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Adult-onset autoimmune diabetes

Nature Reviews Disease Primers volume 8, Article number: 63 (2022) Cite this article

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Abstract

Adult-onset autoimmune (AOA) diabetes pathophysiology starts with immune changes, followed by dysglycaemia and overt disease. AOA diabetes can occur as classic type 1 diabetes when associated with severe loss of insulin secretion. More frequently, it is diagnosed as latent autoimmune diabetes in adults, a slowly progressing form with late onset, a long period not requiring insulin, and it is often misdiagnosed as type 2 diabetes. As its clinical presentation varies remarkably and immune markers often lack specificity, it is challenging to classify each case ad hoc, especially when insulin treatment is not required at diagnosis. Proper care of AOA diabetes aims to prevent complications and to improve quality of life and life expectancy. To achieve these goals, attention should be paid to lifestyle factors, with the aid of pharmacological therapies properly tailored to each individual clinical setting. Given the heterogeneity of the disease, choosing the right therapy for AOA diabetes is challenging. Most of the trials testing disease-modifying therapies for autoimmune diabetes are conducted in people with childhood onset, whereas non-insulin diabetes therapies have mostly been studied in the larger population with type 2 diabetes. More randomized controlled trials of therapeutic agents in AOA diabetes are needed.

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Fig. 1: The adult-onset diabetes spectrum.
Fig. 2: Frequency of islet-specific autoantibodies in adults with a clinical diagnosis of type 2 diabetes mellitus.
Fig. 3: Model for staging of autoimmune diabetes.
Fig. 4: Model for pathogenesis of autoimmune diabetes.
Fig. 5: Diagnostic and therapeutic algorithm for LADA92.
Fig. 6: Priorities to address gaps in understanding of adult-onset autoimmune diabetes.

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Acknowledgements

R.B. was supported by the Italian Ministry of Universities and Research (Project of National Interest–PRIN, #20175L9H7H) and by the Research Foundation of the Italian Society of Diabetology (SID). B.O.B. was supported by the Ministry of Education, Singapore, Ong Tiong Tat Chair Professorship, Boehringer Ingelheim, Ulm University Bio Center (BIU) and Deutsche Forschungsgemeinschaft (DFG) (SFB 518, GRK 104).

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Authors and Affiliations

  1. Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy

    Raffaella Buzzetti & Ernesto Maddaloni

  2. Joslin Diabetes Center, Harvard Medical School, Boston, MA, US

    Jason Gaglia

  3. Centre for Immunobiology, Blizard Institute, Queen Mary University of London, London, UK

    R. David Leslie

  4. Division of Infection and Immunity, Systems Immunity Research Institute, Cardiff School of Medicine, Cardiff University, Cardiff, UK

    F. Susan Wong

  5. Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore

    Bernhard O. Boehm

  6. Department of Endocrinology, Tan Tock Seng Hospital, Singapore, Singapore

    Bernhard O. Boehm

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Contributions

Introduction (R.B., R.D.L.); Epidemiology (R.B., R.D.L.); Mechanisms/pathophysiology (F.S.W.); Diagnosis/screening/prevention (B.O.B.); Management (E.M.); Quality of life (J.G.); Outlook (J.G.); Overview of the Primer (R.B., E.M., B.O.B).

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Correspondence to Raffaella Buzzetti.

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Competing interests

R.B. declares consulting for Sanofi, Novo Nordisk and Eli Lilly; and receiving honoraria for speaker bureaux from AstraZeneca and Abbott. J.G. declares consulting for Vertex Pharmaceuticals, Inc., Dompé farmaceutici and Avotres, Inc. E.M. declares consulting for Merck KGaA and PikDare; and receiving honoraria as speaker from Abbott. R.D.L., F.S.W. and B.O.B. declare no competing interests.

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Nature Reviews Disease Primers thanks A. Michels, who co-reviewed with A. Mitchell; E. Kawasaki; L. Harrison; J. Størling; and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Buzzetti, R., Maddaloni, E., Gaglia, J. et al. Adult-onset autoimmune diabetes. Nat Rev Dis Primers 8, 63 (2022). https://doi.org/10.1038/s41572-022-00390-6

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