The Prevalence of Islet Autoantibodies in Children and Adolescents With Type 1 Diabetes Mellitus: A Global Scoping Review

Abstract

Background and PurposePancreatic islet autoantibodies (iAb) are the hallmark of autoimmunity in type 1 diabetes. A more comprehensive understanding of the global iAb prevalence could help reduce avertible morbidity and mortality among children and adolescents and contribute to the understanding in the observed differences in the incidence, prevalence and health outcomes of children and adolescents with type 1 diabetes across and within countries. We present the first scoping review that provides a global synthesis of the prevalence of iAb in children and adolescents with type 1 diabetes.Research Design and MethodsWe searched Ovid MEDLINE® with Daily Update, Embase (Elsevier, embase.com) and PubMed (National Library of Medicine -NCBI), for studies pertaining to prevalence in children and adolescents (0-19) with type 1 diabetes published between 1 Jan 1990 and 18 June 2021. Results were synthesized using Covidence systematic review software and meta-analysis was completed using R v3·6·1. Two reviewers independently screened abstracts with a third reviewer resolving conflicts (k= 0·92).ResultsThe review revealed 125 studies from 48 different countries, with 92 from high-income countries. Globally, in new-onset type 1 diabetes, IA-2A was the most prevalent iAb 0·714 [95% CI (0·71, 0·72)], followed by ICA 0·681 [95% CI (0·67, 0·69)], ZnT8A was 0·654 [95% CI (0·64, 0·66)], GADA 0·636 [95% CI (0·63, 0·66)] and then IAA 0·424 [95% CI (0·42, 0·43)], with substantial variation across world regions. The weighted mean prevalence of IA-2A was more variable, highest in Europe at 0·749 [95% CI (0·74, 0·76)] followed by Northern America 0·662 [95% CI (0·64, 0·69)], Latin America and the Caribbean 0·632 [95% CI (0·54, 0·72)], Oceania 0·603 [95% CI (0·54, 0·67)], Asia 0·466 [95% CI (0·44, 0·50)] and Africa 0·311 [95% CI (0·23, 0·40)]. In established cases of type 1 diabetes, GADA was the most prevalent iAb 0·407 [95% CI (0·39, 0·42)] followed by ZnT8A 0·322 [95% CI (0·29, 0·36)], IA-2A 0·302 [95% CI (0·29, 0·32)], IAA 0·258 [95% CI (0·24, 0·26)] and ICA 0·145 [95% CI (0·13, 0·16)], again with substantial variation across world regions.ConclusionUnderstanding the global prevalence of iAb in children and adolescents with type 1 diabetes could help with earlier identification of those at-risk of developing type 1 diabetes and inform clinical practice, health policies, resource allocation, and targeted healthcare interventions to better screen, diagnose and manage children and adolescents with type 1 diabetes

Unveiling a novel type 1 diabetes endotype: Opportunities for intervention

“…Type 1 diabetes (T1D) results from the destruction of insulin‐producing pancreatic β ‐cells by auto‐reactive T cells that have escaped central and peripheral immune tolerance 1‐6 . The disease is characterised by a wide heterogeneity especially in terms of age at onset, insulin secretory capacity (mirrored by the residual β ‐cell function) and complication/progression rates.…”

“…diabetes endotypes, immunogene therapy, PD-L1-expressing HSPCs, type 1 diabetes Type 1 diabetes (T1D) results from the destruction of insulinproducing pancreatic β-cells by auto-reactive T cells that have escaped central and peripheral immune tolerance. [1][2][3][4][5][6] The disease is characterised by a wide heterogeneity especially in terms of age at onset, insulin secretory capacity (mirrored by the residual β-cell function) and complication/progression rates. Such heterogeneity represents a major barrier for both pathogenesis and especially for translational therapeutic efforts, thus prompting a reflection on different T1D patient endotypes for identifying the specific one that may benefit most from novel therapeutics.…”

Association between type 1 diabetes and neurodevelopmental disorders in children and adolescents: A systematic review and meta-analysis

“…Type 1 diabetes is characterized by elevated blood glucose levels due to insulin deficiency caused by loss of pancreatic b-cells, and it is a common chronic disease in children and adolescents, along with mental disorders (2,21,22). Studies have shown that T1DM brings great psychological burden to children and adolescents, and greatly increases the risk of mental health problems (23)(24)(25).…”

Anti‐glomerular basement membrane disease in a patient with Type 2 diabetic mellitus: Long‐term remission of the two after immunomodulatory therapy

“…Similarly, the prevalence of IA is not a universal phenomenon in T1DM, and around one-fourth of T1DM may lack IA [3]. Diabetes is a heterogeneous disease with no pathognomonic genetic and autoimmune markers, and the distinction is based on phenotypic and clinical behavior, and with this premise, routine IA testing is also not recommended [3]. Autoimmunity can be implicated in the pathogenesis of disease by demonstrating specific circulating autoantibodies, histopathological evidence of autoimmune inflammation, and the beneficial effects of immunomodulatory therapy [4].…”

“…IA was found in 11.6% of patients with clinically diagnosed T2DM [2]. Similarly, the prevalence of IA is not a universal phenomenon in T1DM, and around one-fourth of T1DM may lack IA [3]. Diabetes is a heterogeneous disease with no pathognomonic genetic and autoimmune markers, and the distinction is based on phenotypic and clinical behavior, and with this premise, routine IA testing is also not recommended [3].…”