Evaluation of the role of atherogenic index of plasma in the reversion from Prediabetes to normoglycemia or progression to Diabetes: a multi-center retrospective cohort study.

BACKGROUND: Atherosclerosis is closely linked with glucose metabolism. We aimed to investigate the role of the atherogenic index of plasma (AIP) in the reversal of prediabetes to normal blood glucose levels or its progression to diabetes. METHODS: This multi-center retrospective cohort study included 15,421 prediabetic participants from 32 regions across 11 cities in China, under the aegis of the Rich Healthcare Group's affiliated medical examination institutions. Throughout the follow-up period, we monitored changes in the glycemic status of these participants, including reversal to normal fasting glucose (NFG), persistence in the prediabetic state, or progression to diabetes. Segmented regression, stratified analysis, and restricted cubic spline (RCS) were performed based on the multivariable Cox regression model to evaluate the association between AIP and the reversal of prediabetes to NFG or progression to diabetes. RESULTS: During a median follow-up period of 2.9 years, we recorded 6,481 individuals (42.03%) reverting from prediabetes to NFG, and 2,424 individuals (15.72%) progressing to diabetes. After adjusting for confounders, AIP showed a positive correlation with the progression from prediabetes to diabetes [(Hazard ratio (HR) 1.42, 95% confidence interval (CI):1.24-1.64)] and a negative correlation with the reversion from prediabetes to NFG (HR 0.89, 95%CI:0.81-0.98); further RCS demonstrated a nonlinear relationship between AIP and the reversion from prediabetes to NFG/progression to diabetes, identifying a turning point of 0.04 for reversion to NFG and 0.17 for progression to diabetes. In addition, we observed significant differences in the association between AIP and reversion from prediabetes to NFG/progression to diabetes across age subgroups, specifically indicating that the risk associated with AIP for progression from prediabetes to diabetes was relatively higher in younger populations; likewise, a younger age within the adult group favored the reversion from prediabetes to NFG in relation to AIP. CONCLUSION: Our study, for the first time, reveals a negative correlation between AIP and the reversion from prediabetes to normoglycemia and validates the crucial role of AIP in the risk assessment of prediabetes progression. Based on threshold analysis, therapeutically, keeping the AIP below 0.04 was of paramount importance for individuals with prediabetes aiming for reversion to NFG; preventatively, maintaining AIP below 0.17 was vital to reduce the risk of diabetes onset for those with prediabetes.

Sex-specific associations between haemoglobin glycation index and the risk of cardiovascular and all-cause mortality in individuals with pre-diabetes and diabetes: A large prospective cohort study.

AIM: The aim of this study was to investigate the relationship between the haemoglobin glycation index (HGI), and cardiovascular disease (CVD) and all-cause mortality in adults with pre-diabetes and diabetes. METHODS: This study included 10 267 adults with pre-diabetes and diabetes from the National Health and Nutrition Examination Survey (NHANES) 1999-2018. Sex-differentiated relationships between HGI and mortality were elucidated using multivariate Cox proportional hazards models, restricted cubic splines and a two-piecewise Cox proportional hazards model. RESULTS: During the median follow-up time of 103.5 months, a total of 535 CVD deaths and 1918 all-cause deaths were recorded. After multivariate adjustment, in males with pre-diabetes and diabetes, there was a U-shaped relationship between HGI and CVD mortality and all-cause mortality, with threshold points of -0.68 and -0.63, respectively. Before the threshold point, HGI was negatively associated with CVD mortality [hazard ratio (HR) 0.60; 95% confidence interval (CI) 0.41, 0.89] and all-cause mortality (HR 0.56; 95% CI 0.43, 0.74), and after the threshold point, HGI was positively associated with CVD mortality (HR 1.46; 95% CI 1.23, 1.73) and all-cause mortality (HR 1.40; 95% CI 1.23, 1.59). In contrast, HGI had an L-shaped relationship with all-cause mortality and no significant association with CVD mortality in females. To the left of the threshold points, the risk of all-cause mortality decreased (HR 0.50; 95% CI 0.35, 0.71) progressively with increasing HGI. CONCLUSIONS: In the cohort study, HGI in pre-diabetic and diabetic populations was found to have a U-shaped association with CVD mortality and all-cause mortality in males and an L-shaped association with all-cause mortality only in females. Further prospective and mechanistic studies are warranted.

The newly proposed plasma-glycosylated hemoglobin A1c/High-Density lipoprotein cholesterol ratio serves as a simple and practical indicator for screening metabolic associated fatty liver disease: an observational study based on a physical examination population.

BACKGROUND: Glycotoxicity and lipotoxicity are key pathophysiological mechanisms underlying the development of metabolic associated fatty liver disease (MAFLD). The primary objective of this study is to investigate the association between the newly proposed Plasma-Glycosylated Hemoglobin A1c/High-Density Lipoprotein Cholesterol Ratio (HbA1c/HDL-C ratio) and the risk of MAFLD. METHODS: A study population of 14,251 individuals undergoing health examinations was included. The association between the HbA1c/HDL-C ratio and MAFLD was analyzed using multivariable logistic regression and restricted cubic spline (RCS) analysis. Exploratory analyses were conducted to assess variations in this association across subgroups stratified by gender, age, body mass index (BMI), exercise habits, drinking status, and smoking status. The discriminatory value of the HbA1c/HDL-C ratio and its components for screening MAFLD was evaluated using receiver operating characteristic (ROC) curves. RESULTS: A total of 1,982 (13.91%) subjects were diagnosed with MAFLD. After adjusting for confounding factors, we found a significant positive association between the HbA1c/HDL-C ratio and MAFLD [odds ratio (OR) 1.34, 95% confidence interval (CI): 1.25, 1.44]. No significant differences in this association were observed across all subgroups (All P for interaction > 0.05). Furthermore, through RCS analysis, we observed a nonlinear positive correlation between the HbA1c/HDL-C ratio and MAFLD (P for non-linearity < 0.001), with a potential threshold effect point (approximately 3 for the HbA1c/HDL-C ratio). Beyond this threshold point, the slope of the MAFLD prevalence curve increased rapidly. Additionally, in further ROC analysis, we found that for the identification of MAFLD, the HbA1c/HDL-C ratio was significantly superior to HbA1c and HDL-C, with an area under the curve (AUC) and optimal threshold of 0.81 and 4.08, respectively. CONCLUSIONS: Our findings suggest that the newly proposed HbA1c/HDL-C ratio serves as a simple and practical indicator for assessing MAFLD, exhibiting well-discriminatory performance in screening for MAFLD.

Association between weight-adjusted waist index and non-alcoholic fatty liver disease: a population-based study.

BACKGROUND: Obesity is the most important driver of non-alcoholic fatty liver disease (NAFLD); nevertheless, the relationship of weight-adjusted waist index (WWI), a new obesity index, with NAFLD is unclear. METHODS: This retrospective study used data from the NAGALA project from 1994 to 2016. WWI values were calculated using waist circumference (WC) and weight measurements of the participants. Three stepwise adjusted logistic regression models were developed to assess the relationship of WWI with NAFLD in the whole population and in both sexes. Additionally, we also conducted a series of exploratory analysis to test the potential impact of body mass index (BMI), age, smoking status and exercise habits on the association of WWI with NAFLD. Receiver operating characteristic (ROC) curves were used to estimate cut-off points for identifying NAFLD in the entire population and in both sexes. RESULTS: The current study included a population of 11,805 individuals who participated in health screenings, including 6,451 men and 5,354 women. After adjusting for all non-collinear variables in the multivariable logistic regression model, we found a significant positive correlation of WWI with NAFLD. For each unit increase in WWI, the risk of NAFLD increased by 72% in the entire population, by 84% in men, and by 63% in women. Furthermore, subgroup analyses revealed no significant discrepancies in the correlation of WWI with NAFLD across individuals with varying ages, exercise habits, and smoking status (all P-interaction > 0.05), except for different BMI groups (P-interaction < 0.05). Specifically, compared to the overweight/obese group, the relationship of WWI with NAFLD was significantly stronger in the non-obese group, especially in non-obese men. Finally, based on the results of ROC analysis, we determined that the WWI cut-off point used to identify NAFLD was 9.7675 in men and 9.9987 in women. CONCLUSIONS: This study is the first to establish a positive correlation between WWI and NAFLD. Moreover, assessing the influence of WWI on NAFLD in individuals without obesity may yield more valuable insights compared to those who are overweight or obese.

Lipids as potential mediators linking body mass index to diabetes: evidence from a mediation analysis based on the NAGALA cohort.

BACKGROUND: Body mass index (BMI) and lipid disorders are both known to be strongly associated with the development of diabetes, however, the indirect effect of lipid parameters in the BMI-related diabetes risk is currently unknown. This study aimed to investigate the mediating role of lipid parameters in the association of BMI with diabetes risk. METHODS: We assessed the association of diabetes risk with BMI, as well as lipid parameters including high-density lipoprotein cholesterol(HDL-C), low-density lipoprotein cholesterol(LDL-CF and LDL-CS), triglycerides(TG), total cholesterol(TC), remnant cholesterol(RC), non-HDL-C, and combined indices of lipid parameters with HDL-C (RC/HDL-C ratio, TG/HDL-C ratio, TC/HDL-C ratio, non-HDL/HDL-C ratio, LDL/HDL-C ratio) using data from 15,453 subjects in the NAGALA project. Mediation models were used to explore the mediating role of lipid parameters in the association of BMI with diabetes risk, and mediation percentages were calculated for quantifying the strength of the indirect effects. Finally, receiver operating characteristic curve (ROC) analysis was used to compare the accuracy of BMI and BMI combined with lipid parameters in predicting incident diabetes. RESULTS: Multivariate regression models, adjusted for confounding factors, demonstrated robust associations of lipid parameters, BMI, with diabetes risk, with the exception of TC, LDL-CF, LDL-CS, and non-HDL-C. Mediation analysis showed that lipid parameters except TC, LDL-CF, LDL-CS, and Non-HDL-C were involved in and mediated the association of BMI with diabetes risk, with the largest mediation percentage being the RC/HDL-C ratio, which was as high as 40%; it is worth mentioning that HDL-C and HDL-C-related lipid ratio parameters also play an important mediating role in the association between BMI and diabetes, with the mediator proportion being greater than 30%. Finally, based on the ROC results, we found that the prediction performance of all lipid parameters in the current study except TC was significantly improved when combined with BMI. CONCLUSION: Our fresh findings suggested that lipid parameters partially mediated the association of BMI with diabetes risk; this result indicated that in the context of diabetes risk screening and disease management, it is important to not only monitor BMI but also pay attention to lipid parameters, particularly HDL-C and HDL-C-related lipid ratio parameters.

Prognostic value of geriatric nutritional risk index in patients with stable coronary artery disease undergoing percutaneous coronary intervention.

BACKGROUND: Malnutrition increases the risk of poor prognosis in patients with cardiovascular disease, and our current research was designed to assess the predictive performance of the Geriatric Nutrition Risk Index (GNRI) for the occurrence of poor prognosis after percutaneous coronary intervention (PCI) in patients with stable coronary artery disease (SCAD) and to explore possible thresholds for nutritional intervention. METHODS: This study retrospectively enrolled newly diagnosed SCAD patients treated with elective PCI from 2014 to 2017 at Shinonoi General Hospital, with all-cause death as the main follow-up endpoint. Cox regression analysis and restricted cubic spline (RCS) regression analysis were used to explore the association of GNRI with all-cause death risk and its shape. Receiver operating characteristic curve (ROC) analysis and piecewise linear regression analysis were used to evaluate the predictive performance of GNRI level at admission on all-cause death in SCAD patients after PCI and to explore possible nutritional intervention threshold points. RESULTS: The incidence of all-cause death was 40.47/1000 person-years after a mean follow-up of 2.18 years for 204 subjects. Kaplan-Meier curves revealed that subjects at risk of malnutrition had a higher all-cause death risk. In multivariate Cox regression analysis, each unit increase in GNRI reduced the all-cause death risk by 14% (HR 0.86, 95% CI 0.77, 0.95), and subjects in the GNRI > 98 group had a significantly lower risk of death compared to those in the GNRI < 98 group (HR 0.04, 95% CI 0.00, 0.89). ROC analysis showed that the baseline GNRI had a very high predictive performance for all-cause death (AUC = 0.8844), and the predictive threshold was 98.62; additionally, in the RCS regression analysis and piecewise linear regression analysis we found that the threshold point for the GNRI-related all-cause death risk was 98.28 and the risk will be significantly reduced when the subjects' baseline GNRI was greater than 98.28. CONCLUSIONS: GNRI level at admission was an independent predictor of all-cause death in SCAD patients after PCI, and GNRI equal to 98.28 may be a useful threshold for nutritional intervention in SCAD patients treated with PCI.

Relative importance of triglyceride glucose index combined with body mass index in predicting recovery from prediabetic state to normal fasting glucose: a cohort analysis based on a Chinese physical examination population.

BACKGROUND: Prediabetes is a high-risk state for diabetes, and numerous studies have shown that the body mass index (BMI) and triglyceride-glucose (TyG) index play significant roles in risk prediction for blood glucose metabolism. This study aims to evaluate the relative importance of BMI combination with TyG index (TyG-BMI) in predicting the recovery from prediabetic status to normal blood glucose levels. METHODS: A total of 25,397 prediabetic subjects recruited from 32 regions across China. Normal fasting glucose (NFG), prediabetes, and diabetes were defined referring to the American Diabetes Association (ADA) criteria. After normalizing the independent variables, the impact of TyG-BMI on the recovery or progression of prediabetes was analyzed through the Cox regression models. Receiver Operating Characteristic (ROC) curve analysis was utilized to visualize and compare the predictive value of TyG-BMI and its constituent components in prediabetes recovery/progression. RESULTS: During the average observation period of 2.96 years, 10,305 individuals (40.58%) remained in the prediabetic state, 11,278 individuals (44.41%) recovered to NFG, and 3,814 individuals (15.02%) progressed to diabetes. The results of multivariate Cox regression analysis demonstrated that TyG-BMI was negatively associated with recovery from prediabetes to NFG and positively associated with progression from prediabetes to diabetes. Further ROC analysis revealed that TyG-BMI had higher impact and predictive value in predicting prediabetes recovering to NFG or progressing to diabetes in comparison to the TyG index and BMI. Specifically, the TyG-BMI threshold for predicting prediabetes recovery was 214.68, while the threshold for predicting prediabetes progression was 220.27. Additionally, there were significant differences in the relationship of TyG-BMI with prediabetes recovering to NFG or progressing to diabetes within age subgroups. In summary, TyG-BMI is more suitable for assessing prediabetes recovery or progression in younger populations (< 45 years old). CONCLUSIONS: This study, for the first time, has revealed the significant impact and predictive value of the TyG index in combination with BMI on the recovery from prediabetic status to normal blood glucose levels. From the perspective of prediabetes intervention, maintaining TyG-BMI within the threshold of 214.68 holds crucial significance.

Assessing temporal differences in the predictive power of baseline TyG-related parameters for future diabetes: an analysis using time-dependent receiver operating characteristics.

BACKGROUND: It is known that measuring the triglyceride glucose (TyG) index and TyG-related parameters [triglyceride glucose-body mass index (TyG-BMI), triglyceride glucose-waist circumference (TyG-WC), and triglyceride glucose-waist to height ratio (TyG-WHtR)] can predict diabetes; this study aimed to compare the predictive value of the baseline TyG index and TyG-related parameters for the onset of diabetes at different future periods. METHODS: We conducted a longitudinal cohort study involving 15,464 Japanese people who had undergone health physical examinations. The subject's TyG index and TyG-related parameters were measured at the first physical examination, and diabetes was defined according to the American Diabetes Association criteria. Multivariate Cox regression models and time-dependent receiver operating characteristic (ROC) curves were constructed to examine and compare the risk assessment/predictive value of the TyG index and TyG-related parameters for the onset of diabetes in different future periods. RESULTS: The mean follow-up period of the current study cohort was 6.13 years, with a maximum of 13 years, and the incidence density of diabetes was 39.88/10,000 person-years. In multivariate Cox regression models with standardized hazard ratios (HRs), we found that both the TyG index and TyG-related parameters were significantly and positively associated with diabetes risk and that the TyG-related parameters were stronger in assessing diabetes risk than the TyG index, with TyG-WC being the best parameter (HR per SD increase: 1.70, 95% CI 1.46, 1.97). In addition, TyG-WC also showed the highest predictive accuracy in time-dependent ROC analysis for diabetes occurring in the short-term (2-6 years), while TyG-WHtR had the highest predictive accuracy and the most stable predictive threshold for predicting the onset of diabetes in the medium- to long-term (6-12 years). CONCLUSIONS: These results suggest that the TyG index combined with BMI, WC, and WHtR can further improve its ability to assess/predict the risk of diabetes in different future periods, where TyG-WC was not only the best parameter for assessing diabetes risk but also the best risk marker for predicting future diabetes in the short-term, while TyG-WHtR may be more suitable for predicting future diabetes in the medium- to long-term.

Lipid metabolism, BMI and the risk of nonalcoholic fatty liver disease in the general population: evidence from a mediation analysis.

BACKGROUND: Body mass index (BMI) and lipid parameters are the most commonly used anthropometric parameters and biomarkers for assessing nonalcoholic fatty liver disease (NAFLD) risk. This study aimed to assess and quantify the mediating role of traditional and non-traditional lipid parameters on the association between BMI and NAFLD. METHOD: Using data from 14,251 subjects from the NAGALA (NAfld in the Gifu Area, Longitudinal Analysis) study, mediation analyses were performed to explore the roles of traditional [total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C)] and non-traditional [non-HDL-C, remnant cholesterol (RC), TC/HDL-C ratio, LDL-C/HDL-C ratio, TG/HDL-C ratio, non-HDL-C/HDL-C ratio, and RC/HDL-C ratio] lipid parameters in the association of BMI with NAFLD and quantify the mediation effect of these lipid parameters on the association of BMI with NAFLD using the percentage of mediation. RESULT: After fully adjusting for confounders, multivariate regression analysis showed that both BMI and lipid parameters were associated with NAFLD (All P-value < 0.001). Mediation analysis showed that both traditional and non-traditional lipid parameters mediated the association between BMI and NAFLD (All P-value of proportion mediate < 0.001), among which non-traditional lipid parameters such as RC, RC/HDL-C ratio, non-HDL-C/HDL-C ratio, and TC/HDL-C ratio accounted for a relatively large proportion, 11.4%, 10.8%, 10.2%, and 10.2%, respectively. Further stratified analysis according to sex, age, and BMI showed that this mediation effect only existed in normal-weight (18.5 kg/m2 ≤ BMI < 25 kg/m2) people and young and middle-aged (30-59 years old) people; moreover, the mediation effects of all lipid parameters except TC accounted for a higher proportion in women than in men. CONCLUSION: The new findings of this study showed that all lipid parameters were involved in and mediated the risk of BMI-related NAFLD, and the contribution of non-traditional lipid parameters to the mediation effect of this association was higher than that of traditional lipid parameters, especially RC, RC/HDL-C ratio, non-HDL-C/HDL-C ratio, and TC/HDL-C ratio. Based on these results, we suggest that we should focus on monitoring non-traditional lipid parameters, especially RC and RC/HDL-C ratio, when BMI intervention is needed in the process of preventing or treating NAFLD.

Evaluation of the value of conventional and unconventional lipid parameters for predicting the risk of diabetes in a non-diabetic population.

BACKGROUND: Conventional and unconventional lipid parameters are associated with diabetes risk, the comparative studies on lipid parameters for predicting future diabetes risk, however, are still extremely limited, and the value of conventional and unconventional lipid parameters in predicting future diabetes has not been evaluated. This study was designed to determine the predictive value of conventional and unconventional lipid parameters for the future development of diabetes. METHODS: The study was a longitudinal follow-up study of 15,464 participants with baseline normoglycemia. At baseline, conventional lipid parameters such as low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) were measured/calculated, and unconventional lipid parameters such as non-HDL-C, remnant cholesterol (RC), LDL/HDL-C ratio, TG/HDL-C ratio, non-HDL/HDL-C ratio, TC/HDL-C ratio and RC/HDL-C ratio were calculated. Hazard ratio (HR) and 95% confidence interval (CI) were estimated by Cox proportional hazard regression adjusting for demographic and diabetes-related risk factors. The predictive value and threshold fluctuation intervals of baseline conventional and unconventional lipid parameters for future diabetes were evaluated by the time-dependent receiver operator characteristics (ROC) curve. RESULTS: The incidence rate of diabetes was 3.93 per 1000 person-years during an average follow-up period of 6.13 years. In the baseline non-diabetic population, only TG and HDL-C among the conventional lipid parameters were associated with future diabetes risk, while all the unconventional lipid parameters except non-HDL-C were significantly associated with future diabetes risk. In contrast, unconventional lipid parameters reflected diabetes risk better than conventional lipid parameters, and RC/HDL-C ratio was the best lipid parameter to reflect the risk of diabetes (HR: 6.75, 95% CI 2.40-18.98). Sensitivity analysis further verified the robustness of this result. Also, time-dependent ROC curve analysis showed that RC, non-HDL/HDL-C ratio, and TC/HDL-C ratio were the best lipid parameters for predicting the risk of medium-and long-term diabetes. CONCLUSIONS: Unconventional lipid parameters generally outperform conventional lipid parameters in assessing and predicting future diabetes risk. It is suggested that unconventional lipid parameters should also be routinely evaluated in clinical practice.

Abdominal obesity phenotypes are associated with the risk of developing non-alcoholic fatty liver disease: insights from the general population.

BACKGROUND: The diversity of obesity-related metabolic characteristics generates different obesity phenotypes and corresponding metabolic diseases. This study aims to explore the correlation of different abdominal obesity phenotypes with non-alcoholic fatty liver disease (NAFLD). METHODS: The current study included 14,251 subjects, 7411 males and 6840 females. Abdominal obesity was defined as waist circumference ≥ 85 cm in males and ≥ 80 cm in females; according to the diagnostic criteria for metabolic syndrome recommended by the National Cholesterol Education Program Adult Treatment Panel III, having more than one metabolic abnormality (except waist circumference criteria) was defined as metabolically unhealthy. All subjects were divided into 4 abdominal obesity phenotypes based on the presence ( +) or absence (- ) of metabolically healthy/unhealthy (MH) and abdominal obesity (AO) at baseline: metabolically healthy + non-abdominal obesity (MH-AO-); metabolically healthy + abdominal obesity (MH-AO+); metabolically unhealthy + non-abdominal obesity (MH+AO-); metabolically unhealthy + abdominal obesity (MH+AO+). The relationship between each phenotype and NAFLD was analyzed using multivariate logistic regression. RESULTS: A total of 2507 (17.59%) subjects in this study were diagnosed with NAFLD. The prevalence rates of NAFLD in female subjects with MH-AO-, MH-AO+, MH+AO-, and MH+AO+ phenotypes were 1.73%, 24.42%, 7.60%, and 59.35%, respectively. Among male subjects with MH-AO-, MH-AO+, MH+AO-, and MH+AO+ phenotypes, the prevalence rates were 9.93%, 50.54%, 25.49%, and 73.22%, respectively. After fully adjusting for confounding factors, with the MH-AO- phenotype as the reference phenotype, male MH-AO+ and MH+AO+ phenotypes increased the risk of NAFLD by 42% and 47%, respectively (MH-AO+: OR 1.42, 95%CI 1.13,1.78; MH+AO+: OR 1.47, 95%CI 1.08,2.01); the corresponding risks of MH-AO+ and MH+AO+ in females increased by 113% and 134%, respectively (MH-AO+: OR 2.13, 95%CI 1.47,3.09; MH+AO+: OR 2.34, 95%CI 1.32,4.17); by contrast, there was no significant increase in the risk of NAFLD in the MH+AO- phenotype in both sexes. CONCLUSIONS: This first report on the relationship of abdominal obesity phenotypes with NAFLD showed that both MH-AO+ and MH+AO+ phenotypes were associated with a higher risk of NAFLD, especially in the female population. These data provided a new reference for the screening and prevention of NAFLD.

The value of combining the simple anthropometric obesity parameters, Body Mass Index (BMI) and a Body Shape Index (ABSI), to assess the risk of non-alcoholic fatty liver disease.

BACKGROUND: Body mass index (BMI) and A Body Shape Index (ABSI) are current independent risk factors for non-alcoholic fatty liver disease (NAFLD). The aim of this study was to explore the value of combining these two most common obesity indexes in identifying NAFLD. METHODS: The subjects in this study were 14,251 individuals from the NAfld in the Gifu Area, Longitudinal Analysis (NAGALA) cohort who underwent routine health examination. We integrated BMI with WC and with ABSI to construct 6 combined obesity indicators-obesity phenotypes, the combined anthropometric risk index (ARI) for BMI and ABSI, optimal proportional combination OBMI+WC and OBMI+ABSI, and multiplicative combination BMI*WC and BMI*ABSI. Several multivariable logistic regression models were established to evaluate the relationship between BMI, WC, ABSI, and the above six combined indicators and NAFLD; receiver operating characteristic (ROC) curves were drawn to compare the ability of each obesity indicator to identify NAFLD. RESULTS: A total of 2,507 (17.59%) subjects were diagnosed with NAFLD. BMI, WC, ABSI, and all other combined obesity indicators were significantly and positively associated with NAFLD in the current study, with BMI*WC having the strongest correlation with NAFLD in female subjects (OR per SD increase: 3.13) and BMI*ABSI having the strongest correlation in male subjects (OR per SD increase: 2.97). ROC analysis showed that ARI and OBMI+ABSI had the best diagnostic performance in both sexes, followed by BMI*WC (area under the curve: female 0.8912; male 0.8270). After further age stratification, it was found that ARI and multiplicative indicators (BMI*WC, BMI*ABSI) and optimal proportional combination indicators (OBMI+WC, OBMI+ABSI) significantly improved the NAFLD risk identification ability of the basic anthropometric parameters in middle-aged females and young and middle-aged males. CONCLUSION: In the general population, BMI combined with ABSI best identified obesity-related NAFLD risk and was significantly better than BMI or WC, or ABSI. We find that ARI and the multiplicative combined indicators BMI*WC and BMI*ABSI further improved risk prediction and may be proposed for possible use in clinical practice.

Association of LDL:HDL ratio with prediabetes risk: a longitudinal observational study based on Chinese adults.

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.

Utility of traditional and non-traditional lipid indicators in the diagnosis of nonalcoholic fatty liver disease in a Japanese population.

BACKGROUND: Traditional and non-traditional (TNNT) lipid indicators are known to be closely related to nonalcoholic fatty liver disease (NAFLD). This study's objective was to compare the degree of associations and diagnostic values of TNNT lipid indicators with NAFLD. METHODS: Participants were 14,251 Japanese adults who undergoing health checkups, and we measured and calculated 11 lipid indicators, including traditional lipid indicators such as high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and triglyceride (TG), as well as non-traditional lipid indicators such as TC/HDL-C ratio, LDL-C/HDL-C ratio, TG/HDL-C ratio, non-HDL-C, remnant cholesterol (RC), RC/HDL-C ratio and non-HDL-C/HDL-C ratio. The associations between these lipid indicators and NAFLD were assessed using multivariate logistic regression, and the performance of these lipid indicators in identifying NAFLD was analyzed by receiver operating characteristic (ROC) curves. RESULTS: After rigorous adjustment for potential confounders, multivariate logistic regression showed that all TNNT lipid indicators were independently associated with NAFLD, among which the RC/HDL-C ratio and RC had the strongest association with NAFLD. ROC analysis showed that non-traditional lipid indicators were superior to traditional lipid indicators in identifying NAFLD, especially in young adults and females. It is worth mentioning that the RC/HDL-C ratio was the best lipid indicator for identifying NAFLD with an area under the curve (AUC) of 0.82 and an optimal cut-off value of 0.43; in addition, TG/HDL-C ratio also had a high recognition performance for NAFLD. CONCLUSION: Overall, in the Japanese population, non-traditional lipid indicators had a higher diagnostic value for NAFLD compared to traditional lipid indicators, and lipid indicators alone had a lower diagnostic value for NAFLD than the ratio of two lipid indicators, with RC/HDL-C and TG/HDL-C being the best lipid indicators for identifying NAFLD.

Waist-to-height ratio and non-alcoholic fatty liver disease in adults.

BACKGROUND: The waist-to-height ratio (WHtR) has been recognised as a powerful indicator to evaluate non-alcoholic fatty liver disease (NAFLD) in recent years, but few related studies are available. Thus, clarifying the association between the WHtR and NAFLD may be beneficial to the prevention and treatment of NAFLD. METHODS: The cross-sectional study population was from a large-scale health examination programme called 'human dock' in Japan. In this study, 14,125 participants in this health examination programme were included. To understand the association between the WHtR and NAFLD more intuitively, we grouped the WHtR values into quintiles and used a multivariable logistic regression model to assess WHtR and its quintile with NAFLD risk. Moreover, we used the generalised additive model to model the association between WHtR and NAFLD to explore their non-linear relationship. RESULTS: The prevalence of NAFLD among participants in this study was 17.59%, with an average age of 43.53 ± 8.89 years. After adjusting for all non-collinear covariables, we observed a 66% increase in the NAFLD risk per SD increase in WHtR. Furthermore, in the quintile groups of WHtR, the participants in quintile 2, quintile 3, quintile 4, and quintile 5 had 3.62-fold, 5.98-fold, 9.55-fold, and 11.08-fold increased risks of NAFLD, respectively, compared with those in quintile 1 (Ptrend < 0.0001). Non-linear relationship analysis revealed threshold and saturation effects between WHtR and NAFLD in which a WHtR of approximately 0.4 might be the threshold effect of NAFLD risk, 0.6 might be the saturation effect of NAFLD risk. Additionally, subgroup analysis showed that the interaction between WHtR and BMI was significant. CONCLUSIONS: Our results suggest that in adults, the WHtR is associated with NAFLD, and the association is not purely linear but non-linear, with significant threshold and saturation effects.

The albumin-to-alkaline phosphatase ratio as an independent predictor of future non-alcoholic fatty liver disease in a 5-year longitudinal cohort study of a non-obese Chinese population.

BACKGROUND: The albumin-to-alkaline phosphatase ratio (AAPR) is a newly developed index of liver function, but its association in patients with non-alcoholic fatty liver disease (NAFLD) has not been established. The aim of this study was to investigate the association between the AAPR and NAFLD in a non-obese Chinese population. METHODS: The study included 10,749 non-obese subjects without NAFLD at baseline and divided them into quintiles according to the AAPR. A Cox multiple regression model was used to examine the association between the AAPR and its quintiles and the incidence of NAFLD. RESULTS: The average age of the study population was 43.65 ± 15.15 years old. During the 5-year follow-up, 1860 non-obese subjects had NAFLD events. In the Cox multiple regression model, after adjusting the model according to important risk factors, the AAPR and NAFLD risk were independently correlated, and with a gradual increase in the AAPR, the NAFLD risk decreased gradually (HR: 0.61, 95% CI: 0.47, 0.81; P-trend< 0.0001). Additionally, there were significant interactions between the AAPR and BMI, blood pressure and lipids (P-interaction < 0.05). Stratified analysis showed that the risk of AAPR-related NAFLD decreased in people with normal blood pressure and lipid levels, while the risk of AAPR-related NAFLD increased abnormally in people who were underweight. CONCLUSIONS: This longitudinal cohort study provides the first evidence that the AAPR is an independent predictor of future NAFLD events in non-obese people. For non-obese people with a low AAPR, especially those with BMI < 18.5 kg/m2, more attention should be given to the management of risk factors for NAFLD to prevent future NAFLD.

LDL/HDL cholesterol ratio is associated with new-onset NAFLD in Chinese non-obese people with normal lipids: a 5-year longitudinal cohort study.

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.

The usefulness of obesity and lipid-related indices to predict the presence of Non-alcoholic fatty liver disease.

BACKGROUND: Conicity index, body-shape index, lipid accumulation product (LAP), waist circumference (WC), triglyceride, triglyceride-glucose (TyG) index, hepatic steatosis index (HSI), waist-to-height ratio (WHtR), TyG index-related parameters (TyG-WHtR, TyG-BMI, TyG-WC), body mass index (BMI), visceral adiposity index, triglyceride to high-density lipoprotein cholesterol ratio and body roundness index have been reported as reliable markers of non-alcoholic fatty liver disease (NAFLD). However, there is debate about which of the above obesity and lipid-related indices has the best predictive performance for NAFLD risk. METHODS: This study included 6870 female and 7411 male subjects, and 15 obesity and lipid-related indices were measured and calculated. NAFLD was diagnosed by abdominal ultrasound. The area under the curve (AUC) of 15 obesity and lipid-related indices were calculated by receiver operating characteristic (ROC) analysis. RESULTS: Among the 15 obesity and lipid-related indices, the TyG index-related parameters had the strongest association with NAFLD. ROC analysis showed that except for ABSI, the other 14 parameters had high predictive value in identifying NAFLD, especially in female and young subjects. Most notably, TyG index-related parameters performed better than other parameters in predicting NAFLD in most populations. In the female population, the AUC of TyG-WC for predicting NAFLD was 0.9045, TyG-BMI was 0.9084, and TyG-WHtR was 0.9071. In the male population, the AUC of TyG-WC was 0.8356, TyG-BMI was 0.8428, and TyG-WHtR was 0.8372. In addition, BMI showed good NAFLD prediction performance in most subgroups (AUC>0.8). CONCLUSIONS: Our data suggest that TyG index-related parameters, LAP, HSI, BMI, and WC appear to be good predictors of NAFLD. Of these parameters, TyG index-related parameters showed the best predictive potential.

Association between fasting plasma glucose and nonalcoholic fatty liver disease in a nonobese Chinese population with normal blood lipid levels: a prospective cohort study.

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.

Association between the alanine aminotransferase/aspartate aminotransferase ratio and new-onset non-alcoholic fatty liver disease in a nonobese Chinese population: a population-based longitudinal study.

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.