Prevalence of Metabolic Obese Normal Weight and Related Risk Factors in South China

Xuehua LUO, Zien LIANG, Yan LI, Qingbin WU, Zhiqiang PAN, Yuqing LIANG, Lingyu LI, Juanjuan MAI, Huijun XIE*, Li HAN

1. Department of Traditional Chinese Medicine, The First Affiliated Hospital of Jinan University, Guangzhou 510630, China; 2. College of Traditional Chinese Medicine, Jinan University, Guangzhou 510632, China; 3. Information Section, The First Affiliated Hospital of Jinan University, Guangzhou 510630, China

Abstract [Objectives] Metabolic obese normal weight (MONW) is becoming one of the pubic problems which are threatening human health. Whereas, MONW was facing a great challenge for limited attention, especially for the female in China. The aim of this research was to estimate the prevalence of MONW and its related risk components in South China. [Methods] A community-based cross-sectional study was performed on 3 349 residents aged 18-93 years in The First Affiliated Hospital of Jinan University, Guangzhou, China, in 2019. Data was collected by physical examination data which included physical measurements and laboratory examinations. [Results] In all subjects, 55% were females (M/F=1 509/1 840). The prevalence of MONW was 16.09% (0.04% for male, 16.05% for female, P<0.001). The prevalence increased significantly with increasing age in both genders (P<0.001). The binary logistic regression analysis shows that among the risk factors with MONW, age, BMI, gender, systolic pressure, hypertension [Male: ORs=2.56, 95% CI (1.23, 5.32); Female: ORs=2.88, 95% CI (1.76, 4.71)] and hypertriglyceridemia [Male: ORs=3.23, 95% CI (1.67, 6.19); Female: ORs=2.57, 95% CI (1.64, 4.03)] were found to be statistically significant. The level of ALT in MONW group was (27.88±15.85) in male and (24.33±15.75) in female, which were significantly higher than those in the non-MetS group. [Conclusions] The prevalence of MONW was pretty high. We considered MONW be significantly associated with the increase of ALT. Female gender, advanced age, and elevated ALT were independent risk factors for MONW. It was high time that the government should raise the public attention toward metabolic function in normal weight population. Effective prevention and treatment strategies for MONW and its risk factors should be developed targeting different ages and genders.

Key words Metabolic Obese Normal Weight, Prevalence, Related risk factor

1 Introduction

Metabolic syndrome (MetS) is a common but health-threatening disease which is a cluster of metabolic abnormality, including central obesity, high blood pressure, elevated blood glucose levels, elevated triglycerides, and low and high-density lipoprotein cholesterol[1]. The prevalence of MetS in China was 50.4% in 2001 and 58.1% in 2010[2]. A China health and nutrition research reported that even in children, the morbidity of MetS had reached 3.37% in 2017[3]. This is a threatening signal indicating that China would meet a great health burden. Considered widely, MetS is closely associated with obesity. However, the fact is not exactly the case. Normal-weight individuals who display metabolic risk factor are not well known. Among the normal weight individuals in the United States, the prevalence of the metabolically abnormal phenotype was 10.3%, and among those aged between 20 and 34 years, the morbidity would continuously rise as the age grows[4]. Metabolic obese normal weight (MONW) has its potential harm. Kwonetal.[5]suggested that MONW was independently associated with higher severity of angiographic coronary artery disease. A Korea study suggested that men with MONW may have a higher risk of developing advanced colorectal adenoma[6]. However, even if the concept of MONW was accepted by most of the scholars, scarcely did the study report, especially in China. Few studies have been conducted to establish the prevalence of MONW among China. The purpose of our investigation was to assess the prevalence of MONW and explore its risk factors in China.

2 Methods

2.1 Basic informationWe launched this cross-sectional community-based health-check investigation in The First Affiliated Hospital of Jinan University. All the health-check programs were completed in the hospital. In 2017, a total of 3 349 patients (1 509 males and 1 840 females) were enrolled in this study for its data acquisition complete. All participants were required to provide a blood sample after fasting blood for 8 h. Body height (BH, cm) and body weight (BW, kg) were measured. Body mass index (BMI) was calculated as weight (kg) divided by height (m) squared. TG (triglyceride), TC (total cholesterol), LDL-C (low-density lipoprotein cholesterol), HDL-C (high-density lipoprotein cholesterol), GLU (glucose), ALT (alanine aminotransferase), AST (aspertate aminotransferase), GGT (galactosyl glucosyl transferase), ALB (albumin), CHE (cholinesterase), TBIL (total bilirubin), BUN (blood urea nitrogen), UA (uric acid), CR (creatinine), WBC (white blood cell), RBC (red blood cell), HGB (hemoglobin), and PLT (platelet) were measured by an auto-analyzer (Hitachi Model 7600 analyzer, Hitachi, Tokyo, Japan). The laboratory data normal reference ranges were as follows: TG: 0.57-1.70 mmol/L; TC: 3.59-5.17 mmol/L; LDL-C: 1.33-3.36 mmol/L; HDL-C: 0.80-2.20 mmol/L; GLU: 3.60-6.1 mmol/L; ALT: 5.00-40.00 U/L; AST: 5.00-40.00 U/L; GGT: 7.00-50.00 U/L; ALB: 35-42 g/L; CHE: 4 000-12 900 U/L; TBIL: 5.1-23 μmol/L; BUN: 1.70-8.30 mmol/L; UR: 140.00-414.00 μmol/L; CR: 44.00-133.00 μmol/L; WBC: (4.0-10.0)×109/L; RBC: (4-5.5) ×1012/L; HGB: 120-160 g/L; PLT: (100-300) ×109/L.

2.2 DefinitionMetS was diagnosed by the modified National Cholesterol Education Program Adult Treatment Panel III (ATP III) criterion: MetS was defined as having three or more of the following conditions or receiving specific treatment for these conditions: (i) waist circumference ≥ 90 cm in men and ≥ 80 cm in women; (ii) fasting plasma glucose ≥ 5.6 mmol/L; (iii) blood pressure ≥ 130/85 mm Hg; 4) triglyceride (TG) ≥ 1.70 mmol/L or (HDL-C) concentration < 1.0 mmol/L for male and < 1.3 mmol/L for female. Normal weight was defined as BMI < 25 kg/m2. Subjects were stratified into four groups based on their metabolic health status: metabolic health and normal weigh (MHNW) refer to those with normal BMI and metabolic health; metabolic obese but normal weight (MONW) refer to those with normal BMI but MetS diagnosis; metabolic health but obese (MHOB) refer to those obese without MetS diagnosis; metabolic obese and obese (MOOB) refer to those with excess BMI and MetS diagnosis.

2.3 Statistical analysisNumerical values are reported as mean±standard deviation and categorical variables are expressed as proportions. IndependentT-Test was used to calculate the differences between genders. Chi-Square Test was used for evaluating the prevalence of MetS and each component in both genders. IndependentT-Test was used to compare the difference between MONW and the other three groups. Multivariate logistic regression analysis was used to perform ORs and 95% CIs among those having risk factors versus no risk factors. All statistical analyses were performed using SPSS software 22.0 (IBM, Armonk, New York, USA). AP-value below 0.05 was considered statistically significant.

2.4 Ethics approvalThe study was approved by the Medical Ethics Committee of The First Affiliated Hospital of Jinan University (2019030).

3 Results and analysis

3.1 Baseline characteristicIn total, 3 349 participants (1 509 males and 1 840 females) were enrolled in this study, and the prevalence of normal weight in male and female was 62.49% and 80.65%, respectively. In male group, the levels of blood pressure, fasting glucose, ALT, BUN and WBC in obese were significantly higher than those with normal weight. For female, the age, systolic pressure and levels of TG, GLU, BUN and WBC in obese group were obviously higher than those with normal weight (Table 1).

Table 1 Baseline population characteristic

3.2 Metabolic syndrome in normal populationMore than 18% of normal-weight subjects were classed as MONW in this study, and the prevalence of MONW was 18.08% (0.07% for male, 18% for female) . Compared with male, the prevalence of central obesity, high blood pressure and decreased HDL-C in female was higher. And as the number of MetS components grows, the risk of MetS in female was also higher than that in male. As age increases, the prevalence of MetS in female was still higher than that in male (Table 2).

Table 2 Metabolic syndrome in the normal-weight individuals

3.3 Relationship between MONW and liver functionIn both male and female, the levels of ALT and CHE in MONW were much higher than those in MHNW and MHOB. Compared with MOOB, there was no significant difference in the aspect of liver function in the female group.

Table 3 Relationship between MONW and liver function

3.4 Relationship between risk factors for MONW and elevated ALT in normal weight populationMultivariate logistic regression analysis display that hypertension [Male: ORs=2.56, 95% CI (1.23, 5.32); Female: ORs=2.88, 95% CI (1.76, 4.71)] and elevated triglyceride [Male: ORs=3.23, 95% CI (1.67, 6.19); Female: ORs=2.57, 95% CI (1.64, 4.03)] were found to be statistically significant.

Table 4 Association between risk factors for MONW and elevated ALT

4 Discussion and conclusions

The topic of MONW is currently attracting considerable interest as the potential factor of developing cardiovascular disease[7]. Whereas, the presence of MetS alone cannot predict global cardiovascular disease risk. But abdominal obesity could tip the dysfunctional condition of adipose tissue, and help clinical diagnosis[8]. Unsimilar with some developed countries, the prevalence of obesity in China was not as large as expected. In the year of 2002, the China Health and Nutrition Survey Database performed that the overall prevalence was 17.6% for overweight and 5.6% for obesity[9]. It’s reported that the prevalence of obesity was 3.3% in 2004, 3.1% in 2007, and 5.2% in 2010[10]. What’s more, normal weight individuals suffering MetS are not so rare in general. Conusetal.[11]stated that the prevalence of MONW syndrome ranges between 5% and 45% and the MONW group also displayed an altered insulin sensitivity, higher risks for type 2 diabetes and cardiovascular diseases. Therefore, clinicians should think highly of metabolic syndrome both in obese and normal weight for the prevention of cardiovascular disease.

As stated in the result, we could see that quite a number of victims with normal weight were suffering from central obesity, even MetS. The situation was more severe in the female group. The prevalence of MONW was up to 40.63% in female with normal weight according to the ATP III definition about MetS, what’s more, the prevalence of hypertension, hyperlipidemia and hypolipoproteinemia was also higher in female. Similar with our result, it’s reported that 7.41 % of normal-weight male and 10.24 % of normal-weight female were diagnosed as MONW in Chinese population[12]. Chenetal.[13]also suggested that 7% of normal-weight subjects had MetS and 8.55% of normal-weight men and 12.62% of women were diagnosed insulin resistance. Conusetal.[14]illustrated that despite the BMI differences, MONW women showed lower physical activity energy expenditure, lower fat-free mass, lower peak oxygen uptake, and higher percent body fat than non-MONW women. Furthermore, Srdietal.[15]also mentioned hypertrophy of adipocytes of visceral adipose tissue in MONW women. The prevalence of MONW in female increases with age, which may be due to the increased oxidative stress in normal-weight postmenopausal women.

A Taiwan cross-sectional study found that abnormal liver function, including ALT, AST and GGT, were all associated with having MetS[16]. The impact of metabolic syndrome on liver enzymes has been analyzed, but little has been explored in normal weight population. Meanwhile, scarcely did we know whether the influence differs between MONW and the other three groups. In the study, the level of ALT in the MONW group was significantly different from the other groups, except the MOOB group. A Taiwan freshmen’s study stated that the risk factors that MetS affect abnormal liver function were suggested to be enlarged waist circumference and elevated triglyceride[17]. Wangetal.[3]displayed that it was gender and age matter. As this study illustrated, high blood pressure and elevated triglyceride were independently associated with aggravated ALT.

Acknowledged widely, blood pressure is closely associated with arterial stiffness. As Lewingtonetal.[18]demonstrated, usual blood pressure is strongly and directly related to vascular mortality in the middle and old age groups. Also, in the tide of obesity epidemic, hypertension was supposed to be the major factor in the cardiovascular morbidity[19]. Furthermore, as the age grows, cardiovascular risk in hypertension was usually accompanied with isolated systolic hypertension due to the increased central arterial stiffness[20]. A possible explanation can be proposed in the greater accumulation of vascular fat causing by elevated ALT. On the other side, the relationship between serum lipids and ALT was still undocumented. The incident elevated ALT was usually associated with the adiposity and features of the MetS[21]. In the US, there were 2.8% of the population with elevated ALT and central adiposity, hyperleptinemia as well as hyperinsulinemia were supposed to be the major determinants[22]. Even in the children, half of the elevated ALT population suffered from MetS[23]. It was reported that ALT can more appropriately evaluate the risk of MetS than AST, but the specific causal relationship remains to be studied[24]. Yet, the mutual relationship between these different patterns is still not clear. Further prospective studies are needed to confirm our findings.

And we must admit that this study had limitations. First, the population was not so large enough, and that no male patient with MONW was suffered from impaired fasting glucose. Second, we could not exclude those with hepatitis and other liver diseases. Third, data on potential factors, such as alcohol, family medical history, smoking, exercise habits, education, and working pressure were not collected in our study, and lack of this information may have caused some inferential error. Finally, this study was designed to be a cross-sectional study, thus we could only determine the correlation among factors, but not among the causalities. Despite of these methodological concerns, for all we know, this was the first evidence-based study to estimate the prevalence of MONW in China. And the check-up data were obtained from standardized laboratory tests, so we think it can be useful in exploring assessing the risk factors for MONW.

In conclusion, this study assessed the prevalence of MONW and related risk factors in Guangzhou, Guangdong Province, China. We found that the prevalence of MONW is very high in China, especially for female, and factors leading to a high risk of MONW included being female and older, as well as increased ALT. To the authors’ knowledge, this is the first study that has aimed to establish the prevalence of MONW and its associated risk factors among adult Chinese in the right south of China. It was high time that the government should raise the public attention toward metabolic function in normal weight population, and the physicians should screen metabolic syndrome in normal weight for the prevention of cardiovascular disease.

Acknowledgements

We would like to express our sincere gratitude to our colleagues in traditional Chinese medicine department, clinical laboratory, information section, and scientific research section of The First Affiliated Hospital of Jinan University.