Prediabetes transitions to normoglycaemia or type 2 diabetes and associated risk factors in the Obesity, Diabetes and Cardiovascular Disease Collaboration: an individual-level pooled analysis of 19 prospective cohort studies

Najmeh Davoodian¹, Mojtaba Lotfaliany², Rachel R Huxley³, Crystal Man Ying Lee⁴, Julie A Pasco⁵, Robert J Adams⁶, Fereidoun Azizi⁷, Alain G Bertoni⁸, Cecilia Björkelund⁹, Stephen Colagiuri¹⁰, Noushin Fahimfar¹¹, Rafael Gabriel¹², Vilmantas Giedraitis¹³, Tiffany K Gill¹⁴, Clicerio González¹⁵, Edward W Gregg¹⁶, Farzad Hadaegh¹⁷, Dominique Hange⁹, Jacob W Harland², Allison M Hodge¹⁸, Kara L Holloway-Kew², Seyed Reza Hosseini¹⁹, David R Jacobs Jr²⁰, Davood Khalili¹⁷, Dianna J Magliano²¹, Morgana Mongraw-Chaffin⁸, Gita D Mishra²², Lauren Lissner⁹, Kirsten Mehlig⁹, Hamid Najafipour²³, Ramfis Nieto-Martinez²⁴, Afshin Ostovar²⁵, Mitra Shadkam²⁶, Jonathan E Shaw²¹, Valter Sundh⁹, Pamela J Schreiner²⁰, Masaru Sakurai²⁷, Gary A Wittert²⁸, Hiroshi Yatsuya²⁹, Bjorn Zethelius³⁰, Mohammadreza Mohebbi³¹

Affiliations

¹ Institute for Mental and Physical Health and Clinical Translation, School of Medicine-Barwon Health, Faculty of Health, Deakin University, Geelong, VIC, Australia. Electronic address: n.davoodian@deakin.edu.au.
² Institute for Mental and Physical Health and Clinical Translation, School of Medicine-Barwon Health, Faculty of Health, Deakin University, Geelong, VIC, Australia.
³ The George Institute for Global Health, University of New South Wales, Sydney, NSW, Australia; Faculty of Health, Deakin University, Melbourne, VIC, Australia.
⁴ School of Population Health, Curtin University, Perth, WA, Australia.
⁵ Institute for Mental and Physical Health and Clinical Translation, School of Medicine-Barwon Health, Faculty of Health, Deakin University, Geelong, VIC, Australia; Department of Medicine, Western Health, The University of Melbourne, St Albans, VIC, Australia; School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia.
⁶ Flinders Health and Medical Research Institute and Adelaide Institute for Sleep Health, Flinders University, Bedford Park, SA, Australia; Respiratory and Sleep Services, Southern Adelaide Local Health Network, Adelaide, SA, Australia.
⁷ Endocrine Research Centre, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
⁸ Department of Epidemiology and Prevention, Division of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
⁹ School of Public Health and Community Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
¹⁰ Faculty of Medicine and Health and Charles Perkins Centre, The University of Sydney, Sydney, NSW, Australia.
¹¹ Osteoporosis Research Centre, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran; School of Public Health, Department of Epidemiology and Biostatistics, Tehran University of Medical Sciences, Tehran, Iran.
¹² National School of Public Health, National Institute of Health Carlos III, Madrid, Spain.
¹³ Clinical Geriatrics, Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden.
¹⁴ Adelaide Medical School, University of Adelaide, Adelaide, SA, Australia.
¹⁵ Population Health Research Centre, National Institute of Public Health, Cuernavaca, Morelos, Mexico.
¹⁶ School of Population Health, RCSI University of Medicine and Health Sciences, Dublin, Ireland; Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.
¹⁷ Prevention of Metabolic Disorders Research Centre, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
¹⁸ Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, VIC, Australia; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, VIC, Australia.
¹⁹ Department of Community Medicine, Social Determinants of Health Research Centre, Health Research Institute, Babol University of Medical Sciences, Babal, Iran.
²⁰ Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN, USA.
²¹ Department of Diabetes and Population Health, Baker Heart and Diabetes Institute, Melbourne, VIC, Australia; School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia.
²² School of Public Health, Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia.
²³ Department of Physiology and Pharmacology, Kerman University of Medical Sciences, Kerman, Iran; Physiology Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran.
²⁴ Department of Global Health and Department of Population and Epidemiology, Harvard TH Chan School of Public Health, Boston, MA, USA; Foundation for Clinic, Public Health, Epidemiology Research of Venezuela, Caracas, Venezuela.
²⁵ Osteoporosis Research Centre, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
²⁶ Cardiovascular Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran.
²⁷ Department of Social and Environmental Medicine, Kanazawa Medical University, Uchinada, Japan.
²⁸ Adelaide Medical School, University of Adelaide, Adelaide, SA, Australia; Lifelong Health Theme, South Australian Health and Medical Research Institute, Adelaide, SA, Australia.
²⁹ Department of Public Health and Health Systems, Nagoya University Graduate School of Medicine, Nagoya, Japan.
³⁰ Clinical Geriatrics, Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden; Swedish Medical Products Agency, Uppsala, Sweden.
³¹ Institute for Mental and Physical Health and Clinical Translation, School of Medicine-Barwon Health, Faculty of Health, Deakin University, Geelong, VIC, Australia; Biostatistics Unit, Faculty of Health, Deakin University, Geelong, VIC, Australia.

PMID: 40845880
DOI: 10.1016/S2214-109X(25)00237-2

Free article

Prediabetes transitions to normoglycaemia or type 2 diabetes and associated risk factors in the Obesity, Diabetes and Cardiovascular Disease Collaboration: an individual-level pooled analysis of 19 prospective cohort studies

Najmeh Davoodian et al. Lancet Glob Health. 2025 Sep.

Free article

. 2025 Sep;13(9):e1533-e1542.

doi: 10.1016/S2214-109X(25)00237-2.

Authors

Affiliations

¹ Institute for Mental and Physical Health and Clinical Translation, School of Medicine-Barwon Health, Faculty of Health, Deakin University, Geelong, VIC, Australia. Electronic address: n.davoodian@deakin.edu.au.
² Institute for Mental and Physical Health and Clinical Translation, School of Medicine-Barwon Health, Faculty of Health, Deakin University, Geelong, VIC, Australia.
³ The George Institute for Global Health, University of New South Wales, Sydney, NSW, Australia; Faculty of Health, Deakin University, Melbourne, VIC, Australia.
⁴ School of Population Health, Curtin University, Perth, WA, Australia.
⁵ Institute for Mental and Physical Health and Clinical Translation, School of Medicine-Barwon Health, Faculty of Health, Deakin University, Geelong, VIC, Australia; Department of Medicine, Western Health, The University of Melbourne, St Albans, VIC, Australia; School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia.
⁶ Flinders Health and Medical Research Institute and Adelaide Institute for Sleep Health, Flinders University, Bedford Park, SA, Australia; Respiratory and Sleep Services, Southern Adelaide Local Health Network, Adelaide, SA, Australia.
⁷ Endocrine Research Centre, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
⁸ Department of Epidemiology and Prevention, Division of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
⁹ School of Public Health and Community Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
¹⁰ Faculty of Medicine and Health and Charles Perkins Centre, The University of Sydney, Sydney, NSW, Australia.
¹¹ Osteoporosis Research Centre, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran; School of Public Health, Department of Epidemiology and Biostatistics, Tehran University of Medical Sciences, Tehran, Iran.
¹² National School of Public Health, National Institute of Health Carlos III, Madrid, Spain.
¹³ Clinical Geriatrics, Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden.
¹⁴ Adelaide Medical School, University of Adelaide, Adelaide, SA, Australia.
¹⁵ Population Health Research Centre, National Institute of Public Health, Cuernavaca, Morelos, Mexico.
¹⁶ School of Population Health, RCSI University of Medicine and Health Sciences, Dublin, Ireland; Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.
¹⁷ Prevention of Metabolic Disorders Research Centre, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
¹⁸ Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, VIC, Australia; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, VIC, Australia.
¹⁹ Department of Community Medicine, Social Determinants of Health Research Centre, Health Research Institute, Babol University of Medical Sciences, Babal, Iran.
²⁰ Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN, USA.
²¹ Department of Diabetes and Population Health, Baker Heart and Diabetes Institute, Melbourne, VIC, Australia; School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia.
²² School of Public Health, Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia.
²³ Department of Physiology and Pharmacology, Kerman University of Medical Sciences, Kerman, Iran; Physiology Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran.
²⁴ Department of Global Health and Department of Population and Epidemiology, Harvard TH Chan School of Public Health, Boston, MA, USA; Foundation for Clinic, Public Health, Epidemiology Research of Venezuela, Caracas, Venezuela.
²⁵ Osteoporosis Research Centre, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
²⁶ Cardiovascular Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran.
²⁷ Department of Social and Environmental Medicine, Kanazawa Medical University, Uchinada, Japan.
²⁸ Adelaide Medical School, University of Adelaide, Adelaide, SA, Australia; Lifelong Health Theme, South Australian Health and Medical Research Institute, Adelaide, SA, Australia.
²⁹ Department of Public Health and Health Systems, Nagoya University Graduate School of Medicine, Nagoya, Japan.
³⁰ Clinical Geriatrics, Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden; Swedish Medical Products Agency, Uppsala, Sweden.
³¹ Institute for Mental and Physical Health and Clinical Translation, School of Medicine-Barwon Health, Faculty of Health, Deakin University, Geelong, VIC, Australia; Biostatistics Unit, Faculty of Health, Deakin University, Geelong, VIC, Australia.

PMID: 40845880
DOI: 10.1016/S2214-109X(25)00237-2

Abstract

Background: With the increasing global burden of type 2 diabetes, prevention strategies that target prediabetes, a state of hyperglycaemia that puts individuals at high risk of type 2 diabetes, are required. We aimed to estimate global rates of transition from prediabetes to normoglycaemia or type 2 diabetes, stratified by age, sex, and race and ethnicity. We also aimed to quantify the effect of modifiable and non-modifiable risk factors on these transitions.

Methods: In this pooled analysis of individual-level data, we included original data from 19 prospective cohort studies conducted in Asia (Iran and Japan), Australia, Europe (Spain and Sweden), North America (USA and Mexico), and South America (Venezuela). We applied discrete-time hidden Markov models to estimate rates and ratios of prediabetes transitions to type 2 diabetes and normoglycaemia specific to age, sex, and race and ethnicity. We used Fine-Gray competing risk models to derive cohort-specific subhazard ratios (SHRs) for potential risk factors influencing these transitions. We subsequently pooled these SHRs using a random-effects meta-analysis. In subgroup analyses stratified by age, sex, race and ethnicity, and recruitment period, we used multivariate Cox models to investigate the degree of heterogeneity between studies.

Findings: 76 092 participants (39 842 [52·3%] women and 36 250 [47·6%] men; mean age 51·1 years [SD 12·7]) with available data on glycaemic status from at least one follow-up visit were included in the analysis, of whom 56 837 (74·7%) had normoglycaemia and 19 255 (25·3%) had prediabetes. Median follow-up was 9·8 years (IQR 5·8-12·5). Within 10 years, individuals with prediabetes had a 12·5% probability of progressing to type 2 diabetes, whereas the probability of reverting to normoglycaemia was 36·1%. However, in the highest fasting plasma glucose quartile, the probability of progression increased to 16·1% and reversion decreased to 13·4%. Male sex, older age (≥55 years), and Latinx populations were associated with an increased risk of transitioning to type 2 diabetes. Risk factors that significantly reduced prediabetes reversion to normoglycaemia were overweight (SHR 0·88 [95% CI 0·76-0·99]), obesity (0·66 [0·52-0·81]), elevated waist-to-height ratio (0·82 [0·70-0·95]), elevated waist-to-hip ratio (0·79 [0·68-0·91]), and reduced HDL concentration (0·72 [0·59-0·84]).

Interpretation: Our findings highlight that reversion to normoglycaemia was more common than progression to type 2 diabetes among individuals with prediabetes, and that these transitions were strongly influenced by modifiable risk factors. The increased risk of progression with advancing age and among men underscores the importance of early identification and targeted interventions in population groups at high risk of type 2 diabetes. Furthermore, the elevated progression risk in individuals with higher fasting plasma glucose concentrations at baseline reinforces the need for timely detection and intervention during this crucial clinical window.

Funding: Deakin University Postgraduate Research Scholarship.

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Conflict of interest statement

Declaration of interests JES reports consulting fees from GSK, AstraZeneca, Sanofi, Novo Nordisk, Eli Lilly, Roche, and Abbott; lecture fees from Boehringer Ingelheim, Novo Nordisk, Roche, Zucleo Pharmaceutical, and Eli Lilly; and receiving honoraria for lectures and programme committee participation from AstraZeneca (all payments made directly to him). PJS reports a contract for the CARDIA study funded by the NHLBI of the US National Institutes of Health. The University of Minnesota is a field centre for the CARDIA study, and PJS is the local principal investigator. JAP has received support from the Australian National Health and Medical Research Council (NHMRC; grant numbers 251638, 299831, and 628582), which is paid to the Institute for Mental and Physical Health and Clinical Translation. AGB reports receiving support from the US National Institutes of Health, with grants or contracts paid to his institution. JWH has received support from the Deakin University Postgraduate Research Scholarship. GDM has received support from the Australian NHMRC (investigator grant), which is paid to the University of Queensland. KLH-K was supported by an Alfred Deakin Postdoctoral Research Fellowship. All other authors declare no competing interests.

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Prediabetes transitions to normoglycaemia or type 2 diabetes and associated risk factors in the Obesity, Diabetes and Cardiovascular Disease Collaboration: an individual-level pooled analysis of 19 prospective cohort studies

Affiliations

Prediabetes transitions to normoglycaemia or type 2 diabetes and associated risk factors in the Obesity, Diabetes and Cardiovascular Disease Collaboration: an individual-level pooled analysis of 19 prospective cohort studies

Authors

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Abstract

Conflict of interest statement

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