Acta Medica Mediterranea, 2020, 36: 813

THE COMPARISION OF VISCERAL ADIPOSITY INDEX AND ATHEROGENIC INDEX OF PLASMA IN AND OBESE PATIENTS

Selma Pekgor1, Cevdet Duran2, Mehmet Ali Eryilmaz1, Ufuk Berberoglu3 1The Department of Family Medicine, Konya Health Application and Research Center, University of Health Sciences, Konya, Turkey - 2The Division of Endocrinology and Metabolism, The Department of Internal Medicine, Usak University, Medical School, Usak, Turkey - 3The Department of Public Health, Usak University, Medical School, Usak, Turkey

ABSTRACT

Introduction: and dyslipidemia are important risk factors for . In this study, we aimed at comparing visceral adiposity index (VAI) levels calculated through anthropometric measurement and lipid levels with atherogenic index of plasma (AIP) levels calculated with only lipid levels in overweight and obese subjects. Materials and methods: Between 18-65 years, 157 obese patients were included. Homeostasis model assessment of insulin re- sistance (HOMA-IR), VAI and AIP levels were calculated. Results: The study was performed in 105 patients (91 women and 14 men). Regarding AIP risk levels, 9.5% (n=10) of patients were found as low-risk, 2.9% (n=3) as medium and 87.6% (n=92) as high. In high-risk group, HOMA-IR (p=0.026) and VAI (p<0.001) were found higher. VAI and AIP levels were higher among those with (BMI) (≥35 kg/m2) than those with BMI (25- 29.9 kg/m2) (p=0.009 and p=0.009, respectively). A positive correlation was detected between AIP, and HOMA-IR and VAI. Each 1-cm increase in waist circumference and each one-unit increase in body mass index (BMI) led to increases of 0.009 and 0.028 in AIP, respectively. Conclusions: As the indicators of atherosclerotic CVDs, as VAI and AIP increased, the severity of obesity increased in patients with obesity. There was a positive association between VAI and AIP, and those in high-risk group for AIP had higher VAI levels than those in low-risk group. Thanks to their easy calculation with the formula, VAI and AIP could be used to determine the atherosclerotic risk in such patients.

Keywords: Atherosclerosis, atherogenic index of plasma, insulin resistance, obesity, visceral adiposity index.

DOI: 10.19193/0393-6384_2020_2_127

Received May 19, 2019; Accepted January 22, 2020

Introduction mass index (BMI), waist circumference (WC), waist hip ratio (WHR) are used in the evaluation of obe- Obesity is a multifactorial chronic disease char- sity, age, gender, hydration status and ethnic factors acterized by visceral and subcutaneous adipose tis- may also affect these measurements. For example, sue accumulation, and leading to cardiometabolic high BMI values may be found in a person with high diseases. In the case of obesity, many factors such as muscle mass, or WC may be elevated in the con- lipid abnormalities, insulin resistance (IR), ditions where subcutaneous is high, mellitus (DM), increased inflammation, endothelial which may make these anthropometric measure- dysfunction and adipokine imbalance are known to ments inadequate in the assessment of obesity, es- cause and accelerate the development of atheroscle- pecially visceral obesity(5, 6). Again, such methods as rosis(1, 2). In the case of visceral obesity, however, the computerized tomography (CT) and dual x-ray en- incidence and severity of cardiometabolic disorders ergy absortiometry (DXA) used in order to evaluate are higher, compared to generalized obesity(3, 4). Al- visceral obesity could not be used in routine practice though such anthropometric measurements as body due to their cost, loss of time and radiation risk(7-9). 814 Selma Pekgor, Cevdet Duran et Al

In many clinical studies, the levels of visceral adi- width of the buttocks. Waist/hip ratio (WHR) was posity index (VAI) obtained by the formulation of calculated by dividing the measurement of WC (cm) BMI, WC, plasma high density lipoprotein choles- to the measurement of HC (cm). BMI was also calcu- terol (HDL-cholesterol) and triglyceride (TG) levels lated as weight (kg)/height square (m2). As to BMI, were shown to be highly successful in predicting the the participants were classified as the overweight cardimetabolic risk(10-15). with BMI scores between 25-29.9 kg/m2, grade 1 Furthermore, VAI levels were shown to be more obese with BMI scores between 30-34.9 kg/m2, superior than traditional adiposity measurements in grade 2 obese with BMI scores between 35-39.9 kg/ predicting an unhealthy metabolic profiles(16). It was m2, and grade 3 obese with BMI scores of 40.0 kg/m2 also demonstrated that as a new indicator of ather- and above(21). Blood samples were drawn after 12-h ogenicity that is easy calculated logarithmically by night fasting and analyzed on the same day. Plas- the ratio of TG/HDL-cholesterol levels, the athero- ma glucose levels [normal range (NR), 70-105 mg/ genic index of plasma (AIP) increases in situations dL] were measured through the hexokinase method where the risk of atherosclerosis is increased and with Olympus AU 5800 device (Beckman Coulter superior to conventional lipid profiles in predicting Inc., CA, USA). Insulin levels [(NR), 6-27 μlU/mL] atherosclerosis and cardiovascular diseases (CVDs) were measured via the chemiluminescence method (17, 18), and AIP levels are also becoming even more in- with Immulite 2000 device (Siemens Healthcare creased, as obesity, especially abdominal obesity in- Diagnostics, Germany). The analytic sensitivity of creases(17, 18). While AIP levels lower than 0.11 were the assay was found as 2 μlU/mL. Total cholesterol reported to be associated with lower cardiovascular was spectrophotometrically measured [(NR), 110- risks in several studies, the levels between 0.11-0.24 200 mg/dL] with the device of Olympus AU 5800 were defined as intermediate risk, and those over (Beckman Coulter Inc, CA, USA). HDL-cholesterol 0.24 were shown to be associated with increased risk levels [(NR), 40-90 mg/dL] were measured with im- of CVDs (19, 20). While AIP levels are calculated, mune reaction (antigen-antibody complex) through and TG and HDL-cholesterol levels are sufficient, an Olympus AU 5800 device (Beckman Coulter Inc, BMI and WC levels are also required in the calcu- CA, USA), and TG levels [(NR), 60-150 mg/dL] lation of VAI levels, along with these parameters. were measured using a routine enzymatic method In the present study; we aimed to compare VAI and with the auto analyzer of Olympus AU 5800 device AIP levels as the indicators of atherosclerotic CVDs, (Beckman Coulter Inc, CA, USA). For calculating which could be easily calculated in overweight and low-density lipoprotein cholesterol (LDL-cholester- obese patients, and saw that as the levels of VAI and ol), the Friedewald equation was used by the formula AIP increased, the severity of obesity increased in (LDL-cholesterol=Total cholesterol-(HDL-choles- those with obesity. Thanks to their easy calculation, terol+TG/5)]. Thyroid stimulating hormone (TSH) VAI and AIP could be used to determine the risk of level (NR, 0.35-5.5 µIU/mL) was also measured atherosclerosis development in such patients. with chemiluminescence method through the device of Advia Cetaur XP (Siemens Healthcare Diagnostic, Material and method Siemens AG, Germany). Intra- and inter-assay coef- ficients of variations for TSH were 2.44 and 3.44. A total of 157 patients aged between 18-65 VAI levels were calculated for women and men by years were included into the study. They were admit- the following formula [(WC/[36.58+(1.89xBMI)] ted to the family medicine outpatient department of x[(TG(mmol/L)/0.81)x(1.52/HDL-cholester- our hospital with the complaint of obesity between ol (mmol/L))] and [(WC/39.68)+(1.88xBMI)] October 2016 and June 2017. An approval from the x[(TG(mmol/L)/1.03)x(1.31/HDL-cholesterol local ethical committee and informed written con- (mmol/L))], respectively(11). sent from each patient were obtained. Physical ex- AIP levels were calculated by taking the loga- amination and anthropometric measurements of the rithm of the ratio of TG to HDL-cholesterol as [Log patients, such as age, gender, height, weight, WC, hip (TG/HDL-cholesterol)]. Based on AIP levels, the circumference (HC) and blood pressure (BP) were risk classification was constituted as lower risk if the recorded by the researcher. Height (m) and weight calculated value was <0.1, as moderate risk if risk if (kg) were measured with underwear clothing. WC it was between 0.1-0.24 and classified as high risk if was measured as the minimum size between iliac it was >0.24 (19, 20). Used as a common marker of crest and lateral costal margin and HC at maximum IR, homeostasis model assessment-insulin resistance The comparision of visceral adiposity index and atherogenic index of plasma in overweight and obese patients 815

(HOMA-IR) index was also calculated using the for- (p=0.001), BMI (p<0.001), WC (p<0.001), HC mula (fasting glucose levels [mg/dl]×fasting insulin (p=0.03), glucose (p=0.042), TG (p<0.001), insulin levels [μU/mL]/405)(22). (p=0.043), HOMA-IR (p=0.026) and VAI (p<0.001) The patients below 18 and over 65 years of age, were determined to be higher in the high-risk group, those taking steroids or lipid-lowering drugs, under- HDL-cholesterol (p <0.001) was found to be low going liposuction, with pregnancy or breast-feeding, (Table 2). However, the levels of systolic BP, height, those with malabsorption, liver and kidney failure, total cholesterol, LDL-cholesterol and TSH were any malignancies and hypo - or hyperthyroidism, similar in both groups (Table 2). those undergoing any surgery in the last 6 months, Women Men p and non-euthyroid patients were excluded out of the Age (years) 34 (45-27) 38 (50-30) 0.380 Height (cm) 157±0.6 171±1.3 <0.001 study. Weight (kg) 81 (91-73) 96 (109-84) 0.001 BMI (kg/m2) 32 (36-29) 33 (36-29) 0.932 Statistical analysis WC (cm) 101 (108-94) 107 (116-102) 0.200 Statistical analyses of the study findings were HC (cm) 114 (123-110) 110 (119-108) 0.269 Systolic BP (mmHg) 110 (125-100) 120 (130-110) 0.286 evaluated with the Statistical Package for the Social Diastolic BP (mmHg) 80 (80-60) 80 (80-70) 0.271 Sciences software version 22.0 (SPSS Inc., Chicago, Glucose (mg/dL) 91 (98-84) 96 (134-95) 0.007 IL,USA) at a level of α= 0.05. Categorical variables Cholesterol (mg/dL) 186 (224-160) 194 (262-150) 0.836 were presented as frequency and percentage, while Triglyceride (mg/dL) 118 (155-80) 130 (198-99) 0.144 numerical variables were given as mean, standard er- HDL-cholesterol (mg/dL) 48±1 37±1.8 <0.001 LDL-cholesterol (mg/dL) 113 (148-94) 117 (148-102) 0.461 ror, median and quartiles. The Kolmogorov-Smirnov TSH (mIU/L) 1.8 (2.4-1.2) 2.2 (3.4-1.1) 0.291 and Shapiro-Wilk tests, used for descriptive statistics Insulin (μIU/mL) 8.6 (12.4-5.7) 17.1 (22.9-11.2) 0.001 and continuous data distribution, were performed to HOMA-IR 1.9 (2.8-1.3) 4.2 (8.0-2.5) <0.001 analyze the single groups. The student’s t test and the AIP 0.85±0.06 1.41±0.18 0.001 VAI 3.3 (4.4-1.9) 5.7 (8.6-2.7) 0.002 Mann Whitney-U test, one of the tests used for non- Table 1: The comparison of study parameters as to gender. parametric values, were performed for two-group Parametric data were given as mean±standard error, and comparisons. In the comparisons of more than two, non-parametric data as median (%75-%25 quartile). BMI: Body the Kruskal-Wallis variance analysis was used, and mass index, WC: Waist circumference, HC: Hip circumference, the Bonferroni correction analysis was used for mul- BP: Blood pressure, HDL-cholesterol: High density lipoprotein tiple comparisons. In order to measure the relation- cholesterol, LDL-cholesterol: Low density lipoprotein choleste- rol, TSH: Thyroid stimulating hormone, HOMA-IR: Homeosta- ship levels, the Pearson and Spearman correlation sis model of assessment for insulin resistance index, AIP: Adipo- analyzes were used, and the linear regression analy- sity index of plasma, VAI: Visceral adiposity index sis was performed for modelling. Low Risk (AIP<0.1) High Risk (AIP>0.24) p Age (years) 25±1.6 37±1.1 <0.001 Results Height (cm) 161 (166-157) 158 (165-154) 0.770 Weight (kg) 75 (77-72) 83 (95-75) 0.001 BMI (kg/m2) 29 (31-27) 34 (37-30) <0.001 The study was completed with a total of 105 pa- WC (cm) 89 (96-83) 103 (112-99) <0.001 HC (cm) 108 (117-105) 114 (123-110) 0.003 tients, including 91 women and 14 men. The levels Systolic BP (mmHg) 110 (110-100) 110 (130-100) 0.082 of age, BP, BMI, HC, total cholesterol, LDL-choles- Diastolic BP (mmHg) 65 (70-60) 80 (80-70) 0.019 Glucose (mg/dL) 84 (90-83) 94 (99-86) 0.042 terol and TSH were found similar in men and wom- Cholesterol (mg/dL) 173 (233-153) 192 (224-162) 0.146 en. While the levels of height (p <0.001), weight Triglyceride (mg/dL) 52 (60-49) 125 (161-95) <0.001 HDL-cholesterol (mg/dL) 58±3.2 45±0.9 <0.001 (p<0.001), WC (p=0.020), glucose (p=0.006), insu- LDL-cholesterol (mg/dL) 105 (159-93) 117 (148-97) 0.260 lin (p=0.001), HOMA-IR (p<0.001), VAI (p=0.001) TSH (mIU/L) 1.5 (1.9-0.9) 1.8 (2.7-1.2) 0.145 Insulin (μIU/mL) 6.8 (8.0-4.4) 9.7 (13.8-6.3) 0.277 ) and AIP (p=0.001) were found to be higher among HOMA-IR 1.4 (1.7-0.9) 2.1 (3.3-1.4) 0.148 men, HDL-cholesterol (p <0.001) level was detected AIP -0.07[0.02- (-0.14)] 1 (1.3-0.6) <0.001 to be lower (Table 1). VAI 1.09 (1.19-0.99) 3.5 (4.9-2.3) <0.001 AIP levels were found as lower risk in 9.5% Table 2: The comparison of study parameters as to AIP Levels. of patients (n=10), as intermediate risk in 2.9% Parametric data were given as mean±standard error, and non-pa- (n=3) and as higher risk in 87.6% (n = 92). In per- rametric data as median (%75-%25 quartile). AIP: Adiposity in- forming the analysis, the low and high-risk groups dex of plasma, BMI: Body mass index, WC: Waist circumference HC: Hip circumference, BP: Blood pressure, HDL-cholesterol: were compared, because the intermediate-risk group High density lipoprotein cholesterol, LDL-cholesterol: Low den- consisted of only three patients. Although the lev- sity lipoprotein cholesterol, TSH: Thyroid stimulating hormone, els of age (p<0.001), diastolic BP (p=0.019), weight HOMA-IR: Homeostasis model of assessment for insulin resis- tance index, VAI: Visceral adiposity index 816 Selma Pekgor, Cevdet Duran et Al

When the patients were re-classified as group and other parameters of MetS component, such as 1 (overweight, BMI between 25-29.9 kg/m2), group WC, glucose and lipid levels, were also found high- 2 (grade 1 obese, BMI between 30-34.9 kg/m2) and er. When compared in terms of the degree of obesity, group 3 (grade 2 and 3 obese, ≥35 kg/m 2) as to the the levels of VAI and AIP were detected to be high- degree of obesity, VAI and AIP levels were seen to er among the group with BMI ≥35 kg/m2 than the be significantly higher only in group 3, compared to overweight group high-risk group compared to the group 1 (p=0.009 and p=0.009, respectively) (Table 3). low-risk group In our study. Additionally, a positive

Overweight (n=28) Grade 1 Obesity (n=34) Grade 2+3 Obesity (n=43) p1 p2 p3 correlation was also determined between AIP levels, Categories for BMI Group A Group B Group C Weight (kg) 72.6 (76.3-68.1) 80.5 (84-74) 95.6 (106-89.2) <0.001 <0.001 <0.001 and VAI and HOMA-IR. BMI (kg/m2) 28.43 (29.0-27-5) 31.34 (33.49-30.68) 37.1 (39.3-35.6) <0.001 <0.001 <0.001 AIP HOMA-IR VAI WC (cm) 94 (100-87.5) 100.5 (104-94) 110 (118-103) 0.009 <0.001 <0.001 HC (cm) 108 (109-104) 112.5 (117-110) 123 (130-115) <0.001 <0.001 <0.001 r 0.279 0.005 0.286 Systolic BP (mmHg) 110 (120-100) 110 (120-100) 120 (130-110) 0.233 0.005 0.052 Age p 0.004 0.964 0.003 Diastolic BP (mmHg) 70 (80-60) 80 (80-60) 80 (90-70) 0.406 0.004 0.037 Cholesterol (mg/dL) 160.5 (186-148) 197 (233-167) 193 (224-170) 0.010 <0.001 0.967 r 0.344 0.159 0.337 Triglyceride (mg/dL) 83.5 (117-61) 123 (167-84) 129 (159-99) 0.015 <0.001 0.473 Weight p <0.001 0.119 <0.001 HDL-cholesterol (mg/dL) 45.72 ±1.92 49.02±1.67 46.41±1.63 0.632 1 0.811 LDL-cholesterol (mg/dL) 98.6 (122-86) 121 (155-98) 122 (153-105) 0.040 0.007 0.858 r 0.290 0.071 0.260 HOMA-IR 1.88 (3.22-0.99) 2.85 (3.83-1.59) 2.15 (2.80-1.53) 0.043 0.298 0.192 BMI p 0.003 0.492 0.007 VAI 2.27 (4.54-1.48) 3.25 (4.43-1.98) 3.9 (5.13-2.63) 0.289 0.009 0.169 AIP 0.67±0.12 0.91±0.10 1.11±0.09 0.357 0.009 0.447 r 0.337 0.167 0.438 WC Table 3: The comparison of study parameters according to p <0.001 0.103 <0.001 r 0.173 0.008 0.233 severity of obesity. HC The value of α⁄3=0,0167 was compared using with Boferroni p 0.078 0.936 0.017 r 0.133 0.182 0.141 correction for α=0,05. Systolic BP p1: (p value for Group A vs Group B), p2: (p value for Group p 0.193 0.086 0.168 r 0.172 0.188 0.181 A vs Group C), p3: (p value for Group B vs Group C). Para- Diastolic BP metric data were given as mean±standard error, and non-pa- p 0.090 0.076 0.074 r 0.204 0.471 0.165 rametric data as median (%75-%25 quartile. BMI: Body mass Glucose p 0.037 <0.001 0.092 index, WC: Waist circumference, HC: Hip circumference, BP: r 0.937 0.395 0.877 Blood pressure, HDL- cholesterol: High density lipoprotein cho- Triglyceride p <0.001 <0.001 <0.001 lesterol, LDL-cholesterol: Low density lipoprotein cholesterol, r -0.596 -0.386 -0.596 HDL-Cholesterol HOMA-IR: Homeostasis model of assessment for insulin resis- p <0.001 <0.001 <0.001 tance index, VAI: Visceral adiposity index, AIP: Adiposity index r 0.031 0.035 0.073 LDL-Cholesterol of plasma p 0.756 0.735 0.460

r 0.442 0.977 0.472 Insulin While a positive correlation was determined p <0.001 <0.001 <0.001 r 0.468 0.948 AIP - between AIP levels, and age, weight, BMI, WC, TG, p <0.001 <0.001 insulin, HOMA-IR and VAI, a negative correlation r 0.468 0.476 HOMA-IR - was found between API and HDL-cholesterol (Table p <0.001 <0.001 r 0.948 0.476 4). Additionally, there was a positive correlation be- VAI - p <0.001 <0.001 tween the levels of VAI, and age, weight, BMI, WC, HC, TG, insulin, HOMA-IR and AIP, while VAI lev- Table 4: The correlation analysis between AIP, VAI and el was negatively correlated with HDL-cholesterol HOMA-IR, and study parameters. AIP: Adiposity index of plasma, VAI: Visceral adiposity index, (Table 4). HOMA-IR: Homeostasis model of assessment for insulin resis- When the linear regression analysis was per- tance index, BMI: Body mass index, WC: Waist circumference, formed, it was found out that every 1-cm increase in HC: Hip circumference, BP: Blood pressure, HDL-cholesterol: WC levels led to an increase of 0.009 in AIP levels, High density lipoprotein-cholesterol, LDL-Cholesterol: Low density lipoprotein cholesterol and every 1-unit increase in BMI caused an increase of 0.028 in AIP levels. While the variability in WC AIP is a new marker used for atherogenicity levels accounted for 72.2% of the variability found and directly related to the risk of developing athero- in AIP levels, the variability in BMI levels account- sclerosis, and among those with high AIP levels, the ed for 73% of the variability in AIP levels. risk of developing coronary artery diseases (CADs) is high(19). In this study, we found that many com- Discussion ponents of VAI, IR and MetS were higher in the group with risky AIP levels. Obesity not only leads This study investigated the association between to increases at proatherogenic lipoprotein levels, VAI and AIP levels. When the patients with higher but also at the sub-fractionations of proatherogen- API levels were compared with those with lower ic lipoproteins, such as high very-low-density-lipo- API levels in our study, VAI, HOMA-IR, BP levels protein (VLDL), small LDL-cholesterol, and small The comparision of visceral adiposity index and atherogenic index of plasma in overweight and obese patients 817

HDL-cholesterol, and thus constituting a risk for the predictors having significant effects on AIP levels; development of CVDs, even when the classical met- BMI levels were responsible for 38.9% of the var- abolic risk factors are absent(23). Although plasma iance in AIP; and, when body adiposity index was TG and HDL-cholesterol were beneficial in deter- included into the model, this rate increased by 42%, mining the poor prognosis after coronary event and while led to a further increase by detecting the risk of CADs in healthy population, the 44.2% in the model(25). TG/HDL-cholesterol ratio was shown to be logarith- However, in the study where 80 cases with mically more predictive than their single use or rates obesity and MetS, and 80 cases with obesity but no in the determination of coronary vascular risk(24). MetS, as well as 80 control patients with no risk of Furthermore, it was found that the TG/HDL-cho- CVDs were investigated as to the effects of obesi- lesterol logarithmic rate on the base 10 was closely ty and MetS on AIP levels, Essiarab et al. showed correlated with the particle size of LDL-cholesterol that AIP levels were approximately two times higher and the esterification rate with apoB-lipoprotein-de- only in those with obesity and MetS, compared to pleted plasma(24). Calculated as another marker by the obese cases with no MetS and healthy control using anthropometric measurements such as BMI patients, and the presence of MetS was an impor- and WC, as well as metabolic measurements such tant risk factor for the development of CVDs(26). In as plasma TG and HDL-cholesterol levels, VAI in- our study, we detected AIP levels were higher in creases in the cases where the risk of atherogenicity the group with BMI ≥35 kg/m2, compared to those is increased(14). In the study performed by Ferreira et with BMI 30 ≤kg/m2. In addition, in the risk group al.(16) in 854 Brazilians, VAI was shown to be supe- with higher AIP levels; we determined abnormali- rior to traditional adiposity measurement methods in ties in such parameters of MetS components as high detecting unhealthy metabolic status, regardless of WC, diastolic BP, TG and glucose levels, and low nutritional status and gender differences. HDL-cholesterol level. The levels of VAI and HOMA-IR were found Also, in the study including 500 male and 500 to be higher in high-risk group (AIP> 0.24) com- female patients, and performed by Niroumand et pared to low-risk group (AIP<0.11). In addition, a al.(27), it was demonstrated that AIP levels were pos- positive correlation was also found between in our itively correlated with WC and BMI, and negatively study. To the best of our knowledge, there are no with physical activity status; AIP levels were high- other studies in literature comparing these parame- er among men than women; all of the patients with ters. Elevated TG and low-HDL cholesterol levels DM, 90% with impaired glucose tolerance, 92% are common lipid abnormalities in the patients with with obesity and 82% of overweight patients were IR. In calculating VAI and AIP, a positive correla- at a higher risk of CVDs, compared to AIP, and also tion found between the two is logically an expected stated that AIP levels could be used in daily practice condition due to the formula used in the calculation. to determine the risk of CVDs, even if lipid levels Unlike AIP, BMI and WC apart from lipid parame- were at normal levels in such patients. As consistent ters are also other parameters used to calculate VAI. with literature, AIP levels were higher in men, com- . In light of the linear regression model performed in pared to women, in our study, as well. our study, it was found that each increase of 1cm in In the study in which 2936 patients with CADs WC levels led to an increase by 0.009 in AIP levels, and 2451 controls were assessed, Cai et al. found while a 1-unit increase in BMI caused an increase AIP levels were higher it the patients, compared to by 0.028 in AIP levels. While the variability seen the controls, and stated that AIP was an independent in WC levels referred to 72.2% of the variability in risk factor and the strongest predictor for the devel- AIP, that observed in BMI levels explained 73% of opment of CADs(28). the variability in AIP levels. In another study inves- However, in another study conducted with tigating the effects of anthropometric measurements 7507 participants in Uganda by Wegesa et al., it was on AIP levels and performed in non-obese Nigeri- reported that 42% of the population were in moder- ans with a sedentary life-style, it was demonstrated ate-to-high atherogenic risk group, and , that even if the anthropometric measurements and untreated HIV infection, glucose tolerance disorder, lipid levels were within the normal limits, the risk presence of obesity and living in less urbanized vil- of atherogenicity was elevated among men maintin- lages were the factors increasing atherogenic risk(20). ing a sedentary life-style; BMI, body adiposity index As opposed to the studies reporting that high and the percentage of body fat were primary factors/ levels of AIP pose a high risk for atherosclerosis(28), 818 Selma Pekgor, Cevdet Duran et Al there are also studies stating that those with AIP lev- Conclusions els of <0.24 had 3.71-fold-increase in deaths due to major adverse cardiovasculer events and all other In conclusion, it was determined that as the lev- reasons after acute myocardial infarction, compared els of VAI and AIP that are the indicators of athero- to those with ≥0.24; however, the culprit mecha- sclerotic CVDs increase, the severity of obesity also nisms have not been discussed in the study(29). Aim- increases among those with obesity. In the study, ing at reducing high AIP levels will have a positive a positive association was found between VAI and effect on CVDs. It was also shown that regular phys- AIP, and the patients in high-risk for AIP had higher ical reduces AIP levels(30), and pioglitazone VAI levels than those in low risk group. Thanks to leads to a decrease in AIP levels, even in the case of their easy calculation with the formula, we consider monotherapy of pioglitazone or combination thera- that VAI and AIP levels could be used to determine py with metformin, sulfonylurea or insulin in type 2 the development of atherosclerosis in such patients, diabetic patients(31). and that the entity should be supported with prospec- As one of the limitation in our study, we did tive studies including larger populations. not evaluate the exercise status of our patients and by encouraging our patients to exercise, not investi- References gate the effects of exercise on AIP or VAI. In addi- tion, the limited number of cases can be as another 1) Lovren F, Teoh H, Verma S; Obesity and atherosclerosis: limitation of our study. Therefore, limited number of mechanistic insights. Can J Cardiol 2015; 31(2): 177-83. doi: 10.1016/j.cjca.2014.11.031. cases remained in the mid-risk group of AIP, and no 2) Fantuzzi G, Mazzone T; Adipose tissue and assessment was performed in this group. Since the atherosclerosis: exploring the connection. Arterioscler number of patients with BMI ≥40 kg/m2 was small, Thromb Vasc Biol 2007; 27(5): 996-1003. doi: 10.1161/ these cases were included and evaluated together ATVBAHA.106.131755. 2 3) Goodpaster BH, Krishnaswami S, Harris TB, et al.; with those in the group with BMI ≥35 kg/m . Obesity, regional body fat distribution, and the metabolic In the case of atherogenic dyslipidemia, IR is syndrome in older men and women. Arch Intern Med an expected condition, and increased VAI levels are 2005; 165(7): 777-83. doi: 10.1001/archinte.165.7.777. associated with IR(15, 32). Even in individuals with 4) Mahabadi AA, Massaro JM, Rosito GA, et al.; normal WC, a strong association was reported be- Association of pericardial fat, intrathoracic fat, and (15) visceral abdominal fat with tween VAI and HOMA IR . Likewise, in the study burden: the Framingham Heart Study. Eur Heart J 2009; where insulin sensitivity and IR were evaluated with 30(7): 850-6. doi: 10.1093/eurheartj/ehn573. HOMA and the quantitative insulin-sensitivity in- 5) Zimmet P, Magliano D, Matsuzawa Y, et al.; The dex (QUICKI) by Tan et al. respectively, a negative : a global public health problem and a new definition. J Atheroscler Thromb 2005; 12(6): correlation was reported between insulin sensitivity 295-300. (31) and AIP levels . As expected, a positive correlation 6) Gallagher D, Heymsfield SB, Heo M, et al.; Healthy was found between not only HOMA-IR and AIP, but percentage body fat ranges: an approach for developing also HOMA-IR and VAI in our study. guidelines based on body mass index. Am J Clin Nutr HOMA-IR levels were significantly higher in 2000; 72(3): 694-701. 2 7) Alberti KG, Zimmet P, Shaw J; Metabolic syndrome--a the patients with BMI between 30-35 kg/m , com- new world-wide definition. A Consensus Statement from pared to those in the overweight group. Although the International Diabetes Federation. Diabet Med 2006; HOMA-IR levels were found to be higher in the pa- 23(5): 469-80. doi: 10.1111/j.1464-5491.2006.01858.x. tients with BMI ≥35 kg/m2, the difference was seen 8) Rossner S, Bo WJ, Hiltbrandt E, et al.; Adipose tissue determinations in cadavers-a comparison between not to reach a significant level. It is known that there cross-sectional planimetry and computed tomography. is an undeniable association between obesity and IR. Int J Obes 1990; 14(10): 893-902. However, when compared to those in the overweight 9) Sasai H, Brychta RJ, Wood RP, et al.; Does Visceral group, we found no significant difference in terms of Fat Estimated by Dual-Energy X-ray Absorptiometry HOMA-IR levels among the patients with BMI ≥35 Independently Predict Cardiometabolic Risks in 2 Adults? J Diabetes Sci Technol 2015; 9(4): 917-24. doi: kg/m , meaning the condition could be associated 10.1177/1932296815577424. with limited number of cases in our study. 10) Amato MC, Giordano C; Visceral adiposity index: an indicator of adipose tissue dysfunction. Int J Endocrinol 2014; 2014: 730827. doi: 10.1155/2014/730827. 11) Amato MC, Giordano C, Galia M, et al.; Visceral Adiposity Index: a reliable indicator of visceral fat function associated with cardiometabolic risk. Diabetes The comparision of visceral adiposity index and atherogenic index of plasma in overweight and obese patients 819

Care 2010; 33(4): 920-2. doi: 10.2337/dc09-1825. 2014; 9: 23798. doi: 10.3402/ljm.v9.23798. 12) Jiang J, Deng S, Chen Y, et al.; Comparison of visceral 26) Essiarab F, Taki H, Lebrazi H, et al.; Usefulness of and body fat indices and anthropometric measures in lipid ratios and atherogenic index of plasma in obese relation to untreated hypertension by age and gender Moroccan women with or without metabolic syndrome. among Chinese. Int J Cardiol 2016; 219: 204-11. doi: Ethn Dis 2014; 24(2): 207-12. 10.1016/j.ijcard.2016.06.032. 27) Niroumand S, Khajedaluee M, Khadem-Rezaiyan M, 13) Liu PJ, Ma F, Lou HP, et al.; Visceral Adiposity Index et al.; Atherogenic Index of Plasma (AIP): A marker Is Associated with Pre-Diabetes and of cardiovascular disease. Med J Islam Repub Iran Mellitus in Chinese Adults Aged 20-50. Ann Nutr Metab 2015;29: 240. 2016; 68(4): 235-43. doi: 10.1159/000446121. 28) Cai G, Shi G, Xue S, et al.; The atherogenic index 14) Oh SK, Cho AR, Kwon YJ, et al.; Derivation and of plasma is a strong and independent predictor for validation of a new visceral adiposity index for coronary artery disease in the Chinese Han population. predicting visceral obesity and cardiometabolic risk in Medicine (Baltimore) 2017; 96(37): e8058. doi: a Korean population. PLoS One 2018; 13(9): e0203787. 10.1097/MD.0000000000008058. doi: 10.1371/journal.pone.0203787. 29) Hartopo AB, Arso IA, Setianto BY; Low Plasma 15) Ji B, Qu H, Wang H, et al.; Association Between the Atherogenic Index Associated with Poor Prognosis in Visceral Adiposity Index and Homeostatic Model Hospitalized Patients with Acute Myocardial Infarction. Assessment of Insulin Resistance in Participants With Acta Med Indones 2016; 48(2): 106-13. Normal Waist Circumference. Angiology 2017; 68(8): 30) Stranska Z, Matoulek M, Vilikus Z, et al.; Aerobic 716-721. doi: 10.1177/0003319716682120. exercise has beneficial impact on atherogenic index 16) Ferreira FG, Juvanhol LL, da Silva DCG, et al.; Visceral of plasma in sedentary overweigh and obese women. adiposity index is a better predictor of unhealthy Neuro Endocrinol Lett 2011; 32(1): 102-8. metabolic phenotype than traditional adiposity measures: 31) Tan MH, Johns D, Glazer NB; Pioglitazone reduces results from a population-based study. Public Health atherogenic index of plasma in patients with type 2 Nutr 2018: 1-10. doi: 10.1017/s136898001800335x. diabetes. Clin Chem 2004; 50(7): 1184-8. doi: 10.1373/ 17) Shen SW, Lu Y, Li F, et al.; Atherogenic index of plasma clinchem.2004.031757. is an effective index for estimating abdominal obesity. 32) Anik Ilhan G, Yildizhan B, Pekin T; The impact Lipids Health Dis 2018; 17(1): 11. doi: 10.1186/s12944- of lipid accumulation product (LAP) and visceral 018-0656-1. adiposity index (VAI) on clinical, hormonal and 18) Zhu X, Yu L, Zhou H, et al.; Atherogenic index of metabolic parameters in lean women with polycystic plasma is a novel and better biomarker associated with ovary syndrome. Gynecol Endocrinol 2018: 1-4. doi: obesity: a population-based cross-sectional study in 10.1080/09513590.2018.1519794. China. Lipids Health Dis 2018;17(1):37. doi: 10.1186/ s12944-018-0686-8. 19) Dobiasova M; [AIP--atherogenic index of plasma as a significant predictor of cardiovascular risk: from research to practice]. Vnitr Lek 2006 ;52(1): 64-71. 20) Wekesa C, Asiki G, Kasamba I, et al.; Atherogenic Risk Assessment among Persons Living in Rural Uganda. J Trop Med 2016; 2016: 7073894. doi: 10.1155/2016/7073894. 21) Wang Y, Beydoun MA, Liang L, et al.; Will all Americans become overweight or obese? estimating the progression and cost of the US obesity epidemic. Obesity (Silver Spring) 2008; 16(10): 2323-30. doi: 10.1038/oby.2008.351. 22) Matthews DR, Hosker JP, Rudenski AS, et al.; Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985; 28(7): 412-9. 23) Magkos F, Mohammed BS, Mittendorfer B; Effect of obesity on the plasma lipoprotein subclass profile in normoglycemic and normolipidemic men and women. Int J Obes (Lond) 2008; 32(11): 1655-64. doi: 10.1038/ ijo.2008.164. ––––––––– 24) Dobiasova M, Frohlich J; The plasma parameter log Corresponding Author: (TG/HDL-C) as an atherogenic index: correlation Cevdet Duran, MD, Prof. with lipoprotein particle size and esterification rate in The Division of Endocrinology and Metabolism, apoB-lipoprotein-depleted plasma (FER(HDL)). Clin Biochem 2001; 34(7): 583-8. The Department of Internal Medicine, Usak University, Medical 25) Ezeukwu AO, Agwubike EO; Anthropometric measures School, 1 Eylül Kampüsü, Usak, 64200, Turkey of adiposity as correlates of atherogenic index of plasma email: [email protected] in non-obese sedentary Nigerian males. Libyan J Med (Turkey)