High-Amplitude and Prolonged Glucose Excursions as a Key Determinant of Discordance Between Glucose Management Indicator and Glycated Hemoglobin in Type 1 Diabetes.

Abstract

Discordance between the glucose management indicator (GMI) and hemoglobin A1c (HbA1c) is frequently observed in diabetes, yet its physiological basis remains unclear. This study investigated how specific glucose excursion patterns captured by continuous glucose monitoring (CGM) contribute to this discordance in individuals with type 1 diabetes. Ninety-day CGM traces from 611 adults with type 1 diabetes were paired with HbA1c results obtained within ±15 days. Glucose excursions were quantified using the glucose rate increase detector (GRID) algorithm with varied peak glucose and time-to-peak thresholds. Discordance was defined using GMI-to-HbA1c and updated GMI (uGMI)-to-HbA1c ratios, and associations with GRID-derived excursion metrics were evaluated alongside conventional CGM-derived variability metrics. Excursions with peak glucose ≥250 mg/dL and time to peak ≥90 min were significantly associated with higher uGMI-to-HbA1c ratios after adjustment for age, sex, eGFR, and HbA1c group, with consistent findings across CGM devices (sensor type 1: β = 0.174, 95% CI 0.147-0.201; sensor type 2: β = 0.102, 95% CI 0.068-0.136; both P < 0.001) and alternative GMI formulations. In restricted cubic spline analyses, adjustment for GRID-derived excursion metrics differentially reshaped the associations of HbA1c, GMI, and uGMI with albuminuria and elevated triglyceride-glucose (TyG) index in an outcome- and context-dependent manner, preferentially enhancing the informativeness of GMI and uGMI-but not HbA1c. Frequent high and prolonged glucose excursions were consistently associated with GMI-HbA1c discordance across devices, HbA1c strata, and analytic conditions. GRID-derived excursion metrics modify the relationship between GMI/uGMI and glycemia-associated risk.