Fasting intact insulin by mass spectrometry is associated with metabolic dysfunction-associated steatotic liver disease in youth.

Abstract

Fasting intact insulin concentrations can predict metabolic dysfunction-associated steatotic liver disease (MASLD) in adults without diabetes; however, research in youth is limited. We sought to determine whether fasting intact insulin, measured by liquid chromatography-tandem mass spectrometry, is associated with MASLD in children. This retrospective cross-sectional analysis used data and samples from children who participated in studies across 3 universities between 2014 and 2022. Key measurements included fasting intact insulin, ALT, and hepatic steatosis assessed by MRI techniques. MASLD was defined as hepatic steatosis ≥5% by MRI with at least 1 cardiometabolic risk factor. The optimal cutoff points to identify MASLD were determined by maximizing the Youden index, and the AUROC curves were compared using the DeLong test. The analysis included 184 children (28% male; 14.9 ± 2.6y; 57% Hispanic race/ethnicity; body mass index 32.5 ± 8.1kg/m2; 64% with MASLD, 43% with polycystic ovary syndrome, and 5% with other liver diseases). Fasting intact insulin and ALT levels were significantly higher in children with MASLD (p < 0.05). Fasting intact insulin was strongly associated with MASLD with an AUROC of 0.83 (0.77-0.90), sensitivity of 71%, and specificity of 85%. When combined with ALT (intact insulin × ALT [μU/mL × U/L]), the AUROC was 0.88 (0.83-0.94), with a sensitivity of 89% and specificity of 81%. The improvement in AUROC over intact insulin alone was not statistically significant (p = 0.089) but was statistically significant from ALT (p = 0.022). Optimal cutoff points for intact insulin and intact insulin × ALT were 20μU/mL and 522μU/mL × U/L, respectively. In pediatric patients, measurements of fasting intact insulin alone and combined with ALT provide a noninvasive strategy for identifying the presence of MASLD.