In our study, we observed that women with NWO had statistically significant increased concentration of insulin and insulin resistance that evaluated by HOMA-IR index compared to the control women who had normal BMI and BF.
In previous studies, the prevalence of cardiometabolic abnormalities in patients with NWO have reported compared to normal and or obese counterparts. The results of Huang, et al., study among youngJapanese female cohort reported that NWO women had higher concentration of fasting insulin levels than lean and or normal weight normal obesity (NWNO) (non-significant) but lower level compared to obese women (P = 0.003). The same results were reported about the HOMA-IR, but the HOMA-β cell in NWO women was higher than lean and or NWNOwhile, it was lower compared to the obese women[10].
The result of this study was important for us, because this study performed among Asian women. Body fat mass deposition and distribution is influenced by race. The prevalence of fat mass accumulation in the upper body region is higher in Asian compared to Caucasian whites in the same BMI[11]. For this reason, Asian women with normal BMI are more susceptible to NWO. In our study, similar to the Huang study among Japans women, BF ≥ 30% of body weight considered as excess body fat.
Madeira et al., conducted a study among 1222 men and women in Brazil and found normal weight obesity was associated with NWO was also associated with HOMA2-IR, low insulin sensitivity, and high insulin secretion[12].
The positive association between increased body fat tissue and cardiomatabolic disorders, despite having normal body weight, have reported among adolescences. Heijden and colleagues have shown that in Hispanic adolescent girls with normal BMI (< 85th percentile) and high body fat (≥ 27%), abdominal and hepatic fat content, insulin resistance, plasma leptin and Hs-CRP concentrations increased significantly in comparison to the girls with normal BMI and BF[13].
Previous studies have shown that individuals with NWO are susceptible to metabolic syndrome and cardiovascular disease due to the increased prevalence of hyperglycemia, insulin resistance, low grade of pro-inflammation status, increased oxidative stress, hyperlipidemic disorders in NWO, which increased parallel to increase the percentage of body fat tissues in adults and adolescents [14–16].
The relationship between abdominal fat depositionswith other components of metabolic syndrome was confirmed in numerous previous studiesin various populations such as subjects with overweight/obesity or type 2 diabetes or syndrome metabolic and or postmenopausal women[17–19].
One of the theories to describe the association between the excessive body fat tissues with component of metabolic syndrome is related to adipokine secretion. The results of the present study reported the higher serum level of leptin and vaspin in NWO women than controls.The results of our study in increasing the concentration of leptin were confirmed in previous studies. Romero-Corral et al., reported the increased the concentration of leptin among American individuals with NWO which was consistence with the results of our study[14]. Another study amongSwiss population showed higher leptin concentration in women with NWO than women in normal range of BMI and BF%[20].
It was confirmed the obese patients have higher level of leptin in comparison to the individuals with normal weight, which is attributed to the leptin resistance in obesity[21].
Leptin is one of the primary hormones that diagnosis as an adipocytokine which is secreted from adipose tissues. Therefore, according to the previous studies, there is positive relationship between blood level of leptin and percentage of body fat[22]. We observed similar results in our study among women with NWO (r = 0.36, P = 0.02). Our data have shown positive association between concentration of leptin with fasting levels of FBS and insulin and HOMA-IR.
According to the past investigations, leptin shows paradox actions which can be increase atherogenesis and insulin resistance or may have antiatherogensis and increase insulin sensitivity. Koh et al reported that these opposite effects of leptin is in balanced conditions in healthy individuals and is disrupted in obesity[23]. It seemed that the action of leptin in increase insulin resistance in subjects with NWO is similar to the patients with obesity.
Otherwise, leptin has positive association with the markers of pro-inflammatory and inflammatory status, which can be describe the role of higher level of leptin in increase the risk factors of cardiometabolic disorders[24, 25].
Similar to the leptin, our results showed the statistically significant association of vaspin concentration and fasting insulin level and HOMA-IR in women with NWO.
Vaspin, a serine protease inhibitor, is another adipokine secreted from adipose tissue. Experimental study showed that injection of vaspin to obese mice improves glucose tolerance by increase insulin sensitivity[26].
Compared to the leptin and adiponectine, limited studies have performed about vaspine in humans and most of the studies have focused on animal models of obesity and type 2 diabetes.
Based on the physiological functions of adipokines, they are classified into two categories including “healthy” adipokines such as adiponectine and omentin and “unhealthy” adipokines. In addition to the TNF-α,IL‐6, plasminogen activator inhibitor‐1, adipocyte fatty acid‐binding protein, lipocalin‐2, chemerin, visfatin and resistin, vaspin and leptin are considered as unhealthy adipokines [27].
Based on the results of Genske, et al., study among 1825 participants of the Study of Health in Pomerania, they found no clear conclusion with respect to the association between blood concentration of vaspin and distribution fat tissues including visceral (VAT), subcutaneous adipose tissue (SAT), or liver fat content (LFC)[28].
In 3T3-L1 cells, it was shown that endogenous vaspin positively associated with insulin signaling which is describes by the role of vaspin in increasing insulin-stimulated phosphorylation of the key mediator protein kinase B (AKT)[29].
On the other hand, the results of experimental study in mice, reported that injection of insulin in fasting status increased positively the hepatic expression of vaspin[30].
Previous studies have identified that the serum concentration of vaspin was increased with worsening insulin resistance in children and with impaired glucose tolerance and obesity in adults[31–33].
This study obtained similar findings to previous studies and we observed statistically significant positive association between serum levels of vaspin and insulin in women with NWO. Therefore, it can be proposed that serum level of vaspin is increased as a compensatory response to elevated concentration of insulin and insulin resistance. According to our knowledge, this is the first study regarding the changes in serum level of vaspin in individuals with NWO. More investigation are needed regarding the changes in the serum concentration of adipkines and their interaction between each other and with component of metabolic syndrome components.
Limitation
Comparing the results of studies regarding to the NWO patricians is difficult because of the difference in the ethnics of study subjects, tools using to assess body composition (bioelectrical impedance vs. DXA) and diverse cutoff points to diagnosis of NWO by considering ethnics and gender.