A new study found that each additional metabolic comorbidity in T2D patients significantly heightens the risk for liver disease progression, particularly MASLD––hypertension and CKD being the most significant factors.
Type 2 diabetes (T2D) significantly increases the risk of major adverse liver outcomes (MALOs), such as cirrhosis and its complications. Patients with T2D often have other traits of metabolic syndrome (MetS). However, it is unclear if the accumulation of these traits synergistically increases the risk of future liver disease.
Methods
This research examined patients with T2D without a history of liver disease, using data from Swedish national registers from 1998 to 2021. MetS traits included – hypertension, low high-density lipoprotein (HDL) cholesterol levels, hypertriglyceridemia, obesity and albuminuria, alongside T2D. MALO events were identified through administrative coding until October 2022 and the data was analysed using Cox regression models.
Results
Overall, 230,992 patients were identified (median age 64 years; 58% male) – of whom 3,215 (1.39%) developed MALOs over a median follow-up of 9.9 years. It was observed that patients with more than one MetS trait had a significantly higher rate of MALOs compared to those with only T2D at baseline. Additionally, the MALOs risk increased progressively with the number of MetS traits. Those who acquired additional MetS traits during follow-up also faced higher MALOs rates. Among the MetS traits, hypertension showed the largest association with incident MALOs.
The results depicted that the presence or acquisition of additional MetS traits heightens liver disease progression rate in T2D patients.
These findings underscored the need for targeted liver disease screening in T2D patients. There exists a direct association between poor metabolic health and liver disease risk in this population.
Results
This large-scale study revealed a stepwise increase in liver disease risk with each added MetS trait. Notably, acquiring additional MetS traits post-T2D diagnosis further elevates this risk. Specifically, hypertension and chronic kidney disease (CKD showed the strongest associations with incident MALOs. Interestingly, hyperlipidaemia was negatively associated with liver disease – likely due to the protective effects of statin treatments, which are known to have hepatoprotective effects.
Hypertension emerged as a critical factor, significantly elevating the risk when combined with other MetS traits. For instance, patients with both hypertension and obesity or low HDL levels faced the highest risk for liver disease progression. This aligns with previous research suggesting that hypertension and metabolic-associated liver disease (MASLD) have a bidirectional relationship––with each condition exacerbating the other.
Discussion
The findings of this study were consistent with earlier studies, which also reported that each additional metabolic trait increases the risk of MALOs, independent of alcohol intake. This supports the idea that metabolic factors alone can significantly impact liver outcomes. Notably, This study extends previous research by including a less selected population, making the findings more generalizable to the broader T2D community.
This study highlighted the importance of treating not only hyperglycaemia in T2D patients but also other metabolic comorbidities to reduce the risk of liver-related complications. Specifically, managing hypertension and obesity is crucial in preventing the development of cirrhosis. Future treatments for MASLD might be more effective if the overall metabolic health is concurrently addressed.
The results also emphasized the need for personalised risk prediction in T2D patients. Future research should explore non-invasive tests, such as – fibrosis 4 score or vibration-controlled transient elastography, to enhance liver disease prediction in T2D patients.
The strengths of this study include – high-quality registers, large sample size, and comprehensive data analysis, making the findings precise and generalizable. The limitations recount – the lack of direct data on MASLD severity and the exclusion of a significant number of patients due to missing data on MetS traits. Future studies should focus on continuous versions of MetS traits for a more detailed understanding and consider the severity of each trait.
The results highlighted that an increasing number of metabolic comorbidities in T2D patients correlates with a higher risk of liver disease progression, particularly MASLD. Hypertension and CKD were the most significant factors, whereas hyperlipidaemia showed no positive association.
These findings can guide targeted screening and management strategies to improve outcomes for T2D patients.
Keywords: Type 2 Diabetes, Liver Disease, Metabolic Syndrome, Cirrhosis Risk, Hypertension and T2D, Metabolic Health, MASLD Prevention
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