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
Authors: 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 ,   IMI DIRECT Consortium, 't Hart Leen M. , Abdalla Moustafa , Adam Jonathan , Adamski Jerzy , Adragni Kofi , Allesøe Rosa L. , Allin Kristine H. , Arumugam Manimozhiyan , Atabaki Pasdar Naeimeh , Baltauss Tania , Banasik Karina , Baum Patrick , Bell Jimmy D. , Bergstrom Margit , Beulens Joline W. , Bianzano Susaana , Bizzotto Roberto , Bonneford Amelie , Brorsson Caroline Anna , Brown Andrew A. , Brunak Søren , Cabrelli Louise , Caiazzo Robert , Canouil Mickael , Cederberg Henna , Dale Matilda , Davtian David , Dawed Adem Y. , De Masi Federico , de Preville Nathalie , Dekkers Koen F. , Dermitzakis Emmanouil T. , Deshmukh Harshal A. , Dings Christiane , Donnelly Louise , Dutta Avirup , Ehrhardt Beate , Elders Petra J. M. , Engelbrechtsen Line , Eriksen Rebeca , Fan Yong , Fernandez Juan , Ferrer Jorge , Fitipaldi Hugo , Forgie Ian M. , Forman Annemette , Franks Paul W. , Frau Francesca , Fritsche Andreas , Froguel Philippe , Frost Gary , Gassenhuber Johann , Giordano Giuseppe N. , Giorgino Toni , Gough Stephen , Graefe-Mody Ulrike , Grallert Harald , Grempler Rolf , Groeneveld Lenka , Groop Leif , Gudmundsdóttir Valborg , Gupta Ramneek , Haid Mark , Hansen Torben , Hansen Tue H. , Hattersley Andrew T. , Haussler Ragna , Heggie Alison J. , Hennige Anita M. , Hill Anita V. , Holl Reinhard W. , Hong Mun-gwan , Hudson Michelle , Jablonka Bernd , Jennison Christopher , Jiao Yunlong , Johansen Joachim , Jones Angus G. , Jonsson Anna , Karaderi Tugce , Kaye Jane , Klintenberg Maria , Koivula Robert W. , Kokkola Tarja , Koopman Anitra D. M. , Kurbasic Azra , Kuulasmaa Teemu , Laakso Markku , Lehr Thorsten , Loftus Heather , Lundgaard Agnete T. , Mahajan Anubha , Mari Andrea , Mazzoni Gianluca , McCarthy Mark I. , McDonald Timothy J. , McEvoy Donna , McRobert Nicky , McVittie Ian , Mourby Miranda , Musholt Petra , Mutie Pascal , Nice Rachel , Nicolay Claudia , Nielsen Agnes Martine , Nilsson Birgitte , Nijpels Giel , Palmer Colin N. , Pattou Francois , Pavo Imre , Pearson Ewan R. , Pedersen Oluf , Pedersen Helle K. , Perry Mandy H. , Pomares-Millan Hugo , Ramisch Anna , Rasmussen Simon , Raverdi Violeta , Ridderstråle Martin , Robertson Neil , Roderick Slieker , Rodriquez Marianne , Ruetten Hartmut , Rutters Femke , Sackett Peter , Scherer Nina , Schwenk Jochen M. , Shah Nisha , Sharma Sapna , Sihinevich Iryna , Sondertoft Nadja B. , Staerfeldt Hans-Henrik , Steckel-Hamann Birgit , Teare Harriet , Thomas Cecilia Engel , Thomas Melissa K. , Thomas Louise , Thomsen Henrik S. , Thorand Barbara , Thorne Claire E. , Tillner Joachim , Troll Martina , Tsirigos Konstantinos D. , Tura Andrea , Uhlen Mathias , Vangipurapu Jagadish , van Leeuwen Nienke , van Oort Sabine , Verkindt Helene , Vestergaard Henrik , Viñuela Ana , Vogt Josef K. , Sackett Peter Wad , Wake Dianne , Walker Mark , Wesolowska-Andersen Agata , Whitcher Brandon , White Margaret W. , Wu Han 
Published: July 2021

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 &lt; 0.002). Conversely, those with IA1c showed higher insulin sensitivity and ISRr (P &lt; 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 &gt;2, P &lt; 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.