Predicting metabolic syndrome by obesity- and lipid-related indices in mid-aged and elderly Chinese: a population-based cross-sectional study

Objective To predict the optimal cut-off values for screening and predicting metabolic syndrome(MetS) in a middle-aged and elderly Chinese population using 13 obesity and lipid-related indicators, and to identify the most suitable predictors. Methods The data for this cross-sectional investigation came from the China Health and Retirement Longitudinal Study (CHARLS), including 9457 middle-aged and elderly people aged 45-98 years old. We examined 13 indicators, including waist circumference (WC), body mass index (BMI), waist-height ratio (WHtR), visceral adiposity index (VAI), a body shape index (ABSI), body roundness index (BRI), lipid accumulation product index (LAP), conicity index (CI), Chinese visceral adiposity index (CVAI), triglyceride-glucose index (TyG-index) and their combined indices (TyG-BMI, TyG-WC, TyG-WHtR). The receiver operating characteristic curve (ROC) was used to determine the usefulness of indicators for screening for MetS in the elderly and to determine their cut-off values, sensitivity, specificity, and area under the curve (AUC). Association analysis of 13 obesity-related indicators with MetS was performed using binary logistic regression analysis. Results A total of 9457 middle-aged and elderly Chinese were included in this study, and the overall prevalence of the study population was 41.87% according to the diagnostic criteria of NCEP ATP III. According to age and gender, the percentage of males diagnosed with MetS was 30.67% (45-54 years old: 30.95%, 55-64 years old: 41.02%, 65-74 years old: 21.19%, ≥ 75 years old: 6.84%). The percentage of females diagnosed with MetS was 51.38% (45-54 years old: 31.95%, 55-64 years old: 39.52%, 65-74 years old: 20.43%, ≥ 75 years old: 8.10%). The predictive power of Tyg-related parameters was more prominent in both sexes. In addition, LAP and CVAI are also good at predicting MetS. ABSI had a poor prediction ability. Conclusions Among the middle-aged and elderly population in China, after adjusting for confounding factors, all the indicators except ABSI had good predictive power. The predictive power of Tyg-related parameters was more prominent in both sexes. In addition, LAP and CVAI are also good at predicting MetS.


Introduction
Metabolic syndrome(MetS) (1,2) refers to an energy disorder characterized by the presence of at least any three or more of the following risk factors: elevated fasting glucose, elevated blood pressure, elevated triglyceride levels, reduced high-density lipoprotein cholesterol (HDL-C), and obesity (especially central obesity). A study by scholars Ranasinghe et al. (3) noted that the Asia-Pacific region faces a serious epidemic of MetS. In most countries, nearly one-fifth or more of adults are affected by MetS with a long-term increase in prevalence (3). MetS is more widespread in the senior population (4)(5)(6). Over 30% of middleaged and older persons globally had MetS (7), while a research conducted in China in 2020 (8) indicated that 33.38% of the Chinese population had MetS.
In addition, obesity and abdominal fat deposition lead to several metabolic abnormalities that result in increased hepatic glucose output and decreased insulin sensitivity in skeletal muscle, liver, and adipose tissue, processes that are closely linked to the pathogenesis of type 2 diabetes (9). In recent years, the clinical identification of MetS is becoming increasingly important because the MetS has been shown to increase the risk of type 2 diabetes by 5-fold and the risk of cardiovascular disease by 2-fold over 5 to 10 years (10). It is found that the mortality rate of patients with MetS is much higher than that of patients without MetS (11). Furthermore, patients with MetS have a 2-to 4-fold increased risk of stroke, a 3-to 4-fold increased risk of myocardial infarction, and a 2-fold increased risk of dying from such events compared to those without MetS, regardless of a previous history of cardiovascular events (12,13). Therefore, it is significant to find the best predictor of MetS.
The World Health Organization (WHO) (14), the International Diabetes Federation (IDF) (15), and the NCEP ATP III (2005) (1,2) have developed some of the more widely used diagnostic criteria for MetS at the moment. However, it can be difficult to use these criteria for diagnosis during extensive screening in primary healthcare facilities. In order to forecast the risk of MetS, there is a clinical need for more simple and user-friendly screening indicators.
Direct assessment of obesity and fat distribution by computed tomography (CT) or magnetic resonance imaging (MRI) is the gold standard (16), but this method is expensive and complex for the general public. The other method is an indirect response to obesity through anthropometric measurements. In recent years, there has been growing epidemiological evidence that simple and easily available anthropometric measures can be used to predict the likelihood of MetS (17,18). Body mass index (BMI) has been utilized as the most common measure of obesity and overweight in earlier research (19). In a study by Navarra (20), it was proposed that the triglyceride-glucose index(Tyg index) is the best predictor of metabolic disorders. In addition, waist-height ratio (WHtR) (21) was the best indicator of dyslipidemia and hyperglycemia, while waist circumference (WC) was also a better predictor of blood pressure abnormalities. In Iran, the results of a study similarly showed (22) that WHtR has a better diagnostic value for MetS in the elderly, followed by BMI, visceral adiposity index (VAI), waist-tohip ratio, and neck circumference, with a body shape index (ABSI) having a weaker predictive value (23). Body roundness index (BRI) has been proposed as a potentially useful clinical predictor of MetS in Peruvian adults (24).
The best way to use anthropometric indicators to predict metabolic disease is still up for debate (25), despite the fact that all of these indicators can be used to assess obesity and metabolic disease. This is because anthropometric indicators are influenced by factors like race, age, and gender, and body composition may differ across populations and ethnicities (26)(27)(28). The development of programs to alter risk factors and aid in delaying the start and progression of MetS later in life can be aided by the early identification of those who are at risk. Consequently, the goal of this study was to explore the screening and predictive roles of obesity and lipid-related indicators for MetS in middle-aged and elderly Chinese, as well as the optimal predicted cutoff values to offer a basis for MetS prevention and therapy.

Study design and setting
The China Center for Economic Research at Peking University performed the 2011 China Health and Retirement Longitudinal Survey Wave (CHARLS Wave 2011), a nationally representative longitudinal investigation, which provided the data for our study (29). Participants in CHARLS were recruited from May 2011 to March 2012. 9,457 individuals from the CHARLS Wave 2011 study were included in our analysis after missing data subjects were removed. Without any direct interaction with people, all data are provided in the open as microdata at http://charls.pku.edu.cn/ index/zh-cn.html. All participants gave their informed consent prior to the collection of data, and the study was approved by the Ethics Committee of the China Center for Economic Research at Peking University.

Individuals
Study subjects for this investigation were chosen from the China Health and Retirement Longitudinal Study (CHARLS), Wave 1 (2011). The CHARLS Wave 2011 was used to choose participants for this study (29)

Baseline characteristics
Baseline characteristics including age, sex, education, marital status, living place, smoking status, drinking status, taking activities, and Having regular exercises, and the counts of Chronic diseases were collected by self-report. Taking activities included communicating with friends or providing help to neighbors, friends, or family, or doing a sport, social, or other kind of club or playing Ma-jong, or playing played cards, chess, or going to community club, or taking part in a community-related organization, or doing voluntary or charity work, or caring for a sick or disabled adult, or attending an educational or training course, or stock investment, or using the Internet were dichotomized as ever (at least once a month) or never (30). Chronic diseases included cancer or malignant tumor, dyslipidemia, hypertension, chronic lung diseases, diabetes or high blood sugar, liver disease, kidney disease, asthma were reported by the respondents, arthritis or rheumatism, stomach or other digestive disease, heart attack, coronary heart disease, angina, congestive heart failure, or other heart problems, emotional, nervous, or psychiatric problems, memory-related disease, stroke (30). Most variables depended on our previous research studies (31)(32)(33)(34)(35)(36).

Definition of MetS
The NCEP ATP III (2005) (1, 2) put forward the definition and diagnostic criteria of MetS. According to the standard Chinese definition (37, 38), components of MetS are divided into five categories (1): the waist circumference of central obesity is defined as ≥ 80 cm for women and ≥ 90 cm for men (2). Elevated TG levels: TG levels ≥ 150 mg/dL (3). Low HDL-C levels: HDL-C levels< 40 mg/dL for men and< 50 mg/dL for women (4). Elevated BP: systolic blood pressure (SBP) ≥130 mmHg and/or diastolic blood pressure (DBP) of ≥ 85 mmHg or using antihypertensive therapy (5). Elevated FPG levels: FPG levels ≥ 100 mg/dL or using antidiabetic medications or self-reported medical history of diabetes. When 3 of 5 of the listed characteristics are present, a diagnosis of metabolic syndrome can be made.

Glucose, HDL, triglycerides measurement
The Chinese Center for Disease Control and Prevention in Beijing received the venous blood samples within two weeks of them leaving the Centers for Disease Control and Prevention (CDC) station. The samples were immediately stored and frozen at -20°C before being delivered. When the necessary assays were completed in the lab of the Chinese Medical University, they were put in a deep refrigerator and kept at -80°C. At the Capital Medical University Youanmen Clinical Laboratory, triglycerides (TG), fasting plasma glucose (FPG), and high-density lipoprotein cholesterol (HDL-C) were measured using the enzyme colorimetric assay. We divided TG levels into two groups, ≥150 mg/dL and<150 mg/dL, in accordance with a classification that has previously been employed in studies (31). When fasting plasma glucose is ≥126 mg/dL or 7.0 mmol/L and above, it indicates abnormal blood glucose (39). HDL-C values below 40 mg/dL in men and below 50 mg/dL in women were considered abnormal (40).

Measurements
BMI was calculated by dividing the body weight (kg) by the square of the height (m 2 ) (41, 42). During the blood pressure measurement, which is done in a quiet environment with the left arm on a flat surface with the palm facing upward so that the upper arm is at the same height as the heart, the subject should be at ease while sitting. The blood pressure is then measured using a blood pressure monitor. Hypertension was formerly described as having a systolic blood pressure (SBP) greater than 130 mmHg and/or a diastolic blood pressure (DBP) less than 85 mmHg (43,44). At the conclusion of expiration, the umbilical level was chosen, and the waist size was measured (45); when the waist circumference of women ≥ 80cm, men ≥ 90cm, known as central obesity. WHtR was calculated by the ratio of waist circumference to height (46). VAI was calculated using BMI, WC, TG and HDL-C, with different formulas for men and women (47). It is important to note that VAI, Chinese visceral adiposity index (CVAI), lipid accumulation product index (LAP) and TyG index were required to perform invasive manipulations to obtain TG and HDL-C. Other indicators were calculated using the following equations (48)(49)(50)(51)(52)(53)(54)(55).

Statistical analysis
Statistical Product Service Solutions (SPSS) software, version 25.0, was used to conduct the analyses (IBM SPSS, Armonk, NY, USA). By sex, sociodemographic traits were analyzed and percentages were provided. To compare the categorical variable distribution across sex, a chi-square test was utilized. The mean and standard deviation were used to express continuous variables. In order to evaluate the variations in mean distributions by sex, independent samples t-tests were utilized. The unadjusted and adjusted relationships between anthropometric and MetS components were evaluated using binary logistic regression. We calculated odds ratios (ORs) and 95% confidence intervals (95%CI) adjusting for age, sex, educational levels, marital status, live place, current smoking, alcohol drinking, activities, exercises, and chronic diseases. To determine the area under the curve (AUC) and 95% confidence interval as a predictor of MetS, the receiver operating characteristic curve (ROC) was utilized (56). The significance of the AUC is that an area greater than 0.9 indicates high accuracy, 0.7-0.9 indicates moderate accuracy, 0.5-0.7 indicates low accuracy, and 0.5 indicates a chance result (57). The ROC curve can also be used to determine sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, and negative likelihood ratio. The Youden index, which is derived using the formula: [maximum (sensitivity + specificity-1)] (58), which is the maximum vertical distance between the ROC curve and the diagonal or chance line, determines the cut-off values of the predictor based on the highest value. Table 1 shows the basic characteristics of the participants. A total of 9457 subjects were included in this study, of whom 4340 (45.89%) were male and 5117 (54.11%) were female. Among them, there were significant differences between men and women in age, education, marital status, alcohol consumption, smoking, number of chronic diseases, WC, BMI, WHtR, VAI, ABSI, BRI, LAP, CI, CVAI, TyG index, TyG-BMI, TyG-WC, TyG -WHtR (P< 0.05). However, the distribution of residence, social activities, and physical activity habits were not statistically significant between the male and female subgroups (P > 0.05). Because of these significant differences between males and females (P< 0.05), we performed the main analyses separately by sex. Table 2 shows the baseline characteristics of the study participants with and without MetS by sex. According to the research results, the proportion of women suffering from MetS was much higher (51.83%, compared to 30.67% for men). Men with MetS had significant differences in age, education, current residence, smoking, alcohol consumption, social activity, physical activity, number of chronic diseases, WC, BMI, WHtR, VAI, ABSI, BRI, LAP, CI, CVAI, TyG index, TyG-BMI, TyG-WC and TyG-WHtR (P< 0.05); women had significant differences in all aspects (P< 0.05), with the exception of education and current residence (P > 0.05). Table 3 shows the cut-off values between the AUC, sensitivity, and specificity for obesity and lipid-related indices to detect MetS by sex. We observed the predictive value of obesity and lipid-related indicators for MetS by sex using the ROC. The ROC curves of each indicator in the prediction of MetS risk in men and women are shown in Figures 1, 2 respectively. As shown in the table and figures, among men, the Tyg-WC index was the best predictor of MetS in the middle-aged and elderly male population (AUC=0.924, SE=0.004, 95% CI [0.915,0.932], and optimal cutoffs=763.595).  Table 4 shows the associations of obesity-and lipid-related indices with MetS and its components. According to the values in Table 3, 13 obesity-and lipid-related indices were transformed into two-category variables in this investigation. Table 4 is based on the transformed variables. A larger OR, in general, suggests a higher risk factor. Both before and after adjusting for age, education, marital status, current residence, current smoking, alcohol drinking, social activity, exercise, and chronic disease counts, the odds of MetS increased progressively with increasing obesity and units of lipid measurement for both men and women. Each unit rise in the Tyg index, for example, was related to a 14.525-fold increase in the likelihood of developing MetS in males(95% CI:   12.349,17.085). Each unit increase in BMI was linked to a 5.769-fold increase in the likelihood of developing MetS in women(95% CI: 5.052,6.588). In addition, 13 indicators had statistical significance after adjustment of confounding factors (P < 0.05). Figures 3, 4 show the forest diagram of or value before and after adjustment of confounding factors for males and females, respectively.

Discussion
A total of 9457 middle-aged and elderly Chinese were included in this study, and the overall prevalence of the study population was 41.87% according to the diagnostic criteria of NCEP ATP III. Among them, there were 4340 males and 30.67% were diagnosed    with MetS. There were 5117 females, and 51.38% were diagnosed with MetS. It is easy to see that the prevalence of MetS is high in our middle-aged and elderly population, both in men and women. Therefore, it is necessary to explore indicators that can predict the prevalence in order to prevent and delay the increase of prevalence.
In this cross-sectional study, 12 indicators were found to have much higher predictive value for MetS than ABSI. In a similar vein, it has been demonstrated (23, 24, 59-61) that although ABSI is linked to insulin resistance in older Chinese adults without diabetes and in general Chinese adults, it does not correlate well with various risks and MetS and is, therefore, a less desirable insulin resistance discriminator. This result is due to the high concentration of ABSI near the average value and relatively small variance, which makes ABSI perform poorly in predicting chronic diseases (62). The predictive power of Tyg-related parameters was more prominent in both sexes. In addition, LAP and CVAI are also good at predicting MetS.
Firstly, the excellent predictive power of Tyg-related parameters has to be mentioned first. In this study, the predictive ability of the TYG-related parameter (Tyg index, Tyg-WC, Tyg-BMI, and Tyg-    Thirdly, Chinese Visceral Adiposity Index (CVAI) (51) was put forward because there are racial restrictions in the measurement of VAI, and it has been proved that CVAI is more suitable for China people's physique (76). The ability of CVAI in predicting MetS is obviously superior to traditional indicators (BMI, WC, etc.) (77,78). In our study, after adjusting for confounding factors such as sex, age and education, the probability of male patients with high CVAI is still high (adjusted OR=26.798). Therefore, CVAI can also be considered as an independent factor of the prevalence of MetS.
Limitations in this study should be aware of. Firstly, because our study was cross-sectional in nature, we were unable to determine a temporal relationship between adiposity measurements and MetS. Future research must evaluate the association between anthropometric measurements and MetS risk throughout time and develop clinical tools, such as cut-off values, to forecast MetS risk. Secondly, even though confounders were taken into account in the multivariate regression model, this link should be investigated prospectively since unmeasured or inaccurately measured covariates may lead to residual confounding. Thirdly, many participants were excluded because of the lack of data, and further research should collect more complete data. The study's very large sample of 9457 middle-aged and older Chinese is another important strength. The analytical approach that managed the various confounders is another strength.

Conclusions
Among the middle-aged and elderly population in China, after adjusting for confounding factors, all the indicators except ABSI had good predictive power. The predictive power of Tyg-related parameters was more prominent in both sexes. In addition, LAP and CVAI are also good at predicting MetS.

Data availability statement
The original contributions presented in the study are included in the article/supplementary materials. Further inquiries can be directed to the corresponding author.

Ethics statement
Approval for this study was given by the medical ethics committee of Wannan medical college (approval number 2021-3). The patients/participants provided their written informed consent to participate in this study.

Funding
This work was supported by the NSFC (70910107022, 71130002) and National Institute on Aging (R03-TW008358-01; R01-AG037031-03S1), World Bank (7159234), and the publication fee was supported by the Support Program for Outstanding Young Talents from the Universities and Colleges of Anhui Province for LZ(gxyqZD2021118).