Discordance between mean glucose and time in range in relation to HbA_1c in individuals with type 1 diabetes: results from the GOLD and SILVER trials

Previous studies have shown that individuals with similar mean glucose levels (MG) or percentage of time in range (TIR) may have different HbA_1c values. The aim of this study was to further elucidate how MG and TIR are associated with HbA_1c.

Data from the randomised clinical GOLD trial (n=144) and the follow-up SILVER trial (n=98) of adults with type 1 diabetes followed for 2.5 years were analysed. A total of 596 paired HbA_1c/continuous glucose monitoring measurements were included. Linear mixed-effects models were used to account for intra-individual correlations in repeated-measures data.

In the GOLD trial, the mean age of the participants (± SD) was 44±13 years, 63 (44%) were female, and the mean HbA_1c (± SD) was 72±9.8 mmol/mol (8.7±0.9%). When correlating MG with HbA_1c, MG explained 63% of the variation in HbA_1c (r=0.79, p<0.001). The variation in HbA_1c explained by MG increased to 88% (r=0.94, p value for improvement of fit <0.001) when accounting for person-to-person variation in the MG–HbA_1c relationship. Time below range (TBR; <3.9 mmol/l), time above range (TAR) level 2 (>13.9 mmol/l) and glycaemic variability had little or no effect on the association. For a given MG and TIR, the HbA_1c of 10% of individuals deviated by >8 mmol/mol (0.8%) from their estimated HbA_1c based on the overall association between MG and TIR with HbA_1c. TBR and TAR level 2 significantly influenced the association between TIR and HbA_1c. At a given TIR, each 1% increase in TBR was related to a 0.6 mmol/mol lower HbA_1c (95% CI 0.4, 0.9; p<0.001), and each 2% increase in TAR level 2 was related to a 0.4 mmol/mol higher HbA_1c (95% CI 0.1, 0.6; p=0.003). However, neither TIR, TBR nor TAR level 2 were significantly associated with HbA_1c when accounting for MG.

Inter-individual variations exist between MG and HbA_1c, as well as between TIR and HbA_1c, with clinically important deviations in relatively large groups of individuals with type 1 diabetes. These results may provide important information to both healthcare providers and individuals with diabetes in terms of prognosis and when making diabetes management decisions.