Addressing shortfalls of laboratory HbA1c using a model that incorporates red cell lifespan.

Laboratory HbA1c does not always predict diabetes complications and our aim was to establish a glycaemic measure that better reflects intracellular glucose exposure in organs susceptible to complications. Six months of continuous glucose monitoring data and concurrent laboratory HbA1c were evaluated from 51 type 1 diabetes (T1D) and 80 type 2 diabetes (T2D) patients. Red blood cell (RBC) lifespan was estimated using a kinetic model of glucose and HbA1c, allowing the calculation of person-specific adjusted HbA1c (aHbA1c). Median (IQR) RBC lifespan was 100 (86-102) and 100 (83-101) days in T1D and T2D, respectively. The median (IQR) absolute difference between aHbA1c and laboratory HbA1c was 3.9 (3.0-14.3) mmol/mol [0.4 (0.3-1.3%)] in T1D and 5.3 (4.1-22.5) mmol/mol [0.5 (0.4-2.0%)] in T2D. aHbA1c and laboratory HbA1c showed clinically relevant differences. This suggests that the widely used measurement of HbA1c can underestimate or overestimate diabetes complication risks, which may have future clinical implications.