Abstract
Background
Few studies have compared the correlation between visceral fat area (VFA) and abdominal subcutaneous fat area (SFA) with arterial stiffness (AS) in patients with type 2 diabetes (T2D). In addition, there is currently controversy regarding the correlation between VFA and SFA with AS. We aimed to investigate the relationship between VFA and SFA with AS in patients with T2D.
Methods
In this cross-sectional study, 1475 Chinese T2D patients with an average age of 52.32 ± 10.96 years were included. VFA and SFA were determined by a dual bioelectrical impedance analyzer, and AS was determined by measurement of brachial-ankle pulse wave conduction velocity (baPWV). Atherosclerosis was deemed present in study participants with baPWV values higher than 75th percentile (1781 cm/s). Independent correlations of logVFA and logSFA with AS were assessed using multiple linear regression and multivariate logistic regression.
Results
The baPWV was linked with VFA, waist circumference, and women’s SFA in a general linear correlation study (P < 0.05), but not with body mass index (P = 0.3783) or men’s SFA (P = 0.1899). In both men and women, VFA and SFA were positively correlated with AS, according to the generalized additive model (GAM). After fully adjusting for confounders, multiple linear regression analyses showed that for every 1-unit increase in logVFA, the beta coefficient of baPWV increased by 63.1 cm/s (95% CI: 18.4, 107.8) (P < 0.05). logSFA did not correlate significantly with baPWV (P = 0.125). In the multiple logistic regression analysis, the odds ratio (OR) of elevated baPWV was 1.8 (95% CI: 1.1, 3.1) (P = 0.019) per 1-unit increase in logVFA. logSFA did not correlate significantly with AS (P = 0.091). In the subgroup analysis, the correlation between logVFA and baPWV did not interact across subgroups (P-interaction > 0.05).
Conclusions
Compared with SFA, VFA had a stronger independent positive correlation with AS in Chinese T2D patients. Patients with T2D should pay more attention to monitoring VFA and lowering it to minimize cardiovascular events.
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Introduction
Currently, cardiovascular disease (CVD) remains the leading cause of death in patients with diabetes. Since diabetics often combine important risk factors for CVD, such as hypertension and dyslipidemia, they have a two- to four-fold increased risk of develo** CVD [1]. Studies have shown that the prevalence of diabetes is increasing, reaching 10.5% of adults globally in 2021, or 536.6 million people, and this number is expected to increase by 51% by 2045 [2]. In addition, there are racial differences in genetic susceptibility to type 2 diabetes (T2D) among Chinese. Compared with Caucasians, Asian populations have a 60% increased risk of diabetes [3]. Arterial stiffness (AS) is a significant CVD event risk factor that is closely linked to the emergence and progression of diabetes complications.
Cardiovascular risk is associated with the location of abdominal fat accumulation, which is composed of two main components: the visceral fat area (VFA) and the abdominal subcutaneous fat area (SFA) [4]. The majority of earlier research, which was done on healthy populations, primarily examined the relationship between VFA and AS only and did not consider the effect of SFA on the results. The correlation between SFA and AS is currently understudied and still controversial [5,6,7,8]. In addition, the correlation of VFA and SFA with AS has been less well reported in a special population of Chinese patients with T2D, who are more prone to insulin resistance (IR), hyperinsulinemia, and abnormal accumulation of fat than healthy individuals. Although the total obesity rate of Asians is lower than that of Africans and Caucasians, Asians are more prone to VFA accumulation. A complex combination of factors, including the sedentary lifestyle of the Chinese, reduced physical activity, and specific dietary patterns (e.g., refined carbohydrates and higher saturated fats), may lead to increased AS and a higher incidence of CVD [4, 9].
Numerous studies have demonstrated that AS has a stronger correlation with abdominal obesity than with overall obesity, despite the fact that obesity is a major risk factor for CVD [10]. Adults in China with a body mass index (BMI) ≥ 28 kg/m2 are defined as overall obesity. Men with a waist circumference (WC) ≥ 90 cm and women with a WC ≥ 85 cm are defined as abdominal obesity [
Subgroup analysis of logVFA and increased risk of AS
To further explore the correlation between logVFA and increased AS in different populations, we performed subgroup analyses (Fig. 3). logVFA was positively associated with the risk of increased AS in all subgroups except the DBP ≥ 90 mmHg group. We dichotomized the SFA groups, and subgroup analyses showed a positive correlation between logVFA and AS in both the low and high SFA groups. After excluding the stratification factor itself and adjusting for effect modifiers, there was no interaction between subgroups (P interaction > 0.05), and the results were stable. Although logVFA was negatively associated with an increased risk of AS at DBP ≥ 90 mmHg and positively associated at DBP < 90 mmHg, there was no interaction in this subgroup (P interaction = 0.0972).
Subgroup analyses for the association between logVFA and elevated baPWV were adjusted for age, sex, SBP, DBP, BMI, smoking, alcohol consumption, work status, HbA1c, TC, TG, HDL-C, LDL-C, FPG, PPG, FCP, glucose-lowering medication, antihypertensive medication, lipid-lowering medications, diabetes duration, and logSFA, except for the stratified variable
Discussion
In this study, the correlation between VFA and SFA with AS in patients with T2D was assessed by baPWV. This cross-sectional study showed a significant positive and dose-response relationship between VFA and baPWV in both males and females, while the dose-response relationship between SFA and baPWV was not significant in males. Furthermore, in multiple logistic regression model 1, We found that VFA and SFA were significantly positively correlated with AS when adjusting only for age and sex, but after adjusting for all confounders, the positive correlation between VFA and AS remained significant; however, the positive correlation between SFA and AS was not significant. Our study confirms a stronger, independent positive association between VFA and an increased risk of AS compared to SFA.
Abdominal fat consists of internal VFA and SFA, and abdominal obesity has a stronger correlation with AS than does total obesity [10]. However, most of the previous studies have only discussed the correlation between VFA and AS, and only a smaller number of studies have compared the correlation between VFA and SFA with AS. The sample sizes of these studies were small, and in addition, there is currently controversy regarding the correlation between SFA and AS [5,6,7,8].
The study by Ryotaro et al. included 148 T2D patients (mean age 65 ± 12 years) in China. The study showed that high VFA and low SFA are determinants of AS in patients with T2D, and high SFA protects against AS in patients with T2D. However, the study used carotid intima-media thickness (CIMT) to assess AS [7]. This is different from our results. This may be related to the different methods used in this study-like assessment of AS. Alterations in the intimal, middle, and tunica layers of the vasculature, both structurally and functionally, are linked to AS. It is controlled by elements coming from various levels of the vessel wall as well as chemicals like insulin and aldosterone in plasma [24]. Studies have shown that CIMT is mainly used as a measure of localized vascular lesions, whereas baPWV is currently used as a measure of AS [25,26,27]. A study by Amparo et al. that included 415 European Americans with an average age of 55 years old confirmed that VFA was independently associated with increased AS and was an independent predictor of CVD, while SFA and BMI did not predict CVD [5]. Another study by Melanie et al. involved 44 early T2D patients between the ages of 30 and 70. They found that VFA was an independent risk factor for arterial inflammation (a marker of early AS), whereas SFA was not. In addition, WC was not associated with arterial inflammation. The study demonstrated that, in comparison to SFA, VFA was more strongly related to early AS in T2D patients [6]. This is consistent with our findings. Studies have shown that both BMI, which assesses overall obesity, and WC, which assesses central obesity, do not correlate as strongly with AS as VFA [12, 13], and a large number of studies have reported no significant correlation between BMI and WC and AS [5, 6, 10, 14]. Furthermore, numerous previous studies have shown that the visceral adiposity index (VAI), which responds to visceral fat, is independently and positively correlated with AS [28,29,30]. In a study involving 5921 Persian adults, Zahra et al. found that among overweight men and women, as well as obese women, VFA linked better with AS than VAI, BMI, and WC [31]. The VAI, which includes lipid-related metabolic markers (TG and HDL-C) and anthropometric indices (BMI and WC), is a newly developed visceral fat index that is thought to be able to depict the distribution of fat [28], but the VFA predicts AS risk better than it. Visceral fat accumulation is more common in men and menopausal women, while subcutaneous fat accumulation is more common in women who are not menopausal [32, 33]. Through the use of general linear correlation analysis, we discovered that baPWV had a stronger association with VFA than with WC, but not with BMI. In women, baPWV is correlated with SFA, but not in men. Because of the different fat distribution in men and women, we found that VFA was significantly and positively linked with AS in both men and women by subgroup analysis. Furthermore, we performed subgroup analyses of whether women were menopausal or not, taking into account changes in hormone levels and altered lipid metabolism in women before and after menopause due to changes in hormone levels in the body [34], and it was discovered that in both menopausal and non-menopausal women, VFA was positively correlated with AS.
Our study found a stronger correlation between VFA than SFA and AS, probably because visceral adipose tissue (VAT) is composed of larger, insulin-resistant adipocytes, which are mainly distributed in the abdominal cavity organs such as the liver and heart [35]. Research has indicated that an increase in VAT also significantly increases the portal vein’s ability to transfer free fatty acids into the liver, which can lead to hepatic IR and elevated LDL-C production and release [8]. Subcutaneous adipose tissue (SAT), which is mainly distributed between the dermis and the fascia, secretes more leptin and lipocalin than VAT and promotes glucose and lipid metabolism [36]. Insulin sensitivity and glucose tolerance were observed to improve in animal trials when SAT was transplanted into the visceral cavity [37]. VAT produces pro-inflammatory cytokines, recruiting more pro-inflammatory macrophages and secreting more vasoconstrictive mediators than SAT [4, 38, 39]. Studies have shown that in people with the same BMI, the risk of CVD increases with the accumulation of visceral fat [40]. In our subgroup analysis, we found that using the Chinese diagnostic criteria for obesity, when the BMI used to diagnose overall obesity was normal (< 24 kg/m2) and when the WC used to diagnose central obesity was normal (men < 90 cm and women < 85 cm), VFA remained positively linked to AS after all confounders were excluded. Although the occurrence of CVD events is more prominent in obese T2D patients, this study found that VFA is an independent risk factor for CVD in T2D patients with normal weight. Therefore, physicians should pay attention to the monitoring of VFA in T2D patients when treating diabetes mellitus to reduce the occurrence of CVD events.
Our study does, however, have certain limitations. Firstly, because it is cross-sectional in nature, it is not possible to draw conclusions about the causal relationship between VFA and SFA with baPWV. Secondly, this study used BIA to measure VFA and SFA. A more objective assessment of the buildup of abdominal fat necessitates abdominal computed tomography or magnetic resonance imaging measurements. However, accumulating evidence has confirmed that the BIA is more cost-effective, simple to perform, and non-invasive in estimating VFA and SFA in diabetic patients [41,42,43,44]. Thirdly, recall bias cannot be completely ruled out due to this study design, but future follow-up data from MMC may provide more precise evidence. Finally, this study only included Chinese patients with T2D; more research is required to determine whether the findings apply to people of other races.
Conclusions
Our study showed that VFA was significantly positively associated with AS and stronger than SFA in patients with T2D. After adjusting for confounders, VFA remained significantly and independently positively associated with AS, whereas SFA was not significantly associated with AS. Therefore, we further emphasize the importance of monitoring and lowering VFA in patients with T2D to reduce the risk of CVD.
