Testing methods used to predict disease progression in children with early-stage type 1 diabetes: A systematic review and meta-analysis.

AimsCurrent guidance on how best to monitor children and young people (CYP) with early-stage type 1 diabetes is evidenced mainly by expert consensus. This systematic review and meta-analysis aims to evaluate the current evidence for tests used to predict disease progression.MethodsData were sourced from PubMed, Cochrane Central, Ovid Embase and Scopus. The association (hazard ratio [HR]) between test positivity and progression to stage 3 type 1 diabetes in CYP aged ≤18 years with ≥2 islet autoantibodies was examined. Data were pooled using random effects models, and the Hartung-Knapp-Sidik-Jonkman (HKSJ) method was used to adjust confidence intervals to account for greater uncertainty. The risk of bias was evaluated using the QUADAS-2 tool (CRD42023393960).ResultsIn this study, 12,923 studies were identified and 285 underwent full-text review. Thirty-four studies (n = 6866 CYP, median age 11.8 years [IQR, 6.6-13.8]) were included. Overall, 2080 (30%) CYP progressed to stage 3 type 1 diabetes over a median follow-up of 5 years (IQR 2-5). The pooled HR for tests that predicted progression were: 1.40 (95% CI 1.07-1.84) for fasting glucose (OGTT), 3.19 (1.75-5.82) for 2-h glucose (OGTT), 6.43 (1.21-34.18) for the M120 above the median value, 3.12 (2.19-4.43) per 1-unit increase in Index 60 and 1.40 (1.17-1.68) per 1.1 mmol/mol increase in HbA1c (C-statistics 0.7-0.8). Evidence for other tests, including CGM, was uncertain.ConclusionsThe OGTT, its related tests (M120, Index60) and HbA1c predict progression to stage 3 in CYP with early-stage type 1 diabetes. Other tests, including CGM, need more evidence to support their use as predictive tests in this context.