Abstract
Purpose This study is aimed at investigating the association between the metabolic score for insulin resistance (METS-IR) index and nonalcoholic fatty liver disease (NAFLD) in the nonobese population and its predictive value. Methods 10730 nonobese subjects were selected from longitudinal cohort research conducted from January 2010 to December 2014. Cox proportional hazards models were employed to assess the relationship between METS-IR and new-onset NAFLD. Generalized additive models were used to identify nonlinear relationships. In addition, we performed subgroup analyses and interaction tests. The time-dependent receiver operating curve (ROC) and area under the ROC (AUC) were utilized to measure the discriminatory ability of METS-IR for new-onset NAFLD. Beyond clinical risk factors, the incremental predictive value of METS-IR was appraised using integrated discrimination improvement (IDI), C-index, and net reclassification index (NRI). Results Over a median period of 804.50 days of follow-up, 1859 (17.33%) participants had a new onset of NAFLD. After adjusting for confounders, the HR for new-onset NAFLD in the Q4 group was 6.40 compared with the Q1 group. When METS-IR was considered a continuous variable, the risk of NAFLD increased by 34% for every 1 SD increase in METS-IR. The smoothing curve shows the dose-response relationship between METS-IR and the presence of new-onset NAFLD. Using a two-piecewise linear regression model, we derived a METS-IR inflection point of 36. HRs were 1.31 on the left side of the inflection point and 1.04 on the right side of the inflection point (log-likelihood ratio test, P < 0.001). Subgroup analyses and interaction tests revealed an interaction between gender and SBP in the association between METS-IR and new-onset NAFLD. In the subgroup analysis of gender and SBP, we observed a higher risk of new-onset NAFLD in men and in those with abnormal SBP levels. We evaluated the ability of METS-IR to identify new-onset NAFLD at different time points. The AUCs at 1, 2, 3, and 4 years were 0.784, 0.756, 0.758, and 0.752, respectively, which represent good discrimination of new-onset NAFLD. The addition of METS-IR greatly improved the reclassification and differentiation of clinical risk factors, with an NRI of 0.276 and an IDI of 0.068. In addition, the addition of METS-IR increased the C-index from 0.719 to 0.771. Conclusion In a nonobese Chinese population, elevated METS-IR was independently associated with an enhanced risk of NAFLD development and a dose-response relationship existed. In addition, METS-IR might be a reliable indicator for screening individuals at risk for early NAFLD, especially in nonobese populations.
Highlights
Nonalcoholic fatty liver disease (NAFLD) is the predominant liver disease worldwide and a primary contributor to the development of diverse chronic hepatic disorders [1,2,3]
A few large cohort reports have recently revealed that nonobese NAFLD individuals have higher all-cause mortality and accelerated disease progression compared to obese NAFLD patients, despite their less severe phenotype of metabolism [15,16,17]
After adjusting for sex, age, BMI, alkaline phosphatase (ALP), TG, GGT, high-density lipoprotein cholesterol (HDL-C), ALT, BUN, AST, Cr, uric acid (UA), FPG, SBP, low-density lipoprotein cholesterol (LDL-C), and DBP, the hazard ratios (HRs) for the new-onset NAFLD was 6.40 in Q4 versus Q1
Summary
Nonalcoholic fatty liver disease (NAFLD) is the predominant liver disease worldwide and a primary contributor to the development of diverse chronic hepatic disorders [1,2,3]. The prevalence of NAFLD in adults is reported to be about 25% globally [4]. In Asia, approximately 30% of individuals in the adult population are impacted by NAFLD, and this is growing by the day with the obesity epidemic [5, 6]. The global incidence of NAFLD in the population of nonobese people has reached 40%, indicating that nonobese NAFLD accounts for a significant portion of the chronic hepatic disease burden [14]. A few large cohort reports have recently revealed that nonobese NAFLD individuals have higher all-cause mortality and accelerated disease progression compared to obese NAFLD patients, despite their less severe phenotype of metabolism [15,16,17]
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