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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

2021; American Diabetes Association; Volume: 70; Issue: 9 Linguagem: Inglês

10.2337/db21-0227

1939-327X

Andrea Tura, Eleonora Grespan, Christian Göbl, Robert W. Koivula, Paul W. Franks, Ewan R. Pearson, Mark Walker, Ian Forgie, Giuseppe N. Giordano, Imre Pávó, Hartmut Ruetten, Emmanouil T. Dermitzakis, Mark I. McCarthy, Oluf Pedersen, Jochen M. Schwenk, Jerzy Adamski, Federico De Masi, Konstantinos D. Tsirigos, Søren Brunak, Ana Viñuela, Anubha Mahajan, Timothy J. McDonald, Tarja Kokkola, Jagadish Vangipurapu, Henna Cederberg, Markku Laakso, Femke Rutters, Petra J. M. Elders, Anitra D.M. Koopman, Joline W. J. Beulens, Martin Ridderstråle, Tue H. Hansen, Kristine H. Allin, Torben Hansen, Henrik Vestergaard, Andrea Mari, Leen M. ‘t Hart, Moustafa Abdalla, Jonathan Adam, Jerzy Adamski, Kofi P. Adragni, Rosa Lundbye Allesøe, Kristine H. Allin, Manimozhiyan Arumugam, Naeimeh Atabaki Pasdar, Tania Baltauss, Karina Banasik, Patrick Baum, Jimmy D. Bell, Margit Bergstrom, Joline W. J. Beulens, Susaana Bianzano, Roberto Bizzotto, Amelie Bonneford, Caroline Brorsson, Andrew Brown, Søren Brunak, Louise Cabrelli, Robert Caïazzo, Mickaël Canouil, Henna Cederberg, Matilda Dale, David Davtian, Adem Y. Dawed, Federico De Masi, Nathalie de Préville, Koen F. Dekkers, Emmanouil T. Dermitzakis, Harshal Deshmukh, Christiane Dings, Louise A. Donnelly, Avirup Dutta, Beate Ehrhardt, Petra J. M. Elders, Line Engelbrechtsen, Rebeca Eriksen, Yong Fan, Juan Fernandez, Jorge Ferrer, Hugo Fitipaldi, Ian M. Forgie, Annemette Forman, Paul W. Franks, Francesca Frau, Andreas Fritsche, Philippe Froguel, Gary Frost, Johann Gassenhuber, Giuseppe N. Giordano, Toni Giorgino, Stephen Gough, Ulrike Graefe‐Mody, Harald Grallert, Rolf Grempler, Lenka Groeneveld, Leif Groop, Valborg Guðmundsdóttir, Ramneek Gupta, Mark Haid, Torben Hansen, Tue H. Hansen, Andrew T. Hattersley, Ragna S. Häussler, Alison Heggie, Anita M. Hennige, Anita Hill, Reinhard W. Holl, Mun‐Gwan Hong, Michelle Hudson, Bernd Jablonka, Christopher Jennison, Yunlong Jiao, Joachim Johansen, Angus G. Jones, Anna Jonsson, Tugce Karaderi, Jane Kaye, Maria Klintenberg, Robert W. Koivula, Tarja Kokkola, Anitra D.M. Koopman, Azra Kurbasic, Teemu Kuulasmaa, Markku Laakso, Thorsten Lehr, Heather Loftus, Agnete Troen Lundgaard, Anubha Mahajan, Andrea Mari, Gianluca Mazzoni, Mark I. McCarthy, Timothy J. McDonald, Donna McEvoy, Nicky McRobert, Ian McVittie, Miranda Mourby, Petra Musholt, Pascal M. Mutie, Rachel Nice, Claudia Nicolay, Agnes Martine Nielsen, Birgitte Nilsson, Giel Nijpels, Nicholette D. Palmer, François Pattou, Imre Pávó, Ewan R. Pearson, Oluf Pedersen, Helle K. Pedersen, Mandy H. Perry, Hugo Pomares‐Millan, Anna Ramisch, Simon Rasmussen, Violeta Raverdi, Martin Ridderstråle, Neil Robertson, Slieker Roderick, Marianne Rodriquez, Hartmut Ruetten, Femke Rutters, Peter Wad Sackett, Nina Scherer, Jochen M. Schwenk, Nisha Shah, Sapna Sharma, Iryna Sihinevich, Nadja B. Søndertoft, Hans‐Henrik Stærfeldt, Birgit Steckel-Hamann, Harriet Teare, Cecilia Engel Thomas, Melissa K. Thomas, E. Louise Thomas, Henrik S. Thomsen, Barbara Thorand, Claire E. Thorne, J. Tillner, Martina Troll, Konstantinos D. Tsirigos, Andrea Tura, Mathias Uhlén, Jagadish Vangipurapu, Nienke van Leeuwen, Sabine van Oort, Hélène Verkindt, Henrik Vestergaard, Ana Viñuela, Josef Korbinian Vogt, Peter Wad Sackett, Dianne Wake, Mark Walker, Agata Wesolowska‐Andersen, Brandon Whitcher, Margaret W. White, Han Wu,

Diabetes, Cardiovascular Risks, and Lipoproteins

Differences in glucose metabolism among categories of prediabetes have not been systematically investigated. In this longitudinal study, participants (N = 2,111) underwent a 2-h 75-g oral glucose tolerance test (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], or HbA1c indicative of prediabetes [IA1c]), two defects (IFG+IGT, IFG+IA1c, or IGT+IA1c), or all defects (IFG+IGT+IA1c). β-Cell function (BCF) and insulin sensitivity were assessed from OGTT. At baseline, in pooling of participants with isolated defects, they showed impairment in both BCF and insulin sensitivity compared with healthy control subjects. Pooled groups with two or three defects showed progressive further deterioration. Among groups with isolated defect, those with IGT showed lower insulin sensitivity, insulin secretion at reference glucose (ISRr), and insulin secretion potentiation (P < 0.002). Conversely, those with IA1c showed higher insulin sensitivity and ISRr (P < 0.0001). Among groups with two defects, we similarly found differences in both BCF and insulin sensitivity. 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 with the pooled group with isolated defects, those with double or triple defect showed progressive differences in diabetes incidence.