study has since been replicated, including in China.

Scientists identify five subtypes of diabetes 

Scientists have identified five subtypes of diabetes, a finding that will pave the way for more personalised treatments for the disease. The work, published in The Lancet Diabetes and Endocrinology, was funded in part by IMI through the projects BEAT-DKD and RHAPSODY. ###Currently, two main types of diabetes are recognised, and diagnosis is through a measurement of a patient’s blood sugar levels. In this study, scientists monitored over 13 000 newly-diagnosed diabetes patients, analysing blood sugar levels, insulin resistance, insulin secretion, and age of onset among other things. This revealed five distinct groups of patients with different risk levels for certain complications associated with diabetes. For example, patients in group 2 (‘severe insulin-deficient diabetes’) are at greatest risk of eye disease, while patients in group 3 (‘severe insulin-resistant diabetes’) had the highest incidence of kidney damage. ‘Current diagnostics and classification of diabetes are insufficient and unable to predict future complications or choice of treatment,’ said Leif Groop of Lund University in Sweden. ‘This is the first step towards personalised treatment of diabetes.’ Until now, the team has only studied people in Sweden and Finland; they now plan to carry out similar studies in China and India, to see if their findings apply in different ethnic groups.

Participants

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EFPIA companies
  • Eli Lilly And Company LTD, Basingstoke, United Kingdom
  • Institut De Recherches Servier, Gif-Sur-Yvette, France
  • Janssen Pharmaceutica Nv, Beerse, Belgium
  • Novo Nordisk A/S, Bagsvaerd, Denmark
Universities, research organisations, public bodies, non-profit groups
  • Academisch Ziekenhuis Groningen, Groningen, Netherlands
  • Academisch Ziekenhuis Leiden, Leiden, Netherlands
  • Azienda Ospedaliera Citta Della Salute E Della Scienza Di Torino, Torino, Italy
  • Centre Hospitalier Regional Et Universitaire De Lille, Lille, France
  • Centre National De La Recherche Scientifique Cnrs, Paris, France
  • Eberhard Karls Universitaet Tuebingen, Tuebingen, Germany
  • Imperial College Of Science Technology And Medicine, London, United Kingdom
  • Institut National De La Sante Et De La Recherche Medicale, Paris, France
  • Itä-Suomen yliopisto, Kuopio, Finland
  • Kobenhavns Universitet, Kobenhavn, Denmark
  • Lunds Universitet, Lund, Sweden
  • Rijksuniversiteit Groningen, Groningen, Netherlands
  • SIB Institut Suisse De Bioinformatique, CH-660-0733998-3, Geneve, Switzerland
  • Stichting Amsterdam Umc, Amsterdam, Netherlands
  • Technische Universitaet Dresden, Dresden, Germany
  • Universita Di Pisa, Pisa, Italy
  • Universite De Lausanne, Lausanne, Switzerland
  • Universite Paris Cite, Paris, France
  • Universite Paris Diderot - Paris 7, Paris, France
  • University Of Dundee, Dundee, United Kingdom
  • University of Oxford, Oxford, United Kingdom
  • Université Libre de Bruxelles, Bruxelles / Brussel, Belgium
Small and medium-sized enterprises (SMEs) and mid-sized companies (<€500 m turnover)
  • Lipotype, Dresden, Germany
  • Sciprom SARL, Saint Sulpice, Switzerland
Third parties
  • Universite De Lille, Lille, France

Participants
NameEU funding in €
Academisch Ziekenhuis Groningen54 869
Academisch Ziekenhuis Leiden213 342
Azienda Ospedaliera Citta Della Salute E Della Scienza Di Torino104 743
Centre Hospitalier Regional Et Universitaire De Lille299 296
Centre National De La Recherche Scientifique Cnrs345 680
Eberhard Karls Universitaet Tuebingen389 966
Imperial College Of Science Technology And Medicine668 523
Institut National De La Sante Et De La Recherche Medicale408 745
Itä-Suomen yliopisto244 944
Kobenhavns Universitet599 151
Lipotype418 969
Lunds Universitet993 168
Rijksuniversiteit Groningen85 389
Sciprom SARL23 750
SIB Institut Suisse De Bioinformatique, CH-660-0733998-3187 500
Stichting Amsterdam Umc194 983
Technische Universitaet Dresden518 723
Universita Di Pisa435 663
Universite De Lausanne124 681
Universite Paris Cite503 970
University Of Dundee499 121
University of Oxford251 936
Université Libre de Bruxelles439 645
 
Third parties
NameFunding in €
Universite De Lille123 243
 
Total Cost8 130 000