Discordance between mean glucose and time in range in relation to HbA1c in individuals with type 1 diabetes: results from the GOLD and SILVER trials.

AIMS/HYPOTHESIS: Previous studies have shown that individuals with similar mean glucose levels (MG) or percentage of time in range (TIR) may have different HbA1c values. The aim of this study was to further elucidate how MG and TIR are associated with HbA1c. METHODS: 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 HbA1c/continuous glucose monitoring measurements were included. Linear mixed-effects models were used to account for intra-individual correlations in repeated-measures data. RESULTS: In the GOLD trial, the mean age of the participants (± SD) was 44±13 years, 63 (44%) were female, and the mean HbA1c (± SD) was 72±9.8 mmol/mol (8.7±0.9%). When correlating MG with HbA1c, MG explained 63% of the variation in HbA1c (r=0.79, p<0.001). The variation in HbA1c 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-HbA1c 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 HbA1c of 10% of individuals deviated by >8 mmol/mol (0.8%) from their estimated HbA1c based on the overall association between MG and TIR with HbA1c. TBR and TAR level 2 significantly influenced the association between TIR and HbA1c. At a given TIR, each 1% increase in TBR was related to a 0.6 mmol/mol lower HbA1c (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 HbA1c (95% CI 0.1, 0.6; p=0.003). However, neither TIR, TBR nor TAR level 2 were significantly associated with HbA1c when accounting for MG. CONCLUSIONS/INTERPRETATION: Inter-individual variations exist between MG and HbA1c, as well as between TIR and HbA1c, 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.

Associations of bolus insulin injection frequency and smart pen engagement with glycaemic control in people living with type 1 diabetes.

AIM: To evaluate whether both bolus insulin injection frequency and smart pen engagement were associated with changes in glycaemic control, using real-world data from adults with type 1 diabetes (T1D). MATERIALS AND METHODS: Adults using a smart pen (NovoPen 6) to administer bolus insulin (fast-acting insulin aspart or insulin aspart) alongside continuous glucose monitoring were eligible for inclusion. Smart pen engagement was characterized by number of days with pen data uploads over the previous 14 days. Glycaemic control was evaluated by analysing glucose metrics. RESULTS: Overall, data from 1194 individuals were analysed. The number of daily bolus injections was significantly associated with time in range (TIR; 3.9-10.0 mmol/L [70-180 mg/dL]; P < 0.0001). Individuals administering, on average, three daily bolus insulin injections had an estimated 11% chance of achieving >70% TIR. The probability of achieving >70% TIR increased with the mean number of daily bolus injections. However, the percentage of TIR was lower on days when individuals administered higher-than-average numbers of injections. The observed mean number of daily bolus injections administered across the study population was lower than the optimal number required to reach glycaemic targets (4.8 injections vs. 6-8 injections). Smart pen engagement was significantly associated with improved TIR. CONCLUSIONS: Glycaemic control was associated with daily bolus insulin injection frequency and smart pen engagement. A treatment regimen combining an optimal bolus injection strategy, and effective smart pen engagement, may improve glycaemic control among adults with T1D.