Insulin Resistance Aids Detection of NAFLD in Lean Patients

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Results presented at ACG 2023 demonstrated the viability of the HOMA-IR model for calculating insulin resistance to identify lean NAFLD.

Findings from a recent study are supporting the role of insulin resistance as an independent predictor of lean nonalcoholic fatty liver disease (NAFLD), validating the clinical utility of the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) model for identifying NAFLD in lean individuals.

Presented by Manasik Abdu, MD, internal medicine chief resident physician at the University at Buffalo, at the American College of Gastroenterology (ACG) 2023 Annual Scientific Meeting in Vancouver, results from multivariable logistic regression analyses revealed HOMA-IR, HbA1c, and waist circumference were independent risk factors for NAFLD.1

“Lean NAFLD often goes undetected due to normal liver enzyme levels and the absence of diabetes. Early identification of lean NAFLD is vital for timely treatment and reducing complications,” wrote investigators.1

The exact cause of fatty liver disease is unknown, although it is frequently linked to being considered overweight, having elevated triglycerides and low-density lipoprotein, diabetes, and increased blood pressure.2 Obesity is present in 50% to 90% of patients diagnosed with NAFLD, but the condition can also affect individuals with a normal weight and body mass index. Often, knowledge gaps among clinicians inhibit their ability to provide adequate disease management for patients with lean NAFLD, highlighting the need for a more comprehensive understanding of best practices for diagnosis and treatment in these patients.3

To assess the clinical utility of the HOMA-IR model for identifying NAFLD in lean individuals, investigators performed multivariable logistic regression analyses using data from the 2017-2020 National Health and Nutrition Examination Survey for lean adults with valid transient elastography measurements. Patients with elevated alcohol consumption, viral hepatitis, or human immunodeficiency virus were excluded. In total, investigators enrolled 860 participants in the study. Among the cohort, the median age was 53 (interquartile range, 33-69) years and 416 (48%) participants were female.1

Investigators defined NAFLD as a controlled attenuation parameter ≥ 302 dB/m using Youden’s index, with lean NAFLD described as NAFLD in individuals with a body mass index < 25 kg/m2. The HOMA-IR model, a tool for measuring pancreatic beta-cell function and insulin resistance using the product of fasting glucose times fasting insulin, was used to calculate insulin resistance.1

Upon analysis, the age-adjusted prevalence of NAFLD in lean individuals was 8.9%. Investigators pointed out lean NAFLD was more prevalent among males than females (9.9% vs 7.9%; P < .01). In analyses adjusted for age, sex, race, and metabolic syndrome, independent risk factors for lean NAFLD included HOMA-IR > 2.0 (adjusted odds ratio [aOR], 1.40; 95% confidence interval [CI], 1.17-1.68), HbA1c (aOR, 1.29; 95% CI, 1.05-1.57), and waist circumference (aOR, 1.07; 95% CI, 1.02-1.12).1

Using receiver operating characteristic (ROC) curve analysis, investigators calculated the area under the ROC curve (AUC) of HOMA-IR for the identification of NAFLD as 0.81. An optimal sensitivity of 92.2% was achieved at HOMA-IR >1.4 cut-off with a negative predictive value of 97.8%. HOMA-IR >3.0 cut-off produced a specificity of 91.6% with a negative predictive value of 93.4%. Investigators noted the positive predictive value remained < 30% irrespective of the HOMA-IR cut-off.1

“This study demonstrated that insulin resistance is a robust independent predictor of lean NAFLD and provides, albeit indirect, evidence to support the role of insulin resistance in the pathogenesis of lean NAFLD. HOMA-IR may help clinicians quickly identify lean patients without diabetes who could benefit from NAFLD screening. Yet, its low positive predictive value limits its diagnostic utility,” concluded investigators.1


  1. Abdu M, Mohamed MFH, Njei B. 37 - Homeostasis Model Assessment of Insulin Resistance as a Clinical Marker of Non-Alcoholic Fatty Liver Disease in Lean Individuals. Paper presented at: ACG 2023 Annual Scientific Meeting. Vancouver, Canada. October 20 – 25, 2023.
  2. Johns Hopkins Medicine. Nonalcoholic Fatty Liver Disease. Conditions and Diseases. Accessed October 25, 2023.
  3. Mayo Clinic. Understanding lean NAFLD: Results from a population-based study. News. October 20, 2021. Accessed October 25, 2023.