| Title: | HbA1c trajectories and the risk of liver-related events in patients with type 2 diabetes mellitus |
| Journal: | Journal of Hepatology |
| Published: | 26 Jun 2026 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/42362059/ |
| DOI: | https://doi.org/10.1016/j.jhep.2026.06.029 |
Publication 20523
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Abstract
BACKGROUND & AIMS: We assessed associations of time-weighted average haemoglobin A1c (HbA1c), time-to-target HbA1c, HbA1c variability, and individual HbA1c trajectories with liver-related events (LREs) in type 2 diabetes mellitus (T2DM).</p>
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 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 competing risk.</p>
RESULTS: Among 294,096 patients identified (mean age, 60.6 years; 50.6% males), 3,438 (1.2%) developed LREs at a median 7.4 (IQR, 4.5-10.0) years follow-up. 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 high variability were associated with a higher risk of LREs, while 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 with patients with baseline HbA1c<7% and 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; whereas rapid decreasing trajectory was not associated with a higher risk (aCSHR 1.05, 95%CI 0.90-1.22, p=0.57).</p>
CONCLUSIONS: Time-weighted average HbA1c, cumulative duration of good glycaemic control, HbA1c variability and trajectories correlated with LREs in T2DM. Rapid decreasing trajectory may mitigate LRE risk in patients with high baseline HbA1c.</p>
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 associated with increased risk of LREs. Our findings suggest that patients with rapid glycaemic control of newly diagnosed T2DM could benefit from reduced risk of LREs, and careful monitoring and intensified intervention should be maintained for patients who develop mild decreasing or increasing HbA1c trajectories.</p>
7 Authors
- Nana Peng
- Sharlot Juan Song
- Mary Yue Wang
- Jimmy Che-To Lai
- Grace Lai-Hung Wong
- Vincent Wai-Sun Wong
- Terry Cheuk-Fung Yip
1 Application
| Application ID | Title |
|---|---|
| 431566 | Secular trend of biomarkers and other factors and unsupervised trajectory clustering for predicting risk of metabolic disorders and liver-related diseases |
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