96-OR: Liver Fibrosis Scores in Novel Subclusters of Patients at Risk for Type 2 Diabetes

Metabolic diseases such as type 2 diabetes (T2D) are linked to the development of fatty liver, steatohepatitis and liver fibrosis. We have previously described novel clusters of patients at risk for T2D. Three clusters (3, 5 and 6) either had a high risk to progress to T2D or to develop cardiorenal complications. While high-risk clusters differ in liver fat content, it remains unknown if they also harbor a different risk for hepatic fibrosis. Thus, we determined clinically applicable scores of liver fibrosis in 1115 subjects at risk for T2D from the TUEF/TULIP study, which were categorized into high-risk clusters (n=602). Liver fat content was determined by ¹H-magnetic resonance spectroscopy. The AST-to-platelet-ratio index (APRI), fibrosis-4 score (FIB-4) and NAFLD fibrosis score (NFS) were used to determine fibrosis risk. ANCOVA model analysis adjusted for liver fat content was performed. Of the high-risk clusters (3: n= 83, 5: n= 203, 6: n= 316), cluster 6 had the highest BMI 44.1±9.7 kg/m² (vs. cluster 3: 29.7±3.1 kg/m², p<0.001 and cluster 5: 42.8.0±8.7, p=0.32) and cluster 5 had the highest liver fat content (13.4±8.8% vs. cluster 3: 8.0±6.5, p<0.001 and cluster 6: 9.0±6.7, p<0.001). All fibrosis scores correlated with liver fat content (e.g. FIB-4: r= 0.45, p< 0.0001). Although FIB-4, APRI and NFS were generally low, they were highest in cluster 5, but despite highest liver fat content, they did not differ from cluster 3 and 6 (e.g. FIB-4: cluster 5: 0.19±0.45 vs. cluster 3: 0.14±0.01, p=0.59 and cluster 6: 0.12±0.15, p=0.39). Interestingly, cluster 3 with the lowest liver fat content exhibited higher FIB-4 compared to cluster 6 (p=0.02). According to clinically applicable scores, the most insulin resistant cluster 5 has the highest FIB-4 score. The insulin deficient cluster 3 has a relatively high FIB-4 score despite relatively low liver fat content and BMI. Further studies are needed to investigate the clinical relevance of these findings.