Beyond the glycation gap: A multicompartment framework for HbA1c-glycemia discordance in Pediatric type 1 diabetes

HbA1c is analytically standardized but biologically indirect: the measured value integrates glucose exposure through erythrocyte survival, age distribution, intracellular glucose handling, hemoglobin chemistry, and assay behavior. Continuous glucose monitoring (CGM) has made this indirection clinically visible by revealing recurrent disagreement between laboratory HbA1c and sensor-derived glycemia in children and adolescents with type 1 diabetes. This focused narrative review reframes pediatric HbA1c-glycemia discordance as a measurement-biology problem rather than a single 'glycation gap.' We separate three non-equivalent residual constructs, organize the evidence across glucose exposure, extracellular protein glycation, and erythrocyte-dependent glycation, and introduce a trait-state-measurement decomposition of discordance. We distinguish glycated albumin from fructosamine, separate CGM analytical error from interstitial-glucose physiology and temporal representativeness, and grade mechanistic claims as established, supported-but-incomplete, or hypothesis-generating. Direct pediatric evidence confirms that discordance is common and partly persistent, but mechanistic adjudication remains limited because most studies measure only two domains. We therefore propose a hypothesis-localization framework - not a validated diagnostic or therapeutic algorithm - in which analytical validity and temporal alignment precede triangulation. The central aim is explainable disagreement: understanding why valid measurements differ before allowing the difference to influence care.