Insulin resistance, metabolic dysfunction-associated steatotic liver disease, and advanced liver fibrosis in lean US adults: a population-based study.

Background: While insulin resistance (IR) and metabolic dysfunction-associated steatotic liver disease (MASLD) are well established in obese individuals, their connection in lean populations remains underexplored.

Methods: This cross-sectional study investigated the relations of IR with MASLD and advanced liver fibrosis based on data from the 2017-2020 US National Health and Nutrition Examination Surveys. The subjects were lean adults (non-Asian body mass index [BMI] < 25 kg/m, Asian BMI <23 kg/m) with transient elastography data, free from viral hepatitis, human immunodeficiency virus, excessive alcohol use, and diabetes. Multivariable generalized linear and logistic regression models were used to relate IR measures to hepatic fat content and visceral adiposity. The IR measures included homeostasis model assessment of insulin resistance (HOMA-IR), the quantitative insulin sensitivity check index (QUICKI), and homeostasis model assessment of β-cell function (HOMA-β).

Results: Among 860 lean adults (median age 53 years; 48% female; 38% White; mean BMI 22.5 kg/m), the age-adjusted prevalence of MASLD was 8.9%. Among individuals with MASLD, 84% had a high visceral adiposity index (>1.92). The percent change in controlled attenuation parameter associated with HOMA-IR, QUICKI, and HOMA-β was 11.62 (95% confidence interval [CI]: 6.31, 16.93), 0.76 (95% CI: 0.26, 1.26), and -162.72 (95% CI: -260.94, -64.50), respectively. HOMA-IR (adjusted odds ratio [aOR]: 2.60, 95% CI: 1.36, 4.98), QUICKI (aOR: 1.06, 95% CI: 1.01, 1.11), and HOMA-β (aOR: 0.04, 95% CI: 0.01, 0.56) were each associated with MASLD. HOMA-IR was associated with advanced liver fibrosis (aOR: 1.51, 95% CI: 1.19, 2.15).

Conclusion: MASLD and advanced liver fibrosis in lean individuals are linked to IR, independently of excess adiposity. Assessing IR could aid in identifying lean individuals at high risk of MASLD and liver fibrosis, regardless of diabetes status.