Journal of hepatology · 2026
HbA1c trajectories and the risk of liver-related events in patients with type 2 diabetes mellitus.
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Peng Nana, Song Sherlot Juan, Wang Mary Yue, Lai Jimmy Che-To, Wong Grace Lai-Hung, Wong Vincent Wai-Sun, Yip Terry Cheuk-Fung
Аннотация
BACKGROUND & AIMS: The relationship between long-term glycaemic control and liver-related events (LREs) in patients with type 2 diabetes mellitus (T2DM) remains unclear. We assessed associations of time-weighted average haemoglobin A1c (HbA1c), time-to-target HbA1c, HbA1c variability, and individual HbA1c trajectories with LREs in T2DM.
METHODS: A territory-wide cohort of adults newly diagnosed with T2DM (Jan 2000-Dec 2016) was identified in Hong Kong. HbA1c trajectories were identified via time-series clustering and externally validated in the UK Biobank. Their associations with LREs were estimated in the Hong Kong territory-wide cohort using cause-specific hazards models, with non-liver-related death as a competing risk.
RESULTS: Among 294,096 patients identified (mean age, 60.6 years; 50.6% males), 3,438 (1.2%) developed LREs over a median follow-up of 7.4 years (IQR 4.5-10.0). Higher time-weighted average HbA1c (adjusted cause-specific hazard ratio [aCSHR] 1.12 per 1%, 95% CI 1.08-1.16, p <0.001) and greater HbA1c variability were associated with a higher risk of LREs, whereas more years with HbA1c <7% were associated with a lower risk (aCSHR 0.95 per year, 95% CI 0.93-0.96, p <0.001). Three trajectories were identified: rapid decreasing (n = 43,712; 14.9%), mild decreasing (n = 114,413; 38.9%), and increasing (n = 135,971; 46.2%). Compared with rapid decreasing, mild decreasing (aCSHR 1.30, 95% CI 1.13-1.50, p <0.001) and increasing (aCSHR 1.37, 95% CI 1.16-1.61, p <0.001) trajectories conferred higher risks. Compared to patients with baseline HbA1c <7% and a mild decreasing trajectory, those with baseline HbA1c ≥9% and mild decreasing (aCSHR 1.27, 95% CI 1.08-1.50, p <0.001) or increasing (aCSHR 1.84, 95% CI 1.45-2.34, p <0.001) trajectories had higher LRE risks. In contrast, a rapid decreasing trajectory was not associated with a higher risk (aCSHR 1.05, 95% CI 0.90-1.22, p = 0.57).
CONCLUSIONS: Time-weighted average HbA1c, cumulative duration of good glycaemic control, HbA1c variability, and HbA1c trajectories were associated with LREs in T2DM. A rapid decreasing trajectory may mitigate LRE risk in patients with high baseline HbA1c.
IMPACT AND IMPLICATIONS: The relationship between long-term glycaemic control and liver-related events (LREs) in patients with type 2 diabetes mellitus (T2DM) remains unclear. In this real-world territory-wide cohort study of 294,096 patients with newly diagnosed T2DM, patients with higher average HbA1c, cumulative exposure to high HbA1c and high HbA1c variability had a higher risk of LREs. Among patients with baseline HbA1c ≥9%, a rapid decreasing HbA1c trajectory was associated with a lower risk of LREs, with no statistically significant difference compared to patients whose baseline HbA1c was <7% and had a mild decreasing HbA1c trajectory, while those with baseline HbA1c ≥9% and mild decreasing or increasing HbA1c trajectories were at increased risk of LREs. These findings suggest that achieving rapid glycaemic improvement after T2DM diagnosis may reduce the risk of LREs, while patients who follow mild decreasing or increasing HbA1c trajectories may benefit from closer monitoring and more intensive intervention.
METHODS: A territory-wide cohort of adults newly diagnosed with T2DM (Jan 2000-Dec 2016) was identified in Hong Kong. HbA1c trajectories were identified via time-series clustering and externally validated in the UK Biobank. Their associations with LREs were estimated in the Hong Kong territory-wide cohort using cause-specific hazards models, with non-liver-related death as a competing risk.
RESULTS: Among 294,096 patients identified (mean age, 60.6 years; 50.6% males), 3,438 (1.2%) developed LREs over a median follow-up of 7.4 years (IQR 4.5-10.0). Higher time-weighted average HbA1c (adjusted cause-specific hazard ratio [aCSHR] 1.12 per 1%, 95% CI 1.08-1.16, p <0.001) and greater HbA1c variability were associated with a higher risk of LREs, whereas more years with HbA1c <7% were associated with a lower risk (aCSHR 0.95 per year, 95% CI 0.93-0.96, p <0.001). Three trajectories were identified: rapid decreasing (n = 43,712; 14.9%), mild decreasing (n = 114,413; 38.9%), and increasing (n = 135,971; 46.2%). Compared with rapid decreasing, mild decreasing (aCSHR 1.30, 95% CI 1.13-1.50, p <0.001) and increasing (aCSHR 1.37, 95% CI 1.16-1.61, p <0.001) trajectories conferred higher risks. Compared to patients with baseline HbA1c <7% and a mild decreasing trajectory, those with baseline HbA1c ≥9% and mild decreasing (aCSHR 1.27, 95% CI 1.08-1.50, p <0.001) or increasing (aCSHR 1.84, 95% CI 1.45-2.34, p <0.001) trajectories had higher LRE risks. In contrast, a rapid decreasing trajectory was not associated with a higher risk (aCSHR 1.05, 95% CI 0.90-1.22, p = 0.57).
CONCLUSIONS: Time-weighted average HbA1c, cumulative duration of good glycaemic control, HbA1c variability, and HbA1c trajectories were associated with LREs in T2DM. A rapid decreasing trajectory may mitigate LRE risk in patients with high baseline HbA1c.
IMPACT AND IMPLICATIONS: The relationship between long-term glycaemic control and liver-related events (LREs) in patients with type 2 diabetes mellitus (T2DM) remains unclear. In this real-world territory-wide cohort study of 294,096 patients with newly diagnosed T2DM, patients with higher average HbA1c, cumulative exposure to high HbA1c and high HbA1c variability had a higher risk of LREs. Among patients with baseline HbA1c ≥9%, a rapid decreasing HbA1c trajectory was associated with a lower risk of LREs, with no statistically significant difference compared to patients whose baseline HbA1c was <7% and had a mild decreasing HbA1c trajectory, while those with baseline HbA1c ≥9% and mild decreasing or increasing HbA1c trajectories were at increased risk of LREs. These findings suggest that achieving rapid glycaemic improvement after T2DM diagnosis may reduce the risk of LREs, while patients who follow mild decreasing or increasing HbA1c trajectories may benefit from closer monitoring and more intensive intervention.