234 results on '"Giordano, Giuseppe N."'
Search Results
2. Correction: Investigating the causal relationships between excess adiposity and cardiometabolic health in men and women
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Mutie, Pascal M., Pomares-Millan, Hugo, Atabaki-Pasdar, Naeimeh, Coral, Daniel, Fitipaldi, Hugo, Tsereteli, Neli, Tajes, Juan Fernandez, Franks, Paul W., and Giordano, Giuseppe N.
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- 2024
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3. Genetic analysis of blood molecular phenotypes reveals common properties in the regulatory networks affecting complex traits
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Brown, Andrew A., Fernandez-Tajes, Juan J., Hong, Mun-gwan, Brorsson, Caroline A., Koivula, Robert W., Davtian, David, Dupuis, Théo, Sartori, Ambra, Michalettou, Theodora-Dafni, Forgie, Ian M., Adam, Jonathan, Allin, Kristine H., Caiazzo, Robert, Cederberg, Henna, De Masi, Federico, Elders, Petra J. M., Giordano, Giuseppe N., Haid, Mark, Hansen, Torben, Hansen, Tue H., Hattersley, Andrew T., Heggie, Alison J., Howald, Cédric, Jones, Angus G., Kokkola, Tarja, Laakso, Markku, Mahajan, Anubha, Mari, Andrea, McDonald, Timothy J., McEvoy, Donna, Mourby, Miranda, Musholt, Petra B., Nilsson, Birgitte, Pattou, Francois, Penet, Deborah, Raverdy, Violeta, Ridderstråle, Martin, Romano, Luciana, Rutters, Femke, Sharma, Sapna, Teare, Harriet, ‘t Hart, Leen, Tsirigos, Konstantinos D., Vangipurapu, Jagadish, Vestergaard, Henrik, Brunak, Søren, Franks, Paul W., Frost, Gary, Grallert, Harald, Jablonka, Bernd, McCarthy, Mark I., Pavo, Imre, Pedersen, Oluf, Ruetten, Hartmut, Walker, Mark, Adamski, Jerzy, Schwenk, Jochen M., Pearson, Ewan R., Dermitzakis, Emmanouil T., and Viñuela, Ana
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- 2023
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4. Identification of biomarkers for glycaemic deterioration in type 2 diabetes
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Slieker, Roderick C., Donnelly, Louise A., Akalestou, Elina, Lopez-Noriega, Livia, Melhem, Rana, Güneş, Ayşim, Abou Azar, Frederic, Efanov, Alexander, Georgiadou, Eleni, Muniangi-Muhitu, Hermine, Sheikh, Mahsa, Giordano, Giuseppe N., Åkerlund, Mikael, Ahlqvist, Emma, Ali, Ashfaq, Banasik, Karina, Brunak, Søren, Barovic, Marko, Bouland, Gerard A., Burdet, Frédéric, Canouil, Mickaël, Dragan, Iulian, Elders, Petra J. M., Fernandez, Celine, Festa, Andreas, Fitipaldi, Hugo, Froguel, Phillippe, Gudmundsdottir, Valborg, Gudnason, Vilmundur, Gerl, Mathias J., van der Heijden, Amber A., Jennings, Lori L., Hansen, Michael K., Kim, Min, Leclerc, Isabelle, Klose, Christian, Kuznetsov, Dmitry, Mansour Aly, Dina, Mehl, Florence, Marek, Diana, Melander, Olle, Niknejad, Anne, Ottosson, Filip, Pavo, Imre, Duffin, Kevin, Syed, Samreen K., Shaw, Janice L., Cabrera, Over, Pullen, Timothy J., Simons, Kai, Solimena, Michele, Suvitaival, Tommi, Wretlind, Asger, Rossing, Peter, Lyssenko, Valeriya, Legido Quigley, Cristina, Groop, Leif, Thorens, Bernard, Franks, Paul W., Lim, Gareth E., Estall, Jennifer, Ibberson, Mark, Beulens, Joline W. J., ’t Hart, Leen M, Pearson, Ewan R., and Rutter, Guy A.
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- 2023
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5. Discovery of drug–omics associations in type 2 diabetes with generative deep-learning models
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Allesøe, Rosa Lundbye, Lundgaard, Agnete Troen, Hernández Medina, Ricardo, Aguayo-Orozco, Alejandro, Johansen, Joachim, Nissen, Jakob Nybo, Brorsson, Caroline, Mazzoni, Gianluca, Niu, Lili, Biel, Jorge Hernansanz, Leal Rodríguez, Cristina, Brasas, Valentas, Webel, Henry, Benros, Michael Eriksen, Pedersen, Anders Gorm, Chmura, Piotr Jaroslaw, Jacobsen, Ulrik Plesner, Mari, Andrea, Koivula, Robert, Mahajan, Anubha, Vinuela, Ana, Tajes, Juan Fernandez, Sharma, Sapna, Haid, Mark, Hong, Mun-Gwan, Musholt, Petra B., De Masi, Federico, Vogt, Josef, Pedersen, Helle Krogh, Gudmundsdottir, Valborg, Jones, Angus, Kennedy, Gwen, Bell, Jimmy, Thomas, E. Louise, Frost, Gary, Thomsen, Henrik, Hansen, Elizaveta, Hansen, Tue Haldor, Vestergaard, Henrik, Muilwijk, Mirthe, Blom, Marieke T., ‘t Hart, Leen M., Pattou, Francois, Raverdy, Violeta, Brage, Soren, Kokkola, Tarja, Heggie, Alison, McEvoy, Donna, Mourby, Miranda, Kaye, Jane, Hattersley, Andrew, McDonald, Timothy, Ridderstråle, Martin, Walker, Mark, Forgie, Ian, Giordano, Giuseppe N., Pavo, Imre, Ruetten, Hartmut, Pedersen, Oluf, Hansen, Torben, Dermitzakis, Emmanouil, Franks, Paul W., Schwenk, Jochen M., Adamski, Jerzy, McCarthy, Mark I., Pearson, Ewan, Banasik, Karina, Rasmussen, Simon, and Brunak, Søren
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- 2023
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6. A phenome-wide comparative analysis of genetic discordance between obesity and type 2 diabetes
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Coral, Daniel E., Fernandez-Tajes, Juan, Tsereteli, Neli, Pomares-Millan, Hugo, Fitipaldi, Hugo, Mutie, Pascal M., Atabaki-Pasdar, Naeimeh, Kalamajski, Sebastian, Poveda, Alaitz, Miller-Fleming, Tyne W., Zhong, Xue, Giordano, Giuseppe N., Pearson, Ewan R., Cox, Nancy J., and Franks, Paul W.
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- 2023
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7. Investigating the causal relationships between excess adiposity and cardiometabolic health in men and women
- Author
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Mutie, Pascal M., Pomares-Millan, Hugo, Atabaki-Pasdar, Naeimeh, Coral, Daniel, Fitipaldi, Hugo, Tsereteli, Neli, Tajes, Juan Fernandez, Franks, Paul W., and Giordano, Giuseppe N.
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- 2023
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8. The Association of Cardiometabolic, Diet and Lifestyle Parameters With Plasma Glucagon-like Peptide-1: An IMI DIRECT Study.
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Eriksen, Rebeca, White, Margaret C, Dawed, Adem Y, Perez, Isabel Garcia, Posma, Joram M, Haid, Mark, Sharma, Sapna, Prehn, Cornelia, Thomas, E Louise, Koivula, Robert W, Bizzotto, Roberto, Mari, Andrea, Giordano, Giuseppe N, Pavo, Imre, Schwenk, Jochen M, Masi, Federico De, Tsirigos, Konstantinos D, Brunak, Søren, Viñuela, Ana, and Mahajan, Anubha
- Subjects
TYPE 2 diabetes ,PEOPLE with diabetes ,MULTIPLE regression analysis ,INSULIN resistance ,FOOD consumption - Abstract
Context The role of glucagon-like peptide-1 (GLP-1) in type 2 diabetes (T2D) and obesity is not fully understood. Objective We investigate the association of cardiometabolic, diet, and lifestyle parameters on fasting and postprandial GLP-1 in people at risk of, or living with, T2D. Methods We analyzed cross-sectional data from the two Innovative Medicines Initiative (IMI) Diabetes Research on Patient Stratification (DIRECT) cohorts, cohort 1 (n = 2127) individuals at risk of diabetes; cohort 2 (n = 789) individuals with new-onset T2D. Results Our multiple regression analysis reveals that fasting total GLP-1 is associated with an insulin-resistant phenotype and observe a strong independent relationship with male sex, increased adiposity, and liver fat, particularly in the prediabetes population. In contrast, we showed that incremental GLP-1 decreases with worsening glycemia, higher adiposity, liver fat, male sex, and reduced insulin sensitivity in the prediabetes cohort. Higher fasting total GLP-1 was associated with a low intake of wholegrain, fruit, and vegetables in people with prediabetes, and with a high intake of red meat and alcohol in people with diabetes. Conclusion These studies provide novel insights into the association between fasting and incremental GLP-1, metabolic traits of diabetes and obesity, and dietary intake, and raise intriguing questions regarding the relevance of fasting GLP-1 in the pathophysiology T2D. [ABSTRACT FROM AUTHOR]
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- 2024
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9. Four groups of type 2 diabetes contribute to the etiological and clinical heterogeneity in newly diagnosed individuals: An IMI DIRECT study
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Wesolowska-Andersen, Agata, Brorsson, Caroline A., Bizzotto, Roberto, Mari, Andrea, Tura, Andrea, Koivula, Robert, Mahajan, Anubha, Vinuela, Ana, Tajes, Juan Fernandez, Sharma, Sapna, Haid, Mark, Prehn, Cornelia, Artati, Anna, Hong, Mun-Gwan, Musholt, Petra B., Kurbasic, Azra, De Masi, Federico, Tsirigos, Kostas, Pedersen, Helle Krogh, Gudmundsdottir, Valborg, Thomas, Cecilia Engel, Banasik, Karina, Jennison, Chrisopher, Jones, Angus, Kennedy, Gwen, Bell, Jimmy, Thomas, Louise, Frost, Gary, Thomsen, Henrik, Allin, Kristine, Hansen, Tue Haldor, Vestergaard, Henrik, Hansen, Torben, Rutters, Femke, Elders, Petra, t’Hart, Leen, Bonnefond, Amelie, Canouil, Mickaël, Brage, Soren, Kokkola, Tarja, Heggie, Alison, McEvoy, Donna, Hattersley, Andrew, McDonald, Timothy, Teare, Harriet, Ridderstrale, Martin, Walker, Mark, Forgie, Ian, Giordano, Giuseppe N., Froguel, Philippe, Pavo, Imre, Ruetten, Hartmut, Pedersen, Oluf, Dermitzakis, Emmanouil, Franks, Paul W., Schwenk, Jochen M., Adamski, Jerzy, Pearson, Ewan, McCarthy, Mark I., and Brunak, Søren
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- 2022
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10. Author Correction: Discovery of drug–omics associations in type 2 diabetes with generative deep-learning models
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Allesøe, Rosa Lundbye, Lundgaard, Agnete Troen, Hernández Medina, Ricardo, Aguayo-Orozco, Alejandro, Johansen, Joachim, Nissen, Jakob Nybo, Brorsson, Caroline, Mazzoni, Gianluca, Niu, Lili, Biel, Jorge Hernansanz, Leal Rodríguez, Cristina, Brasas, Valentas, Webel, Henry, Benros, Michael Eriksen, Pedersen, Anders Gorm, Chmura, Piotr Jaroslaw, Jacobsen, Ulrik Plesner, Mari, Andrea, Koivula, Robert, Mahajan, Anubha, Vinuela, Ana, Tajes, Juan Fernandez, Sharma, Sapna, Haid, Mark, Hong, Mun-Gwan, Musholt, Petra B., De Masi, Federico, Vogt, Josef, Pedersen, Helle Krogh, Gudmundsdottir, Valborg, Jones, Angus, Kennedy, Gwen, Bell, Jimmy, Thomas, E. Louise, Frost, Gary, Thomsen, Henrik, Hansen, Elizaveta, Hansen, Tue Haldor, Vestergaard, Henrik, Muilwijk, Mirthe, Blom, Marieke T., ‘t Hart, Leen M., Pattou, Francois, Raverdy, Violeta, Brage, Soren, Kokkola, Tarja, Heggie, Alison, McEvoy, Donna, Mourby, Miranda, Kaye, Jane, Hattersley, Andrew, McDonald, Timothy, Ridderstråle, Martin, Walker, Mark, Forgie, Ian, Giordano, Giuseppe N., Pavo, Imre, Ruetten, Hartmut, Pedersen, Oluf, Hansen, Torben, Dermitzakis, Emmanouil, Franks, Paul W., Schwenk, Jochen M., Adamski, Jerzy, McCarthy, Mark I., Pearson, Ewan, Banasik, Karina, Rasmussen, Simon, and Brunak, Søren
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- 2023
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11. A Federated Database for Obesity Research: An IMI-SOPHIA Study
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Delfin, Carl, primary, Dragan, Iulian, additional, Kuznetsov, Dmitry, additional, Tajes, Juan Fernandez, additional, Smit, Femke, additional, Coral, Daniel E., additional, Farzaneh, Ali, additional, Haugg, André, additional, Hungele, Andreas, additional, Niknejad, Anne, additional, Hall, Christopher, additional, Jacobs, Daan, additional, Marek, Diana, additional, Fraser, Diane P., additional, Thuillier, Dorothee, additional, Ahmadizar, Fariba, additional, Mehl, Florence, additional, Pattou, Francois, additional, Burdet, Frederic, additional, Hawkes, Gareth, additional, Arts, Ilja C. W., additional, Blanch, Jordi, additional, Van Soest, Johan, additional, Fernández-Real, José-Manuel, additional, Boehl, Juergen, additional, Fink, Katharina, additional, van Greevenbroek, Marleen M. J., additional, Kavousi, Maryam, additional, Minten, Michiel, additional, Prinz, Nicole, additional, Ipsen, Niels, additional, Franks, Paul W., additional, Ramos, Rafael, additional, Holl, Reinhard W., additional, Horban, Scott, additional, Duarte-Salles, Talita, additional, Tran, Van Du T., additional, Raverdy, Violeta, additional, Leal, Yenny, additional, Lenart, Adam, additional, Pearson, Ewan, additional, Sparsø, Thomas, additional, Giordano, Giuseppe N., additional, Ioannidis, Vassilios, additional, Soh, Keng, additional, Frayling, Timothy M., additional, Le Roux, Carel W., additional, and Ibberson, Mark, additional
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- 2024
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12. Replication and cross-validation of type 2 diabetes subtypes based on clinical variables: an IMI-RHAPSODY study
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Slieker, Roderick C., Donnelly, Louise A., Fitipaldi, Hugo, Bouland, Gerard A., Giordano, Giuseppe N., Åkerlund, Mikael, Gerl, Mathias J., Ahlqvist, Emma, Ali, Ashfaq, Dragan, Iulian, Festa, Andreas, Hansen, Michael K., Mansour Aly, Dina, Kim, Min, Kuznetsov, Dmitry, Mehl, Florence, Klose, Christian, Simons, Kai, Pavo, Imre, Pullen, Timothy J., Suvitaival, Tommi, Wretlind, Asger, Rossing, Peter, Lyssenko, Valeriya, Legido-Quigley, Cristina, Groop, Leif, Thorens, Bernard, Franks, Paul W., Ibberson, Mark, Rutter, Guy A., Beulens, Joline W. J., ‘t Hart, Leen M., and Pearson, Ewan R.
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- 2021
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13. A Federated Database for Obesity Research: An IMI-SOPHIA Study
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RWE/Causal inference, Child Health, Delfin, Carl, Dragan, Iulian, Kuznetsov, Dmitry, Tajes, Juan Fernandez, Smit, Femke, Coral, Daniel E, Farzaneh, Ali, Haugg, André, Hungele, Andreas, Niknejad, Anne, Hall, Christopher, Jacobs, Daan, Marek, Diana, Fraser, Diane P, Thuillier, Dorothee, Ahmadizar, Fariba, Mehl, Florence, Pattou, Francois, Burdet, Frederic, Hawkes, Gareth, Arts, Ilja C W, Blanch, Jordi, Van Soest, Johan, Fernández-Real, José-Manuel, Boehl, Juergen, Fink, Katharina, van Greevenbroek, Marleen M J, Kavousi, Maryam, Minten, Michiel, Prinz, Nicole, Ipsen, Niels, Franks, Paul W, Ramos, Rafael, Holl, Reinhard W, Horban, Scott, Duarte-Salles, Talita, Tran, Van Du T, Raverdy, Violeta, Leal, Yenny, Lenart, Adam, Pearson, Ewan, Sparsø, Thomas, Giordano, Giuseppe N, Ioannidis, Vassilios, Soh, Keng, Frayling, Timothy M, Le Roux, Carel W, Ibberson, Mark, RWE/Causal inference, Child Health, Delfin, Carl, Dragan, Iulian, Kuznetsov, Dmitry, Tajes, Juan Fernandez, Smit, Femke, Coral, Daniel E, Farzaneh, Ali, Haugg, André, Hungele, Andreas, Niknejad, Anne, Hall, Christopher, Jacobs, Daan, Marek, Diana, Fraser, Diane P, Thuillier, Dorothee, Ahmadizar, Fariba, Mehl, Florence, Pattou, Francois, Burdet, Frederic, Hawkes, Gareth, Arts, Ilja C W, Blanch, Jordi, Van Soest, Johan, Fernández-Real, José-Manuel, Boehl, Juergen, Fink, Katharina, van Greevenbroek, Marleen M J, Kavousi, Maryam, Minten, Michiel, Prinz, Nicole, Ipsen, Niels, Franks, Paul W, Ramos, Rafael, Holl, Reinhard W, Horban, Scott, Duarte-Salles, Talita, Tran, Van Du T, Raverdy, Violeta, Leal, Yenny, Lenart, Adam, Pearson, Ewan, Sparsø, Thomas, Giordano, Giuseppe N, Ioannidis, Vassilios, Soh, Keng, Frayling, Timothy M, Le Roux, Carel W, and Ibberson, Mark
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- 2024
14. A Federated Database for Obesity Research:An IMI-SOPHIA Study
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Delfin, Carl, Dragan, Iulian, Kuznetsov, Dmitry, Tajes, Juan Fernandez, Smit, Femke, Coral, Daniel E., Farzaneh, Ali, Haugg, Andre, Hungele, Andreas, Niknejad, Anne, Hall, Christopher, Jacobs, Daan, Marek, Diana, Fraser, Diane P., Thuillier, Dorothee, Ahmadizar, Fariba, Mehl, Florence, Pattou, Francois, Burdet, Frederic, Hawkes, Gareth, Arts, Ilja C. W., Blanch, Jordi, Van Soest, Johan, Fernandez-Real, Jose-Manuel, Boehl, Juergen, Fink, Katharina, van Greevenbroek, Marleen M. J., Kavousi, Maryam, Minten, Michiel, Prinz, Nicole, Ipsen, Niels, Franks, Paul W., Ramos, Rafael, Holl, Reinhard W., Horban, Scott, Duarte-Salles, Talita, Tran, Van Du T., Raverdy, Violeta, Leal, Yenny, Lenart, Adam, Pearson, Ewan, Sparso, Thomas, Giordano, Giuseppe N., Ioannidis, Vassilios, Soh, Keng, Frayling, Timothy M., Le Roux, Carel W., Ibberson, Mark, Delfin, Carl, Dragan, Iulian, Kuznetsov, Dmitry, Tajes, Juan Fernandez, Smit, Femke, Coral, Daniel E., Farzaneh, Ali, Haugg, Andre, Hungele, Andreas, Niknejad, Anne, Hall, Christopher, Jacobs, Daan, Marek, Diana, Fraser, Diane P., Thuillier, Dorothee, Ahmadizar, Fariba, Mehl, Florence, Pattou, Francois, Burdet, Frederic, Hawkes, Gareth, Arts, Ilja C. W., Blanch, Jordi, Van Soest, Johan, Fernandez-Real, Jose-Manuel, Boehl, Juergen, Fink, Katharina, van Greevenbroek, Marleen M. J., Kavousi, Maryam, Minten, Michiel, Prinz, Nicole, Ipsen, Niels, Franks, Paul W., Ramos, Rafael, Holl, Reinhard W., Horban, Scott, Duarte-Salles, Talita, Tran, Van Du T., Raverdy, Violeta, Leal, Yenny, Lenart, Adam, Pearson, Ewan, Sparso, Thomas, Giordano, Giuseppe N., Ioannidis, Vassilios, Soh, Keng, Frayling, Timothy M., Le Roux, Carel W., and Ibberson, Mark
- Abstract
Obesity is considered by many as a lifestyle choice rather than a chronic progressive disease. The Innovative Medicines Initiative (IMI) SOPHIA (Stratification of Obesity Phenotypes to Optimize Future Obesity Therapy) project is part of a momentum shift aiming to provide better tools for the stratification of people with obesity according to disease risk and treatment response. One of the challenges to achieving these goals is that many clinical cohorts are siloed, limiting the potential of combined data for biomarker discovery. In SOPHIA, we have addressed this challenge by setting up a federated database building on open-source DataSHIELD technology. The database currently federates 16 cohorts that are accessible via a central gateway. The database is multi-modal, including research studies, clinical trials, and routine health data, and is accessed using the R statistical programming environment where statistical and machine learning analyses can be performed at a distance without any disclosure of patient-level data. We demonstrate the use of the database by providing a proof-of-concept analysis, performing a federated linear model of BMI and systolic blood pressure, pooling all data from 16 studies virtually without any analyst seeing individual patient-level data. This analysis provided similar point estimates compared to a meta-analysis of the 16 individual studies. Our approach provides a benchmark for reproducible, safe federated analyses across multiple study types provided by multiple stakeholders.
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- 2024
15. Trust, happiness and mortality: Findings from a prospective US population-based survey
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Miething, Alexander, Mewes, Jan, and Giordano, Giuseppe N.
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- 2020
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16. Author Correction: An investigation of causal relationships between prediabetes and vascular complications
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Mutie, Pascal M., Pomares-Millan, Hugo, Atabaki-Pasdar, Naeimeh, Jordan, Nina, Adams, Rachel, Daly, Nicole L., Tajes, Juan Fernandes, Giordano, Giuseppe N., and Franks, Paul W.
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- 2021
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17. BALDR: A Web-based platform for informed comparison and prioritization of biomarker candidates for type 2 diabetes mellitus
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Lundgaard, Agnete T., primary, Burdet, Frédéric, additional, Siggaard, Troels, additional, Westergaard, David, additional, Vagiaki, Danai, additional, Cantwell, Lisa, additional, Röder, Timo, additional, Vistisen, Dorte, additional, Sparsø, Thomas, additional, Giordano, Giuseppe N., additional, Ibberson, Mark, additional, Banasik, Karina, additional, and Brunak, Søren, additional
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- 2023
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18. Discovery of biomarkers for glycaemic deterioration before and after the onset of type 2 diabetes: descriptive characteristics of the epidemiological studies within the IMI DIRECT Consortium
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Koivula, Robert W., Forgie, Ian M., Kurbasic, Azra, Viñuela, Ana, Heggie, Alison, Giordano, Giuseppe N., Hansen, Tue H., Hudson, Michelle, Koopman, Anitra D. M., Rutters, Femke, Siloaho, Maritta, Allin, Kristine H., Brage, Søren, Brorsson, Caroline A., Dawed, Adem Y., De Masi, Federico, Groves, Christopher J., Kokkola, Tarja, Mahajan, Anubha, Perry, Mandy H., Rauh, Simone P., Ridderstråle, Martin, Teare, Harriet J. A., Thomas, E. Louise, Tura, Andrea, Vestergaard, Henrik, White, Tom, Adamski, Jerzy, Bell, Jimmy D., Beulens, Joline W., Brunak, Søren, Dermitzakis, Emmanouil T., Froguel, Philippe, Frost, Gary, Gupta, Ramneek, Hansen, Torben, Hattersley, Andrew, Jablonka, Bernd, Kaye, Jane, Laakso, Markku, McDonald, Timothy J., Pedersen, Oluf, Schwenk, Jochen M., Pavo, Imre, Mari, Andrea, McCarthy, Mark I., Ruetten, Hartmut, Walker, Mark, Pearson, Ewan, Franks, Paul W., and for the IMI DIRECT Consortium
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- 2019
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19. An investigation of causal relationships between prediabetes and vascular complications
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Mutie, Pascal M., Pomares-Millan, Hugo, Atabaki-Pasdar, Naeimeh, Jordan, Nina, Adams, Rachel, Daly, Nicole L., Tajes, Juan Fernandes, Giordano, Giuseppe N., and Franks, Paul W.
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- 2020
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20. Whole blood co-expression modules associate with metabolic traits and type 2 diabetes: an IMI-DIRECT study
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Gudmundsdottir, Valborg, Pedersen, Helle Krogh, Mazzoni, Gianluca, Allin, Kristine H., Artati, Anna, Beulens, Joline W., Banasik, Karina, Brorsson, Caroline, Cederberg, Henna, Chabanova, Elizaveta, De Masi, Federico, Elders, Petra J., Forgie, Ian, Giordano, Giuseppe N., Grallert, Harald, Gupta, Ramneek, Haid, Mark, Hansen, Torben, Hansen, Tue H., Hattersley, Andrew T., Heggie, Alison, Hong, Mun-Gwan, Jones, Angus G., Koivula, Robert, Kokkola, Tarja, Laakso, Markku, Løngreen, Peter, Mahajan, Anubha, Mari, Andrea, McDonald, Timothy J., McEvoy, Donna, Musholt, Petra B., Pavo, Imre, Prehn, Cornelia, Ruetten, Hartmut, Ridderstråle, Martin, Rutters, Femke, Sharma, Sapna, Slieker, Roderick C., Syed, Ali, Tajes, Juan Fernandez, Thomas, Cecilia Engel, Thomsen, Henrik S., Vangipurapu, Jagadish, Vestergaard, Henrik, Viñuela, Ana, Wesolowska-Andersen, Agata, Walker, Mark, Adamski, Jerzy, Schwenk, Jochen M., McCarthy, Mark I., Pearson, Ewan, Dermitzakis, Emmanouil, Franks, Paul W., Pedersen, Oluf, and Brunak, Søren
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- 2020
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21. Changes in Social Capital and Cigarette Smoking Behavior Over Time : A Population-Based Panel Study of Temporal Relationships
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Lindström, Martin and Giordano, Giuseppe N.
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- 2016
22. The 2005 London terror attacks: An investigation of changes in psychological wellbeing and social capital pre- and post-attacks (2003-07)-A UK panel study
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Giordano, Giuseppe N. and Lindström, Martin
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- 2016
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23. BALDR:A Web-based platform for informed comparison and prioritization of biomarker candidates for type 2 diabetes mellitus
- Author
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Lundgaard, Agnete T., Burdet, Frédéric, Siggaard, Troels, Westergaard, David, Vagiaki, Danai, Cantwell, Lisa, Röder, Timo, Vistisen, Dorte, Sparsø, Thomas, Giordano, Giuseppe N., Ibberson, Mark, Banasik, Karina, Brunak, Søren, Lundgaard, Agnete T., Burdet, Frédéric, Siggaard, Troels, Westergaard, David, Vagiaki, Danai, Cantwell, Lisa, Röder, Timo, Vistisen, Dorte, Sparsø, Thomas, Giordano, Giuseppe N., Ibberson, Mark, Banasik, Karina, and Brunak, Søren
- Abstract
Novel biomarkers are key to addressing the ongoing pandemic of type 2 diabetes mellitus. While new technologies have improved the potential of identifying such biomarkers, at the same time there is an increasing need for informed prioritization to ensure efficient downstream verification. We have built BALDR, an automated pipeline for biomarker comparison and prioritization in the context of diabetes. BALDR includes protein, gene, and disease data from major public repositories, text-mining data, and human and mouse experimental data from the IMI2 RHAPSODY consortium. These data are provided as easy-to-read figures and tables enabling direct comparison of up to 20 biomarker candidates for diabetes through the public website https://baldr.cpr.ku.dk.
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- 2023
24. The 2008 financial crisis: Changes in social capital and its association with psychological wellbeing in the United Kingdom – A panel study
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Lindström, Martin and Giordano, Giuseppe N.
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- 2016
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25. Who benefits most from outpatient lifestyle intervention? An IMI‐SOPHIA study on pediatric individuals living with overweight and obesity.
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Prinz, Nicole, Pomares‐Millan, Hugo, Dannemann, Almut, Giordano, Giuseppe N., Joisten, Christine, Körner, Antje, Weghuber, Daniel, Weihrauch‐Blüher, Susann, Wiegand, Susanna, Holl, Reinhard W., and Lanzinger, Stefanie
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CHILDHOOD obesity ,OVERWEIGHT children ,OBESITY ,K-means clustering ,MEDICAL registries ,TEENAGE girls - Abstract
Objective: The first‐line approach for childhood obesity is lifestyle intervention (LI); however, success varies. This study aimed first to identify distinct subgroups of response in children living with overweight and obesity and second to elucidate predictors for subclusters. Methods: Based on the obesity patient follow‐up registry the APV (Adipositas‐Patienten‐Verlaufsdokumentation) initiative, a total of 12,453 children and adolescents (median age: 11.5 [IQR: 9.7–13.2] years; BMI z score [BMIz]: 2.06 [IQR: 1.79–2.34]; 52.6% girls) living with overweight/obesity and participating in outpatient LI were studied. Longitudinal k‐means clustering was used to identify individual BMIz response curve for up to 2 years after treatment initiation. Multinomial logistic regression was used to elucidate predictors for cluster membership. Results: A total of 36.3% of children and adolescents experienced "no BMIz loss." The largest subcluster (44.8%) achieved "moderate BMIz loss," with an average delta‐BMIz of −0.23 (IQR: −0.33 to −0.14) at study end. A total of 18.9% had a "pronounced BMIz loss" up to −0.61 (IQR: −0.76 to −0.49). Younger age and lower BMIz at LI initiation, larger initial BMIz loss, and less social deprivation were linked with higher likelihood for moderate or pronounced BMIz loss compared with the no BMIz loss cluster (all p < 0.05). Conclusions: These results support the importance of patient‐tailored intervention and earlier treatment escalation in high‐risk individuals who have little chance of success. [ABSTRACT FROM AUTHOR]
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- 2023
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26. Investigating the causal relationships between excess adiposity and cardiometabolic health in men and women
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Mutie, Pascal M., primary, Pomares-Milan, Hugo, additional, Atabaki-Pasdar, Naeimeh, additional, Coral, Daniel, additional, Fitipaldi, Hugo, additional, Tsereteli, Neli, additional, Tajes, Juan Fernandez, additional, Franks, Paul W., additional, and Giordano, Giuseppe N., additional
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- 2022
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27. Predicting Sensitivity to Adverse Lifestyle Risk Factors for Cardiometabolic Morbidity and Mortality
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Pomares-Millan, Hugo, primary, Poveda, Alaitz, additional, Atabaki-Pasdar, Naemieh, additional, Johansson, Ingegerd, additional, Björk, Jonas, additional, Ohlsson, Mattias, additional, Giordano, Giuseppe N., additional, and Franks, Paul W., additional
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- 2022
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28. Age, period and cohort trends in drug abuse hospitalizations within the total Swedish population (1975–2010)
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Giordano, Giuseppe N., Ohlsson, Henrik, Kendler, Kenneth S., Winkleby, Marilyn A., Sundquist, Kristina, and Sundquist, Jan
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- 2014
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29. Predicting Sensitivity to Adverse Lifestyle Risk Factors for Cardiometabolic Morbidity and Mortality
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Pomares-Millan, Hugo, Poveda, Alaitz, Atabaki-Pasdar, Naemieh, Johansson, Ingegerd, Björk, Jonas, Ohlsson, Mattias, Giordano, Giuseppe N., Franks, Paul W., Pomares-Millan, Hugo, Poveda, Alaitz, Atabaki-Pasdar, Naemieh, Johansson, Ingegerd, Björk, Jonas, Ohlsson, Mattias, Giordano, Giuseppe N., and Franks, Paul W.
- Abstract
People appear to vary in their susceptibility to lifestyle risk factors for cardiometabolic disease; determining a priori who is most sensitive may help optimize the timing, design, and delivery of preventative interventions. We aimed to ascertain a person’s degree of resilience or sensitivity to adverse lifestyle exposures and determine whether these classifications help predict cardiometabolic disease later in life; we pooled data from two population-based Swedish prospective cohort studies (n = 53,507), and we contrasted an individual’s cardiometabolic biomarker profile with the profile predicted for them given their lifestyle exposure characteristics using a quantile random forest approach. People who were classed as ‘sensitive’ to hypertension- and dyslipidemia-related lifestyle exposures were at higher risk of developing cardiovascular disease (CVD, hazards ratio 1.6 (95% CI: 1.3, 1.91)), compared with the general population. No differences were observed for type 2 diabetes (T2D) risk. Here, we report a novel approach to identify individuals who are especially sensitive to adverse lifestyle exposures and who are at higher risk of subsequent cardiovascular events. Early preventive interventions may be needed in this subgroup.
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- 2022
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30. Estimating the Direct Effect between Dietary Macronutrients and Cardiometabolic Disease, Accounting for Mediation by Adiposity and Physical Activity
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Pomares-Millan, Hugo, Atabaki-Pasdar, Naeimeh, Coral, Daniel, Johansson, Ingegerd, Giordano, Giuseppe N., Franks, Paul W., Pomares-Millan, Hugo, Atabaki-Pasdar, Naeimeh, Coral, Daniel, Johansson, Ingegerd, Giordano, Giuseppe N., and Franks, Paul W.
- Abstract
Assessing the causal effects of individual dietary macronutrients and cardiometabolic disease is challenging owing to the complexity to distinguish direct effects from those mediated or confounded by other factors. To estimate these effects, intake of protein, carbohydrate, sugar, fat, and its subtypes were obtained using food frequency data derived from a Swedish population-based cohort (n~60,000). Data on clinical outcomes (i.e., type 2 diabetes (T2D) and cardiovascular disease (CVD) incidence) were obtained by linking health registry data. We assessed the magnitude of direct and mediated effects of diet, adiposity and physical activity on T2D and CVD using structural equation modelling (SEM). To strengthen causal inference, we used Mendelian randomization (MR) to model macronutrient intake exposures against clinical outcomes. We identified likely causal effects of genetically predicted carbohydrate intake (including sugar intake) and T2D, independent of adiposity and physical activity. Pairwise, serial-and parallel-mediational configurations yielded similar results. In the integrative genomic analyses, the candidate causal variant localized to the established type 2 diabetes gene TCF7L2. These findings may be informative when considering which dietary modifications included in nutritional guidelines are most likely to elicit health-promoting effects.
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- 2022
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31. Estimating the Direct Effect between Dietary Macronutrients and Cardiometabolic Disease, Accounting for Mediation by Adiposity and Physical Activity
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Pomares-Millan, Hugo, primary, Atabaki-Pasdar, Naeimeh, additional, Coral, Daniel, additional, Johansson, Ingegerd, additional, Giordano, Giuseppe N., additional, and Franks, Paul W., additional
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- 2022
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32. The impact of changes in different aspects of social capital and material conditions on self-rated health over time: A longitudinal cohort study
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Giordano, Giuseppe N. and Lindstrom, Martin
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- 2010
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33. Inferring causal pathways between metabolic processes and liver fat accumulation: an IMI DIRECT study
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Atabaki-Pasdar, Naeimeh, primary, Pomares-Millan, Hugo, additional, Koivula, Robert W, additional, Tura, Andrea, additional, Brown, Andrew, additional, Viñuela, Ana, additional, Agudelo, Leandro, additional, Coral, Daniel, additional, van Oort, Sabine, additional, Allin, Kristine, additional, Chabanova, Elizaveta, additional, Cederberg, Henna, additional, De Masi, Federico, additional, Elders, Petra, additional, Tajes, Juan Fernandez, additional, Forgie, Ian M, additional, Hansen, Tue H, additional, Heggie, Alison, additional, Jones, Angus, additional, Kokkola, Tarja, additional, Mahajan, Anubha, additional, McDonald, Timothy J, additional, McEvoy, Donna, additional, Tsirigos, Konstantinos, additional, Teare, Harriet, additional, Vangipurapu, Jagadish, additional, Vestergaard, Henrik, additional, Adamski, Jerzy, additional, Beulens, Joline WJ, additional, Brunak, Søren, additional, Dermitzakis, Emmanouil, additional, Hansen, Torben, additional, Hattersley, Andrew T, additional, Laakso, Markku, additional, Pedersen, Oluf, additional, Ridderstråle, Martin, additional, Ruetten, Hartmut, additional, Rutters, Femke, additional, Schwenk, Jochen M, additional, Walker, Mark, additional, Giordano, Giuseppe N, additional, Ohlsson, Mattias, additional, Gupta, Ramneek, additional, Mari, Andrea, additional, McCarthy, Mark I, additional, Thomas, E Louise, additional, Bell, Jimmy D, additional, Pavo, Imre, additional, Pearson, Ewan R, additional, and Franks, Paul W, additional
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- 2021
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34. Distinct Molecular Signatures of Clinical Clusters in People with Type 2 Diabetes: an IMI-RHAPSODY Study
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Slieker, Roderick C, primary, Donnelly, Louise A, primary, Fitipaldi, Hugo, primary, Bouland, Gerard A, primary, Giordano, Giuseppe N., primary, Åkerlund, Mikael, primary, Gerl, Mathias J., primary, Ahlqvist, Emma, primary, Ali, Ashfaq, primary, Dragan, Iulian, primary, Elders, Petra, primary, Festa, Andreas, primary, Hansen, Michael K., primary, Heijden, Amber A van der, primary, Aly, Dina Mansour, primary, Kim, Min, primary, Kuznetsov, Dmitry, primary, Mehl, Florence, primary, Klose, Christian, primary, Simons, Kai, primary, Pavo, Imre, primary, Pullen, Timothy J., primary, Suvitaival, Tommi, primary, Wretlind, Asger, primary, Rossing, Peter, primary, Lyssenko, Valeriya, primary, Quigley, Cristina Legido, primary, Groop, Leif, primary, Thorens, Bernard, primary, Franks, Paul W, primary, Ibberson, Mark, primary, Rutter, Guy A, primary, Beulens, Joline WJ, primary, Hart, Leen M ’t, primary, and Pearson, Ewan R, primary
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- 2021
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35. Distinct Molecular Signatures of Clinical Clusters in People With Type 2 Diabetes: An IMI-RHAPSODY Study
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Slieker, Roderick C., primary, Donnelly, Louise A., additional, Fitipaldi, Hugo, additional, Bouland, Gerard A., additional, Giordano, Giuseppe N., additional, Åkerlund, Mikael, additional, Gerl, Mathias J., additional, Ahlqvist, Emma, additional, Ali, Ashfaq, additional, Dragan, Iulian, additional, Elders, Petra, additional, Festa, Andreas, additional, Hansen, Michael K., additional, van der Heijden, Amber A., additional, Mansour Aly, Dina, additional, Kim, Min, additional, Kuznetsov, Dmitry, additional, Mehl, Florence, additional, Klose, Christian, additional, Simons, Kai, additional, Pavo, Imre, additional, Pullen, Timothy J., additional, Suvitaival, Tommi, additional, Wretlind, Asger, additional, Rossing, Peter, additional, Lyssenko, Valeriya, additional, Legido Quigley, Cristina, additional, Groop, Leif, additional, Thorens, Bernard, additional, Franks, Paul W., additional, Ibberson, Mark, additional, Rutter, Guy A., additional, Beulens, Joline W.J., additional, ’t Hart, Leen M., additional, and Pearson, Ewan R., additional
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- 2021
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36. Profiles of Glucose Metabolism in Different Prediabetes Phenotypes, Classified by Fasting Glycemia, 2-Hour OGTT, Glycated Hemoglobin, and 1-hour OGTT: An IMI DIRECT Study
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Tura, Andrea, primary, Grespan, Eleonora, primary, Göbl, Christian S., primary, Koivula, Robert W., primary, Franks, Paul W., primary, Pearson, Ewan R., primary, Walker, Mark, primary, Forgie, Ian M., primary, Giordano, Giuseppe N., primary, Pavo, Imre, primary, Ruetten, Hartmut, primary, Dermitzakis, Emmanouil T., primary, McCarthy, Mark I., primary, Pedersen, Oluf, primary, Schwenk, Jochen M., primary, Adamski, Jerzy, primary, Masi, Federico De, primary, Tsirigos, Konstantinos D., primary, Brunak, Søren, primary, Viñuela, Ana, primary, Mahajan, Anubha, primary, McDonald, Timothy J., primary, Kokkola, Tarja, primary, Vangipurapu, Jagadish, primary, Cederberg, Henna, primary, Laakso, Markku, primary, Rutters, Femke, primary, Elders, Petra J.M., primary, Koopman, Anitra D.M., primary, Beulens, Joline W., primary, Ridderstråle, Martin, primary, Hansen, Tue H., primary, Allin, Kristine H., primary, Hansen, Torben, primary, Vestergaard, Henrik, primary, Mari, Andrea, primary, and Consortium, IMI DIRECT, primary
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- 2021
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37. Correction to: The role of physical activity in metabolic homeostasis before and after the onset of type 2 diabetes: an IMI DIRECT study (Diabetologia, (2020), 63, 4, (744-756), 10.1007/s00125-019-05083-6)
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Koivula, Robert W., Atabaki-Pasdar, Naeimeh, Giordano, Giuseppe N., White, Tom, Adamski, Jerzy, Bell, Jimmy D., Beulens, Joline, Brage, S. ren, Brunak, S. ren, de Masi, Federico, Dermitzakis, Emmanouil T., Forgie, Ian M., Frost, Gary, Hansen, Torben, Hansen, Tue H., Hattersley, Andrew, Kokkola, Tarja, Kurbasic, Azra, Laakso, Markku, Mari, Andrea, McDonald, Timothy J., Pedersen, Oluf, Rutters, Femke, Schwenk, Jochen M., Teare, Harriet J. A., Thomas, E. Louise, Vinuela, Ana, Mahajan, Anubha, McCarthy, Mark I., Ruetten, Hartmut, Walker, Mark, Pearson, Ewan, Pavo, Imre, Franks, Paul W., Epidemiology and Data Science, ACS - Diabetes & metabolism, APH - Health Behaviors & Chronic Diseases, APH - Aging & Later Life, and ACS - Heart failure & arrhythmias
- Abstract
Unfortunately, ‘Present address’ was omitted from one of the addresses provided for Mark I. McCarthy (#26). The corrected address details are given on the following page.
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- 2021
38. Profiles of glucose metabolism in different prediabetes phenotypes, classified by fasting glycemia, 2-hour OGTT, glycated hemoglobin, and 1-hour OGTT:An IMI DIRECT study
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Tura, Andrea, Grespan, Eleonora, Göbl, Christian S, Koivula, Robert W, Franks, Paul W, Pearson, Ewan R, Walker, Mark, Forgie, Ian M, Giordano, Giuseppe N, Pavo, Imre, Ruetten, Hartmut, Dermitzakis, Emmanouil T, McCarthy, Mark I, Pedersen, Oluf, Schwenk, Jochen M, Adamski, Jerzy, De Masi, Federico, Tsirigos, Konstantinos D, Brunak, Søren, Viñuela, Ana, Mahajan, Anubha, McDonald, Timothy J, Kokkola, Tarja, Vangipurapu, Jagadish, Cederberg, Henna, Laakso, Markku, Rutters, Femke, Elders, Petra J M, Koopman, Anitra D M, Beulens, Joline W, Ridderstråle, Martin, Hansen, Tue H, Allin, Kristine H, Hansen, Torben, Vestergaard, Henrik, Mari, Andrea, Tura, Andrea, Grespan, Eleonora, Göbl, Christian S, Koivula, Robert W, Franks, Paul W, Pearson, Ewan R, Walker, Mark, Forgie, Ian M, Giordano, Giuseppe N, Pavo, Imre, Ruetten, Hartmut, Dermitzakis, Emmanouil T, McCarthy, Mark I, Pedersen, Oluf, Schwenk, Jochen M, Adamski, Jerzy, De Masi, Federico, Tsirigos, Konstantinos D, Brunak, Søren, Viñuela, Ana, Mahajan, Anubha, McDonald, Timothy J, Kokkola, Tarja, Vangipurapu, Jagadish, Cederberg, Henna, Laakso, Markku, Rutters, Femke, Elders, Petra J M, Koopman, Anitra D M, Beulens, Joline W, Ridderstråle, Martin, Hansen, Tue H, Allin, Kristine H, Hansen, Torben, Vestergaard, Henrik, and Mari, Andrea
- Abstract
Differences in glucose metabolism among categories of prediabetes have not been systematically investigated. In this longitudinal study, participants (N=2111) underwent 2h-75g OGTT at baseline and 48 months. HbA1c was also measured. We classified participants as having isolated prediabetes defect (impaired fasting glucose, IFG; impaired glucose tolerance, IGT; HbA1c-prediabetes, IA1c), two defects (IFG+IGT, IFG+IA1c, IGT+IA1c), or all defects (IFG+IGT+IA1c). Beta-cell function (BCF) and insulin sensitivity (IS) were assessed from OGTT. At baseline, when pooling participants with isolated defects, they showed impairment in both BCF and IS compared to healthy controls. Pooled groups with two or three defects showed progressive further deterioration. Among groups with isolated defect, IGT showed lower IS, insulin secretion at reference glucose (ISRr), and insulin secretion potentiation (p<0.002). Conversely, IA1c showed higher IS and ISRr (p<0.0001). Among groups with two defects, we similarly found differences in both BCF and IS. At 48 months, we found higher type 2 diabetes incidence for progressively increasing number of prediabetes defects (odds ratio >2, p<0.008). In conclusion, the prediabetes groups showed differences in type/degree of glucometabolic impairment. Compared to the pooled group with isolated defects, those with double or triple defect showed progressive differences in diabetes incidence.
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- 2021
39. Replication and cross-validation of type 2 diabetes subtypes based on clinical variables:an IMI-RHAPSODY study
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Slieker, Roderick C., Donnelly, Louise A, Fitipaldi, Hugo, Bouland, Gerard A., Giordano, Giuseppe N., Åkerlund, Mikael, Gerl, Mathias J, Ahlqvist, Emma, Ali, Ashfaq, Dragan, Iulian, Festa, Andreas, Hansen, Michael K., Mansour Aly, Dina, Kim, Min, Kuznetsov, Dmitry, Mehl, Florence, Klose, Christian, Simons, Kai, Pavo, Imre, Pullen, Timothy J, Suvitaival, Tommi, Wretlind, Asger, Rossing, Peter, Lyssenko, Valeriya, Legido-Quigley, Cristina, Groop, Leif, Thorens, Bernard, Franks, Paul W., Ibberson, Mark, Rutter, Guy A, Beulens, Joline W J, ‘t Hart, Leen M, Pearson, Ewan R, Slieker, Roderick C., Donnelly, Louise A, Fitipaldi, Hugo, Bouland, Gerard A., Giordano, Giuseppe N., Åkerlund, Mikael, Gerl, Mathias J, Ahlqvist, Emma, Ali, Ashfaq, Dragan, Iulian, Festa, Andreas, Hansen, Michael K., Mansour Aly, Dina, Kim, Min, Kuznetsov, Dmitry, Mehl, Florence, Klose, Christian, Simons, Kai, Pavo, Imre, Pullen, Timothy J, Suvitaival, Tommi, Wretlind, Asger, Rossing, Peter, Lyssenko, Valeriya, Legido-Quigley, Cristina, Groop, Leif, Thorens, Bernard, Franks, Paul W., Ibberson, Mark, Rutter, Guy A, Beulens, Joline W J, ‘t Hart, Leen M, and Pearson, Ewan R
- Abstract
Aims/hypothesis: Five clusters based on clinical characteristics have been suggested as diabetes subtypes: one autoimmune and four subtypes of type 2 diabetes. In the current study we replicate and cross-validate these type 2 diabetes clusters in three large cohorts using variables readily measured in the clinic. Methods: In three independent cohorts, in total 15,940 individuals were clustered based on age, BMI, HbA1c, random or fasting C-peptide, and HDL-cholesterol. Clusters were cross-validated against the original clusters based on HOMA measures. In addition, between cohorts, clusters were cross-validated by re-assigning people based on each cohort’s cluster centres. Finally, we compared the time to insulin requirement for each cluster. Results: Five distinct type 2 diabetes clusters were identified and mapped back to the original four All New Diabetics in Scania (ANDIS) clusters. Using C-peptide and HDL-cholesterol instead of HOMA2-B and HOMA2-IR, three of the clusters mapped with high sensitivity (80.6–90.7%) to the previously identified severe insulin-deficient diabetes (SIDD), severe insulin-resistant diabetes (SIRD) and mild obesity-related diabetes (MOD) clusters. The previously described ANDIS mild age-related diabetes (MARD) cluster could be mapped to the two milder groups in our study: one characterised by high HDL-cholesterol (mild diabetes with high HDL-cholesterol [MDH] cluster), and the other not having any extreme characteristic (mild diabetes [MD]). When these two milder groups were combined, they mapped well to the previously labelled MARD cluster (sensitivity 79.1%). In the cross-validation between cohorts, particularly the SIDD and MDH clusters cross-validated well, with sensitivities ranging from 73.3% to 97.1%. SIRD and MD showed a lower sensitivity, ranging from 36.1% to 92.3%, where individuals shifted from SIRD to MD and vice versa. People belonging to the SIDD cluster showed the fastest progression towards insulin requiremen
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- 2021
40. Distinct Molecular Signatures of Clinical Clusters in People With Type 2 Diabetes:An IMI-RHAPSODY Study
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Slieker, Roderick C., Donnelly, Louise A., Fitipaldi, Hugo, Bouland, Gerard A., Giordano, Giuseppe N., Åkerlund, Mikael, Gerl, Mathias J., Ahlqvist, Emma, Ali, Ashfaq, Dragan, Iulian, Elders, Petra, Festa, Andreas, Hansen, Michael K., van der Heijden, Amber A., Mansour Aly, Dina, Kim, Min, Kuznetsov, Dmitry, Mehl, Florence, Klose, Christian, Simons, Kai, Pavo, Imre, Pullen, Timothy J., Suvitaival, Tommi, Wretlind, Asger, Rossing, Peter, Lyssenko, Valeriya, Legido Quigley, Cristina, Groop, Leif, Thorens, Bernard, Franks, Paul W., Ibberson, Mark, Rutter, Guy A., Beulens, Joline W.J., 't Hart, Leen M., Pearson, Ewan R., Slieker, Roderick C., Donnelly, Louise A., Fitipaldi, Hugo, Bouland, Gerard A., Giordano, Giuseppe N., Åkerlund, Mikael, Gerl, Mathias J., Ahlqvist, Emma, Ali, Ashfaq, Dragan, Iulian, Elders, Petra, Festa, Andreas, Hansen, Michael K., van der Heijden, Amber A., Mansour Aly, Dina, Kim, Min, Kuznetsov, Dmitry, Mehl, Florence, Klose, Christian, Simons, Kai, Pavo, Imre, Pullen, Timothy J., Suvitaival, Tommi, Wretlind, Asger, Rossing, Peter, Lyssenko, Valeriya, Legido Quigley, Cristina, Groop, Leif, Thorens, Bernard, Franks, Paul W., Ibberson, Mark, Rutter, Guy A., Beulens, Joline W.J., 't Hart, Leen M., and Pearson, Ewan R.
- Abstract
Type 2 diabetes is a multifactorial disease with multiple underlying aetiologies. To address this heterogeneity, investigators of a previous study clustered people with diabetes according to five diabetes subtypes. The aim of the current study is to investigate the etiology of these clusters by comparing their molecular signatures. In three independent cohorts, in total 15,940 individuals were clustered based on five clinical characteristics. In a subset, genetic (N = 12,828), metabolomic (N = 2,945), lipidomic (N = 2,593), and proteomic (N = 1,170) data were obtained in plasma. For each data type, each cluster was compared with the other four clusters as the reference. The insulin-resistant cluster showed the most distinct molecular signature, with higher branched-chain amino acid, diacylglycerol, and triacylglycerol levels and aberrant protein levels in plasma were enriched for proteins in the intracellular PI3K/Akt pathway. The obese cluster showed higher levels of cytokines. The mild diabetes cluster with high HDL showed the most beneficial molecular profile with effects opposite of those seen in the insulin-resistant cluster. This study shows that clustering people with type 2 diabetes can identify underlying molecular mechanisms related to pancreatic islets, liver, and adipose tissue metabolism. This provides novel biological insights into the diverse aetiological processes that would not be evident when type 2 diabetes is viewed as a homogeneous disease.
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- 2021
41. Processes Underlying Glycemic Deterioration in Type 2 Diabetes:An IMI DIRECT Study
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Bizzotto, Roberto, Jennison, Christopher, Jones, Angus G., Kurbasic, Azra, Tura, Andrea, Kennedy, Gwen, Bell, Jimmy D., Thomas, E. Louise, Frost, Gary, Eriksen, Rebeca, Koivula, Robert W., Brage, Soren, Kaye, Jane, Hattersley, Andrew T., Heggie, Alison, McEvoy, Donna, 't Hart, Leen M., Beulens, Joline W., Elders, Petra, Musholt, Petra B., Ridderstrale, Martin, Hansen, Tue H., Allin, Kristine H., Hansen, Torben, Vestergaard, Henrik, Lundgaard, Agnete T., Thomsen, Henrik S., De Masi, Federico, Tsirigos, Konstantinos D., Brunak, Søren, Vinuela, Ana, Mahajan, Anubha, McDonald, Timothy J., Kokkola, Tarja, Forgie, Ian M., Giordano, Giuseppe N., Pavo, Imre, Ruetten, Hartmut, Dermitzakis, Emmanouil, McCarthy, Mark I., Pedersen, Oluf, Schwenk, Jochen M., Adamski, Jerzy, Franks, Paul W., Walker, Mark, Pearson, Ewan R., Mari, Andrea, Bizzotto, Roberto, Jennison, Christopher, Jones, Angus G., Kurbasic, Azra, Tura, Andrea, Kennedy, Gwen, Bell, Jimmy D., Thomas, E. Louise, Frost, Gary, Eriksen, Rebeca, Koivula, Robert W., Brage, Soren, Kaye, Jane, Hattersley, Andrew T., Heggie, Alison, McEvoy, Donna, 't Hart, Leen M., Beulens, Joline W., Elders, Petra, Musholt, Petra B., Ridderstrale, Martin, Hansen, Tue H., Allin, Kristine H., Hansen, Torben, Vestergaard, Henrik, Lundgaard, Agnete T., Thomsen, Henrik S., De Masi, Federico, Tsirigos, Konstantinos D., Brunak, Søren, Vinuela, Ana, Mahajan, Anubha, McDonald, Timothy J., Kokkola, Tarja, Forgie, Ian M., Giordano, Giuseppe N., Pavo, Imre, Ruetten, Hartmut, Dermitzakis, Emmanouil, McCarthy, Mark I., Pedersen, Oluf, Schwenk, Jochen M., Adamski, Jerzy, Franks, Paul W., Walker, Mark, Pearson, Ewan R., and Mari, Andrea
- Abstract
OBJECTIVEWe investigated the processes underlying glycemic deterioration in type 2 diabetes (T2D).RESEARCH DESIGN AND METHODSA total of 732 recently diagnosed patients with T2D from the Innovative Medicines Initiative Diabetes Research on Patient Stratification (IMI DIRECT) study were extensively phenotyped over 3 years, including measures of insulin sensitivity (OGIS), beta-cell glucose sensitivity (GS), and insulin clearance (CLIm) from mixed meal tests, liver enzymes, lipid profiles, and baseline regional fat from MRI. The associations between the longitudinal metabolic patterns and HbA(1c) deterioration, adjusted for changes in BMI and in diabetes medications, were assessed via stepwise multivariable linear and logistic regression.RESULTSFaster HbA(1c) progression was independently associated with faster deterioration of OGIS and GS and increasing CLIm; visceral or liver fat, HDL-cholesterol, and triglycerides had further independent, though weaker, roles (R-2 = 0.38). A subgroup of patients with a markedly higher progression rate (fast progressors) was clearly distinguishable considering these variables only (discrimination capacity from area under the receiver operating characteristic = 0.94). The proportion of fast progressors was reduced from 56% to 8-10% in subgroups in which only one trait among OGIS, GS, and CLIm was relatively stable (odds ratios 0.07-0.09). T2D polygenic risk score and baseline pancreatic fat, glucagon-like peptide 1, glucagon, diet, and physical activity did not show an independent role.CONCLUSIONSDeteriorating insulin sensitivity and beta-cell function, increasing insulin clearance, high visceral or liver fat, and worsening of the lipid profile are the crucial factors mediating glycemic deterioration of patients with T2D in the initial phase of the disease. Stabilization of a single trait among insulin sensitivity, beta-cell function, and insulin clearance may be relevant to prevent
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- 2021
42. Unexpected adverse childhood experiences and subsequent drug use disorder: a Swedish population study (1995–2011)
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Giordano, Giuseppe N., Ohlsson, Henrik, Kendler, Kenneth S., Sundquist, Kristina, and Sundquist, Jan
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- 2014
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43. Novel biomarkers for glycaemic deterioration in type 2 diabetes: an IMI RHAPSODY study
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Slieker, Roderick C, primary, Donnelly, Louise A, additional, Lopez-Noriega, Livia, additional, Muniangi-Muhitu, Hermine, additional, Akalestou, Elina, additional, Sheikh, Mahsa, additional, Georgiadou, Eleni, additional, Giordano, Giuseppe N., additional, Åkerlund, Mikael, additional, Ahlqvist, Emma, additional, Ali, Ashfaq, additional, Barovic, Marko, additional, Bouland, Gerard A, additional, Burdet, Frédéric, additional, Canouil, Mickaël, additional, Dragan, Iulian, additional, Elders, Petra JM, additional, Fernandez, Celine, additional, Festa, Andreas, additional, Fitipaldi, Hugo, additional, Froguel, Phillippe, additional, Gudmundsdottir, Valborg, additional, Gudnason, Vilmundur, additional, Gerl, Mathias J., additional, van der Heijden, Amber A, additional, Jennings, Lori L, additional, Hansen, Michael K., additional, Kim, Min, additional, Leclerc, Isabelle, additional, Klose, Christian, additional, Kuznetsov, Dmitry, additional, Aly, Dina Mansour, additional, Mehl, Florence, additional, Marek, Diana, additional, Melander, Olle, additional, Niknejad, Anne, additional, Ottosson, Filip, additional, Pavo, Imre, additional, Efanov, Alexander, additional, Duffin, Kevin, additional, Pullen, Timothy J., additional, Simons, Kai, additional, Solimena, Michele, additional, Suvitaival, Tommi, additional, Wretlind, Asger, additional, Rossing, Peter, additional, Lyssenko, Valeriya, additional, Quigley, Cristina Legido, additional, Groop, Leif, additional, Thorens, Bernard, additional, Franks, Paul W, additional, Ibberson, Mark, additional, Beulens, Joline WJ, additional, ’t Hart, Leen M, additional, Pearson, Ewan R, additional, and Rutter, Guy A, additional
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- 2021
- Full Text
- View/download PDF
44. The role of physical activity in metabolic homeostasis before and after the onset of type 2 diabetes: an IMI DIRECT study
- Author
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Koivula, Robert W, Atabaki-Pasdar, Naeimeh, Giordano, Giuseppe N, White, Tom, Adamski, Jerzy, Bell, Jimmy D, Beulens, Joline, Brage, Søren, Brunak, Søren, De Masi, Federico, Dermitzakis, Emmanouil T, Forgie, Ian M, Frost, Gary, Hansen, Torben, Hansen, Tue H, Hattersley, Andrew, Kokkola, Tarja, Kurbasic, Azra, Laakso, Markku, Mari, Andrea, McDonald, Timothy J, Pedersen, Oluf, Rutters, Femke, Schwenk, Jochen M, Teare, Harriet JA, Thomas, E Louise, Vinuela, Ana, Mahajan, Anubha, McCarthy, Mark I, Ruetten, Hartmut, Walker, Mark, Pearson, Ewan, Pavo, Imre, Franks, Paul W, IMI DIRECT Consortium, Koivula, Robert W [0000-0002-1646-4163], and Apollo - University of Cambridge Repository
- Subjects
Blood Glucose ,Male ,Denmark ,Glycemic Control ,Ectopic fat ,Cohort Studies ,Glycaemic control ,Homeostasis ,Humans ,Exercise ,Finland ,Aged ,Netherlands ,Sweden ,Physical activity ,Beta cell function ,Type 2 diabetes ,Glucose Tolerance Test ,Middle Aged ,Insulin sensitivity ,Cross-Sectional Studies ,Diabetes Mellitus, Type 2 ,Structural equation modelling ,Female ,Insulin Resistance ,Energy Metabolism ,Prediabetes - Abstract
AIMS/HYPOTHESIS: It is well established that physical activity, abdominal ectopic fat and glycaemic regulation are related but the underlying structure of these relationships is unclear. The previously proposed twin-cycle hypothesis (TC) provides a mechanistic basis for impairment in glycaemic control through the interactions of substrate availability, substrate metabolism and abdominal ectopic fat accumulation. Here, we hypothesise that the effect of physical activity in glucose regulation is mediated by the twin-cycle. We aimed to examine this notion in the Innovative Medicines Initiative Diabetes Research on Patient Stratification (IMI DIRECT) Consortium cohorts comprised of participants with normal or impaired glucose regulation (cohort 1: N ≤ 920) or with recently diagnosed type 2 diabetes (cohort 2: N ≤ 435). METHODS: We defined a structural equation model that describes the TC and fitted this within the IMI DIRECT dataset. A second model, twin-cycle plus physical activity (TC-PA), to assess the extent to which the effects of physical activity in glycaemic regulation are mediated by components in the twin-cycle, was also fitted. Beta cell function, insulin sensitivity and glycaemic control were modelled from frequently sampled 75 g OGTTs (fsOGTTs) and mixed-meal tolerance tests (MMTTs) in participants without and with diabetes, respectively. Abdominal fat distribution was assessed using MRI, and physical activity through wrist-worn triaxial accelerometry. Results are presented as standardised beta coefficients, SE and p values, respectively. RESULTS: The TC and TC-PA models showed better fit than null models (TC: χ2 = 242, p = 0.004 and χ2 = 63, p = 0.001 in cohort 1 and 2, respectively; TC-PA: χ2 = 180, p = 0.041 and χ2 = 60, p = 0.008 in cohort 1 and 2, respectively). The association of physical activity with glycaemic control was primarily mediated by variables in the liver fat cycle. CONCLUSIONS/INTERPRETATION: These analyses partially support the mechanisms proposed in the twin-cycle model and highlight mechanistic pathways through which insulin sensitivity and liver fat mediate the association between physical activity and glycaemic control.
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- 2020
45. Additional file 1 of Whole blood co-expression modules associate with metabolic traits and type 2 diabetes: an IMI-DIRECT study
- Author
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Gudmundsdottir, Valborg, Pedersen, Helle Krogh, Mazzoni, Gianluca, Allin, Kristine H., Artati, Anna, Beulens, Joline W., Banasik, Karina, Brorsson, Caroline, Cederberg, Henna, Chabanova, Elizaveta, Masi, Federico De, Elders, Petra J., Forgie, Ian, Giordano, Giuseppe N., Grallert, Harald, Ramneek Gupta, Haid, Mark, Hansen, Torben, Hansen, Tue H., Hattersley, Andrew T., Heggie, Alison, Mun-Gwan Hong, Jones, Angus G., Koivula, Robert, Kokkola, Tarja, Laakso, Markku, Løngreen, Peter, Anubha Mahajan, Mari, Andrea, McDonald, Timothy J., McEvoy, Donna, Musholt, Petra B., Pavo, Imre, Prehn, Cornelia, Ruetten, Hartmut, Ridderstråle, Martin, Rutters, Femke, Sharma, Sapna, Slieker, Roderick C., Syed, Ali, Tajes, Juan Fernandez, Thomas, Cecilia Engel, Thomsen, Henrik S., Jagadish Vangipurapu, Vestergaard, Henrik, Viñuela, Ana, Wesolowska-Andersen, Agata, Walker, Mark, Adamski, Jerzy, Schwenk, Jochen M., McCarthy, Mark I., Pearson, Ewan, Dermitzakis, Emmanouil, Franks, Paul W., Pedersen, Oluf, and Brunak, Søren
- Abstract
Additional file 1. Supplementary Figures. This file contains Fig. S1 – S13.
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- 2020
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46. Predicting and elucidating the etiology of fatty liver disease:A machine learning modeling and validation study in the IMI DIRECT cohorts
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Atabaki-Pasdar, Naeimeh, Ohlsson, Mattias, Viñuela, Ana, Frau, Francesca, Pomares-Millan, Hugo, Haid, Mark, Jones, Angus G, Thomas, E Louise, Koivula, Robert W, Kurbasic, Azra, Mutie, Pascal M, Fitipaldi, Hugo, Fernandez, Juan, Dawed, Adem Y, Giordano, Giuseppe N, Forgie, Ian M, McDonald, Timothy J, Rutters, Femke, Cederberg, Henna, Chabanova, Elizaveta, Dale, Matilda, Masi, Federico De, Thomas, Cecilia Engel, Allin, Kristine H., Hansen, Tue H, Heggie, Alison, Hong, Mun-Gwan, Elders, Petra J M, Kennedy, Gwen, Kokkola, Tarja, Pedersen, Helle Krogh, Mahajan, Anubha, McEvoy, Donna, Pattou, Francois, Raverdy, Violeta, Häussler, Ragna S, Sharma, Sapna, Thomsen, Henrik S, Vangipurapu, Jagadish, Vestergaard, Henrik, Adamski, Jerzy, Musholt, Petra B, Brage, Søren, Brunak, Søren, Dermitzakis, Emmanouil, Frost, Gary, Hansen, Torben, Laakso, Markku, and Pedersen, Oluf
- Abstract
BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is highly prevalent and causes serious health complications in individuals with and without type 2 diabetes (T2D). Early diagnosis of NAFLD is important, as this can help prevent irreversible damage to the liver and, ultimately, hepatocellular carcinomas. We sought to expand etiological understanding and develop a diagnostic tool for NAFLD using machine learning.METHODS AND FINDINGS: We utilized the baseline data from IMI DIRECT, a multicenter prospective cohort study of 3,029 European-ancestry adults recently diagnosed with T2D (n = 795) or at high risk of developing the disease (n = 2,234). Multi-omics (genetic, transcriptomic, proteomic, and metabolomic) and clinical (liver enzymes and other serological biomarkers, anthropometry, measures of beta-cell function, insulin sensitivity, and lifestyle) data comprised the key input variables. The models were trained on MRI-image-derived liver fat content (CONCLUSIONS: In this study, we developed several models with different combinations of clinical and omics data and identified biological features that appear to be associated with liver fat accumulation. In general, the clinical variables showed better prediction ability than the complex omics variables. However, the combination of omics and clinical variables yielded the highest accuracy. We have incorporated the developed clinical models into a web interface (see: https://www.predictliverfat.org/) and made it available to the community.TRIAL REGISTRATION: ClinicalTrials.gov NCT03814915.
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- 2020
47. Additional file 2 of Whole blood co-expression modules associate with metabolic traits and type 2 diabetes: an IMI-DIRECT study
- Author
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Gudmundsdottir, Valborg, Pedersen, Helle Krogh, Mazzoni, Gianluca, Allin, Kristine H., Artati, Anna, Beulens, Joline W., Banasik, Karina, Brorsson, Caroline, Cederberg, Henna, Chabanova, Elizaveta, Masi, Federico De, Elders, Petra J., Forgie, Ian, Giordano, Giuseppe N., Grallert, Harald, Ramneek Gupta, Haid, Mark, Hansen, Torben, Hansen, Tue H., Hattersley, Andrew T., Heggie, Alison, Mun-Gwan Hong, Jones, Angus G., Koivula, Robert, Kokkola, Tarja, Laakso, Markku, Løngreen, Peter, Anubha Mahajan, Mari, Andrea, McDonald, Timothy J., McEvoy, Donna, Musholt, Petra B., Pavo, Imre, Prehn, Cornelia, Ruetten, Hartmut, Ridderstråle, Martin, Rutters, Femke, Sharma, Sapna, Slieker, Roderick C., Syed, Ali, Tajes, Juan Fernandez, Thomas, Cecilia Engel, Thomsen, Henrik S., Jagadish Vangipurapu, Vestergaard, Henrik, Viñuela, Ana, Wesolowska-Andersen, Agata, Walker, Mark, Adamski, Jerzy, Schwenk, Jochen M., McCarthy, Mark I., Pearson, Ewan, Dermitzakis, Emmanouil, Franks, Paul W., Pedersen, Oluf, and Brunak, Søren
- Subjects
Data_FILES - Abstract
Additional file 2. Supplementary Methods. This file contains methods descriptions for omics data generation and preprocessing.
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- 2020
- Full Text
- View/download PDF
48. Dietary metabolite profiling brings new insight into the relationship between nutrition and metabolic risk:An IMI DIRECT study
- Author
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Eriksen, Rebeca, Perez, Isabel Garcia, Posma, Joram M, Haid, Mark, Sharma, Sapna, Prehn, Cornelia, Thomas, Louise E, Koivula, Robert W, Bizzotto, Roberto, Mari, Andrea, Giordano, Giuseppe N, Pavo, Imre, Schwenk, Jochen M, De Masi, Federico, Tsirigos, Konstantinos D, Brunak, Søren, Viñuela, Ana, Mahajan, Anubha, McDonald, Timothy J, Kokkola, Tarja, Rutter, Femke, Teare, Harriet, Hansen, Tue H, Fernandez, Juan, Jones, Angus, Jennison, Chris, Walker, Mark, McCarthy, Mark I, Pedersen, Oluf, Ruetten, Hartmut, Forgie, Ian, Bell, Jimmy D, Pearson, Ewan R, Franks, Paul W, Adamski, Jerzy, Holmes, Elaine, Frost, Gary, Eriksen, Rebeca, Perez, Isabel Garcia, Posma, Joram M, Haid, Mark, Sharma, Sapna, Prehn, Cornelia, Thomas, Louise E, Koivula, Robert W, Bizzotto, Roberto, Mari, Andrea, Giordano, Giuseppe N, Pavo, Imre, Schwenk, Jochen M, De Masi, Federico, Tsirigos, Konstantinos D, Brunak, Søren, Viñuela, Ana, Mahajan, Anubha, McDonald, Timothy J, Kokkola, Tarja, Rutter, Femke, Teare, Harriet, Hansen, Tue H, Fernandez, Juan, Jones, Angus, Jennison, Chris, Walker, Mark, McCarthy, Mark I, Pedersen, Oluf, Ruetten, Hartmut, Forgie, Ian, Bell, Jimmy D, Pearson, Ewan R, Franks, Paul W, Adamski, Jerzy, Holmes, Elaine, and Frost, Gary
- Abstract
BACKGROUND: Dietary advice remains the cornerstone of prevention and management of type 2 diabetes (T2D). However, understanding the efficacy of dietary interventions is confounded by the challenges inherent in assessing free living diet. Here we profiled dietary metabolites to investigate glycaemic deterioration and cardiometabolic risk in people at risk of or living with T2D.METHODS: We analysed data from plasma collected at baseline and 18-month follow-up in individuals from the Innovative Medicines Initiative (IMI) Diabetes Research on Patient Stratification (DIRECT) cohort 1 n = 403 individuals with normal or impaired glucose regulation (prediabetic) and cohort 2 n = 458 individuals with new onset of T2D. A dietary metabolite profile model (Tpred) was constructed using multivariable regression of 113 plasma metabolites obtained from targeted metabolomics assays. The continuous Tpred score was used to explore the relationships between diet, glycaemic deterioration and cardio-metabolic risk via multiple linear regression models.FINDINGS: A higher Tpred score was associated with healthier diets high in wholegrain (β=3.36 g, 95% CI 0.31, 6.40 and β=2.82 g, 95% CI 0.06, 5.57) and lower energy intake (β=-75.53 kcal, 95% CI -144.71, -2.35 and β=-122.51 kcal, 95% CI -186.56, -38.46), and saturated fat (β=-0.92 g, 95% CI -1.56, -0.28 and β=-0.98 g, 95% CI -1.53, -0.42 g), respectively for cohort 1 and 2. In both cohorts a higher Tpred score was also associated with lower total body adiposity and favourable lipid profiles HDL-cholesterol (β=0.07 mmol/L, 95% CI 0.03, 0.1), (β=0.08 mmol/L, 95% CI 0.04, 0.1), and triglycerides (β=-0.1 mmol/L, 95% CI -0.2, -0.03), (β=-0.2 mmol/L, 95% CI -0.3, -0.09), respectively for cohort 1 and 2. In cohort 2, the Tpred score was negatively associated with liver fat (β=-0.74%, 95% CI -0.67, -0.81), and lower fasting concentrations of HbA1c (β=-0.9 mmol/mol, 95% CI -1.5, -0.1), glucose (β=-0.2 mmol/L, 95% CI -0.4, -0.05) an
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- 2020
49. The role of physical activity in metabolic homeostasis before and after the onset of type 2 diabetes:an IMI DIRECT study
- Author
-
Koivula, Robert W, Atabaki-Pasdar, Naeimeh, Giordano, Giuseppe N, White, Tom, Adamski, Jerzy, Bell, Jimmy D, Beulens, Joline, Brage, Søren, Brunak, Søren, De Masi, Federico, Dermitzakis, Emmanouil T, Forgie, Ian M, Frost, Gary, Hansen, Torben, Hansen, Tue H, Hattersley, Andrew, Kokkola, Tarja, Kurbasic, Azra, Laakso, Markku, Mari, Andrea, McDonald, Timothy J, Pedersen, Oluf, Rutters, Femke, Schwenk, Jochen M, Teare, Harriet J A, Thomas, E Louise, Vinuela, Ana, Mahajan, Anubha, McCarthy, Mark I, Ruetten, Hartmut, Walker, Mark, Pearson, Ewan, Pavo, Imre, Franks, Paul W, Koivula, Robert W, Atabaki-Pasdar, Naeimeh, Giordano, Giuseppe N, White, Tom, Adamski, Jerzy, Bell, Jimmy D, Beulens, Joline, Brage, Søren, Brunak, Søren, De Masi, Federico, Dermitzakis, Emmanouil T, Forgie, Ian M, Frost, Gary, Hansen, Torben, Hansen, Tue H, Hattersley, Andrew, Kokkola, Tarja, Kurbasic, Azra, Laakso, Markku, Mari, Andrea, McDonald, Timothy J, Pedersen, Oluf, Rutters, Femke, Schwenk, Jochen M, Teare, Harriet J A, Thomas, E Louise, Vinuela, Ana, Mahajan, Anubha, McCarthy, Mark I, Ruetten, Hartmut, Walker, Mark, Pearson, Ewan, Pavo, Imre, and Franks, Paul W
- Abstract
AIMS/HYPOTHESIS: It is well established that physical activity, abdominal ectopic fat and glycaemic regulation are related but the underlying structure of these relationships is unclear. The previously proposed twin-cycle hypothesis (TC) provides a mechanistic basis for impairment in glycaemic control through the interactions of substrate availability, substrate metabolism and abdominal ectopic fat accumulation. Here, we hypothesise that the effect of physical activity in glucose regulation is mediated by the twin-cycle. We aimed to examine this notion in the Innovative Medicines Initiative Diabetes Research on Patient Stratification (IMI DIRECT) Consortium cohorts comprised of participants with normal or impaired glucose regulation (cohort 1: N ≤ 920) or with recently diagnosed type 2 diabetes (cohort 2: N ≤ 435).METHODS: We defined a structural equation model that describes the TC and fitted this within the IMI DIRECT dataset. A second model, twin-cycle plus physical activity (TC-PA), to assess the extent to which the effects of physical activity in glycaemic regulation are mediated by components in the twin-cycle, was also fitted. Beta cell function, insulin sensitivity and glycaemic control were modelled from frequently sampled 75 g OGTTs (fsOGTTs) and mixed-meal tolerance tests (MMTTs) in participants without and with diabetes, respectively. Abdominal fat distribution was assessed using MRI, and physical activity through wrist-worn triaxial accelerometry. Results are presented as standardised beta coefficients, SE and p values, respectively.RESULTS: The TC and TC-PA models showed better fit than null models (TC: χ2 = 242, p = 0.004 and χ2 = 63, p = 0.001 in cohort 1 and 2, respectively; TC-PA: χ2 = 180, p = 0.041 and χ2 = 60, p = 0.008 in cohort 1 and 2, respectively). The association of physical activity with glycaemic control was primarily mediated by variables in the liver fat cycle.CONCLUSIONS/INTERPRETATION: These analyses partially
- Published
- 2020
50. The role of physical activity in metabolic homeostasis before and after the onset of type 2 diabetes: an IMI DIRECT study
- Author
-
Koivula, Robert W., Atabaki-Pasdar, Naeimeh, Giordano, Giuseppe N., White, Tom, Adamski, Jerzy, Bell, Jimmy D., Beulens, Joline, Brage, Søren, Brunak, Søren, De Masi, Federico, Dermitzakis, Emmanouil T., Forgie, Ian M., Frost, Gary, Hansen, Torben, Hansen, Tue H., Hattersley, Andrew, Kokkola, Tarja, Kurbasic, Azra, Laakso, Markku, Mari, Andrea, McDonald, Timothy J., Pedersen, Oluf, Rutters, Femke, Schwenk, Jochen M., Teare, Harriet J.A., Thomas, E. Louise, Vinuela, Ana, Mahajan, Anubha, McCarthy, Mark I., Ruetten, Hartmut, Walker, Mark, Pearson, Ewan, Pavo, Imre, Franks, Paul W., Koivula, Robert W., Atabaki-Pasdar, Naeimeh, Giordano, Giuseppe N., White, Tom, Adamski, Jerzy, Bell, Jimmy D., Beulens, Joline, Brage, Søren, Brunak, Søren, De Masi, Federico, Dermitzakis, Emmanouil T., Forgie, Ian M., Frost, Gary, Hansen, Torben, Hansen, Tue H., Hattersley, Andrew, Kokkola, Tarja, Kurbasic, Azra, Laakso, Markku, Mari, Andrea, McDonald, Timothy J., Pedersen, Oluf, Rutters, Femke, Schwenk, Jochen M., Teare, Harriet J.A., Thomas, E. Louise, Vinuela, Ana, Mahajan, Anubha, McCarthy, Mark I., Ruetten, Hartmut, Walker, Mark, Pearson, Ewan, Pavo, Imre, and Franks, Paul W.
- Abstract
Aims/hypothesis: It is well established that physical activity, abdominal ectopic fat and glycaemic regulation are related but the underlying structure of these relationships is unclear. The previously proposed twin-cycle hypothesis (TC) provides a mechanistic basis for impairment in glycaemic control through the interactions of substrate availability, substrate metabolism and abdominal ectopic fat accumulation. Here, we hypothesise that the effect of physical activity in glucose regulation is mediated by the twin-cycle. We aimed to examine this notion in the Innovative Medicines Initiative Diabetes Research on Patient Stratification (IMI DIRECT) Consortium cohorts comprised of participants with normal or impaired glucose regulation (cohort 1: N ≤ 920) or with recently diagnosed type 2 diabetes (cohort 2: N ≤ 435). Methods: We defined a structural equation model that describes the TC and fitted this within the IMI DIRECT dataset. A second model, twin-cycle plus physical activity (TC-PA), to assess the extent to which the effects of physical activity in glycaemic regulation are mediated by components in the twin-cycle, was also fitted. Beta cell function, insulin sensitivity and glycaemic control were modelled from frequently sampled 75 g OGTTs (fsOGTTs) and mixed-meal tolerance tests (MMTTs) in participants without and with diabetes, respectively. Abdominal fat distribution was assessed using MRI, and physical activity through wrist-worn triaxial accelerometry. Results are presented as standardised beta coefficients, SE and p values, respectively. Results: The TC and TC-PA models showed better fit than null models (TC: χ2 = 242, p = 0.004 and χ2 = 63, p = 0.001 in cohort 1 and 2, respectively; TC-PA: χ2 = 180, p = 0.041 and χ2 = 60, p = 0.008 in cohort 1 and 2, respectively). The association of physical activity with glycaemic control was primarily mediated by variables in the liver fat cycle. Conclusions/interpretation: These analyses partially suppo
- Published
- 2020
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