A classification and regression tree analysis identifies subgroups of childhood type 1 diabetes

Achenbach, Peter; Hippich, Markus; Zapardiel‐Gonzalo, Jose; Karges, Beate; Holl, Reinhard W.; Petrera, Agnese; Bonifacio, Ezio; Ziegler, Anette‐G.

doi:10.1016/j.ebiom.2022.104118

Cited by 25 publications

(22 citation statements)

References 57 publications

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“…Furthermore, a very recent analysis by Achenbach and colleagues identified multiple variables that classified young type 1 diabetes patients into seven islet autoantibody-positive and three islet autoantibodynegative subgroups. These subgroups demonstrated substantial differences in pathogenic and prognostic outcomes, which could have therapeutic relevance [57]. Machine learning approaches have also been helpful in identifying autoantibody and disease trajectories [58].…”

Section: Preventionmentioning

confidence: 99%

Precision medicine in type 1 diabetes

Evans‐Molina

Oram

2022

Diabetologia

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First envisioned by early diabetes clinicians, a person-centred approach to care was an aspirational goal that aimed to match insulin therapy to each individual’s unique requirements. In the 100 years since the discovery of insulin, this goal has evolved to include personalised approaches to type 1 diabetes diagnosis, treatment, prevention and prediction. These advances have been facilitated by the recognition of type 1 diabetes as an autoimmune disease and by advances in our understanding of diabetes pathophysiology, genetics and natural history, which have occurred in parallel with advancements in insulin delivery, glucose monitoring and tools for self-management. In this review, we discuss how these personalised approaches have improved diabetes care and how improved understanding of pathogenesis and human biology might inform precision medicine in the future. Graphical abstract

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Section: Preventionmentioning

confidence: 99%

Precision medicine in type 1 diabetes

Evans‐Molina

Oram

2022

Diabetologia

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“…Zunehmend wird eine Subtypisierung des Typ-1- und des Typ-2-Diabetes diskutiert 66 67 . Während die Relevanz der Subtypisierung des Typ-1-Diabetes derzeit in der Praxis fraglich ist, findet die Subtypisierung des Typ-2-Diabetes bereits statt, um eine angemessene Therapie, z.…”

Section: Ausblickunclassified

Definition, Klassifikation, Diagnostik und Differenzialdiagnostik des Diabetes mellitus: Update 2023

Pleus,

Tytko,

Landgraf

et al. 2023

Diabetologie und Stoffwechsel

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“…1 The disease is heterogeneous and multivariable analysis identifies subgroups of people with diabetes with potentially different pathogenesis. 2 Heterogeneity may impact effectiveness of immunotherapy. 3 Studies of the pancreas in the disease have identified two distinct patterns of inflammation that are distinguished primarily by numbers of cells expressing the B-cell marker CD20.…”

Section: Introductionmentioning

confidence: 99%

“…Type 1 diabetes results from destruction of pancreatic beta cells caused by an inflammation predominated by CD8 + cytotoxic T cells 1 . The disease is heterogeneous and multivariable analysis identifies subgroups of people with diabetes with potentially different pathogenesis 2 . Heterogeneity may impact effectiveness of immunotherapy 3 .…”

Section: Introductionmentioning

confidence: 99%

Differential expression of genes controlling lymphocyte differentiation and migration in two distinct endotypes of type 1 diabetes

et al. 2023

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AimsMorphological studies of pancreas samples obtained from young people with recent‐onset type 1 diabetes have revealed distinct patterns of immune cell infiltration of the pancreatic islets suggestive of two age‐associated type 1 diabetes endotypes that differ by inflammatory responses and rates of disease progression. The objective of this study was to investigate whether these proposed disease endotypes are associated with pathological differences in immune cell activation and cytokine secretion by applying multiplexed gene expression analysis to pancreatic tissue from recent‐onset type 1 diabetes cases.MethodsRNA was extracted from samples of fixed, paraffin‐embedded pancreas tissue from type 1 diabetes cases characterised by endotype and from controls without diabetes. Expression levels of 750 genes associated with autoimmune inflammation were determined by hybridisation to a panel of capture and reporter probes and these were counted as a measure of gene expression. Normalised counts were analysed for differences in expression between 29 type 1 diabetes cases and 7 controls without diabetes, and between the two type 1 diabetes endotypes.ResultsTen inflammation‐associated genes, including INS, were significantly under‐expressed in both endotypes and 48 genes were more highly expressed. A different set of 13 genes associated with the development, activation and migration of lymphocytes was uniquely overexpressed in the pancreas of people developing diabetes at younger age.ConclusionsThe results provide evidence that histologically defined type 1 diabetes endotypes differ in their immunopathology and identify inflammatory pathways specifically involved in disease developing at a young age, essential for a better understanding of disease heterogeneity.

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A classification and regression tree analysis identifies subgroups of childhood type 1 diabetes

Cited by 25 publications

References 57 publications

Precision medicine in type 1 diabetes

Precision medicine in type 1 diabetes

Definition, Klassifikation, Diagnostik und Differenzialdiagnostik des Diabetes mellitus: Update 2023

Differential expression of genes controlling lymphocyte differentiation and migration in two distinct endotypes of type 1 diabetes

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