insulin resistance ( ir ) plays a crucial role in the pathophysiology of metabolic syndrome ( mets ) , which is associated with an increased risk of cardiovascular disease and type  2 diabetes . from the standpoint of primary prevention , it is important to identify the patients at risk of mets , especially at an early stage when ir contributes to the clustering of borderline metabolic risk factors .
homeostasis model assessment of ir ( homair ) is a useful model for assessing ir in largescale clinical research , and it has been validated by the gold standard method  the hyperinsulinemiceuglycemic clamp technique .
healthassociated reference interval of homair , which covers the central 95% of 2153 healthy japanese subjects , by applying the stringent c28a3 document from the clinical and laboratory standards institute .
we have established the reference interval for homair as between 0.4 and 2.4 , and proposed that homair    2.5 be considered a reasonable indicator of ir in a japanese population as recommended by the japan diabetes society .
healthassociated reference interval and is defined for use by clinicians to diagnose or manage patients .
the present study focused on ir as a marker of earlystage mets and aimed to establish a 
an optimal cutoff point for homair to discriminate mets in nondiabetic japanese subjects was determined by receiver 
of the 7305 healthcheck examinees ( 4042 men and 3263 women ) who first visited the health evaluation and promotion center at tokai university hachioji hospital between april 2007 and march 2011 , 6868 examinees ( 3727 men and 3141 women ) were included in the present study after exclusion of those with fasting plasma glucose ( fpg ) 126  mg / dl and those on medication for diabetes .
the present study was crosssectional in design , and was approved by the ethics committee of tokai university school of medicine ( 11r096 ) and complied with the helsinki declaration .
waist circumference ( wc ) was assessed at the end of expiration , measuring the minimum circumference at the level of the umbilicus to the nearest 0.1  cm .
blood pressure ( bp ) was measured at the right upper arm with the patient in a sitting position .
fasting serum immunoreactive insulin ( iri ) was measured by fluorescenceenzyme immunoassay ( st aiapack iri ; toso , tokyo , japan ) .
the intra and interassay coefficients of variation were 1.42.3 and 2.64.6% , respectively , and crossreactivity with proinsulin molecules was 2.0% .
homair was calculated as : fpg ( in mg / dl )    iri ( in u / ml)/405 .
mets was diagnosed if subjects had increased waist circumference ( 85  cm for men and 90  cm for women ) plus at least two of the following criteria : fpg 110125  mg / dl , hypertension ( systolic bp    130  mmhg , diastolic bp    85  mmhg , or on medication ) and dyslipidemia ( tg    150  mg / dl , highdensity lipoprotein cholesterol < 40  mg / dl , or on medication ) .
the roc curve of homair for detecting mets was produced , and the area under the curve ( auc ) with its 95% confidence interval ( ci ) was calculated . to determine the optimal point , the square root of [ ( 1    sensitivity )  +  ( 1    specificity ) ] was calculated , which is the point on the roc curve with the shortest distance from the upper left corner .
spss statistics version 19.0 software ( spss , chicago , il , usa ) was used for statistical analyses .
the average homair was 1.63 for men and 1.36 for women . among the 3727 men and 3141 women ,
mets was diagnosed in 594 men ( 15.9% ) and 81 women ( 2.6% ) .
homair values were significantly higher in mets subjects ( 2.68    1.70 for men and 3.21    2.44 for women ) compared with nonmets subjects ( 1.43    0.90 for men and 1.31    0.83 for women ) .
the auc ( 95% ci ) was 0.794 ( 0.7750.813 ) for men and 0.883 ( 0.8520.913 ) for women .
the optimal point of homair yielding the minimum value of the square root of [ ( 1   
sensitivity )  +  ( 1    specificity ) ] was 1.7 for both sexes , which was lower than the upper limit of the reference interval .
a homair value of 1.7 was also the point that maximized the product of sensitivity and specificity , with a sensitivity and specificity of 73.4% and 70.5% for men , and 81.5% and 77.0% for women , respectively .
the prevalence of homair    1.7 was 36.5% in men and 24.5% in women .
hypertension is defined as systolic blood pressure ( bp )    130  mmhg , diastolic bp    85  mmhg , or on medication .
dyslipidemia is defined as triglycerides ( tg )    150  mg / dl , highdensity lipoprotein cholesterol ( hdlc )  <  40  mg / dl , or on medication .
bmi , body mass index ; firi , fasting immunoreactive insulin ; fpg , fasting plasma glucose ; homair , homeostasis model assessment of insulin resistance ; mets , metabolic syndrome . 
the receiver  operating characteristic curves of homeostasis model assessment of insulin resistance ( homair ) for detecting metabolic syndrome in men and women .
the optimal points were determined by calculating the square root of [ ( 1    sensitivity )  +  ( 1    specificity ) ] .
the present study aimed to determine the optimal cutoff point for homair to discriminate mets , and the proposed optimal cutoff value was 1.7 , based on the point producing the greatest discriminatory ability on roc analysis .
the concept of ir as a common etiology of mets , proposed around 1990 and given various names including 
syndrome x and  the insulin resistance syndrome , was included in the first diagnostic criteria for mets by the world health organization in 1998 .
however , in the later mets definitions , the central feature of the syndrome has shifted entirely away from ir to a collective of metabolic abnormalities that have better predictive value for cardiovascular disease , perhaps because there has been hardly any consensus on the cutoff points for the classification of ir .
it is also problematic that the types of range or limit for homair ( i.e.  healthassociated or 
reference interval that is derived from the central 95% of a normal distribution of healthy reference individuals , there is no single standard method to determine a  decisionbased range or limit .
rather , it depends on the type of decision to be made , such as screening , assessment of risk , diagnosis of disease or disease management .
roc analysis was used in the present study , which is one of the most useful approaches to specify the cutoff points that have the greatest clinical value in discrimination . in the present study , the optimal cutoff value for homair to discriminate mets was 1.7 , as determined by roc analysis using 6868 nondiabetic japanese subjects . to the best of our knowledge , this is the first study to determine a cutoff point for homair to discriminate mets in a japanese population .
several reports have determined homair cutoff points for the diagnosis of mets as 1.22 , 1.7 , 2.3 and 2.34 by roc analysis in other ethnic populations ( table  2 ) .
the possible reasons for the inconsistency might be the differences in ethnicity and clinical backgrounds , including body mass index . therefore , the cutoff value specific for the japanese population is needed , and the present result shows higher sensitivity and specificity than the values of the other studies .
aha / nhlbi , american heart association / national heart , lung , and blood institute ; atp iii , adult treatment panel iii ; homair , homeostasis model assessment of insulin resistance ; idf , international diabetes federation ; m , men ; w , women .
the prevalence of homair    1.7 was 36.5% in men and 24.5% in women , whereas 15.9% of men and 2.6% of women had mets .
the discrepancy between the prevalence of homair    1.7 and that of mets was larger in women than in men . when maximal sensitivity , as well as maximal specificity , is to be prioritized , the issue of a high falsepositive rate is inevitable . from the standpoint of primary prevention ,
we consider that it is much more important not to overlook mets than to exclude nonmets , and to give advice on lifestyle modifications to as many people as possible . in addition
, we consider that it is not appropriate to diagnose mets by homair , because the prevalence of mets was 32.1% for men and
just 8.6% for women , even in the subjects with homair    1.7 . in conclusion ,
homair  =  1.7 was determined as the optimal cutoff value for identifying subjects at high risk for mets . with the aim of health guidance for mets
, we propose that homair  <  1.7 should be considered as a target .
 abstractwe have recently established a  healthassociated reference interval of homeostasis model assessment of insulin resistance ( homair ) between 0.4 and 2.4 . in the present study , 
 the aim was to establish a  
 decisionbased limit of homair for the discrimination of metabolic syndrome ( mets ) in nondiabetic japanese subjects . 
 the receiver  
 operating characteristic curve of homair for detecting mets was developed using data from 6868 nondiabetic subjects ( 3727 men , 3141 women ) . 
 the optimal cutoff point was determined based on the point that yielded the minimum value of the square root of [ ( 1    
 sensitivity)2  +  ( 1    specificity)2 ] . 
 homair  
 =  1.7 was determined as the optimal cutoff value , with a sensitivity and specificity of 73.4% and 70.5% for men , and 81.5% and 77.0% for women , respectively . in conclusion 
 , the optimal cutoff value for homair to discriminate mets in nondiabetic japanese subjects appears to be 1.7 . 
 ( j diabetes invest , doi : 10.1111/j.20401124.2012.00194.x , 2012 ) 
Introduction
Materials and Methods
Results
Discussion