The prevalence of obesity is dramatically increasing annually around the world. Due to westernized lifestyle and lack of physical activity, the rise of obesity in China is especially alarming. According to the latest epidemiological survey conducted in China, the national prevalence were 34.3% for overweight and 16.4% for obesity in adults [11], which had been soaring far more than double in the past few decades. There is strong evidence that obesity can lead to increased risks of major cardiometabolic diseases including MAFLD, T2DM, hypertension, dyslipidemia and hyperuricemia. Obesity has become a global public health challenge.
BMI might be a simple and easily accessible index in clinical practice, therefore it is still used as the main criteria for assessing obesity. However, numerous studies have found that individuals diagnosed as overweight or obese by BMI might have no or few cardiometabolic risk factors and even the lowest all-cause mortality [12, 13]. People with similar BMI values might have substantially different levels of health risk [14]. These unexpected findings have come to be termed as the “obesity paradox”. One of the main explanations for mechanisms of the “obesity paradox” might be that these studies used BMI to define obesity, which could not perfectly reflect the amount and distribution of body fat, nor could it precisely differentiate between fat mass and lean body mass [15]. A growing body of evidence has suggested that visceral adiposity and skeletal muscle loss may be both associated with cardiometabolic outcomes. Skeletal muscle loss usually coexists with excessive fat mass, which has come to be known as sarcopenic obesity, a new category of obesity [16]. Based on this fact, we investigated the synergistic effect of visceral fat and skeletal muscle mass on cardiometabolic disorders and explored the sex difference of this association between men and women.
This study was conducted in a natural population undergoing regular health checkup. The mean age of all the participants was around 44 years old, indicating that this study population was mainly middle-aged and was the backbone of social production and development. However, the prevalence of the five cardiometabolic diseases of this population was alarming, with MAFLD being the highest (30.9%), followed by dyslipidemia (27%), hypertension (25.4%), hyperuricemia (12.6%) and hyperglycemia (6.0%). These prevalence rates were similar to those found in previous epidemiological studies in Chinese ethnic except for hyperglycemia [17, 18, 19]. According to the latest epidemiological survey, the prevalence of diabetes in China is around 12.8% [20], which is much higher than the result in our study. This discrepancy may be attributed to the fact that some patients with T2DM may have elevated postprandial blood glucose at the early stage of the disease, but their FPG can be still remained in the normal range [21]. The data in this study came from a population receiving their annual health checkup, with only one fasting blood sample taken and FPG measured, which might miss some diabetic patients. In addition, participants recruited in this study were mainly young and middle-aged people, which might also lead to the relatively low prevalence of hyperglycemia. Since there exist considerable differences in both body fat distribution and mass of body fat and skeletal muscle between men and women due to different sex hormone levels, all the participants were divided into two groups by sex. We can see that BMI, BFM, FFM, SMM and SMI were significantly higher in male than in female. VFA as the most critical risk factor for cardiometabolic diseases, however, was obviously higher in female than that in male, displaying an absolutely opposite trend to that of BMI. Thus, VSR calculated as the ratio of VFA to SMM was significantly higher in women than in men.
Based on the quartiles of VSR, men and women were further divided into four subgroups, respectively. Results showed that with the increase of VSR, the prevalence of the five cardiometabolic diseases rose up both in male and female. Participants with VSR in the fourth quartile had the highest prevalence of the above-mentioned cardiometabolic diseases, regardless of sex. This suggested that VSR was positively associated with the development of cardiometabolic diseases. To our knowledge, this is the first study that evaluates the relationship between VSR and cardiometabolic diseases in relatively large-scale natural population in China. In addition, in each of the same quartile, the prevalence of cardiometabolic diseases in male was higher than in female, which is consistent with the outcomes of previous researches [22]. Of note, MAFLD may be more common in postmenopausal women than in men, for women in this stage have lost the protective effect of estrogen [23]. The prevalence of MAFLD was the highest among the five cardiometabolic diseases, which might owe to the strong correlations between low muscle mass or sarcopenia and MAFLD [24].
To further clarify the associations between VSR and cardiometabolic diseases, we then performed binary logistic regression analysis. Results showed that VSR was positively correlated with the five cardiometabolic diseases and with the increase of VSR by one quartile, the ORs increased significantly for all the five cardiometabolic diseases both in male and female, which further robustly confirmed the associations between VSR and cardiometabolic diseases. With regard to the highest versus the lowest quartile, the ORs for the five diseases were dramatically higher in female than in male, which meant that the risk of these cardiometabolic diseases was obviously higher in female than in male. Furthermore, we used restricted cubic splines to visualize the relations of VSR with the five cardiometabolic diseases in men and women. We found that there were significant positive non-linear relationships between VSR and the risk of MAFLD, dyslipidemia, hyperglycemia and hypertension in both sex. Nevertheless, there were still differences between men and women. In women, the risk started to rise up rapidly after VSR reached a certain threshold. In men, however, the risk increased initially but tended to slow down when VSR arrived at a certain value and the curve became flat and even tended to decline. This also indicated that as VSR increased, the risk of cardiometabolic diseases was higher in women than in men, consistent with the result of binary logistic regression analysis. Similar results are found in numerous previous studies, which have shown that compared with men, women have greater risk of cardiometabolic diseases, such as MAFLD, diabetes, cardiovascular disease and hypertriglyceridemia [25, 26].
There are several strengths in our study. First of all, this is the first analysis to examine the associations of the joint effect of visceral fat and skeletal muscle mass on cardiometabolic disorders in a large natural population of Chinese ethnic. Secondly, this study has clarified sex differences of these associations based on the significant differences of body composition in men and women. Thirdly, we have used restricted cubic spline curves to clearly visualize the non-linear relationships between VSR and cardiometabolic diseases when they are not linearly related. The study also has several limitations. Firstly, this is a cross-sectional study, which can not prove the causality between VSR and cardiometabolic diseases. Secondly, body composition has been measured by BIA method, which is not the most perfect way to measure actual body lean mass and fat mass. However, BIA is a relatively simple and harmless yet reliable and popular tool for assessing body composition. Thirdly, the participants enrolled in this study were those who received their annual health checkup and only their fasting blood samples could be obtained, which might lead to the missed diagnosis of some patients with hyperglycemia.
Perspectives and significance
Our study found that the risk of cardiometabolic diseases rose up in both males and females with the increasing of VSR. Nevertheless, there existed sex difference in the association between VSR and cardiometabolic diseases. Women were at higher risk of cardiometabolic diseases with the increase of VSR compared with men. Further research is needed to elucidate more possible mechanisms for the sex difference of the association between the synergistic effect of visceral fat and skeletal muscle mass and cardiometabolic diseases.