Type 2 diabetes (T2DM) substantially increases the risk of steatotic liver disease and fibrosis, yet the specific clinical, metabolic, and genetic determinants of fibrosis in Indian-origin individuals remain poorly understood. South Asians are known to develop liver fat and metabolic complications at lower body-mass indices than White Europeans, but robust population-level data on hepatic fibrosis in this group are lacking.
This project will use UK Biobank data to identify factors associated with significant or advanced liver fibrosis among participants of Indian ancestry with T2DM. We will integrate demographic, clinical, biochemical, and lifestyle variables with known genetic variants implicated in metabolic liver disease (PNPLA3 I148M, TM6SF2 E167K, HSD17B13, MARC1 and related polymorphisms). Fibrosis will be assessed using validated non-invasive indices (FIB-4, NFS, APRI) derived from baseline laboratory values and will be linked to liver-related outcomes through hospital and mortality records.
The primary research question is: Which clinical, metabolic, and genetic factors independently predict advanced hepatic fibrosis in Indian-origin individuals with T2DM? Secondary objectives include quantifying the relative contributions of glycaemic control, adiposity, lipid profile, inflammatory markers, and medication use, and exploring gene-metabolic interactions (e.g., PNPLA3 × BMI, TM6SF2 × triglycerides).
By focusing on an ethnically distinct, high-risk subgroup, this study will generate new evidence on ethnic-specific drivers of fibrosis progression and inform targeted prevention and screening strategies for South-Asian populations worldwide.