HbA1c-GMI relative gap as emerging risk factor for early onset retinopathy in type 1 diabetes

Fabian Lurquin; Elise Petit; Philippe Oriot; Sylvie Ahn; Michel Hermans

doi:10.1530/endoabs.112.021

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Endocrine Abstracts (2025) 112 021 | DOI: 10.1530/endoabs.112.021

BES2025 BES 2025 CLINICAL STUDIES (21 abstracts)

HbA1c-GMI relative gap as emerging risk factor for early onset retinopathy in type 1 diabetes

Fabian Lurquin ¹ , Elise Petit ² , Philippe Oriot ³ , Sylvie Ahn ⁴ & Michel Hermans ¹

Author affiliations

¹Department of Endocrinology and Nutrition, Cliniques Universitaires Saint-Luc, Brussels, Belgium; ²Institute for Interdisciplinary Innovation in Healthcare (I3H) / TIMES 2, European Center for Advanced Research in Economics and Statistics (ECARES), Université Libre de Bruxelles, Brussels, Belgium; ³Centre Hospitalier de Mouscron, Service d’Endocrinologie-Diabétologie, Mouscron, Belgium; ⁴P ôle de Recherche Cardiovasculaire, Institut de Recherche ExP érimentale et Clinique (IREC), Université Catholique de Louvain, Brussels, Belgium

Introduction: To evaluate the phenotype of individuals with type 1 diabetes wearing Continuous Glucose Monitoring (CGM), identified as hyperglycators based on discrepancy between haemoglobin A1c (HbA1c) and Glucose Management Indicator (GMI). The primary outcome was to determine whether hyperglycators are at higher risk of diabetic retinopathy (DR) compared to individuals whose GMI is concordant or lower than HbA1c. The secondary outcome aimed at identifying factors associated with hyperglycation.

Methods: This retrospective study investigated 411 CGM-wearing patients with type 1 diabetes as regards HbA1c-GMI and cardiometabolic phenotype, including micro- and macroangiopathies, with longitudinal followup for onset of DR. Patients, with underlying conditions altering red blood cell lifespan, were excluded. We hypothesized that defining hyperglycation as relative HbA1c-GMI difference (Δ_HbA1c-GMI) was appropriate, given heteroskedasticity between HbA1c and GMI (White test P <0.001). A Delphi panel established a Δ_HbA1c-GMIof ±5% as clinically relevant, thus defining hyperglycation as an HbA1c value ≥5% above the corresponding GMI figure. Patients were categorized into 3 groups according to Δ_HbA1c-GMI (≥5%; hyperglycator, <5 & >-5%; normoglycator, ≤-5%; hypoglycator) of equivalent periods.

Results: 143 patients (35%) were hyperglycators. Hyperglycation was associated with higher odds of new-onset DR over the retrospective study period (adjusted Cox hazard ratio 1.78). On average, retinopathy was diagnosed 6 and 7 years earlier in hyperglycators compared to hypoglycators and normoglycators, respectively. Current smoking, and non-HDL-C were associated with hyperglycation (adjusted OR 2.41 and 1.01, respectively). Association of hyperglycation approached statistical significance with metformin use, red blood cell distribution width coefficient of variation, and reduced glomerular filtration rate. Using an absolute difference of 0.4% yielded similar results, equally classifying absolute hyperglycators at higher microvascular risk.

Conclusion: An HbA1c value ≥5% greater than matching GMI is associated with earlier onset DR among patients with type 1 diabetes. Current smoking and non-HDL-C were significantly associated with hyperglycation.

Keywords: Type 1 diabetes, hyperglycation, glycation gap, HbA1c-GMI discordance, retinopathy