metabolic syndrome ( mets ) or syndrome of resistance to insulin involves metabolic abnormalities indicated by central obesity , hypertriglyceridemia , decreased high density lipoprotein ( hdl ) , hyperglycemia , obstructive sleep apnea , and hypertension . according to theadult treatment panel iii ( atp iii ) report , the prevalence of mets is about 22% , which is increased by age . many metabolic abnormalities such as non - alcoholic fatty liver disease ( nafld ) and steatohepatitis are observed along with mets . nafld is a hepatic manifestation of metabolic syndrome ; it is closely related to other clinical features of metabolic syndrome  . nafld is an inflammatory liver disease in which fat accumulates in hepatocytes and results in increased number of inflammatory cells in liver tissue . nafld is the most common liver disease in developed countries with the incidence rate of 20 - 40% , however , its prevalence is rising in developing countries such as asian nations . most frequently , nafld is asymptomatic and is detected when a physician performs precise laboratory or ultrasound studies for check - up or increase in aminotransferases occurs . this disease was first observed among middle aged obese men with diabetes mellitus ( dm ) but recently it is believed that non - obese and non - diabetic men with iron overload could be predisposed to this disease . therefore , currently the role of serum iron , ferritin , and transferrin in this disease is more studied . also , a newly diagnosed condition of liver called  insulin resistance - hepatic iron overload ir - hio  is observed in patients with hyper ferritinemia and normal transferrin without mutation in gene of hemochromatosis . although patients with ir - hio suffer from a wide verity of metabolic disorders , the relationship between ir - hio and nafld is not yet definite . on the other hand , there are several hypotheses about the pathophysiology of the relationship between nafld and mets . one of the most acceptable hypotheses is insulin resistance indicated by postprandial ineffective hyperinsulinemia and subsequently postprandial hyperglycemia and increase in free fatty acid . furthermore , oxidant and antioxidant imbalance is another trigger suggested for justifying this relationship whereas ferritin is an acute phase reactant . both mechanisms could support the hypothesis on the role of iron or iron carriers in this correlation between mets and nafld . in this study we assessed clinical and para - clinical evidence for this relationship . a case - control study was conducted between 2010 and 2011 among patients with elevated aminotransferases referred to baqiyatallah clinic , tehran , iran . the diagnosis of nafld was confirmed after ruling out other causes of elevated aminotransferases such as viral hepatitis ( by testing hbs ag , hbs ab , hbc ab , and hcv ab ) , alcohol consumption , infectious diseases , and other medical conditions , which could affect liver function test . based on the following criteria ( table 1 ) , the patients were divided into two groups with mets ( mets group ) or without mets ( non - mets group ) . the clinical assessment , included demographic and anthropometric characteristics , and physical examination were done by a clinical practitioner . paraclinical studies were also performed consisting of ultrasonography and lab tests aspartate aminotransferase(ast ) , alanine transaminase(alt),low - density lipoprotein ( ldl ) , high - density lipoprotein ( hdl ) , triglyceride ( tg ) , cholesterol , fasting blood sugar ( fbs ) , ferritin , and serum iron ) , which were done in the laboratory of baqiyatallah hospital after 12 hours fasting . diagnosis and grading of nafld ( diffuse hepatic steatosis ) based on ultrasonography was determined by a radiologist according to the following guideline ; 
 
 1- increased echogenicity and beam attenuation , which is known as a diffuse hyperechoic texture ( bright liver ) 
 
 2- increased echo texture compared with kidney ( liver and renal cortex have normally a similar echogenicity ) 
 
 3- vascular blurring ( absence of the normal echogenic walls of the portal veins and hepatic veins ) . 
 
 using the sample size formula shown below , the sample size was calculated as 280 cases , while d=0.05 , p=0.68 , and =0.05 . 
 
 for aminotransferases was 40 mg / dl . for serum iron it was 190 g / dl for men and 175 g / dl for women . cut point for serum ferritin was 300 g / dl for men and 200 g / dl for women . chi2 ( or fisher 
 
 n=(z1/2)2p(1p)d2 
 
 exact test ) , independent t test , one way anova , and pearson ( or spearman ) tests were used for univariate analysis in using spss software version 16 . finally , variables with p value less than 0.2 was entered in a model of logistic regression . a total of 299 patients ( 198 men and 101 women ) with nafld were included and were divided intomets ( n=143 ; 47.8% ) and non - mets ( n=156 ; 52.2% ) groups . there is a significant difference between mean age and sex ratio in the two groups ( p=0.001 ) . as expected , the age , systolic and diastolic blood pressure , body mass index ( bmi ) , waist / hip ratio , glucose tolerance test ( gtt ) , serum insulin , c. peptide , tg , and hemoglobin a1c ( hba1c ) were different between mets and non - mets groups ( p<0.05 ) . moreover , the history of diabetes mellitus , hypertension , and coronary artery disease was significantly different between the groups ( p<0.05 ) . there was no significant difference in grade of disease according to the ultrasound study , aminotransferases and bilirubin levels between mets and non - mets groups . after adjusting for confounder variables such as age , we found no differences in alt ( p=0.557 ) and ast level ( p=0.205 ) among the two groups . however , a significant correlation was found between serum ferritin and alt ( p=0.005 ) and also ast ( p=0.032 ) . 
 
 despite adjusting the confounding role of sex on serum ferritin and iron , we could not find any significant difference in serum iron and ferritin level between the two groups ( table 4 ) . in a regression model , only sex ( p<0.001 , exp b : 3.912 , ci 95% : 1.892 - 8.088 ) , systolic blood pressure ( p=0.013 , exp b : [ 1.040 ] ci 95% : 1.008 - 1.072 ) , bmi ( p=0.001 , exp b : 1.158 , ci 95% : 1.061 - 1.264 ) , dm ( p=0.007 , exp b : 4.305 , ci 95% : 1.481 - 12.509 ) , total iron binding capacity ( tibc ) ( p=0.017 , exp b : 1.007 , ci 95% : 1.001 - 1.017 ) , hemoglobin ( p=0.017 , exp b : 1.007 , ci 95% : 1.001 - 1.017 ) , tg ( p=0.017 , exp b : 1.007 , ci 95% : 1.001 - 1.017 ) , hdl ( p=0.017 , exp b : 1.007 , ci 95% : 1.001 - 1.017 ) , alkaline phosphatase ( alp ) ( p=0.017 , exp b : 1.007 , ci 95% : 1.001 - 1.017 ) , ast ( p=0.017 , exp b : 1.007 , ci 95% : 1.001 - 1.017 ) , alt ( p=0.017 , exp b : 1.007 , ci 95% : 1.001 - 1.017 ) , and serum insulin ( p=0.017 , exp b : 1.007 , ci 95% : 1.001 - 1.017 ) could predict mets in patients with nafld . given the results of this study , no significant relationship was observed between serum iron and presence of mets in patients with nafld . also , the same results were obtained for serum ferritin . in other words , there is no prominent difference in the role of iron ( both serum iron and ferritin as a form of iron for storage ) in presence of nafld in both groups . a hypothesis has been presented on the role of iron especially iron deposit in liver in patients with nafld on resistance to insulin , however , there is much controversy in determination of definite mechanism . 
 
 in late 1990s , two studies posed the hypothesis about irrespective resistance to insulin among patients with hepatic iron overload , which was indicated by hyperferritinemia and normal transferrin . patients with unexplained hepatic iron overload are characterized by a mild to moderate iron burden and the nearly constant association of an insulin resistance syndrome irrespective of liver damage .  moirand and co - workers also presented this condition as a new non - hla - linked iron overload syndrome , which suggests a relationship between iron excess and an abnormal metabolic condition including obesity , hyperlipidemia , abnormal glucose metabolism , or hypertension known as mets . an epidemiological finding that  the dysmetabolic iron overload syndrome is detected in about one third of patients with nafld and the mets  and also a therapeutic - based approach that showed decreased metabolic alterations and liver enzymes in nafld patients undergone iron depletion by phlebotomy uphold this hypothesis . 
 
 mechanisms of the relationship between iron accretion and insulin resistance , as the main pathogenesis of mets , in patients with nafld have been poorly studied . genetic factors , oxidative stress , cell toxicity , and genotoxicity can predispose iron deposits due to circulatory iron excess . these factors can induce iron storage in hepatocytes and kupffer / sinusoidal cells . in molecular and histopathological point of view , kupffer cells can accumulate iron via phagocytosis of necrotic hepatocytes , or probably erythrophagocytosis . conversely in this study , a significant correlation was obtained between serum ferritin and alt and also ast indicating for hepatocytes injuries by depositing fat . also , we found higher levels of hemoglobin and tibc in mets group compared with non - mets group . regularly , these indexes correlate with red blood cell ( rbc ) count and also erythrophagocytosis . there are some pivotal factors that induce hepatic iron uptake such as deficiency of micronutrients , inflammation , dysregulation of iron trafficking molecules , and hyperinsulinemia . insulin stimulates cellular iron uptake through increased externalization of the transferring , receptor in adipocytes  . on the other hand , in the adipocyte , the stored iron can affect insulin sensitivity of the cell . both aforementioned mechanisms can cause unsuppressed lipolysis , and therefore liver is predisposed to fat storage . stimulation of intestinal iron absorption , by hyperinsulinism and insulin resistance , is the other mechanism for the increase of body iron stores while in the present study we did not find any difference between the amount of storage form of iron , ferritin , between the two groups , although there was a difference in serum insulin levels between the two groups . given the findings of the present study in keeping with previous findings , tibc ( indicator for the transferrin activity ) is the sole iron trafficking index that was different between the two groups . as expected , age , blood pressure , bmi , hip / waist ratio , prevalence of dm and coronary artery diseases ( cad ) , serum tg , and hdl were higher in mets group compared with non - mets group . it was previously clarified that patients with mets with or without other medical conditions , such as nafld , are more frequently involved in dm , cad , hypertension , obesity , and hyperlipidemia which is in line with our findings . abdominal obesity indicated by high waist / hip ratio albeit is an important risk factor for metabolic disturbances , including fatty liver . after adjusting the confounders , we could not find a significant relationship between abdominal fat levels and presence of mets . but international normalized ratio ( inr ) as a coagulation status index was different between the two groups . usually coagulation defect occur when nafld leads to cirrhosis while none of the patients suffered from cirrhosis . the sonographic grade of nafld was not significantly different between mets and non - mets group . the role of iron in coagulation was previously declared , however , we could not precisely associate these two with the difference in inr and iron level in the two groups . one of the limitations of this study was the lack of pathological and genomic studies to compare mets and non - mets groups . to verify this comparison , liver biopsies would be helpful but this is ethically unfeasible since it is unnecessary in patients with uncomplicated nafld . ferrannini demonstrated an association between hyperinsulinemia and the excess hepatic iron storage in inflammatory conditions . over transcriptions of ferritin mrna in macrophages due to inflammatory cytokine consistent with our findings , previous studies that showed a prominent relationship between the presence of mets and serum iron or ferritin in patients with nafld recommended searching for hepatic iron accumulation in biopsy samples of patients with nafld , even in cases with normal serum iron , ferritin , and transferrin . conversely , choi and colleagues , evaluated serum ferritin and aminotransferases among 994 post menaupose women . they found that women with mets had a higher level of serum ferritin compared with women without mets . many other studies indicated a probable relationship between nafld as one of the manifestations of mets and serum level of ferritin . but , consistent with our findings , freixenet and co - workers also demonstrated that iron level had no correlation with existing dm and mets . moreover , this difference between the findings of various reports can be due to sociodemographic varieties . therefore , if an adapted cut point is determined for every population , a significant relationship may be obtained . although we could not find a similar relationship , but we found that serum level of ferritin in patients with nafld and mets was above 125 - 130 . 
 
 our findings did not show a significant relationship between iron , in free or storage form , and the presence of mets among patients with nafld , but serum ferritin can correlate with hepatocytes injuries indicated by raised aminotransferases . nevertheless , to clarify this relationship further molecular , genomic , and histopathological studies are required . the authors are grateful to all patients for their collaboration in this study . also , the authors thank baqiyatallah research center of gastroenterology and liver diseases for supporting this survey financially .
background 
 a hypothesis has been presented about the role of serum iron , ferritin and transferrin saturation among patients with non - alcoholic fatty liver disease ( nafld ) and resistance to insulin ( metabolic syndrome [ mets ] ) , but there is much controversy . this study aimed at investigating the level of serum iron and demographic characteristics in patients with nafld with or without mets . 
 methods 

 a case - control study was conducted on patients with elevated liver enzymes referring to baqiyatallah clinic , tehran , iran during 2010 - 2011 . 
 after ruling out other causes of increased aminotransferases and approving the diagnosis of nafld , the patients were divided into two groups of with or without mets . 
 then , the individuals demographic , sonographic , and laboratory characteristics were recorded . 
 results 

 this research included 299 patients suffering from nafld who were divided into mets ( n=143 ; 47.8% ) and non - mets ( n=156 ; 52.2% ) groups . the age , systolic and diastolic blood pressure , body mass index , waist / hip ratio , glucose tolerance test , serum insulin , c. peptide , triglyceride , and hb a1c were different between mets and non - mets groups ( p<0.05 ) . 
 there was no significant difference in serum iron and ferritin levels between the two groups , however , a significant correlation was found between serum ferritin and alanine transaminase ( p=0.005 ) and also aspartate aminotransferase ( p=0.032 ) . 
 conclusion 

 our findings did not show a significant relationship between iron , in free or storage form , and the presence of mets among patients with nafld , but serum ferritin can correlate with hepatocytes injuries indicated by raised aminotransferases . 
 nevertheless , to clarify this relationship further molecular , genomic , and histopathological studies are required .