Introduction

Epidemiological data show that the worldwide prevalence of overweight or obesity, which has reached nearly 33.3%, has doubled since 1980 [1]. Both overweight and obesity have been considered risk factors for hemodynamic, endothelial, or inflammatory disorders [2], type 2 diabetes (T2DM) and its complications [3, 4], and even all-cause mortality [5]. Interestingly, some studies have determined that the distribution of adipose tissue rather than the amount may play a more crucial role in the development of vascular complications [4,5,6].

In fact, the methods to detect abdominal adiposity include dual-energy X-ray absorptiometry (DEXA), computed tomography (CT), magnetic resonance imaging (MRI) and dual bioelectrical impedance analysis (BIA) [7, 8], which are unsuitable for routine clinical practices in a general population on account of the radiation exposure, time requirements and high costs [9, 10]. Thus, many indices to estimate central or abdominal obesity have been established, including the visceral adiposity index (VAI) and the lipid accumulation product (LAP), which are calculated using the data of WC, BMI, triglycerides (TG), and high-density lipoprotein (HDL) [32]. Visceral fat mass is positively related to plasma sphingosine-1-phosphate, fibroblast growth factor 23, and neutrophil gelatinase-associated lipocalin levels [33, 34], while serum osteocalcin and serum meteorin-like levels inversely correlate with visceral fat mass [34, 35]. Liraglutide decreases visceral adipose tissue volume and has been associated with improved glycemic control in South Asians [36]. However, studies focused on the associations of abdominal obesity indices with diabetic complications, especially the NC and CVAI, are limited.

In the present study, we found that CVAI had the strongest associations with the prevalence of CVD and DKD among these abdominal obesity indices; NC had a unique association with the prevalence of CCA plaque. All the associations were independent of BMI. However, all the abdominal obesity indices were not associated with the prevalence of DR, regardless of adjustment for BMI or not. To the best of our knowledge, this is the first study to evaluate the relationships between NC, WC, WHR, LAP, VAI, CVAI and the prevalence of CVD, DKD and DR simultaneously. The different associations between the abdominal obesity indices and the prevalence of CVD, DKD and DR may partly account for the different incidence rates of diabetic complications. In addition, calculating CVAI in diabetic adults and improving the abnormal distribution of adipose tissue in a timely fashion might be helpful for both prevention and intervention of CVD and DKD.

Consistent associations of CVAI with CVD and DKD both in men and women

CVAI is a novel visceral adiposity index developed in Chinese adults that is associated with visceral fat area and insulin resistance [12, 37]. In our study, only CVAI was associated with CVD and DKD independently of BMI both in men and women, while NC, WC and WHR were associated with CVD independently of BMI in men but not in women. In women, NC, WC, WHR and LAP were significantly associated with CVD without adjusting for BMI (Additional file 2: Table S1). One reason for this finding may be that fat distribution differs between men and women; apple-shaped obesity is more common in men and pear-shaped obesity in women [1]. The other reason may be that NC, WC, WHR and LAP only reflect fat mass in the abdominal region without distinguishing between visceral and subcutaneous fat mass, however CVAI reflects visceral fat mass [37]. The gender differences in the associations of NC, WC, WHR, LAP with CVD and the gender consistency in the associations of CVAI with CVD suggested that CVAI may be more suitable and convenient for the prevention and control of CVD than other abdominal obesity indices in adults with diabetes.

Stronger associations of CVAI with CVD and DKD than BMI

Previous studies reported that CVAI was superior to BMI, WC or VAI for the diagnosis of diabetes and prediabetes [12, 13, 37], which is similar to the results of our study. In our study, the area under the ROC curve of CVAI for the diagnosis of CVD and DKD was largest, and the OR per 1 SD increase in CVAI with CVD and DKD was highest among NC, WC, WHR, LAP, VAI, and CVAI both in men and women, which suggested that CVAI had the strongest association with CVD and DKD among the abdominal obesity indices, independent of BMI. Compared with BMI, the area under the ROC curve of CVAI for the diagnosis of CVD and DKD was larger, and the OR per 1 SD increase in CVAI with CVD and DKD was higher when adjusting for the same confounders (Additional file 2: Table S1), which supported that abdominal obesity is more closely associated with CVD and DKD compared with generalized obesity [9, 17, 38]. Furthermore, in the subgroup analyses, we found that the positive association of CVAI with CVD and DKD among men and women without obesity remained significant, indicating that combining BMI with CVAI for the prevention and treatment of diabetes may be a beneficial approach.

The unique association between NC and the prevalence of CCA plaque

NC has been considered a marker of upper body subcutaneous fat deposits and a simple and valuable screening tool for identifying individuals with obesity [11, 14]. Studies have reported that NC is independently associated with hyperuricemia [39], non-alcoholic fatty liver disease [40], metabolic syndrome [14, 41] and obstructive sleep apnea [42]. Furthermore, cross-sectional and prospective cohort studies suggested that large NC values may be associated with cardiovascular risk factors, even all-cause mortality, in both men and women [43,44,45], which was similar to the results found in our study. Interestingly, we further found that a larger NC was not only independently associated with a higher prevalence of CVD but also CCA plaque, which has been considered a strong predictor of cardiovascular outcomes [46]. However, not all of the other abdominal obesity indices, including WC, WHR, LAP, VAI and CVAI were significantly associated with the prevalence of CCA plaque. These findings may indicate that the harmful effects of large NC on the kidneys may start in the early stages in patients with diabetes. Lipolytic activity may be one of the mechanisms underlying NC with CVD. It has been demonstrated that free fatty acids released from upper body subcutaneous fat, which result in oxidative stress and vascular injury [47], were more harmful than free fatty acids released from lower body subcutaneous fat [48]. However, much of the pathogenesis of NC and CVD remains unknown.

This study has several strengths. First, it is the first study to detect the associations of obesity phenotype indices with CVD, DKD and DR concurrently. Second, the participants were enrolled from a community with a relatively large sample size, and thus the results may be more reflective of the general population of diabetic individuals. Third, anthropometric measurements and questionnaires were administered by the same trained research group, ensuring the quality of the data. However, there are also some limitations in our study. First, being a cross-sectional study, causal inference between obesity phenotype indices and diabetic complications cannot be established. Second, the ethnic group investigated was only Han Chinese, thus generalizing the results to other ethnic groups should be done cautiously. Third, we did not test for oxidative stress markers in the initial design. Further testing the oxidative stress markers such as malondialdehyde and advanced oxidation protein product levels in the plasma samples of visceral obesity patients should be considered in the future.

Conclusions

The present study demonstrates that CVAI had the strongest association with the prevalence of CVD and DKD among the abdominal obesity indices, and NC had a unique association with the prevalence of CCA plaque. CVAI might be a useful and powerful tool for the prevention and treatment of CVD and DKD, and NC may be a convenient and valuable anthropometric measurement for early prevention of CVD. Further prospective studies are necessary to examine our findings in external populations.