ISPAD Clinical Practice Consensus Guidelines 2024: Screening, Staging, and Strategies to Preserve Beta-Cell Function in Children and Adolescents with Type 1 Diabetes

Abstract

The International Society for Pediatric and Adolescent Diabetes (ISPAD) guidelines represent a rich repository that serves as the only comprehensive set of clinical recommendations for children, adolescents, and young adults living with diabetes worldwide. This guideline serves as an update to the 2022 ISPAD consensus guideline on staging for type 1 diabetes (T1D). Key additions include an evidence-based summary of recommendations for screening for risk of T1D and monitoring those with early-stage T1D. In addition, a review of clinical trials designed to delay progression to Stage 3 T1D and efforts seeking to preserve beta-cell function in those with Stage 3 T1D are included. Lastly, opportunities and challenges associated with the recent US Food and Drug Administration (FDA) approval of teplizumab as an immunotherapy to delay progression are discussed. The International Society for Pediatric and Adolescent Diabetes (ISPAD) guidelines represent a rich repository that serves as the only comprehensive set of clinical recommendations for children, adolescents, and young adults living with diabetes worldwide. This guideline serves as an update to the 2022 ISPAD consensus guideline on staging for type 1 diabetes (T1D). Key additions include an evidence-based summary of recommendations for screening for risk of T1D and monitoring those with early-stage T1D. In addition, a review of clinical trials designed to delay progression to Stage 3 T1D and efforts seeking to preserve beta-cell function in those with Stage 3 T1D are included. Lastly, opportunities and challenges associated with the recent US Food and Drug Administration (FDA) approval of teplizumab as an immunotherapy to delay progression are discussed.

Keywords: Beta cell; Children; Preservation; Screening; Stages; Type 1 diabetes.

Fig. 1.

Stages of type 1 diabetes (T1D). A small proportion of people who have increased genetic risk of T1D progress at variable rates to immune activation and the development of islet autoimmunity. Clinically available islet AABs include ICA, GADA, IAA, IA-2A, and ZnT8A. Once 2 or more islet AABs are confirmed (Stage 1) there is near certainty of progression to clinical diabetes during the person’s lifetime. Stage 1 is typically followed by the development of dysglycemia (Stage 2), though this stage may not be detected when T1D progression is rapid. People who develop Stage 3 T1D may be asymptomatic (Stage 3a) or symptomatic (Stage 3b). Discussions regarding initiation of insulin in people with Stage 3a T1D must balance risk and benefit. Established T1D is described as Stage 4. All people with Stage 1 or greater have T1D and should not be referred to as having “risk” for the condition. Use of stages should not be overly dogmatic as many people with T1D fluctuate between stages. Many of the glycemic thresholds are arbitrary but remain useful to describe people with T1D for both clinical and research purposes. Rates of decline of beta-cell function vary as does the course of insulin requirements after diagnosis.

Fig. 2.

Screening and monitoring in children and adolescents with single or multiple AABs. Age and number of islet AABs dictate the frequency and intensity of recommended monitoring for those with single or multiple AABs. Single or multiple AABs status should be confirmed in a second sample. AAB, autoantibodies; CGM, continuous glucose monitoring; OGTT, oral glucose tolerance test.