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Prediabetes

Nature Reviews Disease Primers volume 11, Article number: 49 (2025) Cite this article

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Abstract

Prediabetes or intermediate hyperglycaemia represents a preliminary stage in the development of type 2 diabetes mellitus (T2DM). In addition to an increased likelihood of developing T2DM, individuals with prediabetes have an elevated risk of various vascular and non-vascular complications. No consensus has been achieved on the ideal screening strategy for prediabetes, with fasting plasma glucose concentration, glycated haemoglobin (HbA1c) and the oral glucose tolerance test being the most frequently measured parameters. The two major phenotypes of prediabetes, that is, impaired fasting glucose and impaired glucose tolerance, may represent different pathophysiologies with varying natural history, risk of adverse outcomes and responsiveness to treatment. Most of the evidence for managing prediabetes focuses on lifestyle modification with or without medications in individuals with overweight or obesity and impaired glucose tolerance. Whether these interventions are beneficial in individuals with impaired fasting glucose and those of normal body weight is unclear, as is the cost-effectiveness and sustainability of pharmacotherapy for treating prediabetes. Large-scale national T2DM prevention programmes are currently under way to assess whether the benefits of interventions for prediabetes can be translated to the community setting.

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Fig. 1: Global prevalence of prediabetes.
Fig. 2: Regulation of glycaemia and insulin signalling.
Fig. 3: Trajectories of glycaemia in the UK Whitehall II study.
Fig. 4: Models of β-cell dysfunction in prediabetes and T2DM.
Fig. 5: Comparison of pathophysiology of IFG and IGT.
Fig. 6: Stepped-care approach to diagnosis and management of prediabetes.
Fig. 7: Effect of lifestyle intervention on type 2 diabetes mellitus incidence and risk according to prediabetes phenotype.

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Acknowledgements

The authors acknowledge T. A. Pramod Kumar for his assistance in preparation of Tables.

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Authors and Affiliations

  1. Madras Diabetes Research Foundation, ICMR-Collaborating Centre of Excellence, Chennai, India

    Ranjit Unnikrishnan & Viswanathan Mohan

  2. Dr. Mohan’s Diabetes Specialities Centre, IDF Centre of Excellence in Diabetes Care, Chennai, India

    Ranjit Unnikrishnan & Viswanathan Mohan

  3. Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia

    Jonathan E. Shaw

  4. Department of Medicine and Therapeutics, Li Ka Shing Institute of Health Sciences, Prince of Wales Hospital, Shatin, Hong Kong SAR, China

    Juliana C. N. Chan

  5. Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong SAR, China

    Juliana C. N. Chan

  6. Usher Institute, University of Edinburgh, Edinburgh, UK

    Sarah H. Wild

  7. Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA

    Anne L. Peters & Sharon Orrange

  8. Department of Endocrinology and Diabetology, Medical Faculty and University Hospital Düsseldorf, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany

    Michael Roden

  9. Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich-Heine-University, Düsseldorf,, Germany

    Michael Roden

  10. German Center for Diabetes Research, Partner Düsseldorf, München-Neuherberg, Germany

    Michael Roden

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Contributions

Introduction (R.U. and V.M.); Epidemiology (S.H.W.); Mechanisms/pathophysiology (M.R.); Diagnosis and screening (R.U., V.M. and J.E.S.); Management (A.L.P.); Quality of life (S.O.); Outlook (R.U. and V.M.); overview of the Primer (R.U. and V.M.).

Corresponding author

Correspondence to Viswanathan Mohan.

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Competing interests

V.M. has acted as consultant and speaker, and received research or educational grants from Abbott, Medtronics, Novo Nordisk, Sanofi, Servier, Boehringer-Ingelheim, Eli Lilly, Johnson & Johnson, Lifescan, Roche, MSD, Novartis, Aventis, Bayer, USV, Dr. Reddy’s, Sun Pharma, INTAS, Lupin, Glenmark, Zydus, IPCA, Torrent, Cipla, Biocon, Primus, Franco Indian, Wockhardt, Emcure, Mankind, Fourrts, Apex, GSK and Alembic. M.R. has received lecture fees or served on advisory boards for AstraZeneca, Boehringer-Ingelheim, Echosens, Eli Lilly, Madrigal, MSD, Novo Nordisk and Target RWE and has performed investigator-initiated research with support from Boehringer-Ingelheim and Novo Nordisk to the German Diabetes Center (DDZ). J.E.S. has received lecture fees or served on advisory boards for and/or received honoraria from Zuellig Pharma, AstraZeneca, Sanofi, Novo Nordisk, Eli Lilly, Abbott, Mylan, Boehringer-Ingelheim, Roche, Pfizer and GSK. R.U., S.H.W. and S.O. declare no competing interests.

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Nature Reviews Disease Primers thanks W. Knowler; A.E. Sumner, who co-reviewed with K. Ntabadde; and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Unnikrishnan, R., Shaw, J.E., Chan, J.C.N. et al. Prediabetes. Nat Rev Dis Primers 11, 49 (2025). https://doi.org/10.1038/s41572-025-00635-0

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