Our novel results show that AIP level at baseline was independently associated with the risk of new-onset NAFLD in non-obese Chinese populations, and this association remained significantly even after adjusting covariates. The model-based effect sizes can be interpreted as every one-SD (0.28) of AIP level increasing is associated with increasing 52% in the incidence of NAFLD. To our knowledge, no previous studies have explored the association between AIP and new-onset NAFLD among non-obese participants.
AIP as an atherogenic index is a practical tool for assessing changes in the lipoprotein profile. Ampuero et al. found AIP level was positively associated the presence of adverse metabolic factors. The relationship between TG and HDL-c in this simple ratio theoretically reflects the balance between risk and protective lipoprotein forces. Studies indicated a positive association between AIP and cholesterol esterification rates, lipoprotein particle size, and remnant lipoproteinemia[6, 16]. Compared with either plasma TG or HDL-C levels, AIP provided a more accurate predictive abilities in incident NAFLD, it appears that simultaneous use of these variables (and their mutual relationship) provides more accurate information.
Recently, Wang et al. conducted a cross-sectional study including 538 obese participants. They demonstrated AIP was strongly correlated with NAFLD in those participants. To further address the question of whether the abnormalities in AIP level precede incident NAFLD or whether incident NAFLD leads to elevated AIP level, we conducted the longitudinal study. Our study indicated AIP level at baseline could predict incident NAFLD. In addition, we found that the optimal cut-off point of AIP for incident NAFLD was 0.00. A practical advantage of using AIP is that individuals with low risk for NAFLD have AIP values in the negative (“safe”) range, those with higher risk for NAFLD have AIP values in the positive (“danger”) range.
The clinical value of our study is as follows (1) To our knowledge, it is the first time to observe AIP is a strong predictor of incident NAFLD in Chinese non-obese individuals. Through subgroup analysis, our results revealed the need for early emphasis on lifestyle modification in individuals with positive (“danger”) range of AIP, even those with normal values of BMI, blood pressure, plasma lipids, or fasting plasma glucose; (2) Considering the measurement of TG and HDL-c is convenient and standardized in routine clinical practice, AIP may be clinically useful in identifying people at higher risk of developing NAFLD. These findings of our study may help to build a useful predictive model for incident NAFLD.
Our study has some strengths: (1) Compared with previous studies, the sample size of our study is relatively large; (2) We used strict statistical adjustment including Generalized additive model, penalized spline method, Cox regression, PSM, multiple imputation, and sensitivity analysis to minimize residual confounders. We handled the target independent variable as both continuous variable and categorical variable. Such an approach can reduce the contingency in the data analysis and enhance the robustness of results; (3) We did a subgroup analysis to explore the effect of AIP on incident NAFLD in different populations. Our findings provide evidence for early stage lifestyle intervention in individuals with positive (“danger”) AIP values, even those with metabolically healthy.
There are several limitations to our study. First, some participants missed clinical data. However, to minimize bias that might occur if individuals with missing data were excluded from multivariate analyses, we performed multiple imputations and then compared the results of complete data cohort with the results multiple imputation cohort. We found that the results from the two cohorts were similar (Supplementary Table 1). Second, NAFLD was diagnosed by a non-invasive test (ultrasound). liver biopsy remains the ‘gold standard’ for diagnosing NAFLD. However, in population-based studies, liver biopsy is logistically challenging and unethical in asymptomatic participants who undergone routine health checkups.