| Title: | The role of insulin resistance in the longitudinal progression from NAFLD to cardiovascular-kidney-metabolic disease |
| Journal: | Cardiovascular Diabetology |
| Published: | 15 Oct 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/41094544/ |
| DOI: | https://doi.org/10.1186/s12933-025-02953-9 |
| URL: | https://cardiab.biomedcentral.com/counter/pdf/10.1186/s12933-025-02953-9 |
Publication 19172
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Abstract
Background and objectiveThis study aimed to elucidate the role of insulin resistance in the progression from non-alcoholic fatty liver disease (NAFLD) to cardiovascular-kidney-metabolic (CKM) diseases, and to explore the potential influence of lifestyle factors.MethodsThis study included participants free of NAFLD and CKM diseases from the UK Biobank. Insulin resistance was assessed using the TyG index. CKM diseases include ischemic stroke (IS), ischemic heart disease (IHD), type 2 diabetes (T2D), and chronic kidney disease (CKD). Markov multi-state models were used to assess the associations between the TyG index and disease transitions.ResultsAmong 377,757 participants (median age 57 years), 4949 developed NAFLD over a median follow-up of 13.6 years. Of these, 12.65% progressed to T2D, 9.11% to IHD, 8.63% to CKD, and 4.61% to IS. Elevated TyG levels significantly accelerated transitions from NAFLD to first-onset CKM disease (HR = 1.25, 95% CI 1.05-1.49), double CKM disease (HR = 1.46, 95% CI 1.19-1.80), and triple CKM disease (HR = 1.81, 95% CI 1.28-2.55). Similar progression risk increases were observed for individual CKM components: T2D (HR = 1.41, 95% CI 1.11-1.78), CKD (HR = 1.37, 95% CI 1.08-1.75), and IS (HR = 1.70, 95% CI 1.27-2.27). A J-shaped dose-response relationship was identified. Transitions risk remained pronounced among individuals with healthy sleep and regular physical activity.ConclusionsInsulin resistance independently accelerated the progression from NAFLD to CKM diseases, particularly ischemic stroke. Healthy sleep and regular physical activity failed to offset this detrimental impact.Graphical abstract</p>
20 Keywords
- Adult
- Aged
- Biomarkers
- Cardiovascular Diseases
- Diabetes Mellitus, Type 2
- Disease Progression
- Female
- Humans
- Insulin Resistance
- Longitudinal Studies
- Male
- Middle Aged
- Myocardial Ischemia
- Non-alcoholic Fatty Liver Disease
- Prognosis
- Renal Insufficiency, Chronic
- Risk Assessment
- Risk Factors
- Time Factors
- United Kingdom
9 Authors
- Chao Hou
- Xiangling Yuan
- Min Peng
- Xuan Shi
- Dahong Yang
- Fang Wang
- Ke Song
- Gelin Xu
- Jianzhong Shi
1 Application
| Application ID | Title |
|---|---|
| 540121 | Omics Data Reveals Mechanisms of Neurological Diseases |
Enabling scientific discoveries that improve human health