ABC | Volume 114, Nº4, April 2020

Original Article Güneş et al. Epicardial adipose tissue and insulin resistance Arq Bras Cardiol. 2020; 114(4):675-682 BMI were significantly greater in patients with insulin resistance. Additionally, diastolic and systolic blood pressure measurements were significantly greater in the IR group. A comparison of laboratory parameters revealed that the IR group had significantly higher serum insulin and glucose levels (p < 0.001, p = 0.002, respectively). The other laboratory parameters were similar between the groups (Table 1). Among standard echocardiographic measurements, EAT thickness was significantly increased in the group with IR (p = 0.004). Other standard echocardiographic and laboratory parameters were similar between the two groups. Atrial electromechanical delays recorded from different annular segments are given in Table 2. Lateral and septal PA was significantly higher in the IR group (62.2 ± 8.3 vs. 56.6 ± 8.4, p = 0.002; 46.1 ± 6.1 vs. 42.7 ± 5.9, p = 0.019 respectively). Tricuspid PAwas similar between the groups. Inter- and intra-atrial EMDwas significantly prolonged in the IR group compared to the group without insulin resistance (23 (18–30) vs. 19.5 (15–23.5), p < 0.010; 9.5 (6.2–10.0) vs. 6 (4–9.2), p = 0.032, respectively) The echocardiographic parameters that showed correlations with HOMA-IR are summarized in Table 3. EAT thickness, inter- and intra-atrial EMD, lateral and septal PA were positively correlated to HOMA-IR. The best cut-off value for EAT for the prediction of insulin resistance was >3.85 mm, with 92.5% specificity and 68.5% sensitivity (AUC = 0.672; 95% CI, 0.563–0.781; p = 0.002 (Figure 1). In the multivariate logistic regression model using the backward stepwise method, EAT thickness (OR = 1.256, 95% CI: 1.016–1.53, p=0.035) and SBP (OR = 1.039, 95% CI: 1.007–1.072, p = 0.015) still remained significant predictors of IR after adjusting for the confounding variables, which were both found to be statistically significant in the univariate analysis (Table 4). Discussion This study investigated the relationship between epicardial adipose tissue and insulin resistance among obese children. It has been shown that epicardial adipose tissue is positively correlated to IR and an independent predictor of IR. IR denotes a condition of relative insensitivity of peripheral tissues (e.g. muscle, liver, and adipose tissue) to the effects of the hormone. IR plays a pivotal role in the development and progression of cardio-metabolic risk factors that, in association with obesity, due to lipolytic effects of adipocytes, leading to large amounts of free fatty acids and impaired secretion of adipokines, both involved in the modulation of insulin sensitivity. 20-22 Although the prevalence of IR is variable among obese patients, Gabato et al. reported it to be 29.1% in their study. 23 In many other studies, this rate has been shown to be over 50%. 24-27 In our study, the rate of IR was found to be 43%. The reason for this difference can be explained by the use of constant HOMA-IR value in other studies, but, in our study, we used HOMA-IR percentile values according to age and gender. The HOMA-IR is a proxy estimate of IR based upon the relationship between fasting glucose and insulin levels, with higher values of HOMA-IR representing more severe IR. 10 Increased IR andHOMA-IR values increase cardio-metabolic risk. There is no evidence of an association between IR measures and incident AF. 28 Many studies have shown that IR is closely related to atrial functions. 29,30 In our study, it was observed that HOMA-IR values were positively correlated with atrial tissue Doppler parameters which are indicative of atrial function in obese children and tissue atrial conduction was increased in the IR group. Obesity causes prolongation of electromechanical conduction time by many mechanisms such as fat inflammation on the atrial wall, increase in sympathetic nervous system activity, increased inflammatory process, adipokinin dysregulation and activation of pro-fibrotic signaling pathways. Electromechanical conduction prolongation has been shown to be prone to atrial fibrillation. 31 IR, which is frequently associated with obesity, has an effect on atrial functions due to existing subclinical inflammation. In our study, both intra- and inter-atrial conduction time was found to be higher in obese children with insulin resistance, according to the literature, compared to the non-IR group. This may be explained by the inflammatory process associated with insulin resistance and by the delayed transmission of this inflammatory process on the atrial tissue. In the light of this information, it can be said that obese children who have insulin resistance may be more prone to atrial fibrillation. Epicardial fat is a visceral fat accumulation that has most of the pathophysiological properties of other visceral adipose tissues, like lipid deposition and release of hormones, cytokines, and chemokines; and it also causes local inflammation. 32-35 It has been shown that body fat distribution, particularly abdominal fat distribution, is correlated with epicardial adipose tissue. 33 Hence, the relationship between epicardial adipose tissue thickness obtained from echocardiography and a number of pathological conditions such as metabolic syndrome, coronary artery disease, hyperlipidemia, blood pressure elevation, and IR has been studied in obese adult and pediatric patients. Epicardial adipose tissue causes the development and/or worsening of IR by increasing free fatty acids, TNF, IL1, IL6, and resistin release and decreasing adiponectin levels. 36 Several studies that examined the relationship between epicardial adipose tissue and IR demonstrated a correlation between epicardial adipose tissue and BMI in obese adults. 37-39 Abacı et al. showed a significant correlation with epicardial fatty tissue among obese children. 40 In line with the literature available, our study demonstrated a correlation between BMI and epicardial fatty tissue. Ishorbagy et al. reported that epicardial fatty tissue was larger in amount in obese patients than in healthy controls, although it did not predict metabolic syndrome. 41 Similarly, Abacı et al. suggested that epicardial fatty tissue failed to predict IR among obese children. 40 On the other hand, we found that epicardial fatty tissue was an independent predictor of IR. The cause of this discrepancy is that our study was a nested case-control study that only included patients instead of healthy controls. Another important reason was that in our study, IR was taken using determined percentiles according to age and gender. The relationship between arterial blood pressure and IR has been shown in many studies 42,43 In our study, we found that systolic blood pressure is an independent predictor of IR. This may be due to increased fat tissue in the body that plays an important role in IR and subclinical inflammation caused 677