Development and application of a novel model to predict the risk of non-alcoholic fatty liver disease among lean pre-diabetics with normal blood lipid levels

Abstract

Background: Non-alcoholic fatty liver disease (NAFLD) has been associated with type 2 diabetes, but its relationship with pre-diabetes is still unknown. This study aims to determine whether pre-diabetes is associated with NAFLD, followed by establishing a NAFLD predictive nomogram for lean Chinese pre-diabetics with normal blood lipids.

Methods: Datasets from 3 previous studies, 1 (2774 pre-diabetics with normal blood lipids for training, 925 for validation), 2 (546 for longitudinal internal validation, post-5-year follow-up), and 3 (501 from another institution for external validation), were used. Kaplan-Meier determined cumulative NAFLD hazard, and least absolute shrinkage and selection operator regression analysis uncovered its risk factors. Multivariate logistic regression analysis constructed the nomogram, followed by validation with receiver operating characteristic curve, calibration plot, and decision curve analyses.

Results: NAFLD incidence increased with diabetes progression, and pre-diabetics had higher cumulative risk versus non-diabetics, even for lean individuals with normal blood lipids. Six risk factors were identified: body mass index, total cholesterol, alanine aminotransferase:aspartate aminotransferase, triglyceride:high density lipoprotein cholesterol, fasting blood glucose and γ-glutamyl-transferase. The nomogram yielded areas under the curve of 0.808, 0.785, 0.796 and 0.832, for respectively, training, validation, longitudinal internal validation, and external validation, which, along with calibration curve values of p = 0.794, 0.875, 0.854 and 0.810 for those 4 datasets and decision curve analyses, validated its clinical utility.

Conclusions: Lean pre-diabetic Chinese with normal blood lipids have higher NAFLD risk versus non-diabetics. The nomogram is able to predict NAFLD among such individuals, with high discrimination, enabling its use for early detection and intervention.

Keywords: Least absolute shrinkage and selection operator regression analysis; Nomogram; Non-alcoholic fatty liver disease; Pre-diabetes; Screening tool.