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

The stated goal of RHAPSODY is to define a molecular taxonomy of type 2 diabetes mellitus (T2D) that will support patient segmentation, inform clinical trial design, and the establishment of regulatory paths for the adoption of novel strategies for diabetes prevention and treatment.

Our plans are built upon:

access to large European cohorts with comprehensive genetic analyses, rich longitudinal clinical, biochemical data and samples
detailed multi-omic maps of key T2D-relevant tissues and organs
large expertise in the development and use of novel genetic, epigenetic, biochemical and physiological experimental approaches
the ability to combine existing and novel data sets through effective data federation and use of these datasets in systems biology approaches towards precision medicine;
expertise in regulatory approval, health economics and patient engagement.

These activities will lead to the discovery of novel biomarkers for improved T2D taxonomy, to support development of pharmaceutical activities, and for use in precision medicine to improve health in Europe and worldwide.

Most recent publications

See all publications

Gerst, F., Jaghutriz, B. A., Staiger, H., Schulte, A. M., Lorza-Gil, E., Kaiser, G., Panse, M., Haug, S., Heni, M., Schütz, M., Stadion, M., Schürmann, A., Marzetta, F., Ibberson, M., Sipos, B., Fend, F., Fleming, T., Nawroth, P. P., Königsrainer, A., Nadalin, S., Wagner, S., Peter, A., Fritsche, A., Richter, D., Solimena, M., Häring, H.-U., Ullrich, S. & Wagner, R.

The Expression of Aldolase B in Islets Is Negatively Associated With Insulin Secretion in Humans.

The Journal of Clinical Endocrinology & Metabolism 103, 4373-4383 (2018). doi:10.1210/jc.2018-00791

Cosentino, C., Toivonen, S., Diaz Villamil, E., Atta, M., Ravanat, J.-L., Demine, S., Schiavo, A., Pachera, N., Deglasse, J.-P., Jonas, J.-C., Balboa, D., Otonkoski, T., Pearson, E. R., Marchetti, P., Eizirik, D. L., Cnop, M. & Igoillo-Esteve, M.

Pancreatic β-cell tRNA hypomethylation and fragmentation link TRMT10A deficiency with diabetes.

Nucleic Acids Research 46, 10302-10318 (2018). doi:10.1093/nar/gky839

Babbar, R., Heni, M., Peter, A., Hrabě de Angelis, M., Häring, H.-U., Fritsche, A., Preissl, H., Schölkopf, B. & Wagner, R.

Prediction of Glucose Tolerance without an Oral Glucose Tolerance Test.

Frontiers in Endocrinology 9, (2018). doi:10.3389/fendo.2018.00082

Ahlqvist, E., Storm, P., Käräjämäki, A., Martinell, M., Dorkhan, M., Carlsson, A., Vikman, P., Prasad, R. B., Aly, D. M., Almgren, P., Wessman, Y., Shaat, N., Spégel, P., Mulder, H., Lindholm, E., Melander, O., Hansson, O., Malmqvist, U., Lernmark, Åke, Lahti, K., Forsén, T., Tuomi, T., Rosengren, A. H. & Groop, L.

Novel subgroups of adult-onset diabetes and their association with outcomes: a data-driven cluster analysis of six variables.

The Lancet Diabetes & Endocrinology 6, 361-369 (2018). doi:10.1016/S2213-8587(18)30051-2

Diedisheim, M., Oshima, M., Albagli, O., Huldt, C. W., Ahlstedt, I., Clausen, M., Menon, S., Aivazidis, A., Andreasson, A.-C., Haynes, W. G., Marchetti, P., Marselli, L., Armanet, M., Chimienti, F. & Scharfmann, R.

Modeling human pancreatic beta cell dedifferentiation.

Molecular Metabolism 10, 74-86 (2018). doi:10.1016/j.molmet.2018.02.002

Martinez-Sanchez, A., Nguyen-Tu, M.-S., Leclerc, I. & Rutter, G. A.

Manipulation and Measurement of AMPK Activity in Pancreatic Islets.

in AMPK (Neumann, D. & Viollet, B.eds. ) 1732, 413-431 (Springer New York, 2018). http://link.springer.com/10.1007/978-1-4939-7598-3_26.

Richards, P., Rachdi, L., Oshima, M., Marchetti, P., Bugliani, M., Armanet, M., Postic, C., Guilmeau, S. & Scharfmann, R.

MondoA Is an Essential Glucose-Responsive Transcription Factor in Human Pancreatic β-Cells.

Diabetes 67, 461-472 (2018). doi:10.2337/db17-0595

Slieker, R. C., van der Heijden, A. A. W. A., van Leeuwen, N., Mei, H., Nijpels, G., Beulens, J. W. J. & ’t Hart, L. M.

HbA1c is associated with altered expression in blood of cell cycle- and immune response-related genes.

Diabetologia 61, 138-146 (2018). doi:10.1007/s00125-017-4467-0

Cnop, M., Toivonen, S., Igoillo-Esteve, M. & Salpea, P.

Endoplasmic reticulum stress and eIF2α phosphorylation: The Achilles heel of pancreatic β cells.

Molecular Metabolism 6, 1024-1039 (2017). doi:10.1016/j.molmet.2017.06.001

10.

Franks, P. W. & Poveda, A.

Lifestyle and precision diabetes medicine: will genomics help optimise the prediction, prevention and treatment of type 2 diabetes through lifestyle therapy?.

Diabetologia 60, 784-792 (2017). doi:10.1007/s00125-017-4207-5

11.

Leal, J., Khurshid, W., Pagano, E. & Feenstra, T.

Computer simulation models of pre-diabetes populations: a systematic review protocol.

BMJ Open 7, e014954 (2017). doi:10.1136/bmjopen-2016-014954

12.

McCarthy, M. I.

Painting a new picture of personalised medicine for diabetes.

Diabetologia 60, 793-799 (2017). doi:10.1007/s00125-017-4210-x

13.

Mutie, P. M., Giordano, G. N. & Franks, P. W.

Lifestyle precision medicine: the next generation in type 2 diabetes prevention?.

BMC Medicine 15, (2017). doi:10.1186/s12916-017-0938-x

14.

Rutter, G. A., Hodson, D. J., Chabosseau, P., Haythorne, E., Pullen, T. J. & Leclerc, I.

Local and regional control of calcium dynamics in the pancreatic islet: RUTTER et al .

Diabetes, Obesity and Metabolism 19, 30-41 (2017). doi:10.1111/dom.12990

The Expression of Aldolase B in Islets Is Negatively Associated With Insulin Secretion in Humans.

The Journal of Clinical Endocrinology & Metabolism 103, 4373-4383 (2018). doi:10.1210/jc.2018-00791

Pancreatic β-cell tRNA hypomethylation and fragmentation link TRMT10A deficiency with diabetes.

Nucleic Acids Research 46, 10302-10318 (2018). doi:10.1093/nar/gky839

Babbar, R., Heni, M., Peter, A., Hrabě de Angelis, M., Häring, H.-U., Fritsche, A., Preissl, H., Schölkopf, B. & Wagner, R.

Prediction of Glucose Tolerance without an Oral Glucose Tolerance Test.

Frontiers in Endocrinology 9, (2018). doi:10.3389/fendo.2018.00082

Novel subgroups of adult-onset diabetes and their association with outcomes: a data-driven cluster analysis of six variables.

The Lancet Diabetes & Endocrinology 6, 361-369 (2018). doi:10.1016/S2213-8587(18)30051-2

Modeling human pancreatic beta cell dedifferentiation.

Molecular Metabolism 10, 74-86 (2018). doi:10.1016/j.molmet.2018.02.002

Martinez-Sanchez, A., Nguyen-Tu, M.-S., Leclerc, I. & Rutter, G. A.

Manipulation and Measurement of AMPK Activity in Pancreatic Islets.

in AMPK (Neumann, D. & Viollet, B.eds. ) 1732, 413-431 (Springer New York, 2018). http://link.springer.com/10.1007/978-1-4939-7598-3_26.

Richards, P., Rachdi, L., Oshima, M., Marchetti, P., Bugliani, M., Armanet, M., Postic, C., Guilmeau, S. & Scharfmann, R.

MondoA Is an Essential Glucose-Responsive Transcription Factor in Human Pancreatic β-Cells.

Diabetes 67, 461-472 (2018). doi:10.2337/db17-0595

Slieker, R. C., van der Heijden, A. A. W. A., van Leeuwen, N., Mei, H., Nijpels, G., Beulens, J. W. J. & ’t Hart, L. M.

HbA1c is associated with altered expression in blood of cell cycle- and immune response-related genes.

Diabetologia 61, 138-146 (2018). doi:10.1007/s00125-017-4467-0

Cnop, M., Toivonen, S., Igoillo-Esteve, M. & Salpea, P.

Endoplasmic reticulum stress and eIF2α phosphorylation: The Achilles heel of pancreatic β cells.

Molecular Metabolism 6, 1024-1039 (2017). doi:10.1016/j.molmet.2017.06.001

10.

Franks, P. W. & Poveda, A.

Lifestyle and precision diabetes medicine: will genomics help optimise the prediction, prevention and treatment of type 2 diabetes through lifestyle therapy?.

Diabetologia 60, 784-792 (2017). doi:10.1007/s00125-017-4207-5

11.

Leal, J., Khurshid, W., Pagano, E. & Feenstra, T.

Computer simulation models of pre-diabetes populations: a systematic review protocol.

BMJ Open 7, e014954 (2017). doi:10.1136/bmjopen-2016-014954

12.

McCarthy, M. I.

Painting a new picture of personalised medicine for diabetes.

Diabetologia 60, 793-799 (2017). doi:10.1007/s00125-017-4210-x

13.

Mutie, P. M., Giordano, G. N. & Franks, P. W.

Lifestyle precision medicine: the next generation in type 2 diabetes prevention?.

BMC Medicine 15, (2017). doi:10.1186/s12916-017-0938-x

14.

Rutter, G. A., Hodson, D. J., Chabosseau, P., Haythorne, E., Pullen, T. J. & Leclerc, I.

Local and regional control of calcium dynamics in the pancreatic islet: RUTTER et al .

Diabetes, Obesity and Metabolism 19, 30-41 (2017). doi:10.1111/dom.12990

The Expression of Aldolase B in Islets Is Negatively Associated With Insulin Secretion in Humans.

The Journal of Clinical Endocrinology & Metabolism 103, 4373-4383 (2018). doi:10.1210/jc.2018-00791

Pancreatic β-cell tRNA hypomethylation and fragmentation link TRMT10A deficiency with diabetes.

Nucleic Acids Research 46, 10302-10318 (2018). doi:10.1093/nar/gky839

Babbar, R., Heni, M., Peter, A., Hrabě de Angelis, M., Häring, H.-U., Fritsche, A., Preissl, H., Schölkopf, B. & Wagner, R.

Prediction of Glucose Tolerance without an Oral Glucose Tolerance Test.

Frontiers in Endocrinology 9, (2018). doi:10.3389/fendo.2018.00082

Novel subgroups of adult-onset diabetes and their association with outcomes: a data-driven cluster analysis of six variables.

The Lancet Diabetes & Endocrinology 6, 361-369 (2018). doi:10.1016/S2213-8587(18)30051-2

Modeling human pancreatic beta cell dedifferentiation.

Molecular Metabolism 10, 74-86 (2018). doi:10.1016/j.molmet.2018.02.002

Martinez-Sanchez, A., Nguyen-Tu, M.-S., Leclerc, I. & Rutter, G. A.

Manipulation and Measurement of AMPK Activity in Pancreatic Islets.

in AMPK (Neumann, D. & Viollet, B.eds. ) 1732, 413-431 (Springer New York, 2018). http://link.springer.com/10.1007/978-1-4939-7598-3_26.

Richards, P., Rachdi, L., Oshima, M., Marchetti, P., Bugliani, M., Armanet, M., Postic, C., Guilmeau, S. & Scharfmann, R.

MondoA Is an Essential Glucose-Responsive Transcription Factor in Human Pancreatic β-Cells.

Diabetes 67, 461-472 (2018). doi:10.2337/db17-0595

Slieker, R. C., van der Heijden, A. A. W. A., van Leeuwen, N., Mei, H., Nijpels, G., Beulens, J. W. J. & ’t Hart, L. M.

HbA1c is associated with altered expression in blood of cell cycle- and immune response-related genes.

Diabetologia 61, 138-146 (2018). doi:10.1007/s00125-017-4467-0

Cnop, M., Toivonen, S., Igoillo-Esteve, M. & Salpea, P.

Endoplasmic reticulum stress and eIF2α phosphorylation: The Achilles heel of pancreatic β cells.

Molecular Metabolism 6, 1024-1039 (2017). doi:10.1016/j.molmet.2017.06.001

10.

Franks, P. W. & Poveda, A.

Lifestyle and precision diabetes medicine: will genomics help optimise the prediction, prevention and treatment of type 2 diabetes through lifestyle therapy?.

Diabetologia 60, 784-792 (2017). doi:10.1007/s00125-017-4207-5

11.

Leal, J., Khurshid, W., Pagano, E. & Feenstra, T.

Computer simulation models of pre-diabetes populations: a systematic review protocol.

BMJ Open 7, e014954 (2017). doi:10.1136/bmjopen-2016-014954

12.

McCarthy, M. I.

Painting a new picture of personalised medicine for diabetes.

Diabetologia 60, 793-799 (2017). doi:10.1007/s00125-017-4210-x

13.

Mutie, P. M., Giordano, G. N. & Franks, P. W.

Lifestyle precision medicine: the next generation in type 2 diabetes prevention?.

BMC Medicine 15, (2017). doi:10.1186/s12916-017-0938-x

14.

Rutter, G. A., Hodson, D. J., Chabosseau, P., Haythorne, E., Pullen, T. J. & Leclerc, I.

Local and regional control of calcium dynamics in the pancreatic islet: RUTTER et al .

Diabetes, Obesity and Metabolism 19, 30-41 (2017). doi:10.1111/dom.12990

The Expression of Aldolase B in Islets Is Negatively Associated With Insulin Secretion in Humans.

The Journal of Clinical Endocrinology & Metabolism 103, 4373-4383 (2018). doi:10.1210/jc.2018-00791

Pancreatic β-cell tRNA hypomethylation and fragmentation link TRMT10A deficiency with diabetes.

Nucleic Acids Research 46, 10302-10318 (2018). doi:10.1093/nar/gky839

Babbar, R., Heni, M., Peter, A., Hrabě de Angelis, M., Häring, H.-U., Fritsche, A., Preissl, H., Schölkopf, B. & Wagner, R.

Prediction of Glucose Tolerance without an Oral Glucose Tolerance Test.

Frontiers in Endocrinology 9, (2018). doi:10.3389/fendo.2018.00082

Novel subgroups of adult-onset diabetes and their association with outcomes: a data-driven cluster analysis of six variables.

The Lancet Diabetes & Endocrinology 6, 361-369 (2018). doi:10.1016/S2213-8587(18)30051-2

Modeling human pancreatic beta cell dedifferentiation.

Molecular Metabolism 10, 74-86 (2018). doi:10.1016/j.molmet.2018.02.002

Martinez-Sanchez, A., Nguyen-Tu, M.-S., Leclerc, I. & Rutter, G. A.

Manipulation and Measurement of AMPK Activity in Pancreatic Islets.

in AMPK (Neumann, D. & Viollet, B.eds. ) 1732, 413-431 (Springer New York, 2018). http://link.springer.com/10.1007/978-1-4939-7598-3_26.

Richards, P., Rachdi, L., Oshima, M., Marchetti, P., Bugliani, M., Armanet, M., Postic, C., Guilmeau, S. & Scharfmann, R.

MondoA Is an Essential Glucose-Responsive Transcription Factor in Human Pancreatic β-Cells.

Diabetes 67, 461-472 (2018). doi:10.2337/db17-0595

Slieker, R. C., van der Heijden, A. A. W. A., van Leeuwen, N., Mei, H., Nijpels, G., Beulens, J. W. J. & ’t Hart, L. M.

HbA1c is associated with altered expression in blood of cell cycle- and immune response-related genes.

Diabetologia 61, 138-146 (2018). doi:10.1007/s00125-017-4467-0

Cnop, M., Toivonen, S., Igoillo-Esteve, M. & Salpea, P.

Endoplasmic reticulum stress and eIF2α phosphorylation: The Achilles heel of pancreatic β cells.

Molecular Metabolism 6, 1024-1039 (2017). doi:10.1016/j.molmet.2017.06.001

10.

Franks, P. W. & Poveda, A.

Lifestyle and precision diabetes medicine: will genomics help optimise the prediction, prevention and treatment of type 2 diabetes through lifestyle therapy?.

Diabetologia 60, 784-792 (2017). doi:10.1007/s00125-017-4207-5

11.

Leal, J., Khurshid, W., Pagano, E. & Feenstra, T.

Computer simulation models of pre-diabetes populations: a systematic review protocol.

BMJ Open 7, e014954 (2017). doi:10.1136/bmjopen-2016-014954

12.

McCarthy, M. I.

Painting a new picture of personalised medicine for diabetes.

Diabetologia 60, 793-799 (2017). doi:10.1007/s00125-017-4210-x

13.

Mutie, P. M., Giordano, G. N. & Franks, P. W.

Lifestyle precision medicine: the next generation in type 2 diabetes prevention?.

BMC Medicine 15, (2017). doi:10.1186/s12916-017-0938-x

14.

Rutter, G. A., Hodson, D. J., Chabosseau, P., Haythorne, E., Pullen, T. J. & Leclerc, I.

Local and regional control of calcium dynamics in the pancreatic islet: RUTTER et al .

Diabetes, Obesity and Metabolism 19, 30-41 (2017). doi:10.1111/dom.12990

The Expression of Aldolase B in Islets Is Negatively Associated With Insulin Secretion in Humans.

The Journal of Clinical Endocrinology & Metabolism 103, 4373-4383 (2018). doi:10.1210/jc.2018-00791

Pancreatic β-cell tRNA hypomethylation and fragmentation link TRMT10A deficiency with diabetes.

Nucleic Acids Research 46, 10302-10318 (2018). doi:10.1093/nar/gky839

Babbar, R., Heni, M., Peter, A., Hrabě de Angelis, M., Häring, H.-U., Fritsche, A., Preissl, H., Schölkopf, B. & Wagner, R.

Prediction of Glucose Tolerance without an Oral Glucose Tolerance Test.

Frontiers in Endocrinology 9, (2018). doi:10.3389/fendo.2018.00082

Novel subgroups of adult-onset diabetes and their association with outcomes: a data-driven cluster analysis of six variables.

The Lancet Diabetes & Endocrinology 6, 361-369 (2018). doi:10.1016/S2213-8587(18)30051-2

Modeling human pancreatic beta cell dedifferentiation.

Molecular Metabolism 10, 74-86 (2018). doi:10.1016/j.molmet.2018.02.002

Martinez-Sanchez, A., Nguyen-Tu, M.-S., Leclerc, I. & Rutter, G. A.

Manipulation and Measurement of AMPK Activity in Pancreatic Islets.

in AMPK (Neumann, D. & Viollet, B.eds. ) 1732, 413-431 (Springer New York, 2018). http://link.springer.com/10.1007/978-1-4939-7598-3_26.

Richards, P., Rachdi, L., Oshima, M., Marchetti, P., Bugliani, M., Armanet, M., Postic, C., Guilmeau, S. & Scharfmann, R.

MondoA Is an Essential Glucose-Responsive Transcription Factor in Human Pancreatic β-Cells.

Diabetes 67, 461-472 (2018). doi:10.2337/db17-0595

Slieker, R. C., van der Heijden, A. A. W. A., van Leeuwen, N., Mei, H., Nijpels, G., Beulens, J. W. J. & ’t Hart, L. M.

HbA1c is associated with altered expression in blood of cell cycle- and immune response-related genes.

Diabetologia 61, 138-146 (2018). doi:10.1007/s00125-017-4467-0

Cnop, M., Toivonen, S., Igoillo-Esteve, M. & Salpea, P.

Endoplasmic reticulum stress and eIF2α phosphorylation: The Achilles heel of pancreatic β cells.

Molecular Metabolism 6, 1024-1039 (2017). doi:10.1016/j.molmet.2017.06.001

10.

Franks, P. W. & Poveda, A.

Lifestyle and precision diabetes medicine: will genomics help optimise the prediction, prevention and treatment of type 2 diabetes through lifestyle therapy?.

Diabetologia 60, 784-792 (2017). doi:10.1007/s00125-017-4207-5

11.

Leal, J., Khurshid, W., Pagano, E. & Feenstra, T.

Computer simulation models of pre-diabetes populations: a systematic review protocol.

BMJ Open 7, e014954 (2017). doi:10.1136/bmjopen-2016-014954

12.

McCarthy, M. I.

Painting a new picture of personalised medicine for diabetes.

Diabetologia 60, 793-799 (2017). doi:10.1007/s00125-017-4210-x

13.

Mutie, P. M., Giordano, G. N. & Franks, P. W.

Lifestyle precision medicine: the next generation in type 2 diabetes prevention?.

BMC Medicine 15, (2017). doi:10.1186/s12916-017-0938-x

14.

Rutter, G. A., Hodson, D. J., Chabosseau, P., Haythorne, E., Pullen, T. J. & Leclerc, I.

Local and regional control of calcium dynamics in the pancreatic islet: RUTTER et al .

Diabetes, Obesity and Metabolism 19, 30-41 (2017). doi:10.1111/dom.12990

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This project receives funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 115881. This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA.

This work is supported by the Swiss State Secretariat for Education‚ Research and Innovation (SERI) under contract number 16.0097-2.

The opinions expressed and arguments employed herein do not necessarily reflect the official views of these funding bodies.