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Adult-onset autoimmune diabetes: current knowledge and implications for management

Key Points

  • Adult-onset autoimmune diabetes encompasses a wide spectrum of heterogeneous genotypes and phenotypes, ranging from classic adult-onset type 1 diabetes mellitus to latent autoimmune diabetes in adults (LADA)

  • The heterogeneity of LADA arises from its definition as being present in any adult with diabetes who does not require insulin and who is positive for any islet autoantibody, regardless of titre, number or epitope specificity

  • The heterogeneity of LADA manifests in different clinical phenotypes, ranging from prevalent insulin resistance to prevalent insulin deficiency, each of which might be associated with different autoimmune and metabolic markers

  • Although patients with LADA are leaner and have healthier lipid and blood pressure profiles, evidence shows that there is no difference in cardiovascular outcomes between these patients and those with type 2 diabetes mellitus

  • The extensive heterogeneity of adult-onset autoimmune diabetes, and particularly LADA, makes it difficult to determine an a priori algorithm for treatment

  • The successful treatment of adult-onset autoimmune diabetes will require a personalized medicine approach that takes into account the intrinsic characteristics of each patient

Abstract

Adult-onset autoimmune diabetes is a heterogeneous disease that is characterized by a reduced genetic load, a less intensive autoimmune process and a mild metabolic decompensation at onset compared with young-onset type 1 diabetes mellitus (T1DM). The majority of patients with adult-onset autoimmune diabetes do not require insulin treatment for at least 6 months after diagnosis. Such patients are defined as having latent autoimmune diabetes in adults (LADA), which is distinct from classic adult-onset T1DM. The extensive heterogeneity of adult-onset autoimmune diabetes is apparent beyond the distinction between classic adult-onset T1DM and LADA. LADA is characterized by genetic, phenotypic and humoral heterogeneity, encompassing different degrees of insulin resistance and autoimmunity; this heterogeneity is probably a result of different pathological mechanisms, which have implications for treatment. The existence of heterogeneous phenotypes in LADA makes it difficult to establish an a priori treatment algorithm, and therefore, a personalized medicine approach is required. In this Review, we discuss the current understanding and gaps in knowledge regarding the pathophysiology and clinical features of adult-onset autoimmune diabetes and highlight the similarities and differences with classic T1DM and type 2 diabetes mellitus.

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Figure 1: Bimodal distribution of the glutamic acid decarboxylase autoantibody titre in patients with latent autoimmune diabetes in adults.
Figure 2: Potential pathological mechanisms of latent autoimmune diabetes in adults.
Figure 3: Prevalence of chronic diabetes-related complications in latent autoimmune diabetes in adults and type 2 diabetes mellitus.
Figure 4: Interactions between β-cell function, autoimmunity and insulin sensitivity.

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Acknowledgements

The Non Insulin Requiring Autoimmune Diabetes Study was sponsored by 'Fondazione Diabete e Ricerca' of the Italian Society of Diabetology.

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Correspondence to Raffaella Buzzetti.

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Buzzetti, R., Zampetti, S. & Maddaloni, E. Adult-onset autoimmune diabetes: current knowledge and implications for management. Nat Rev Endocrinol 13, 674–686 (2017). https://doi.org/10.1038/nrendo.2017.99

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