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are resulted with MA&#46; An increasing number of evidence indicates low-grade inflammation as a cause of MA&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">7</span></a> Also obesity is a well-known risk factor for focal segmental glomerulosclerosis&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">8</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">One of the suggested mechanisms in the pathogenesis of microalbuminuria is overexpression of adhesion molecules including ICAM-1 which closely associated with severe inflammatory processes that usually resulted with tissue injury&#46;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">9</span></a> Patients with obesity and diabetic nephropathy exhibit overexpression of ICAM-1&#46;<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">10&#44;11</span></a> Experimental studies showed that hyperglycemia is associated with overexpression of ICAM-1 in renal glomerular tissue and renal endothelial injury&#46;<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">12</span></a> However&#44; varying degree of renal injury among patients with normal ICAM-1 level or disassociation of ICAM-1 level with microalbuminuria may suggest the role of genetic mutations in ICAM-1 gene&#46; As a marker of cell integrity and complexity&#44; the effect of ICAM-1 on renal tissue is well-documented however lack of available data exist regarding to the role of ICAM-1 gene 1462A&#62;G &#40;K469E polymorphism on microalbuminuria in obese individuals&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Our aim is to examine the role of serum ICAM-1 level and ICAM-1 gene 1462A&#62;G polymorphism on urine albumin loss in metabolically normal obese and nonobese individuals&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Material and methods</span><p id="par0025" class="elsevierStylePara elsevierViewall">A total of 194 participants&#59; 98 obese and 96 nonobese&#44; older than 18 years without a history of systemic disorder that admitted to obesity outpatient service of Bagcilar Education and Research Hospital between February 2015 and June 2015 were enrolled&#46; 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Serum ICAM-1 concentration was analyzed by enzyme linked immunosorbent assay &#40;ELISA&#41; by commercially available kits &#40;Invitrogen&#44; Thermo Fisher Scientific&#44; USA&#41;&#46; Whole blood count was performed in blood samples that were taken into tubes with EDTA using an automatic blood counter &#40;XE-5000&#59; Sysmex Corp&#44; Kobe&#44; Japan&#41;&#46; Biochemical variables including serum glucose&#44; urea&#44; creatinine&#44; uric acid&#44; aspartat aminotransferase &#40;AST&#41;&#44; alanine aminotransferase &#40;ALT&#41;&#44; lactate dehidrogenase &#40;LDH&#41;&#44; calcium&#44; sodium&#44; potassium&#44; clor&#44; total protein&#44; albumin&#44; total cholesterol&#44; low density lipoprotein &#40;LDL&#41;&#44; high density lipoprotein &#40;HDL&#41;&#44; trigliceride&#44; were analyzed by photometric method in Siemens Advia 1800 device &#40;Siemens Healthcare Diagnostics&#44; Kobe&#44; Japan&#41;&#46; Hormon parameters including HbA1c&#44; insulin&#44; C-peptide&#44; TSH were analyzed by chemiluminescence immunoassay method in Siemens Advia Centaur device &#40;XE-5000&#44; Sysmex Corp&#46;&#44; Kobe&#44; Japan&#41;&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Urine analysis was performed by spectrophotometric method in Siemens Advia 1800 device &#40;XE-5000&#44; Sysmex Corp&#46;&#44; Kobe&#44; Japan&#41;&#46; Urinary albumin was measured by immunoturbidimetric method in Cobas auto analyzer &#40;Roche Diagnostics&#44; Germany&#41;&#46; Urinary creatinine was analyzed by Aeroset autoanalyzer &#40;Abbott Laboratories Inc&#46;&#44; Abbott Park&#44; IL&#44; USA&#41;&#46; Urine albumin excretion rate exceeding 20<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;min &#40;30<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#41;&#59; in the absence of uncontrolled hypertension or urinary tract infection&#44; was defined as microalbuminuria&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">DNA extraction</span><p id="par0040" class="elsevierStylePara elsevierViewall">Total genomic DNA was extracted from peripheral blood leucocytes using a purification kit &#40;Thermo Scientific GeneJET&#8482; Whole Blood Genomic DNA Purification Kit&#41; according to previously described&#46;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">16</span></a></p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Genotyping analysis</span><p id="par0045" class="elsevierStylePara elsevierViewall">To analyze ICAM-1 gene 1462A&#62;G polymorphism &#40;K469E&#59; rs5498 polymerase chain reaction-restriction fragment length polymorphism &#40;PCR-RFLP&#41; method was&#46; PCR amplification was generated using the following oligonucleotide primers&#58; 5&#8242;-GGAACCCATTGCCCGAGC-3&#8242; and reverse 5&#8242;-GGTGAGGATTGCATTAGGTC-3&#8242; &#40;product of 223<span class="elsevierStyleHsp" style=""></span>bp&#41;&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">A PCR reaction was carried out in a 10<span class="elsevierStyleHsp" style=""></span>&#956;l reaction volume containing 1<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>PCR buffer&#44; 2<span class="elsevierStyleHsp" style=""></span>mM MgCl<span class="elsevierStyleInf">2</span>&#44; 0&#46;2<span class="elsevierStyleHsp" style=""></span>mM each deoxynucleotide triphosphate &#40;dNTPs&#44; Fermentas&#44; St&#46; Leon-Rot&#44; Germany&#41;&#44; 40<span class="elsevierStyleHsp" style=""></span>ng of DNA&#44; 0&#46;2<span class="elsevierStyleHsp" style=""></span>&#956;M of each primer &#40;Bio Basic Inc&#46;&#44; Ontario&#44; Canada&#41;&#44; and 0&#46;5 unit of Taq DNA Polymerase &#40;Fermentas&#41;&#46; The PCR conditions were&#58; 3<span class="elsevierStyleHsp" style=""></span>min of initial denaturation at 94<span class="elsevierStyleHsp" style=""></span>&#176;C&#44; followed by 30 cycles at 95<span class="elsevierStyleHsp" style=""></span>&#176;C for 30<span class="elsevierStyleHsp" style=""></span>s&#44; 30<span class="elsevierStyleHsp" style=""></span>s at 65<span class="elsevierStyleHsp" style=""></span>&#176;C for annealing&#44; and 30<span class="elsevierStyleHsp" style=""></span>s at 72<span class="elsevierStyleHsp" style=""></span>&#176;C for extension&#44; followed by 5<span class="elsevierStyleHsp" style=""></span>min at 72<span class="elsevierStyleHsp" style=""></span>&#176;C for final extension&#46; The PCR products were 223<span class="elsevierStyleHsp" style=""></span>bp&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">For the RFLP analysis&#44; PCR-amplified products were digested with BanII for 2&#8211;5<span class="elsevierStyleHsp" style=""></span>h at 37<span class="elsevierStyleHsp" style=""></span>&#176;C &#40;New England Biolabs Inc&#46;&#44; Hertfordshire&#44; UK&#41;&#46; The amplicon with the homozygous GG allele of ICAM was cleaved by BanII&#44; yielding 136 and 87<span class="elsevierStyleHsp" style=""></span>bp fragments&#44; whereas the amplicon with the homozygous AA allele remained uncut&#44; yielding a 223<span class="elsevierStyleHsp" style=""></span>bp band&#46; The amplicon with the heterozygous AG allele yielded three fragments of 223&#44; 136 and 87<span class="elsevierStyleHsp" style=""></span>bp length&#46; The digested products were separated on 3&#37; agarose gel along with a 100&#8211;1500<span class="elsevierStyleHsp" style=""></span>bp DNA ladder &#40;Bio Basic Inc&#46;&#41;&#46; Ethidium bromide-stained gels were visualized under UV light using the Alpha Imager System &#40;Alpha Innotech&#44; San Leandro&#44; CA&#44; USA&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Statistical analysis</span><p id="par0060" class="elsevierStylePara elsevierViewall">Data were analyzed using the SPSS for Windows computer program &#40;release 22&#46;0&#59; SPSS Inc&#46; Chicago&#44; IL&#44; USA&#41;&#46; All data expressed as the mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD&#46; Differences between the study groups were analyzed by using Student&#39;s <span class="elsevierStyleItalic">t</span>-test&#46; Quantitative data were analyzed by chi-square test&#46; Pearson correlation analysis and Spearman&#39;s rho correlation analysis were used to evaluate the correlation of variables&#46; The variables significant in univariate analysis were included to multivariate logistic regression analysis &#40;only significant correlation coefficients are reported&#41;&#46; A <span class="elsevierStyleItalic">p</span> value &#60;0&#46;05 was considered to be statistically significant&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Findings</span><p id="par0065" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> shows demographic characteristics and laboratory parameters of obese and nonobese participants&#46; Mean age of groups were similar however obese individuals had significantly higher uric acid&#44; platelet count&#44; microalbuminuria and proteinuria level &#40;<span class="elsevierStyleItalic">p</span>&#58; 0&#46;001&#44; <span class="elsevierStyleItalic">p</span>&#58; 0&#46;004&#44; <span class="elsevierStyleItalic">p</span>&#58; 0&#46;043 and <span class="elsevierStyleItalic">p</span>&#58; 0&#46;011&#59; respectively&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; Serum ICAM-1 level of obese individuals was significantly higher &#40;<span class="elsevierStyleItalic">p</span>&#58; 0&#46;001&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0070" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> demonstrates comparison of different genotypes of ICAM-1 gene with regard to demographic characteristics and laboratory parameters&#46; Obese individuals with GG genotype had significantly higher uric acid&#44; microalbuminuria and proteinuria when compared to individuals with AA or AG genotype &#40;<span class="elsevierStyleItalic">p</span>&#58; 0&#46;038&#44; <span class="elsevierStyleItalic">p</span>&#58; 0&#46;042 and <span class="elsevierStyleItalic">p</span>&#58; 0&#46;014&#59; respectively&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0075" class="elsevierStylePara elsevierViewall">Male participants had significantly higher urea&#44; creatinine&#44; AST&#44; ALT&#44; LDH&#44; triglyceride&#44; total protein&#44; albumin&#44; FT4&#44; hemoglobin and urine creatinine level while female participants had higher levels of body fat ratio and platelet count &#40;<span class="elsevierStyleItalic">p</span>&#58; 0&#46;001&#44; <span class="elsevierStyleItalic">p</span>&#58; 0&#46;001&#44; <span class="elsevierStyleItalic">p</span>&#58; 0&#46;001&#44; <span class="elsevierStyleItalic">p</span>&#58; 0&#46;001&#44; <span class="elsevierStyleItalic">p</span>&#58; 0&#46;001&#44; <span class="elsevierStyleItalic">p</span>&#58; 0&#46;023&#44; <span class="elsevierStyleItalic">p</span>&#58; 0&#46;001&#44; <span class="elsevierStyleItalic">p</span>&#58; 0&#46;001&#44; <span class="elsevierStyleItalic">p</span>&#58; 0&#46;001&#44; <span class="elsevierStyleItalic">p</span>&#58; 0&#46;001&#44; <span class="elsevierStyleItalic">p</span>&#58; 0&#46;001&#44; <span class="elsevierStyleItalic">p</span>&#58; 0&#46;001 and <span class="elsevierStyleItalic">p</span>&#58; 0&#46;002&#59; respectively&#41;&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">Correlation analysis indicated a significant correlation between serum ICAM-1 with HbA1c&#44; creatinine&#44; uric acid&#44; AST&#44; ALT&#44; LDH&#44; total cholesterol&#44; LDL-c&#44; albumin&#44; hemoglobin and microalbuminuria &#40;<span class="elsevierStyleItalic">p</span>&#58; 0&#46;027&#44; <span class="elsevierStyleItalic">p</span>&#58; 0&#46;002&#44; <span class="elsevierStyleItalic">p</span>&#58; 0&#46;001&#44; <span class="elsevierStyleItalic">p</span>&#58; 0&#46;011&#44; <span class="elsevierStyleItalic">p</span>&#58; 0&#46;001&#44; <span class="elsevierStyleItalic">p</span>&#58; 0&#46;006&#44; <span class="elsevierStyleItalic">p</span>&#58; 0&#46;043&#44; <span class="elsevierStyleItalic">p</span>&#58; 0&#46;012&#44; <span class="elsevierStyleItalic">p</span>&#58; 0&#46;046&#44; <span class="elsevierStyleItalic">p</span>&#58; 0&#46;001 and <span class="elsevierStyleItalic">p</span>&#58; 0&#46;030&#59; respectively&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46; Association of creatinine with urea&#44; uric acid&#44; AST&#44; ALT&#44; LDH&#44; albumin&#44; TSH&#44;FT4&#44; WBC&#44; hemoglobin&#44; platelet count&#44; urine creatinine and body fat mass were significant &#40;<span class="elsevierStyleItalic">p</span>&#58; 0&#46;001&#44; <span class="elsevierStyleItalic">p</span>&#58; 0&#46;001&#44; <span class="elsevierStyleItalic">p</span>&#58; 0&#46;001&#44; <span class="elsevierStyleItalic">p</span>&#58; 0&#46;001&#44; <span class="elsevierStyleItalic">p</span>&#58; 0&#46;024&#44; <span class="elsevierStyleItalic">p</span>&#58; 0&#46;004&#44; <span class="elsevierStyleItalic">p</span>&#58; 0&#46;001&#44; <span class="elsevierStyleItalic">p</span>&#58; 0&#46;001&#44; <span class="elsevierStyleItalic">p</span>&#58; 0&#46;001 and <span class="elsevierStyleItalic">p</span>&#58; 0&#46;001&#59; respectively&#41;&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0085" class="elsevierStylePara elsevierViewall">Multivariate analysis and Logistic regression analysis were performed to predict microalbuminuria risk in obese individuals with different genotypes of ICAM-1 gene single nucleotide polymorphism and determined that obese individuals with GG genotype of ICAM-1 gene 1462A&#62;G polymorphism have 7&#46;39 fold increased risk of microalbumin&#305;ria &#40;<span class="elsevierStyleItalic">p</span>&#58; 0&#46;049&#41; while the risk of microalbuminuria in individuals with AA or AG genotype were nonsignificant &#40;<a class="elsevierStyleCrossRefs" href="#tbl0020">Tables 4 and 5</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><elsevierMultimedia ident="tbl0025"></elsevierMultimedia></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Discussion</span><p id="par0090" class="elsevierStylePara elsevierViewall">The present study indicated that obese individuals have worse metabolic control and evident microalbuminuria when compared to nonobese counterparts&#46; Female individuals had significantly higher body fat ratio however metabolic deteriorament of male individuals was evident&#46; GG genotype of ICAM-1 gene is associated with microalbuminuria and proteinuria&#46; Finally&#44; we determined a significant correlation between serum ICAM-1 level with microalbuminuria and metabolic control&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">Endothelial dysfunction is the initial step of vascular changes which eventually progress to evident atherosclerosis &#40;AS&#41; and AS related complications&#46;<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">17</span></a> Endothelial injury and related disorders are five times more frequent and significantly seen at earlier ages among obese population&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">1</span></a> For more than a century ago&#44; relation of obesity and AS has been known&#46;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">18</span></a> Obesity is a well-known criteria of metabolic syndrome &#40;MS&#41; and accounts four times higher risk for atherosclerotic disorders&#46;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">19</span></a> In a study including 9961 obese subjects&#44; it has been shown that obesity is risk factor for microalbuminuria independent from diabetes and hypertension&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">20</span></a> In agreement with the literature&#44; our obese population had higher blood pressure&#44; lipid and uric acid levels&#44; and excrete significantly higher amount of microalbumin and protein&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">A growing body of evidence indicate that subclinical inflammation is evident in obese individuals which is closely related to AS and insulin resistance &#40;IR&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">21</span></a> Inflammatory conditions are associated with increased endothelial activation and overexpression of adhesion molecules&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">22</span></a> Adhesion molecules regulates leukocyte migration across the endothelium and involved in integral part of inflammation&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">10</span></a> Obese individuals exhibit increased mRNA expression of ICAM-1 leading to infiltration of adipose tissue and other systems including kidneys by macrophages&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">23</span></a> Independent from fat distribution&#44; total fat volume is major determinant of serum levels of adhesion molecules&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">24</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">Obese individuals or diabetic patients without well-controlled glycemia have increased ICAM-1 levels when compared to nonobese or diabetic patients with glycemic control&#46;<a class="elsevierStyleCrossRefs" href="#bib0310"><span class="elsevierStyleSup">25&#44;26</span></a> A well-known correlation has been established between diabetic complications including nephropathy and adhesion molecules&#46;<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">27</span></a> A number of studies determined that patients with ICAM-1 gene K469E polymorphism&#44; the K allele are significantly more prone to endothelial injury and CVD&#44; and may predict future cardiovascular events&#46;<a class="elsevierStyleCrossRefs" href="#bib0325"><span class="elsevierStyleSup">28&#8211;30</span></a> There are controversial reports regarding to relation of ICAM-1 gene polymorphism and microvascular complications of DM&#46; Sun et al&#46; showed that ICAM-1 gene polymorphism has nonsignificant effect on diabetic retinopathy &#40;DR&#41; while Liu et all&#46; determined an increased risk of DR in patients with ICAM-1 gene polymorphism<a class="elsevierStyleCrossRefs" href="#bib0340"><span class="elsevierStyleSup">31&#44;32</span></a></p><p id="par0110" class="elsevierStylePara elsevierViewall">Increased serum levels of adhesion molecules may considered as early markers of endothelial injury which is resulted with systemic vascular disorder including renal microvasculature&#46;<a class="elsevierStyleCrossRefs" href="#bib0350"><span class="elsevierStyleSup">33&#44;34</span></a> There is a positive correlation between serum ICAM-1 level and ICAM-1 gene polymorphism&#46;<a class="elsevierStyleCrossRefs" href="#bib0360"><span class="elsevierStyleSup">35&#44;36</span></a> It would be reasonable to expect microalbuminuria in obese individuals with overexpression of adhesion molecules because obese individuals have impaired insulin sensitivity&#44; and also adhesion molecules destruct beta-cells leading to insulitis&#44; hyperglycemia and hyperglycemia related nephrotoxicity that all may resulted with microalbuminuria&#46; Adhesion molecules including ICAM-1 have been demonstrated in atherosclerotic lesions which is regressed by adiponectin&#44; a adipocyte secretory protein decreased in obesity&#46;<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">37</span></a></p><p id="par0115" class="elsevierStylePara elsevierViewall">The present study has some potential drawbacks&#46; First&#44; sample size of the study was relatively low&#46; We included relatively young obese and nonobese individuals without diabetes&#44; hypertension&#44; hyperlipidemia&#44; renal parenchymal or cardiovascular disorders to eliminate cumulative effect of these entities on microalbuminuria&#46; Second&#44; this study was conducted in Turkish population that limits us to generalize our results to other populations&#46; Finally&#44; evaluation of complex interaction of weight loss and serum ICAM-1 level may provide complementary data on microalbuminuria in obesity&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">The importance&#47;novelty of the study is that it is the first report that examined the role of ICAM-1 gene 1462A&#62;G polymorphism on microalbuminuria in obesity&#44; and established that GG genotype of ICAM-1 gene is an independent risk factor of microalbuminuria in obesity&#46; There is a limited data on the genetic background of microalbuminuria in obese individuals&#46; Understanding molecular and genetic mechanisms of microalbuminuria may help to identify obese patients under risk of nephropathy that is initially manifested with microalbuminuria&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">Based on the fact that ICAM-1 is involved in endothelial injury and atherosclerosis&#44; synthesis and genetic basis of this molecule may be therapeutic target for the complications of obesity&#46; Further studies with large sample size are warranted to reach more precise conclusion&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Ethical disclosure</span><p id="par0130" class="elsevierStylePara elsevierViewall">The study was performed in accordance with Helsinki Declaration&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">Ethics Committee approval was obtained&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">Informed consent was obtained from all participants&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Conflict of interests</span><p id="par0145" class="elsevierStylePara elsevierViewall">Authors declare that there is no conflict interest&#46;</p></span></span>"
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    "fechaRecibido" => "2016-04-14"
    "fechaAceptado" => "2016-11-17"
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            0 => "Obesity"
            1 => "Microalbuminuria"
            2 => "Adhesion molecule"
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            0 => "Obesidad"
            1 => "Oligoalbuminuria"
            2 => "Mol&#233;cula de adhesi&#243;n"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Background</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">A growing body of evidence suggest that obese individuals are under risk of renal parenchymal disorders when compared to nonobese counterparts&#46; Microalbuminuria is the early marker of renal involvement&#46; Although most of obese patients carries multiple risk factors for microalbuminuria&#44; some obese individuals without risk factor may progress to microalbuminuria&#46; The present study was performed to examine the role of ICAM-1 gene 1462A&#62;G &#40;K469E&#41; polymorphism on microalbuminuria in obese subjects without diabetes mellitus&#44; hypertension&#44; hiperlipidemia and older age&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Ninety eight obese and 96 nonobese individuals without a comorbidity enrolled into the study&#46; Serum ICAM-1 level was measured by enzyme linked immunoabsorbent assay &#40;ELISA&#41; method&#46; ICAM-1 gene 1462A&#62;G &#40;K469E&#41; polymorphism was examined by restriction fragment length polymorphism-polymerase chain reaction &#40;RFLP-PCR&#41;&#46; Nepholometric method was used to examine urinary albumin loss&#44; and microalbuminuria was measured by albumin to creatinine ratio&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Obese individuals had significantly higher microalbuminuria and proteinuria level compared to nonobese subjects &#40;<span class="elsevierStyleItalic">p</span>&#58; 0&#46;043 and <span class="elsevierStyleItalic">p</span>&#58; 0&#46;011&#59; respectively&#41;&#46; GG genotype of ICAM-1 carriers have significantly higher microalbuminuria compared to individuals with AA or AG genotype carriers &#40;<span class="elsevierStyleItalic">p</span>&#58; 0&#46;042&#41;&#46; Serum ICAM-1 level was significantly correlated with creatinine and microalbuminuria &#40;<span class="elsevierStyleItalic">p</span>&#58; 0&#46;002 and <span class="elsevierStyleItalic">p</span>&#58; 0&#46;03&#59; respectively&#41;&#46; Logistic regression analysis indicated a 7&#46;39 fold increased risk of microalbuminuria in individuals with GG genotype of ICAM-1 gene 1462A&#62;G &#40;K469E&#41; polymorphism&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">GG genotype of ICAM-1 gene K469E polymorphism is associated with increased microalbuminuria in obese individuals without another metabolic risk factor&#46;</p></span>"
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            "titulo" => "Background"
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          1 => array:2 [
            "identificador" => "abst0010"
            "titulo" => "Methods"
          ]
          2 => array:2 [
            "identificador" => "abst0015"
            "titulo" => "Results"
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          3 => array:2 [
            "identificador" => "abst0020"
            "titulo" => "Conclusions"
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      "es" => array:3 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introducci&#243;n</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Un conjunto de datos en aumento indica que los individuos obesos corren m&#225;s riesgo de sufrir trastornos del par&#233;nquima renal si se los compara con sus hom&#243;logos no obesos&#46; La oligoalbuminuria es un primer rasgo de afectaci&#243;n renal&#46; Aunque la mayor&#237;a de los pacientes obesos presentan m&#250;ltiples factores de riesgo de oligoalbuminuria&#44; esta puede manifestarse en algunos individuos obesos sin factores de riesgo&#46; El presente estudio se realiz&#243; para analizar el papel del polimorfismo 1462A&#62;G &#40;K469E&#41; del gen <span class="elsevierStyleItalic">ICAM-1</span> en la oligoalbuminuria de individuos obesos sin diabetes mellitus&#44; hipertensi&#243;n&#44; hiperlipidemia ni vejez&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">M&#233;todos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Para el estudio fueron reclutados 98 individuos obesos y 96 individuos no obesos sin comorbilidad&#46; Se midi&#243; el nivel s&#233;rico de ICAM-1 mediante el ensayo de inmunoabsorci&#243;n enzim&#225;tica &#40;ELISA&#41;&#46; Se analiz&#243; el polimorfismo 1462A&#62;G &#40;K469E&#41; del gen <span class="elsevierStyleItalic">ICAM-1</span> por reacci&#243;n en cadena de la polimerasay polimorfismo de longitud de los fragmentos de restricci&#243;n &#40;RFLP-PCR&#41;&#46; El m&#233;todo nefolom&#233;trico se utiliz&#243; para analizar la p&#233;rdida urinaria de alb&#250;mina&#44; y la oligoalbuminuria se midi&#243; con la tasa de alb&#250;mina&#47;creatinina&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Los individuos obesos presentaron unos niveles de oligoalbuminuria y proteinuria considerablemente m&#225;s elevados que los individuos no obesos &#40;p&#58; 0&#44;043 y p&#58; 0&#44;011&#44; respectivamente&#41;&#46; La oligoalbuminuria en los portadores del genotipo GG de <span class="elsevierStyleItalic">ICAM-1</span> fue bastante mayor que la de los portadores del genotipo&#160;AA o AG &#40;p&#58; 0&#44;042&#41;&#46; El nivel s&#233;rico de ICAM-1 se correlacion&#243; notablemente con la creatinina y la oligoalbuminuria &#40;p&#58; 0&#44;002 y p&#58; 0&#44;03&#44; respectivamente&#41;&#46; El an&#225;lisis de regresi&#243;n log&#237;stica mostr&#243; un riesgo 7&#44;39 veces mayor de oligoalbuminuria en los individuos con el genotipo&#160;GG del polimorfismo 1462A&#62;G &#40;K469E&#41; del gen <span class="elsevierStyleItalic">ICAM-1</span>&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">El genotipo GG del polimorfismo 1462A&#62;G &#40;K469E&#41; del gen <span class="elsevierStyleItalic">ICAM-1</span> se asocia con un aumento de la oligoalbuminuria en personas obesas sin otro factor de riesgo metab&#243;lico&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0025"
            "titulo" => "Introducci&#243;n"
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          1 => array:2 [
            "identificador" => "abst0030"
            "titulo" => "M&#233;todos"
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          2 => array:2 [
            "identificador" => "abst0035"
            "titulo" => "Resultados"
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          3 => array:2 [
            "identificador" => "abst0040"
            "titulo" => "Conclusiones"
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        "etiqueta" => "Fig&#46; 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
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          "en" => "<p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">2&#37; agarose gel electrophoresis stained with ethidium bromide showing the PCR-RFLP analysis of the ICAM-1&#46; Lanes M&#58; DNA marker&#46; Lanes 1&#44; 2&#58; AA allelic polymorphism&#59; Lane 3&#44; 4&#58; AG allelic polymorphism&#59; Lane 5&#44; 6&#58; GG allelic polymorphism&#46;</p>"
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                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col">Obese &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>98&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col">Nonobese &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>96&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</th><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleBold">NS</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Urea&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">27&#46;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>8&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">27&#46;11<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>8&#46;24&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleBold">NS</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Creatinin&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;74<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleBold">NS</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Uric acid&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5&#46;29<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&#46;27<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;04&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a><span class="elsevierStyleBold">0&#46;001</span><a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">&#42;&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">AST&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">23&#46;35<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>14&#46;44&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">17&#46;94<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#46;36&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a><span class="elsevierStyleBold">0&#46;038</span><a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">ALT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">33&#46;31<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>38&#46;83&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">16&#46;64<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>8&#46;56&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleBold">NS</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">LDH&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">204&#46;28<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>32&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">187&#46;85<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>32&#46;17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a><span class="elsevierStyleBold">0&#46;001</span><a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">&#42;&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Trygliceride&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">146&#46;54<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>90&#46;32&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">114&#46;54<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>73&#46;55&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleBold">NS</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Cholesterol&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">187&#46;02<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>41&#46;79&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">182&#46;47<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>32&#46;32&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleBold">NS</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">HDL-c&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">52&#46;01<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>42&#46;51&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">54&#46;91<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>14&#46;08&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleBold">NS</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">LDL-c&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">111&#46;14<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>34&#46;83&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">105&#46;51<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>30&#46;22&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleBold">NS</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Ca&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">9&#46;54<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;48&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">9&#46;45<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;79&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleBold">NS</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Na&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">140&#46;51<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>14&#46;22&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">141&#46;45<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;26&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleBold">NS</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">K&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&#46;52<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;28&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&#46;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;36&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a><span class="elsevierStyleBold">0&#46;008</span><a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">&#42;&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">CI&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">113<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>9&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">104<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>10&#46;77&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a><span class="elsevierStyleBold">0&#46;027</span><a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">CRP&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5&#46;07<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#46;44&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&#46;55<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&#46;37&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleBold">NS</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">T&#46; protein&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">7&#46;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;41&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">7&#46;39<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;44&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleBold">NS</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Albumin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&#46;56<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;31&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&#46;66<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;36&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a><span class="elsevierStyleBold">0&#46;039</span><a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">TSH&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&#46;37<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;37&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;24&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleBold">NS</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">S T4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;13<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;21<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a><span class="elsevierStyleBold">0&#46;001</span><a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">&#42;&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Insulin&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">9&#46;74<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>6&#46;35&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleBold">NS</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">C peptide&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3&#46;68<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;85&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&#46;37<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;96&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleBold">NS</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Leukocyte count&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">8&#46;03<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;98&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">8&#46;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;73&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleBold">NS</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Hemoglobine&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">13&#46;76<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;89&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">13&#46;72<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;67&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleBold">NS</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Platelet count&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">282&#46;01<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>69&#46;74&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">254&#46;76<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>59&#46;28&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a><span class="elsevierStyleBold">0&#46;004</span><a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">&#42;&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Mean platelet volume&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">7&#46;74<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;22&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">8&#46;24<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;82&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleBold">NS</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Urine density&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1018&#46;59<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&#46;27&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleBold">NS</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Urine protein&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;04<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;19&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a><span class="elsevierStyleBold">0&#46;011</span><a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">186&#46;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>83&#46;71&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">165&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>83&#46;24&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleBold">NS</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Spot MA&#47;Cr&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>13&#46;17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">6&#46;58<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>7&#46;08&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleBold">NS</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Spot microalbumin&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;16<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;65&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\tvoid\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">36&#46;97<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>9&#46;83&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">37&#46;18<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>8&#46;74&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">37&#46;92<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>9&#46;12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">BMI&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">28&#46;95<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>7&#46;23&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">29&#46;26<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>6&#46;45&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">29&#46;87<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>8&#46;13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Systolic blood pressure&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">122&#46;87<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>13&#46;32&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">123&#46;46<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>13&#46;81&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">125&#46;78<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>13&#46;21&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Diastolic blood pressure&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">74&#46;63<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>9&#46;87&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">77&#46;08<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>10&#46;22&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">77&#46;13<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>8&#46;89&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Glucose&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">95&#46;12<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>11&#46;36&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">93&#46;39<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>10&#46;29&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">95&#46;32<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>12&#44;&#46;02&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Urea&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">28&#46;16<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>9&#46;47&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">26&#46;32<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>6&#46;71&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">28&#46;43<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>7&#46;18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Creatinin&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;89<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;37&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;78<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;19&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">&#220;ric acid&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&#46;56<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&#46;71<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;38&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5&#46;37<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;71&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><a class="elsevierStyleCrossRef" href="#tblfn0035"><span class="elsevierStyleSup">a</span></a><span class="elsevierStyleBold">0</span>&#46;<span class="elsevierStyleBold">038</span><a class="elsevierStyleCrossRef" href="#tblfn0045"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">T&#46;protein&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">7&#46;43<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;45&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">7&#46;38<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;41&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">7&#46;41<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;43&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Albumin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&#46;61<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;41&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&#46;57<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;29&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&#46;63<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;24&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Urine density&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1015&#46;56<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&#46;91&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1007&#46;35<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>6&#46;02&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1018&#46;76<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&#44;&#46;42&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Urine protein&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;08<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;26&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;04<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;19<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;39&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><a class="elsevierStyleCrossRef" href="#tblfn0040"><span class="elsevierStyleSup">b</span></a><span class="elsevierStyleBold">0</span>&#46;<span class="elsevierStyleBold">014</span><a class="elsevierStyleCrossRef" href="#tblfn0045"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Spot creatinin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">184&#46;78<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>86&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">171&#46;36<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>78&#46;97&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">190&#46;67<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>87&#46;86&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Spot MA&#47;Cr&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">7&#46;76<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>14&#46;33&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">7&#46;68<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>9&#46;23&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">8&#46;68<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>8&#46;78&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;34<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;84&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;93<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;14&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">ICAM-1</th></tr><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Diastolic blood pressure&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8722;0&#46;078&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">HbA1c&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;162&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;027<a class="elsevierStyleCrossRef" href="#tblfn0025"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Glucose&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8722;0&#46;010&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Urea&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;080&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Creatinin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;222&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;002<a class="elsevierStyleCrossRef" href="#tblfn0030"><span class="elsevierStyleSup">&#42;&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Uric acid&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;297&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;001<a class="elsevierStyleCrossRef" href="#tblfn0030"><span class="elsevierStyleSup">&#42;&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">AST&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;183&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;011<a class="elsevierStyleCrossRef" href="#tblfn0025"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">ALT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;264&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;001<a class="elsevierStyleCrossRef" href="#tblfn0030"><span class="elsevierStyleSup">&#42;&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">LDH&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;197&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;006<a class="elsevierStyleCrossRef" href="#tblfn0030"><span class="elsevierStyleSup">&#42;&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Trygliceride&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;106&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Cholesterol&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;148&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;043<a class="elsevierStyleCrossRef" href="#tblfn0025"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">HDL-c&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8722;0&#46;114&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">LDL-c&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;182&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;012<a class="elsevierStyleCrossRef" href="#tblfn0025"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Ca&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;198&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;006<a class="elsevierStyleCrossRef" href="#tblfn0030"><span class="elsevierStyleSup">&#42;&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Na&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;127&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">K&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;007&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">CI&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8722;0&#46;043&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">CRP&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;092&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">T&#46;protein&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;165&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;023<a class="elsevierStyleCrossRef" href="#tblfn0025"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Albumin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;145&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;046<a class="elsevierStyleCrossRef" href="#tblfn0025"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">TSH&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;083&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">S T4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;112&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Insulin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;059&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">C peptide&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;067&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Leukocyte count&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;090&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Hemoglobine&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;243&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;001<a class="elsevierStyleCrossRef" href="#tblfn0030"><span class="elsevierStyleSup">&#42;&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Hematocryte&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;230&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;001<a class="elsevierStyleCrossRef" href="#tblfn0030"><span class="elsevierStyleSup">&#42;&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Platelet count&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8722;0&#46;015&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Mean platelet volume&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8722;0&#46;146&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;044<a class="elsevierStyleCrossRef" href="#tblfn0025"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Urinedensity&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8722;0&#46;059&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Urine protein&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8722;0&#46;051&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Spot creatinin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8722;0&#46;008&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Spot MA&#47;Cr&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8722;0&#46;030&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Spot microalbumin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8722;0&#46;035&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</th><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Upper&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">ICAMgr2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top"><span class="elsevierStyleBold">0&#46;048</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;48&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top"><span class="elsevierStyleBold">0&#46;042</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;341&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;133&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;875&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">ICAM GG&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8722;0&#46;84&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;44&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top"><span class="elsevierStyleBold">0&#46;025</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;179&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;042&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
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Vol. 37. Issue. 4.July - August 2017
Pages 357-460
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Vol. 37. Issue. 4.July - August 2017
Pages 357-460
Original
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Serum ICAM-1 level and ICAM-1 gene 1462A>G (K469E) polimorphism on microalbuminuria in nondiabetic, nonhypertensive and normolipidemic obese patients: Genetical background of microalbuminuria in obesity
Polimorfismo 1462A>G (K469E) del gen ICAM-1 y nivel sérico de ICAM-1 en la oligoalbuminuria de pacientes obesos no diabéticos, no hipertensos y normolipidémicos: acervo genético de la oligoalbuminuria en la obesidad
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Ahmet Engin Ataya, Bennur Esenb,
Corresponding author
bennuresen@yahoo.com

Corresponding author.
, Halit Akbasc, Emel Saglam Gokmena, Saadet Piltend, Hale Gulerc, Dilek Gogas Yavuze
a Division of Nephrology, Department of Internal Medicine, Bagcilar Research and Training Hospital, Istanbul, Turkey
b Division of Nephrology, Department of Internal Medicine, Acıbadem University School of Medicine, Istanbul, Turkey
c Department of Medical Biology and Genetics, Medical School of Harran University, Sanlıurfa, Turkey
d Department of Biochemistry, Bagcilar Research and Training Hospital, Istanbul, Turkey
e Department of Endocrinology and Metabolism, Marmara University School of Medicine, Istanbul, Turkey
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Figures (1)
Tables (5)
Table 1. Comparison of demographic characteristics and laboratory data between obese and nonobese individuals.
Table 2. Clinical and laboratory characteristics of obese group according to genotypes.
Table 3. Correlation of serum ICAM-1 with demographic and laboratory variables.
Table 4. Multivariate analysis of different ICAM-1 genotypes.
Table 5. Logistic regression analysis to predict microalbuminuria in different genotypes of ICAM-1 gene K469E polymorphism.
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Abstract
Background

A growing body of evidence suggest that obese individuals are under risk of renal parenchymal disorders when compared to nonobese counterparts. Microalbuminuria is the early marker of renal involvement. Although most of obese patients carries multiple risk factors for microalbuminuria, some obese individuals without risk factor may progress to microalbuminuria. The present study was performed to examine the role of ICAM-1 gene 1462A>G (K469E) polymorphism on microalbuminuria in obese subjects without diabetes mellitus, hypertension, hiperlipidemia and older age.

Methods

Ninety eight obese and 96 nonobese individuals without a comorbidity enrolled into the study. Serum ICAM-1 level was measured by enzyme linked immunoabsorbent assay (ELISA) method. ICAM-1 gene 1462A>G (K469E) polymorphism was examined by restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR). Nepholometric method was used to examine urinary albumin loss, and microalbuminuria was measured by albumin to creatinine ratio.

Results

Obese individuals had significantly higher microalbuminuria and proteinuria level compared to nonobese subjects (p: 0.043 and p: 0.011; respectively). GG genotype of ICAM-1 carriers have significantly higher microalbuminuria compared to individuals with AA or AG genotype carriers (p: 0.042). Serum ICAM-1 level was significantly correlated with creatinine and microalbuminuria (p: 0.002 and p: 0.03; respectively). Logistic regression analysis indicated a 7.39 fold increased risk of microalbuminuria in individuals with GG genotype of ICAM-1 gene 1462A>G (K469E) polymorphism.

Conclusions

GG genotype of ICAM-1 gene K469E polymorphism is associated with increased microalbuminuria in obese individuals without another metabolic risk factor.

Keywords:
Obesity
Microalbuminuria
Adhesion molecule
ICAM-1 gene
Polymorphism
Resumen
Introducción

Un conjunto de datos en aumento indica que los individuos obesos corren más riesgo de sufrir trastornos del parénquima renal si se los compara con sus homólogos no obesos. La oligoalbuminuria es un primer rasgo de afectación renal. Aunque la mayoría de los pacientes obesos presentan múltiples factores de riesgo de oligoalbuminuria, esta puede manifestarse en algunos individuos obesos sin factores de riesgo. El presente estudio se realizó para analizar el papel del polimorfismo 1462A>G (K469E) del gen ICAM-1 en la oligoalbuminuria de individuos obesos sin diabetes mellitus, hipertensión, hiperlipidemia ni vejez.

Métodos

Para el estudio fueron reclutados 98 individuos obesos y 96 individuos no obesos sin comorbilidad. Se midió el nivel sérico de ICAM-1 mediante el ensayo de inmunoabsorción enzimática (ELISA). Se analizó el polimorfismo 1462A>G (K469E) del gen ICAM-1 por reacción en cadena de la polimerasay polimorfismo de longitud de los fragmentos de restricción (RFLP-PCR). El método nefolométrico se utilizó para analizar la pérdida urinaria de albúmina, y la oligoalbuminuria se midió con la tasa de albúmina/creatinina.

Resultados

Los individuos obesos presentaron unos niveles de oligoalbuminuria y proteinuria considerablemente más elevados que los individuos no obesos (p: 0,043 y p: 0,011, respectivamente). La oligoalbuminuria en los portadores del genotipo GG de ICAM-1 fue bastante mayor que la de los portadores del genotipo AA o AG (p: 0,042). El nivel sérico de ICAM-1 se correlacionó notablemente con la creatinina y la oligoalbuminuria (p: 0,002 y p: 0,03, respectivamente). El análisis de regresión logística mostró un riesgo 7,39 veces mayor de oligoalbuminuria en los individuos con el genotipo GG del polimorfismo 1462A>G (K469E) del gen ICAM-1.

Conclusiones

El genotipo GG del polimorfismo 1462A>G (K469E) del gen ICAM-1 se asocia con un aumento de la oligoalbuminuria en personas obesas sin otro factor de riesgo metabólico.

Palabras clave:
Obesidad
Oligoalbuminuria
Molécula de adhesión
Gen ICAM-1
Polimorfismo
Full Text
Introduction

Obesity is becoming worldwide epidemic which accounts a risk factor for metabolic and hormonal disorders.1 Because insulin resistance is frequently seen, obese individuals are considered as candidates of diabetes mellitus (DM) and associated microvascular complications.2 Additionally, increased adipose tissue is also a source of subclinic inflammation which is closely related to endothelial damage.

Microalbuminuria (MA) is initial stage of diabetic nephropathy which is strongly correlated with endothelial injury.3 MA comprise an independent risk factor for coronary artery disease in both diabetic and nondiabetic population.4 Obese individuals even without overt DM and hypertension may exhibit microalbuminuria.5,6 Enhanced blood flow and glomerular filtration rate (GFR) are resulted with MA. An increasing number of evidence indicates low-grade inflammation as a cause of MA.7 Also obesity is a well-known risk factor for focal segmental glomerulosclerosis.8

One of the suggested mechanisms in the pathogenesis of microalbuminuria is overexpression of adhesion molecules including ICAM-1 which closely associated with severe inflammatory processes that usually resulted with tissue injury.9 Patients with obesity and diabetic nephropathy exhibit overexpression of ICAM-1.10,11 Experimental studies showed that hyperglycemia is associated with overexpression of ICAM-1 in renal glomerular tissue and renal endothelial injury.12 However, varying degree of renal injury among patients with normal ICAM-1 level or disassociation of ICAM-1 level with microalbuminuria may suggest the role of genetic mutations in ICAM-1 gene. As a marker of cell integrity and complexity, the effect of ICAM-1 on renal tissue is well-documented however lack of available data exist regarding to the role of ICAM-1 gene 1462A>G (K469E polymorphism on microalbuminuria in obese individuals.

Our aim is to examine the role of serum ICAM-1 level and ICAM-1 gene 1462A>G polymorphism on urine albumin loss in metabolically normal obese and nonobese individuals.

Material and methods

A total of 194 participants; 98 obese and 96 nonobese, older than 18 years without a history of systemic disorder that admitted to obesity outpatient service of Bagcilar Education and Research Hospital between February 2015 and June 2015 were enrolled. Height and weight of participants were measured in Tanita Body Composition Analyzer (Tanita Corporation of America, Illinois, USA). Body mass index (BMI) was calculated as weight/height2 (kg/m2). Body mass index (BMI) ≥30kg/m2 was defined as obesity.13 Exclusion criterias were secondary obesity, fasting glucose ≥100mg/dl, HbA1c ≥5.8, hypertension, hyperlipidemia, CVD, renal parenchymal disorder or urolitiazis.14 Hypertension was defined as systolic blood pressure ≥140mmHg and/or diastolic blood pressure ≥90mmHg, or receiving any antihypertensive agent. Renal parenchymal disorder or urolitiazis was diagnosed by ultrasonographic examination. National Cholesterol Education Programme (NCEP) was used to define hyperlipidemia (LDL-cholesterol>130mg/dl or trygliceride>200mg/dl).15 Ethics committee of Bagcilar Education and Research Hospital approved the study. Written informed consent was obtained from all participants. The study was performed in accordance with Declaration of Helsinki. Clinical Trials Registration number was 09.2014.0310. Registration date was 16/01/2015

Sample collection and analysis

Blood samples were obtained after 8-h fasting period. Serum ICAM-1 concentration was analyzed by enzyme linked immunosorbent assay (ELISA) by commercially available kits (Invitrogen, Thermo Fisher Scientific, USA). Whole blood count was performed in blood samples that were taken into tubes with EDTA using an automatic blood counter (XE-5000; Sysmex Corp, Kobe, Japan). Biochemical variables including serum glucose, urea, creatinine, uric acid, aspartat aminotransferase (AST), alanine aminotransferase (ALT), lactate dehidrogenase (LDH), calcium, sodium, potassium, clor, total protein, albumin, total cholesterol, low density lipoprotein (LDL), high density lipoprotein (HDL), trigliceride, were analyzed by photometric method in Siemens Advia 1800 device (Siemens Healthcare Diagnostics, Kobe, Japan). Hormon parameters including HbA1c, insulin, C-peptide, TSH were analyzed by chemiluminescence immunoassay method in Siemens Advia Centaur device (XE-5000, Sysmex Corp., Kobe, Japan).

Urine analysis was performed by spectrophotometric method in Siemens Advia 1800 device (XE-5000, Sysmex Corp., Kobe, Japan). Urinary albumin was measured by immunoturbidimetric method in Cobas auto analyzer (Roche Diagnostics, Germany). Urinary creatinine was analyzed by Aeroset autoanalyzer (Abbott Laboratories Inc., Abbott Park, IL, USA). Urine albumin excretion rate exceeding 20μg/min (30mg/day); in the absence of uncontrolled hypertension or urinary tract infection, was defined as microalbuminuria.

DNA extraction

Total genomic DNA was extracted from peripheral blood leucocytes using a purification kit (Thermo Scientific GeneJET™ Whole Blood Genomic DNA Purification Kit) according to previously described.16

Genotyping analysis

To analyze ICAM-1 gene 1462A>G polymorphism (K469E; rs5498 polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was. PCR amplification was generated using the following oligonucleotide primers: 5′-GGAACCCATTGCCCGAGC-3′ and reverse 5′-GGTGAGGATTGCATTAGGTC-3′ (product of 223bp).

A PCR reaction was carried out in a 10μl reaction volume containing 1×PCR buffer, 2mM MgCl2, 0.2mM each deoxynucleotide triphosphate (dNTPs, Fermentas, St. Leon-Rot, Germany), 40ng of DNA, 0.2μM of each primer (Bio Basic Inc., Ontario, Canada), and 0.5 unit of Taq DNA Polymerase (Fermentas). The PCR conditions were: 3min of initial denaturation at 94°C, followed by 30 cycles at 95°C for 30s, 30s at 65°C for annealing, and 30s at 72°C for extension, followed by 5min at 72°C for final extension. The PCR products were 223bp.

For the RFLP analysis, PCR-amplified products were digested with BanII for 2–5h at 37°C (New England Biolabs Inc., Hertfordshire, UK). The amplicon with the homozygous GG allele of ICAM was cleaved by BanII, yielding 136 and 87bp fragments, whereas the amplicon with the homozygous AA allele remained uncut, yielding a 223bp band. The amplicon with the heterozygous AG allele yielded three fragments of 223, 136 and 87bp length. The digested products were separated on 3% agarose gel along with a 100–1500bp DNA ladder (Bio Basic Inc.). Ethidium bromide-stained gels were visualized under UV light using the Alpha Imager System (Alpha Innotech, San Leandro, CA, USA) (Fig. 1).

Fig. 1.

2% agarose gel electrophoresis stained with ethidium bromide showing the PCR-RFLP analysis of the ICAM-1. Lanes M: DNA marker. Lanes 1, 2: AA allelic polymorphism; Lane 3, 4: AG allelic polymorphism; Lane 5, 6: GG allelic polymorphism.

(0.06MB).
Statistical analysis

Data were analyzed using the SPSS for Windows computer program (release 22.0; SPSS Inc. Chicago, IL, USA). All data expressed as the mean±SD. Differences between the study groups were analyzed by using Student's t-test. Quantitative data were analyzed by chi-square test. Pearson correlation analysis and Spearman's rho correlation analysis were used to evaluate the correlation of variables. The variables significant in univariate analysis were included to multivariate logistic regression analysis (only significant correlation coefficients are reported). A p value <0.05 was considered to be statistically significant.

Findings

Table 1 shows demographic characteristics and laboratory parameters of obese and nonobese participants. Mean age of groups were similar however obese individuals had significantly higher uric acid, platelet count, microalbuminuria and proteinuria level (p: 0.001, p: 0.004, p: 0.043 and p: 0.011; respectively) (Table 1). Serum ICAM-1 level of obese individuals was significantly higher (p: 0.001).

Table 1.

Comparison of demographic characteristics and laboratory data between obese and nonobese individuals.

  Obese (n=98)  Nonobese (n=96)  p 
  Mean±SD  Mean±SD   
Age (years)  37.8±9.79  37.77±8.83  NS 
Glucose  93.4±6.11  92.98±7.87  NS 
Urea  27.4±8.1  27.11±8.24  NS 
Creatinin  0.94±1.57  0.74±0.15  NS 
Uric acid  5.29±1.5  4.27±1.04  a0.001** 
AST  23.35±14.44  17.94±4.36  b0.038* 
ALT  33.31±38.83  16.64±8.56  NS 
LDH  204.28±32.6  187.85±32.17  a0.001** 
Trygliceride  146.54±90.32  114.54±73.55  NS 
Cholesterol  187.02±41.79  182.47±32.32  NS 
HDL-c  52.01±42.51  54.91±14.08  NS 
LDL-c  111.14±34.83  105.51±30.22  NS 
Ca  9.54±0.48  9.45±0.79  NS 
Na  140.51±14.22  141.45±2.26  NS 
4.52±0.28  4.4±0.36  a0.008** 
CI  113±9.3  104±10.77  b0.027* 
CRP  5.07±4.44  2.55±5.37  NS 
T. protein  7.4±0.41  7.39±0.44  NS 
Albumin  4.56±0.31  4.66±0.36  a0.039* 
TSH  2.37±2.37  2±2.24  NS 
S T4  1.13±0.15  1.21±0.18  a0.001** 
Insulin  22.66±26.24  9.74±6.35  NS 
C peptide  3.68±1.85  2.37±0.96  NS 
Leukocyte count  8.03±1.98  8.4±1.73  NS 
Hemoglobine  13.76±1.89  13.72±1.67  NS 
Platelet count  282.01±69.74  254.76±59.28  a0.004** 
Mean platelet volume  7.74±1.22  8.24±1.82  NS 
Urine density  1018.59±5.27  1006.07±10.39  NS 
Urine protein  0.15±0.36  0.04±0.19  b0.011* 
Spot creatinin  186.5±83.71  165.9±83.24  NS 
Spot MA/Cr  9±13.17  6.58±7.08  NS 
Spot microalbumin  1.94±4.31  1.16±1.65  b0.043* 
Serum ICAM-1  293.1±231.4  250.7±152.2  a0.001** 
a

Student t test.

b

Mann Whitney U test.

*

p<0.05.

**

p<0.01.

Significance of bold values are provided.

Table 2 demonstrates comparison of different genotypes of ICAM-1 gene with regard to demographic characteristics and laboratory parameters. Obese individuals with GG genotype had significantly higher uric acid, microalbuminuria and proteinuria when compared to individuals with AA or AG genotype (p: 0.038, p: 0.042 and p: 0.014; respectively) (Table 2).

Table 2.

Clinical and laboratory characteristics of obese group according to genotypes.

  ICAM-1p 
  AA (n=26)  AG (n=48)  GG (n=24)   
  Mean±SD  Mean±SD  Mean±SD   
Age (years)  36.97±9.83  37.18±8.74  37.92±9.12  NS 
BMI  28.95±7.23  29.26±6.45  29.87±8.13  NS 
Systolic blood pressure  122.87±13.32  123.46±13.81  125.78±13.21  NS 
Diastolic blood pressure  74.63±9.87  77.08±10.22  77.13±8.89  NS 
Glucose  95.12±11.36  93.39±10.29  95.32±12,.02  NS 
Urea  28.16±9.47  26.32±6.71  28.43±7.18  NS 
Creatinin  0.71±0.12  0.89±0.37  0.78±0.19  NS 
Üric acid  4.56±1.17  4.71±1.38  5.37±1.71  a0.038* 
T.protein  7.43±0.45  7.38±0.41  7.41±0.43  NS 
Albumin  4.61±0.41  4.57±0.29  4.63±0.24  NS 
Urine density  1015.56±5.91  1007.35±6.02  1018.76±5,.42  NS 
Urine protein  0.08±0.26  0.04±0.18  0.19±0.39  b0.014* 
Spot creatinin  184.78±86.4  171.36±78.97  190.67±87.86  NS 
Spot MA/Cr  7.76±14.33  7.68±9.23  8.68±8.78  NS 
Spot microalbumin  1.61±1.58  1.34±1.84  1.93±2.14  b0.042* 
a

Student t test.

b

Mann Whitney U test.

*

p < 0.05.

**p < 0.01.

Male participants had significantly higher urea, creatinine, AST, ALT, LDH, triglyceride, total protein, albumin, FT4, hemoglobin and urine creatinine level while female participants had higher levels of body fat ratio and platelet count (p: 0.001, p: 0.001, p: 0.001, p: 0.001, p: 0.001, p: 0.023, p: 0.001, p: 0.001, p: 0.001, p: 0.001, p: 0.001, p: 0.001 and p: 0.002; respectively).

Correlation analysis indicated a significant correlation between serum ICAM-1 with HbA1c, creatinine, uric acid, AST, ALT, LDH, total cholesterol, LDL-c, albumin, hemoglobin and microalbuminuria (p: 0.027, p: 0.002, p: 0.001, p: 0.011, p: 0.001, p: 0.006, p: 0.043, p: 0.012, p: 0.046, p: 0.001 and p: 0.030; respectively) (Table 3). Association of creatinine with urea, uric acid, AST, ALT, LDH, albumin, TSH,FT4, WBC, hemoglobin, platelet count, urine creatinine and body fat mass were significant (p: 0.001, p: 0.001, p: 0.001, p: 0.001, p: 0.024, p: 0.004, p: 0.001, p: 0.001, p: 0.001 and p: 0.001; respectively).

Table 3.

Correlation of serum ICAM-1 with demographic and laboratory variables.

  ICAM-1
  r  p 
Age (years)  −0.137  NS 
BMI  0.096  NS 
Metabolic age (years)  −0.085  NS 
Systolic blood pressure  0.003  NS 
Diastolic blood pressure  −0.078  NS 
HbA1c  0.162  0.027* 
Glucose  −0.010  NS 
Urea  0.080  NS 
Creatinin  0.222  0.002** 
Uric acid  0.297  0.001** 
AST  0.183  0.011* 
ALT  0.264  0.001** 
LDH  0.197  0.006** 
Trygliceride  0.106  NS 
Cholesterol  0.148  0.043* 
HDL-c  −0.114  NS 
LDL-c  0.182  0.012* 
Ca  0.198  0.006** 
Na  0.127  NS 
0.007  NS 
CI  −0.043  NS 
CRP  0.092  NS 
T.protein  0.165  0.023* 
Albumin  0.145  0.046* 
TSH  0.083  NS 
S T4  0.112  NS 
Insulin  0.059  NS 
C peptide  0.067  NS 
Leukocyte count  0.090  NS 
Hemoglobine  0.243  0.001** 
Hematocryte  0.230  0.001** 
Platelet count  −0.015  NS 
Mean platelet volume  −0.146  0.044* 
Urinedensity  −0.059  NS 
Urine protein  −0.051  NS 
Spot creatinin  −0.008  NS 
Spot MA/Cr  −0.030  NS 
Spot microalbumin  −0.035  0.030* 

Spearman Rho test.

*

p<0.05.

**

p<0.01.

Multivariate analysis and Logistic regression analysis were performed to predict microalbuminuria risk in obese individuals with different genotypes of ICAM-1 gene single nucleotide polymorphism and determined that obese individuals with GG genotype of ICAM-1 gene 1462A>G polymorphism have 7.39 fold increased risk of microalbuminıria (p: 0.049) while the risk of microalbuminuria in individuals with AA or AG genotype were nonsignificant (Tables 4 and 5).

Table 4.

Multivariate analysis of different ICAM-1 genotypes.

  B  S.E.  p  Exp(B95.0% C.I. for Exp(B)
          Lower  Upper 
ICAMgr2      0.048       
ICAM AG  −1.08  0.48  0.042  0.341  0.133  0.875 
ICAM GG  −0.84  0.44  0.025  0.432  0.179  1.042 

Variable(s) entered on step 1: ICAMgr2.

Table 5.

Logistic regression analysis to predict microalbuminuria in different genotypes of ICAM-1 gene K469E polymorphism.

  <0.3 Microalbuminuria>0.3 Microalbuminuriap  OR %95 GA 
Obesity group
AA  31.82%  18  25.35%     
AG heterezygote  14  63.64%  34  47.89%  0.91  0.94 (0.32–2.76) 
GG homozygote  4.55%  19  26.76%  0.049  7.39 (0.83–66.2) 
AG+GG  15  68.18%  53  74.65%  0.58  1.37 (0.48–3.91) 
Discussion

The present study indicated that obese individuals have worse metabolic control and evident microalbuminuria when compared to nonobese counterparts. Female individuals had significantly higher body fat ratio however metabolic deteriorament of male individuals was evident. GG genotype of ICAM-1 gene is associated with microalbuminuria and proteinuria. Finally, we determined a significant correlation between serum ICAM-1 level with microalbuminuria and metabolic control.

Endothelial dysfunction is the initial step of vascular changes which eventually progress to evident atherosclerosis (AS) and AS related complications.17 Endothelial injury and related disorders are five times more frequent and significantly seen at earlier ages among obese population.1 For more than a century ago, relation of obesity and AS has been known.18 Obesity is a well-known criteria of metabolic syndrome (MS) and accounts four times higher risk for atherosclerotic disorders.19 In a study including 9961 obese subjects, it has been shown that obesity is risk factor for microalbuminuria independent from diabetes and hypertension.20 In agreement with the literature, our obese population had higher blood pressure, lipid and uric acid levels, and excrete significantly higher amount of microalbumin and protein.

A growing body of evidence indicate that subclinical inflammation is evident in obese individuals which is closely related to AS and insulin resistance (IR).21 Inflammatory conditions are associated with increased endothelial activation and overexpression of adhesion molecules.22 Adhesion molecules regulates leukocyte migration across the endothelium and involved in integral part of inflammation.10 Obese individuals exhibit increased mRNA expression of ICAM-1 leading to infiltration of adipose tissue and other systems including kidneys by macrophages.23 Independent from fat distribution, total fat volume is major determinant of serum levels of adhesion molecules.24

Obese individuals or diabetic patients without well-controlled glycemia have increased ICAM-1 levels when compared to nonobese or diabetic patients with glycemic control.25,26 A well-known correlation has been established between diabetic complications including nephropathy and adhesion molecules.27 A number of studies determined that patients with ICAM-1 gene K469E polymorphism, the K allele are significantly more prone to endothelial injury and CVD, and may predict future cardiovascular events.28–30 There are controversial reports regarding to relation of ICAM-1 gene polymorphism and microvascular complications of DM. Sun et al. showed that ICAM-1 gene polymorphism has nonsignificant effect on diabetic retinopathy (DR) while Liu et all. determined an increased risk of DR in patients with ICAM-1 gene polymorphism31,32

Increased serum levels of adhesion molecules may considered as early markers of endothelial injury which is resulted with systemic vascular disorder including renal microvasculature.33,34 There is a positive correlation between serum ICAM-1 level and ICAM-1 gene polymorphism.35,36 It would be reasonable to expect microalbuminuria in obese individuals with overexpression of adhesion molecules because obese individuals have impaired insulin sensitivity, and also adhesion molecules destruct beta-cells leading to insulitis, hyperglycemia and hyperglycemia related nephrotoxicity that all may resulted with microalbuminuria. Adhesion molecules including ICAM-1 have been demonstrated in atherosclerotic lesions which is regressed by adiponectin, a adipocyte secretory protein decreased in obesity.37

The present study has some potential drawbacks. First, sample size of the study was relatively low. We included relatively young obese and nonobese individuals without diabetes, hypertension, hyperlipidemia, renal parenchymal or cardiovascular disorders to eliminate cumulative effect of these entities on microalbuminuria. Second, this study was conducted in Turkish population that limits us to generalize our results to other populations. Finally, evaluation of complex interaction of weight loss and serum ICAM-1 level may provide complementary data on microalbuminuria in obesity.

The importance/novelty of the study is that it is the first report that examined the role of ICAM-1 gene 1462A>G polymorphism on microalbuminuria in obesity, and established that GG genotype of ICAM-1 gene is an independent risk factor of microalbuminuria in obesity. There is a limited data on the genetic background of microalbuminuria in obese individuals. Understanding molecular and genetic mechanisms of microalbuminuria may help to identify obese patients under risk of nephropathy that is initially manifested with microalbuminuria.

Based on the fact that ICAM-1 is involved in endothelial injury and atherosclerosis, synthesis and genetic basis of this molecule may be therapeutic target for the complications of obesity. Further studies with large sample size are warranted to reach more precise conclusion.

Ethical disclosure

The study was performed in accordance with Helsinki Declaration.

Ethics Committee approval was obtained.

Informed consent was obtained from all participants.

Conflict of interests

Authors declare that there is no conflict interest.

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