Using Homeostatic Model Assessment of Insulin Resistance to Improve Metabolic Dysfunction-Associated Steatotic Liver Disease Risk Stratification in Individuals with Type 2 Diabetes from Primary Care and Endocrinology Settings.

Abstract

Objectives: Current metabolic dysfunction-associated steatotic liver disease (MASLD) guidelines recommend fibrosis screening in individuals with type 2 diabetes (T2D) because of their increased risk of clinically significant fibrosis (≥F2). However, fibrosis risk is variable, and clinical tools to identify individuals at lower risk are lacking. We evaluated whether assessment of insulin resistance by homeostatic model assessment of insulin resistance (HOMA-IR) could improve risk stratification for clinically significant fibrosis.

Methods: We prospectively recruited 501 adults with T2D from primary care and endocrinology clinics. Participants were classified as insulin-resistant (HOMA-IR ≥2.5; n=350) or insulin-sensitive (HOMA-IR <2.5; n=151). Liver steatosis was assessed using VCTE, MRI/MRE, or liver biopsy according to the most accurate test, and the prevalence of clinically significant fibrosis (≥F2) was compared between groups.

Results: Insulin-resistant participants had higher prevalence of clinically significant fibrosis than insulin-sensitive participants (≥F2: 10% vs. <1%; p<0.001). They also had greater hepatic steatosis, higher ALT, AST, CK-18, HbA1c, and adipose tissue insulin resistance (Adipo-IR) levels, and lower adiponectin concentrations (all p<0.001). Fibrosis was infrequent among insulin-sensitive participants and almost exclusively limited to mild fibrosis (stage F1). Among participants with steatosis, ≥F2 fibrosis was present in 1% of insulin-sensitive participants compared with 13% of insulin-resistant participants (p<0.001).

Conclusions: Clinically significant fibrosis (≥F2) was uncommon among insulin-sensitive individuals with T2D and largely limited to mild fibrosis (F1). HOMA-IR <2.5 identified a subgroup at very low risk for fibrosis, supporting its potential use as a simple, clinically accessible tool for MASLD risk stratification in primary care and endocrinology settings.