Purpose: Diabetes is one of the most prevalent chronic diseases in the world, and its prevalence is expected to rise further. To help understand the utility of the ratio of non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol (NHHR) in diabetes prevention, this large-scale longitudinal cohort study aims to explore the association of NHHR with diabetes risk and compare it as a risk predictor with conventional lipid parameters. Patients and Methods: This observational study extracted data from the NAGALA longitudinal cohort study conducted in Japan between 2004 and 2015. Multivariate Cox regression analysis was used to evaluate the association between NHHR and the risk of diabetes. The dose–response relationship was analyzed by restricted cubic spline (RCS) regression and the potential risk threshold was estimated. The receiver operator characteristic curve (ROC) was used to analyze and calculate the predictive value and optimal threshold of NHHR and other conventional lipids for new-onset diabetes. Results: Of the 15,464 people aged 18– 79, 373 (2.41%) were diagnosed with new-onset diabetes during the study period, with a median age of 46 years. The sensitivity analysis based on multivariate adjustment showed that the independent positive correlation between diabetes and NHHR was stable in different populations. RCS and ROC analysis indicated that the association between NHHR and diabetes was non-linear, and the NHHR was a better marker for predicting diabetes risk than other conventional lipid parameters; Additionally, it is worth noting that an NHHR of approximately 2.74 may be the optimal threshold for intervention in diabetes risk. Conclusion: In the general population, NHHR is a better marker for predicting diabetes risk than conventional lipid parameters, and an NHHR of about 2.74 may be the optimal threshold for assessing diabetes risk.

Background: The alanine aminotransferase (ALT)/aspartate aminotransferase (AST) ratio has been considered an alternative marker for hepatic steatosis. However, few studies have investigated the association of the ALT/AST ratio with non-alcoholic fatty liver disease (NAFLD) in nonobese people. Methods: A total of 12,127 nonobese participants who were free of NAFLD participated in this study. The participants were divided into quintiles of the ALT/AST ratio. Multiple Cox regression models were used to explore the association of the ALT/AST ratio with new-onset NAFLD. Results: During the five-year follow-up period, 2147 individuals (17.7%) developed new-onset NAFLD. After adjusting for all non-collinear covariates, the multiple Cox regression analysis results showed that a higher ALT/AST ratio was independently associated with new-onset NAFLD in nonobese Chinese (adjusted hazard ratios [aHRs]: 2.10, 95% confidence intervals: 1.88, 2.36). The aHRs for NAFLD across increasing quintiles of the ALT/AST ratio were 1, 1.63 (1.30, 2.04), 2.07 (1.65, 2.60), 2.84 (2.33, 3.48) and 3.49 (2.78, 4.39) (P for trend< 0.001). The positive association was more significant among people with high blood pressure, high blood lipids and hyperglycaemia, as well as in men. Additionally, the regression spline showed that the saturation effect of the ALT/AST ratio on NAFLD risk was at 0.93 in this study population, which was 1.22 in males and 0.89 in females. Conclusions: In nonobese Chinese individuals without NAFLD at baseline, the increase in the ALT/AST ratio is closely associated with the risk of new-onset NAFLD.

Background: Low-density lipoprotein to high density lipoprotein (LDL/HDL) cholesterol ratio has been reported to predict the risk of many metabolic diseases. However, the association between the LDL/HDL cholesterol ratio and nonalcoholic fatty liver disease (NAFLD) has not been established. Methods: A longitudinal cohort design was adopted in this study; 9767 non-obese subjects without NAFLD were included and analyzed. The subjects were grouped according to the quintile of LDL/HDL cholesterol ratio. The cumulative incidence of NAFLD and the independent effect of the LDL/HDL cholesterol ratio on NAFLD during 5 years of follow-up were calculated using the Kaplan-Meier method and Cox proportional-hazards regression model. Results: During the 5-year follow-up period, 841 subjects were diagnosed with new-onset NAFLD, and the 1-, 2-, 3-, 4-, and 5-year cumulative incidence rates of NAFLD were 1.16, 4.65, 8.33, 12.43, and 25.14%, respectively. In the multivariable-adjusted Cox proportional-hazards regression model, the LDL/HDL cholesterol ratio was significantly associated with the risk for NAFLD (HR: 1.66, 95% CI: 1.38–1.99, P trend< 0.001), especially among young people (HR: 3.96, 95% CI: 1.50–10.46, P interaction< 0.05). Additionally, receiver operating characteristic curve analysis showed that the LDL/HDL cholesterol ratio was better than HDL cholesterol and LDL cholesterol in predicting new-onset NAFLD. Conclusions: LDL/HDL cholesterol ratio is an independent predictor of NAFLD in Chinese non-obese people with normal lipids, and its predictive value is higher than that of other lipoproteins. In clinical practice, the LDL/HDL cholesterol ratio can be used to identify people at high risk of NAFLD.

Background: Fasting plasma glucose (FPG) is an easily quantifiable and inexpensive metabolic marker, which is often used to assess cardiovascular disease and diabetes. However, there have been limited studies on the association between FPG and nonalcoholic fatty liver disease (NAFLD) risk in nonobese people, especially in Chinese individuals. The purpose of this study was to investigate the association between FPG and NAFLD in nonobese Chinese people with normal blood lipid levels. Methods: In this prospective cohort study, 9767 nonobese participants with normal blood lipid levels without NAFLD were recruited and prospectively followed for 5 years. The Cox proportional hazard model was used to evaluate the risk factors of NAFLD. Moreover, a Cox model with cubic spline functions and smooth curve fitting (the cubic spline smoothing) were used to identify the nonlinear association between FPG and NAFLD. Results: During the 5-year follow-up, 841 (8.61%) participants were diagnosed with NAFLD. The good functional results (without NAFLD) estimated by the Kaplan-Meier method for 1 year, 2 years, 3 years, 4 years, and 5 years were 98.84, 95.35, 91.67%, 87.57 and 74.86%, respectively. Additionally, through the Cox proportional hazard model, after adjusting for other covariates, there was an independent positive correlation between FPG and increased NAFLD risk (HR:1.21, 95% CI:1.15–1.28, P < 0.0001), and the NAFLD risk was incrementally higher with the rising FPG quartile. The nonlinear association between FPG and NAFLD was visualized by cubic spline smoothing technique. It was calculated that the inflection point of FPG was 5.54. When FPG ≤ 5.54, there was a positive correlation between FPG and the risk of NAFLD (HR:2.20, 95% CI:1.78–2.73, P < 0.0001). When FPG > 5.54, the risk of NAFLD increased by 50% (HR:1.10, 95% CI:1.02–1.18, P = 0.0159) compared with the left side of the inflection point and gradually leveled off. Conclusions: In a nonobese Chinese population with normal lipid levels, there is an independent nonlinear association between FPG and NAFLD, and the increase in FPG may indicate an increased risk of NAFLD. Additionally, this independent association is more obvious in the short stature population.

Objective: The newly proposed Metabolic Visceral Fat Score (METS-VF) is considered a more effective measure for visceral adipose tissue (VAT) than other obesity indicators. This study aimed to reveal the association between METS-VF and non-alcoholic fatty liver disease (NAFLD), and its variations across age groups within both sexes.Methods: Data from 14,251 medical examiners in the NAGALA project were employed in this study. 3D fitted surface plots were constructed based on multivariate logistic regression models to visualize the isolated and combined effects of aging and METS-VF on NAFLD. Receiver operating characteristic curve (ROC) analysis was conducted to compare the diagnostic performance of METS-VF with other VAT surrogate markers in predicting NAFLD.Results: The results of multivariate logistic regression analysis showed that each unit increase in METS-VF was independently associated with a 333% and 312% increase in the odds of NAFLD in males and females, respectively. Additionally, the 3D fitted surface plot showed that age significantly influenced the association between METS-VF and the odds of NAFLD in both sexes, as follows: (i) In males, when METS-VF was less than 6.2, the METS-VF-related odds of NAFLD increased gradually with age in the 20-45 age group, reached a plateau in the 45-65 age group, and then decreased in the group above 65 years old; however, when male METS-VF exceeded 6.2, aging and METS-VF combined to further increase the odds of NAFLD in all age groups, particularly in the 45-65 age group. (ii) In females, aging seemed to reduce METS-VF-related odds of NAFLD in the 18-40 age group, but significantly increased it in the 40-60 age group, particularly for those with higher METS-VF levels. Further ROC analysis revealed that compared to other VAT surrogate markers, METS-VF showed the highest diagnostic accuracy for NAFLD in females, especially in those under 45 years of age [area under the curve (AUC) = 0.9256].Conclusions: This study firstly revealed a significant positive correlation between METS-VF and the odds of NAFLD, with METS-VF surpassing other VAT surrogate markers in NAFLD diagnosis. Moreover, age significantly influenced the METS-VF-related odds of NAFLD and METS-VF’s diagnostic efficacy for NAFLD in both sexes.

Background: Low-density lipoprotein:high-density lipoprotein cholesterol ratio (LDL:HDL ratio) has a good performance in identifying diabetes mellitus (DM) and insulin resistance. However, it is not yet clear whether the LDL:HDL ratio is associated with a high-risk state of prediabetes. Methods: This cohort study retrospectively analyzed the data of 100,309 Chinese adults with normoglycemia at baseline. The outcome event of interest was new-onset prediabetes. Using multivariate Cox regression and smoothing splines to assess the association of LDL:HDL ratio with prediabetes. Results: During an average observation period of 37.4 months, 12,352 (12.31%) subjects were newly diagnosed with prediabetes. After adequate adjustment for important risk factors, the LDL:HDL ratio was positively correlated with the prediabetes risk, and the sensitivity analysis further suggested the robustness of the results. Additionally, in stratified analysis, we discovered significant interactions between LDL:HDL ratio and family history of DM, sex, body mass index and age (all P-interaction < 0.05); among them, the LDL:HDL ratio-related prediabetes risk decreased with the growth of body mass index and age, and increased significantly in women and people with a family history of DM. Conclusions: The increased LDL:HDL ratio in the Chinese population indicates an increased risk of developing prediabetes, especially in women, those with a family history of DM, younger adults, and non-obese individuals.