Identification of pediatric MASLD using insulin resistance indices

Abstract

Background & aims: We investigated the triglyceride-to-high density lipoprotein (HDL) ratio (TG/HDL), triglyceride-glucose index (TyG), single-point insulin sensitivity estimator (SPISE), and metabolic score for insulin resistance (METS-IR) as potential predictors of pediatric metabolic dysfunction-associated steatotic liver disease (MASLD) by addressing the limited research on insulin-resistance markers in this population.

Methods: This cross-sectional study included data from 1,150 and 260 youths from the National Health and Nutrition Examination Survey (NHANES) and a real-world clinic, respectively. Hepatic steatosis was assessed using transient elastography and abdominal sonography. Logistic regression analysis was performed using MASLD as the dependent variable. Receiver operating characteristic (ROC) curves were used to evaluate predictability.

Results: The MASLD group had higher TG/HDL, TyG, METS-IR, and obesity proportions but lower SPISE than the normal group in both NHANES and real-world data. All markers were significantly related to MASLD in logistic regression analyses, even after adjusting for age and sex, in both the NHANES and real-world clinic data (all p <0.001). The areas under the ROC curves (AUCs) for SPISE and METS-IR were 0.91 and 0.91 in the total group, 0.92 and 0.92 in the male group, and 0.90 and 0.89 in the female group, respectively-all higher than those for TG/HDL and TyG in the NHANES dataset (all p <0.001). In the real-world clinical data, the AUCs of SPISE and METS-IR were significantly higher than those of TG/HDL and TyG in the total and male groups (all p <0.001). In the female group, the AUC for SPISE was significantly higher than that for TG/HDL or TyG.

Conclusions: METS-IR and SPISE are effective, non-invasive markers for predicting pediatric MASLD, which offer valuable tools for early detection and improved clinical management.

Impact and implications: The increasing prevalence of pediatric metabolic dysfunction-associated steatotic liver disease (MASLD) and its strong association with cardiometabolic risk factors underscore the need for effective early detection tools. Our study demonstrates that single-point insulin sensitivity estimator (SPISE) and metabolic score for insulin resistance (METS-IR) are superior, non-invasive markers for predicting MASLD in children and adolescents, with validated cut-off values applicable to both population-based and real-world clinical settings. These findings are particularly relevant for clinicians and healthcare policymakers, as they provide practical, easily accessible screening tools derived from routine laboratory tests, aiding in the early identification and risk stratification of pediatric MASLD. However, given the study's retrospective design and variations in diagnostic methods across datasets, further validation in larger, diverse cohorts is warranted to refine age-specific cut-off values and optimize screening approaches.

Keywords: Adolescent; Biomarkers; Child; Insulin resistance; Metabolic dysfunction-associated steatotic liver disease.

Graphical abstract

Fig. 1

Flowchart of participant inclusion. (A) Participants in the NHANES. (B) Participants in the real-world clinic data. GSH, Gangnam Severance Hospital; NHANES, National Health and Nutrition Examination Survey; SLD, steatotic liver disease; TG, triglycerides; YSH, Yongin Severance Hospital.

Fig. 2

ROC curve of each parameter for predicting MASLD among the total participants. (A) ROC curve of each parameter for predicting MASLD among the total participants in the NHANES. (B) ROC curve of each parameter for predicting MASLD among the total participants in the real-world clinic data. MASLD, metabolic dysfunction-associated steatotic liver disease; METS-IR, metabolic score for insulin resistance; NHANES, National Health and Nutrition Examination Survey; ROC, receiver operating characteristic; SPISE, single-point insulin sensitivity estimator; TG, triglycerides; TyG, triglyceride–glucose index.

Fig. 3

Proportion of participants with MASLD relative to the cut-off points of each parameter among the total participants. (A) NHANES. (B) Real-world clinic data. The numbers on the bars indicate the proportion (%) of participants with MASLD. MASLD, metabolic dysfunction-associated steatotic liver disease; METS-IR, metabolic score for insulin resistance; NHANES, National Health and Nutrition Examination Survey; SPISE, single-point insulin sensitivity estimator; TG, triglycerides; TyG, triglyceride–glucose index.