Glycemic Markers and Cardiometabolic Multiple Long-Term Conditions: Comparative Roles of Glycated Hemoglobin and Fasting Plasma Glucose in the English Longitudinal Study of Ageing

Objective To examine and contrast the associations of glycated hemoglobin (HbA1c) and fasting plasma glucose (FPG) with the risk of cardiometabolic multiple long-term conditions (cMLTC) and evaluate their incremental predictive utility. Patients and Methods The study analyzed 2233 adults (mean age 63; 1009 (45.2%) men) free of hypertension, coronary disease, diabetes, and stroke at baseline (wave 4; 2008-2009). Incident cardiometabolic multimorbidity (≥2 of these conditions) was assessed at wave 10 (2021-2023). Logistic regression, restricted cubic splines, and discrimination metrics evaluated predictors and predictive performance. Results Over 12-15 years, 129 participants developed cMLTC (57.8 per 1000; 95% CI, 48.5-68.3). Restricted cubic splines showed continuous, dose–response relationships between HbA1c and FPG with cMLTC risk. HbA1c was strongly associated with cMLTC (per 1% increase, OR 1.99; 95% CI, 1.51-2.63; highest vs lowest tertile, OR 3.15; 95% CI, 2.00-4.94), whereas FPG associations were more modest (per 1 mmol/L: OR 1.39; 95% CI, 1.18-1.64; tertile: OR 1.98; 95% CI, 1.23-3.19) and attenuated after mutual adjustment. Adding HbA1c to established risk factors improved discrimination (ΔC-index=0.0344, P <.001) and fit ( P <.001) more than FPG (ΔC-index=0.0171, P =.017; between-marker P =.050). Conclusion In this nationally representative cohort of older adults in England, higher HbA1c and FPG levels were each associated with an increased risk of cMLTC and enhanced risk prediction. However, HbA1c emerged as a substantially stronger and more informative marker than FPG.