Unveiling a novel type 1 diabetes endotype: Opportunities for intervention

Fiorina, Paolo; Pozzilli, Paolo

doi:10.1002/dmrr.3536

Cited by 5 publications

(3 citation statements)

References 42 publications

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“…This concept] is supported by the observation that individuals with LADA or SPIDDM 124 Persistent residual β-cell function, although not sustained, underlies the proposed response of LADA to non-insulin therapies such as certain thiazolidinediones 126 , dipeptidylpeptidase IV inhibitors 127 , disease modifying therapies such as alum-formulated recombinant GAD65 (GAD-alum) 128 , and other agents (reviewed in 129 ) but their respective efficacies require more detailed verification. Although it has been proposed that LADA represents a further T1DM endotype 130 , in our view, it is a particularly slowly progressive form of the T1DE2 endotype. Adding to the ongoing controversy, other investigators argue that LADA represents a mix of two subsets of individuals with either T1DM or T2DM 131 .…”

Section: [H1] T1dm Endotypesmentioning

confidence: 58%

Heterogeneity and endotypes in type 1 diabetes mellitus

Redondo

Morgan

2023

Nat Rev Endocrinol

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Despite major advances over the past decade, prevention and treatment of type 1 diabetes mellitus (T1DM) remain suboptimal, with large and unexplained variations in individual responses to interventions. The current classification schema for diabetes mellitus does not capture the complexity of this disease or guide clinical management effectively. One of the approaches to achieve the goal of applying precision medicine in diabetes mellitus is to identify endotypes (that is, well-defined subtypes) of the disease each of which has a distinct aetiopathogenesis that might be amenable to specific interventions. Here, we describe epidemiological, clinical, genetic, immunological, histological and metabolic differences within T1DM that, together, suggest heterogeneity in its aetiology and pathogenesis. We then present the emerging endotypes and their impact on T1DM prediction, prevention and treatment.

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Section: [H1] T1dm Endotypesmentioning

confidence: 58%

Heterogeneity and endotypes in type 1 diabetes mellitus

Redondo

Morgan

2023

Nat Rev Endocrinol

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“…104 Ben Nasr et al demonstrated that HSPCs overexpressing PD-L1 could reverse diabetes in mice but only in those with a level of preserved Cpeptide. 105 These findings indicate the potential for HSPCs in patients with diabetes, particularly T1DE4 patients, 106 who have a greater degree of β-cell functionality. The PD-1/PD-L1 system is not just confined to adult onset T1D, 107,108 with Granados et al…”

Section: Potential Therapies For T1de4mentioning

confidence: 93%

Type 1 diabetes: A new vision of the disease based on endotypes

Weston,

Boehm,

Pozzilli

2024

Diabetes Metabolism Res

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Diagnosis and management of type 1 diabetes (T1D) have remained largely unchanged for the last several years. The management of the disease remains primarily focused on its phenotypical presentation and less on endotypes, namely the specific biological mechanisms behind the development of the disease. Furthermore, the treatment of T1D is essentially universal and indiscriminate—with patients administering insulin at varying dosages and frequencies to maintain adequate glycaemic control. However, it is now well understood that T1D is a heterogeneous disease with many different biological mechanisms (i.e. endotypes) behind its complex pathophysiology. A range of factors, including age of onset, immune system regulation, rate of β‐cell destruction, autoantibodies, body weight, genetics and the exposome are recognised to play a role in the development of the condition. Patients can be classified into distinct diabetic subtypes based on these factors, which can be used to categorise patients into specific endotypes. The classification of patients into endotypes allows for a greater understanding of the natural progression of the disease, giving rise to more accurate and patient‐centred therapies and follow‐up monitoring, specifically for other autoimmune diseases. This review proposes 6 unique endotypes of T1D based on the current literature. The recognition of these endotypes could then be used to direct therapeutic modalities based on patients' individual pathophysiology.

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“…23 It is possible that at the time of the clinical intervention (i.e., T1D onset), aberrant innate immune cells have already triggered specific anti-pancreatic adaptive immune responses. Nonetheless, heterogeneity in the disease pathogenesis, also due to different T1D patient endotypes, 24 may represent a major barrier to therapeutic efforts. Thus, it is reasonable to hypothesise that an early intervention direct on innate immunity in autoantibody-positive at-risk subjects or specific vaccination against the major T1D-associated virus could be helpful to control the disease development.…”

Section: F I G U R E 1 Schematic Representation Of the Pathogenic Int...mentioning

confidence: 99%