Main findings
In the present study, we found that an elevated VAI was positively associated with UACR in the population with prediabetes and a significant sex difference was observed. The significant association between VAI and increased UACR was only revealed in prediabetic women, whereas such association was no longer significant in prediabetic men after controlling for the potential risk factors. Importantly, after further adjusting for blood pressure, HbA1c, and LDL, the association was weakened, suggesting that abnormal blood pressure, glucose and lipid metabolism would increase the risk of albuminuria in people with prediabetes. Furthermore, stratified analysis revealed that participants with higher VAI were more likely to have increased UACR than those with lower VAI, especially in subjects who were young, overweight or obese, with blood pressure and blood glucose abnormalities, as well as normal values of eGFR. To best of our current knowledge, this is the first multicenter and the largest sample study to investigate the association between VAI and increased UACR in the Chinese population with prediabetes. Therefore, early prevention and intervention are vital for albuminuria, and modification of the abnormal fat distribution may contribute to the early detection and prevention of adverse outcomes, especially in people with obesity, blood pressure and blood glucose abnormalities.
Visceral obesity and CVD
As we all know, obesity contributes to hyperglycemia, hypertension, insulin resistance (IR), and is also associated with higher CVD risk. It has been reported that visceral obesity rather than general obesity was closely associated with higher CVD risk[19]. According to the International Diabetes Federation, the distribution of visceral obesity can be accurately assessed by magnetic resonance imaging (MRI) and computed tomography (CT), which is considered as the gold standard. However, these measures are time-consuming, costly, and risky due to radiation exposure, so they are not routinely available, especially in epidemiological research. Therefore, VAI has been proposed as an emerging surrogate, which is an effective, convenient and routinely applicable indicator of visceral fat distribution and dysfunction[8]. A prospective study of 3042 adults in Europe demonstrated a significant association between VAI and CVD risk. In this study, a higher level of VAI was independently related with the increased 10-year CVD risk in men[20]. In addition, a cross-sectional study conducted in Germany confirmed that VAI is a simple and effective tool to identify CVD risk[21]. The study included 731 adults who were free of CVD but were at high risk of T2DM, and found that VAI was associated with subclinical atherosclerosis independent of other cardiometabolic risk factors. Similar results were also found in another study. It has been reported that visceral obesity was positively related with arterial inflammation and people with increased visceral obesity were at higher risk for CVD events[21].
Albuminuria and CVD
In univariate analysis of our study, we found that CVD was significantly associated with increased albuminuria. Albuminuria has been recognized as a significant indicator of generalized atherosclerosis, because of its association with atherosclerotic risk factors and microvascular endothelial dysfunction[22]. Data from population-based studies showed that albuminuria is related with a higher risk for CVD and cardiovascular mortality[6, 23]. Similar results were found in nondiabetic and normotensive people[24]. A prospective study of 2484 white subjects aged over 50 years reported that albuminuria is associated with 3.22-fold, 1.38-fold increased risk of cardiovascular mortality in all and nondiabetic subjects after adjusting for a wide spectrum of risk factors. And the risk is markedly higher (5.68-fold) in diabetic subjects[25]. The relationship was also observed in the general population. The PREVEND study including 40548 participants indicated that a two-fold increment in albuminuria conferred a 1.29-fold increased risk of cardiovascular death[26]. Additionally, an association has also been reported between albuminuria, myocardial ischemia, stroke and peripheral vascular diseases in several studies[27–29]. The above evidence could support our findings. The presence of albumin in the urine may be generated due to vascular damage, suggesting systemic endothelia dysfunction. Therefore, early identification of warning indicators for albuminuria is of great significance and could contribute to reduce the risk of CVD.
The relationship between visceral obesity and albuminuria
Previous studies have reported that visceral obesity was significantly associated with albuminuria. In a cross-sectional study of 208 adults with T2DM, visceral obesity presented a significant association with UACR[30]. Similarly, another 4-year follow-up study including 2393 participants observed that participants with the greater increase in visceral fat mass had a higher risk for albuminuria[31]. However, these studies are less reliable, due to the small sample size. Sun et al. also investigated a positive relationship between visceral obesity and albuminuria[15]. However, in their study, participants with renal or liver diseases were not excluded, possibly resulting in residual confounding effects. Importantly, few studies investigated the relationship between VAI and albuminuria in prediabetic individuals who are most likely to develop T2DM and have more potential cardiovascular risk factors.
In our study, 24871 participants with prediabetes were included and we found that higher visceral obesity evaluated by VAI was independently associated with the increased risk of albuminuria. The results were consistent with previous studies. Furthermore, a sex difference was detected in our study, which may be partly explained by the gender-specific hormone in the elderly people. Elderly women who are in the perimenopausal or postmenopausal stage, are more prone to fat redistribution, owing to hormones alteration. The decreased estrogen levels after menopause is closely associated with increased adiposity and visceral fat accumulation[32]. This could be supported by the studies from Ryan et al. [33]. Therefore, women probably have the more accumulation of visceral fat [34], leading to a greater risk for the progression of inflammation and kidney damage.
Notably, we found that the association between VAI and albuminuria was attenuated after further adjusting for the HbA1c, blood pressure and LDL in model 5, suggesting that metabolism abnormalities may increase the risk of albuminuria. Many cross-sectional and prospective studies have reported significant relationships between albuminuria, hypertension, diabetes and dyslipidemia, which could partly explain the results. In this study, we also analyzed the relationship between VAI and albuminuria in different stratification. Significant associations were detected in people who were overweight, obese and with abnormal blood pressure and blood glucose metabolisms as well as normal eGFR. Thus, not only modification of the distribution of visceral fat, but also the early detection and intervention of established risk factors in such people are of great importance. Interestingly, we found that the association was only significant in younger participants rather than older ones in this study. However, no interaction of VAI and age in UACR groups was observed. The speculation is that older participants were inclined to keep a healthy diet and have a better compliance, possibly contributing to the favorable effect of albuminuria prevention.
It is well established that WC has been considered as a major clinical parameter of visceral adiposity distribution. However, WC alone is unable to distinguish visceral adiposity from subcutaneous adiposity[35]. In this considerable drawback, VAI has been confirmed as a useful and valid indicator of visceral adiposity distribution and dysfunction, which combined the measurement of anthropometric indices (WC and BMI) with the assessment of lipid metabolism (TG and HDL). Numerous studies have supported that regional visceral fat deposition was a key adiposity phenotype associated with the development of CVD, T2DM, hypertension, CKD and metabolic complications. UACR as a known indicator of kidney damage is well predictive of atherogenic state. Accordingly, population-based studies pointed out that UACR is valuable in predicting clinical cardiovascular outcomes [6, 23]. By using VAI to evaluate visceral obesity, the relationship between visceral obesity and UACR has been reported in some studies[15, 30, 31]. Most studies on this issue, however, have failed to investigate the relationship in prediabetic individuals who are at high risk for the development of T2DM and metabolic complications. People with prediabetes may not be aware of glycemic control and the improvement of fat distribution for a long time, resulting in the progression of T2DM and the incidence of diabetic nephropathy. In this regard, our study provided more evidence to corroborate the association of visceral adiposity assessed by VAI and albuminuria in prediabetic population and indicate the value of VAI as a simple, reliable and efficient screening tool for metabolic complications. Improving the distribution and deposition of visceral fat rather than just weight loss should be proposed to reduce related-CVD risk in clinical practice.