recent studies reported the prevalence of diabetes in china soared from 1.9 to 11.6% between 1993 and 2010 [ 1 , 2 ] . the prevalence of prediabetes is rising which is an important risk factor for the development of overt diabetes and cardiovascular disease . china has to face the major public health problem and economic burden of potential diabetic patients . thus , clarifying its etiology and looking for modifiable risk factors are of paramount importance for diabetes control and prevention . iron is an important mineral in normal physiological processes , and ferritin is a specialized iron storage protein , which reflects iron stores in the body . serum ferritin ( sf ) has been found to be a reliable tool , providing that confounding effects by inflammatory , hepatic , or neoplastic diseases are excluded . it has been used as a surrogate variable to reflect body iron stores in healthy individuals . previous studies have demonstrated an association between increased sf levels and higher risks of diabetes [ 5 , 6 ] . however , the exact mechanism through which elevated sf promotes the development of type 2 diabetes is unknown . obesity has become a major global health problem and is associated with the risk of type 2 diabetes and insulin resistance . in recent years , a number of studies have investigated the association between sf levels and various types of adiposity . is serum ferritin associated with insulin resistance or islet  cell function when the interference factor of obesity has been ruled out ? therefore , in the present study , we aimed to investigate the changes of ferritin metabolism in nonobese han adults with different status of glucose tolerance and the relationship between serum ferritin ( sf ) and insulin resistance . the 96 ( male / female , 62/34 ) ( aged 49.8  11.9 years ) subjects were recruited from the first hospital of qinhuangdao for health examinations that bmi was normal and undiagnosed diabetes in qinhuangdao , hebei province during 2011 . the inclusion criteria included the following : ( 1 ) subjects were clinically stable with no previous medical history of diabetes , hypertension , dyslipidemia , coronary artery diseases , or cerebral stroke ; ( 2 ) subjects were without clinical evidence of endocrinopathy ; ( 3 ) subjects were not taking medications known to affect glucose and lipid metabolism , such as statins , glucocorticoids , thyroid hormones , and thiazide diuretics ; ( 4 ) subjects were not neoplasia and liver disease ; ( 5 ) female subjects were postmenopausal . the exclusion criteria included the following : ( 1 ) subjects with hepatic or renal dysfunction ( > 1.5-fold elevation of alanine aminotransferase , aspartate aminotransferase , or serum creatinine > 115  mol / l ) and ( 2 ) subjects with anemia , blood transfusion , and the recent use of iron , who smokers , consuming alcohol , and having acute and chronic inflammation . anthropometric measurements , including height , weight , waist circumference ( wc ) , and blood pressure , were obtained while the subjects were in light clothing and not wearing shoes . body mass index ( bmi ) was calculated by dividing weight ( kg ) by height squared ( m ) . blood pressure was measured twice with a mercury sphygmomanometer after 10  min of rest while the subjects were seated , and the average of the two measurements was used for analysis . after an overnight fast of 8  h , blood samples were drawn from an antecubital vein in each subject into vacutainer tubes . all subjects underwent oral glucose tolerance test ( ogtt ) with 75  g of oral anhydrous glucose at 8:00 am after 8  h of fasting . peripheral venous blood samples were taken at 0 , 1 , 2 , and 3 hours after glucose loading . fasting plasma glucose ( fpg ) concentration and 2 h plasma glucose ( 2-hpg ) of ogtt concentration were measured using the glucose oxidase method , and serum lipid levels were measured using enzymatic assays with an autoanalyzer ( hitachi , tokyo , japan ) . plasma concentrations of fasting true insulin ( fti ) and 2 h insulin of ogtt were measured by enzyme linked immunosorbent assay ( elisa ) with model 680 microplate reader ( bio - rad , america ) . the elisa kits were purchased from uscnlife company , america ( intra - assay < 3% and interassay < 4% ) . plasma concentrations of sf were measured by electrochemiluminescence with model elecsys 2010 immunity analyzer ( roche , german ) . the kits were purchased from roche company , german ( intra - assay < 3% and interassay < 5% ) . the following equation was used to calculate the homeostasis model assessment ( homa- ) ir index ( fasting insulin level  fasting glucose level)/22.5 and ( homa- )  index ( 20  fasting insulin level)/(fasting glucose level  3.5 ) [ 911 ] . glucose metabolism classification using 2008 american diabetes association recommended standards . the definition of nonobese is bmi < 25  kg / m , and it was identified by who ( 1999 ) criteria . the subjects were divided into three groups according to the result of ogtt with 75  g oral anhydrous glucose . the group ngt consisted of 32 normal glucose tolerant subjects ( male / female 19/13 , age 49.3  10.9 years ) , group igr consisted of 33 impaired glucose tolerant and/or impaired fasting glucose subjects ( male / female 22/11 , age 50.1  11.1 years ) , and group dm consisted of 31 newly diagnosed diabetes mellitus subjects ( male / female 21/10 , age 49.8  11.2 years ) . all analyses were performed using the spss 14.0 statistical software ( spss 14.0 for windows ; spss , inc . , chicago , il ) . the data were ln - transformed for analysis and are expressed as medians with interquartile ranges . comparisons were done between the three groups using analysis of variance ( anova ) and pearson chi - square analysis . correlation analysis was made by spearman test . to examine the association between serum ferritin and other variables , multiple linear regression analyses were tested . anthropometric and biochemical data are presented in table 1 . the age ( x = 0.756 , p = 0.913 ) and gender ( x = 0.541 , p = 0.73 ) were similar in three groups ( p > 0.05 ) . diastolic blood pressure ( dbp ) , systolic blood pressure ( sbp ) , fpg , 2-hpg , triglycerides ( tg ) , sf , and homa - ir were all significantly higher and high density lipoprotein cholesterol ( hdl - c ) was significantly lower in the dm subjects than igr and ngt subjects ( p < 0.05 ) . fti was decreased in the dm subjects than igr subjects ( p < 0.05 ) . fpg , 2-hpg , fti , tg , sf , and homa - ir were all significantly higher in the igr subjects than ngt subjects ( p < 0.05 ) . homa- , 2 h insulin were decreased and wc was increased in the dm and igr subjects than ngt subjects ( p < 0.05 ) . after adjustment for age and gender of the partial correlation analysis showed that sf positively correlated with fpg ( r = 0.451 , p = 0.000 ) , fti ( r = 0.455 , p = 0.000 ) , tg ( r = 0.383 , p = 0.003 ) , and homa - ir ( r = 0.482 , p = 0.000 ) ( table 2 ) . when homa - ir was considered as the dependent variables in a multiple regression analysis with age , sex , wc , sbp , dbp , 2-hpg , 2 h insulin , tg , hdl - c , and sf as independent variables , sf (  = 12.13 , p = 0.023 ) and tg (  = 0.102 , p = 0.041 ) maintained independent association with homa - ir ( table 3 ) . when homa- was considered as the dependent variables in a multiple regression analysis with age , sex , wc , sbp , dbp , 2-hpg , 2 h insulin , tg , hdl - c , and sf as independent variables , 2-hpg (  = 0.101 , p = 0.013 ) maintained independent association with homa- ( table 4 ) . in the present study , we found that the sf levels significantly increased in nonobese adults of china when the glucose metabolic disorder was deteriorated . our results showed that , in different glucose metabolism , the increased sf levels were associated with the increase of fpg , blood pressure , triglycerides , and homa - ir . however , compared with increased sf levels , hdl - c level was lower in different glucose metabolism in nonobese adults . it is well known that obesity , hyperglycemia , hypertension , and dyslipidemia are the main components of the metabolic syndrome . our results further illustrated that abnormal glucose metabolism , hypertension , dyslipidemia , insulin resistance , and high sf levels were synchronous when the interference factors of obesity were avoided . in our study , there was positive correlation between fpg , fti , tg , homa - ir , and sf levels . in multiple linear regression analysis showed that elevated sf levels and tg were significant independent predictors for homa - ir . however , 2 h plasma glucose was significant independent predictor for homa-. our findings provided us with new evidence of sf being regarded as a biomarker for insulin resistance but not relevant with beta cell function . several studies showed the association between sf and diabetes , and most of them were based on caucasian samples [ 1214 ] . however , the observation in north indians was in sharp contrast to the earlier studies published from the west stressing that sf was increased in obesity and diabetes . they conclude that sf may not be a strong risk factor in the pathogenesis of obesity and diabetes . in 2014 , a cross - sectional survey of 8,235 participants in china reported that elevated sf levels were associated with higher risks of diabetes , higher levels of hba1c , and homa - ir independent of several confounders . recent studies reported higher sf levels were associated with diabetes incidence in an elderly chinese population   and korean men . of course the exact mechanism of the association between sf and diabetic disorder remains to be clarified . so far , several possible biological pathways might be proposed to explain the observed findings . firstly , sf is regarded as a biomarker of body iron store , whose catalytic effects could induce lipid peroxidation . secondly , excess body iron may be directly involved in insulin signaling   and is able to form highly reactive free radicals , which can lead to disturbed glucose metabolism and subsequent hyperglycemia . finally , there are some evidences of a relevant relationship between sf levels and inflammation . in addition , hepcidin , a peptide made in the liver , is elevated in response to hypoxia or inflammation and is correlated with increases in ferritin . it has been suggested that leptin seems to induce the expression of hepcidin via the jak2/stat3 pathway [ 23 , 24 ] . admittedly , our study had some limitations that deserved to be considered when interpreting the results . . we can not determine the causal relationship between sf and glucose metabolism in nonobese han adults . experimental and prospective studies are warranted to elucidate the role of sf in glucose metabolism . many of the research conclusion showed that gender might modify the effects of sf on diabetes and insulin resistance [ 5 , 16 , 2527 ] . this might be merely statistical interaction , which does not mean biological interaction between gender and ferritin . therefore , the longitudinal relationship study between sf levels and glucose metabolism in nonobese han adults needs to be confirmed . in conclusion , ferritin concentration in igr and dm subjects of nonobese already significantly increased when compared with ngt subjects of nonobesity . elevated sf levels are associated with insulin resistance and may be not associated with the decline of insulin beta cells in different status of glucose tolerance in nonobese han adults .