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. 2024 Nov 25;8(12):e0582.
doi: 10.1097/HC9.0000000000000582. eCollection 2024 Dec 1.

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

Helaina E Huneault  1 , Jaclyn S Lo  2 , Shasha Bai  3 , Zhulin He  3 , Michael J McPhaul  4 , Fernando Bril  5 , Miriam B Vos  1   6   7 , Melanie G Cree  2   8
Affiliations

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

Helaina E Huneault et al. Hepatol Commun. .

Abstract

Background: 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.

Methods: 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.

Results: The analysis included 184 children (28% male; 14.9 ± 2.6 y; 57% Hispanic race/ethnicity; body mass index 32.5 ± 8.1 kg/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 20 μU/mL and 522 μU/mL × U/L, respectively.

Conclusions: In pediatric patients, measurements of fasting intact insulin alone and combined with ALT provide a noninvasive strategy for identifying the presence of MASLD.

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Conflict of interest statement

Miriam B. Vos serves as a consultant for Boehringer Ingelheim, Novo Nordisk, Eli Lilly, Intercept, Takeda, and Alberio. She has stock options in Thiogenesis and Tern Pharmaceuticals. Her institution has received research grants (or in-kind research services) from Target Real World Evidence, Quest, Labcorp, and Sonic Incytes Medical Corp. Michael J. McPhaul: Quest Diagnostics. Michael J. McPhaul is affiliated with Quest Diagnostics. Melanie G. Cree is a Research Investigator for Polly Inc. and is also associated with Self Amino Corp. The remaining authors have no conflicts to report.

Figures

FIGURE 1
FIGURE 1
ROC curves demonstrating the association of MASLD with intact insulin, ALT, or intact insulin × ALT (n = 184). p values represent the comparison against intact insulin × ALT. p values <0.05 were considered statistically significant. Abbreviations: MASLD, metabolic dysfunction–associated steatotic liver disease; ROC, receiver operating characteristic.
FIGURE 2
FIGURE 2
ROC curves demonstrating the association of MASLD with intact insulin, ALT, or intact insulin × ALT excluding children with other liver diseases (n = 174). p values represent the comparison against intact insulin × ALT. p values <0.05 were considered statistically significant. Abbreviations: MASLD, metabolic dysfunction–associated steatotic liver disease; ROC, receiver operating characteristic.
See this image and copyright information in PMC

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