Body mass index-stratified inflammatory predictors of insulin resistance in non-obese adults: a retrospective study.

Abstract

Background: Insulin resistance (IR) is a key mechanism underlying type 2 diabetes mellitus and cardiometabolic disease. Although obesity-related inflammation is a major contributor to IR, increasing evidence indicates that IR may also develop in non-obese individuals. However, readily available inflammatory markers applicable to this population remain limited. We evaluated the association between inflammatory markers and insulin resistance in non-obese adults and assessed their predictive performance across body mass index (BMI) strata.

Methods: This retrospective cross-sectional study included 149 non-obese adults (BMI < 30 kg/m²) evaluated in an internal medicine outpatient clinic between January and December 2025. Insulin resistance was defined as a homeostasis model assessment of insulin resistance (HOMA-IR) ≥ 2.5. Inflammatory markers and composite indices, including the C-reactive protein to high-density lipoprotein cholesterol (CRP/HDL) ratio, were calculated. Multivariable logistic regression, BMI-stratified analyses, and receiver operating characteristic (ROC) curve analyses were performed.

Results: Insulin resistance was identified in 54 participants (36.2%). Individuals with IR had higher white blood cell (WBC) counts, CRP levels, and CRP/HDL ratios (all p < 0.05). In multivariable analysis, WBC count was independently associated with IR (OR = 1.407, 95% CI [1.090-1.815]; p = 0.009). BMI-stratified analyses showed that WBC count independently predicted IR in normal-weight individuals (OR = 1.789, 95% CI [1.218-2.627]; p = 0.003), whereas in overweight participants (BMI 25-30 kg/m²), the CRP/HDL ratio was independently associated with IR (OR = 7.793, 95% CI [1.056-57.499]; p = 0.044). ROC analyses demonstrated higher discriminative performance of WBC count in normal-weight individuals (AUC = 0.720) and greater predictive ability of the CRP/HDL ratio in overweight individuals (AUC = 0.695).

Conclusions: Low-grade systemic inflammation is independently associated with insulin resistance in non-obese adults, with distinct inflammatory predictors across BMI categories. WBC count may reflect early immune activation in normal-weight individuals, whereas the CRP/HDL ratio appears more informative among overweight subjects.