in january 2010 , the use of a1c to diagnose dm was officially recommended by the ada . a1c has been shown to correlate with the occurrence of diabetic retinopathy in previous reports . however , it was not recommended to diagnose dm at that time , mainly because of the lack of standardization of the assay . after the years of effort , the assays for a1c have been highly standardized , at least in the usa . therefore , the ada revised their diagnostic criteria for dm by adopting the use of a1c , which is more practical and timesaving than an ogtt . after the announcement , many studies were carried out to evaluate the diagnostic performance of a1c for dm in different populations . as the optimal a1c cutoff can vary in different races , the performance of the currently recommended a1c cutoff should be evaluated in different ethnic groups . for example , araneta et  al . reported that using the a1c cutoff of 6.5% might delay the diagnosis of dm , especially in asian americans who frequently have isolated postchallenge hyperglycemia . suggested a a1c cutoff of 6.3% for diagnosis of dm in the chinese population , which was lower than the adaproposed cutoff . besides , to apply a1c as a new diagnostic or screening tool , it is important to know if a1c and ogtt criteria identified a similar group of people . if these criteria highly agree with each other , a1c can simply replace the ogtt test as a simple method of diagnosis . if not , a1c could be used to decide whether ogtt should be carried out . therefore , the aim of the present study was to investigate the following two questions : ( i ) can a1c criteria replace ogtt criteria to diagnose dm ; and ( ii ) what is the screening strategy to find dm using a1c as one of the tools ? during 20062009 , residents in yunlin county aged 18  years and above were invited to participate in the present study , termed the taiwan lifestyle study . a questionnaire was given to discover if participants had dm or received medication for dm , with the aid of a trained nurse . participants who reported dm or received medication for dm were excluded . written informed consent was obtained from each individual , and the study was reviewed and approved by the institutional review board . normal glycemia ( fpg  <  5.56  mmol / l and 2h pg  <  7.8 mmol / l ) , ifg ( fpg 5.566.9  mmol / l ) , igt ( 2h pg 7.811.0 mmol / l ) and dm ( fpg    7  mmol / l and/or 2h pg    11.1 mmol / l ) were diagnosed according to the results of ogtt by the criteria of the ada proposed in 2003 . plasma glucose and a1c were measured by automatic analyzers ( toshiba tba 120fr , toshiba medical systems co. , tokyo , japan ; and hlc723 g7 hplc systems , tosoh corporation , tokyo , japan , respectively ) . the coefficients of variation ( cv ) for plasma glucose were 1.11.4% at 86  mg / dl ( 4.8  mmol / l ) and 0.80.9% at 293  mg / dl ( 16.3  mmol / l ) . the cv for a1c were 1.61.8% at 5.55.7% ( 3739  mmol / mol ) and 0.91.0% at 9.710.1% ( 8387 the laboratory attends and is qualified by an external quality assurance program by the taiwan society of laboratory medicine twice a year . the a1c assay was certified by the ngsp and standardized to the dcct reference assay . kappa statistics were used to evaluate the degree of agreement between a1c cutoffs and ogtt criteria . optimal cutoffs were derived from the roc curve with the shortest distance to sensitivity  =  1 , and 1    specificity  =  0 , and the youden index ( y  =  sensitivity  +  specificity    1 ) . the statistical analyses were carried out with stata / se 11.0 for windows ( statacorp lp , college station , tx , usa ) . a total of 1362 participants were enrolled in the present study , including 512 ( 38% ) men and 850 ( 62% ) women , aged 1888  years with a median of 50  years ( iqr 4159  years ) . in this communitybased chinese population , the median for fpg , 2h pg and a1c were 4.94  mmol / l ( iqr 4.675.33  mmol / l ) , 6.22  mmol / l ( iqr 5.067.72  mmol / l ) and 5.6% ( 38  mmol / mol ; iqr 5.45.9% , 3641  mmol / mol ) , respectively . their clinical characteristics are summarized in table  1 . among them , 101 ( 7% ) and 100 participants ( 7% ) were diagnosed as dm by ogtt criteria and a1c    6.5% ( 48  mmol / mol ) , respectively . among 135 patients with dm by either criteria , there were 66 patients ( 48.9% ) who met both ogtt and a1c criteria , 35 patients ( 25.9% ) who met ogtt criteria only and 34 patients ( 25.2% ) who met a1c criteria only ( figure  1a ) . fpg and 2h pg were similar in those with dm by a1c    6.5% than those with dm by abnormal ogtt results ( fpg 7.2    2.6 vs 7.4    2.6  mmol / l , p  =  0.7 ; 2h pg 13.5    5.9 vs 15.0    4.8  mmol / l , p  =  0.054 ) . 2hpg , plasma glucose 2  h after oral glucose tolerance test ; a1c , hemoglobin a1c ; dm , diabetes ; fpg , fasting plasma glucose ; ifg , impaired fasting glucose ; igt , impaired glucose tolerance ; ngt , normal glucose tolerance . the relationship between diabetes by ogtt and a1c cutoffs at ( a ) 6.5% and ( b ) 6.1% . the area under the roc curve for a1c to diagnosed dm by ogtt criteria in the present population was 0.91 ( 95% ci 0.870.95 ) , with the optimal cutoff of 6.1% . among the 213 patients who had a1c    6.1% or dm by abnormal ogtt results , there were 81 subjects ( 38.0% ) who met both criteria , 20 patients ( 9.4% ) who met ogtt criteria only and 112 patients ( 52.6% ) who had a1c    6.1% only ( figure  1b ) . as shown in table  2 , the sensitivity , specificity , ppv and npv to diagnose dm by ogtt were 65 , 97 , 66 and 97% for a1c    6.5% criteria , and 80 , 91 , 44 and 97% for a1c    6.1% criteria , respectively . both a1c cutoffs showed unsatisfactory agreement with ogtt criteria for dm ( kappa 0.50 and 0.63 ) . a similar pattern was also found in both men and women ( supporting information table  s1 ) . as there is a nationwide fpg screening program in taiwan , which is free for all adults older than 45  years and is provided every 3  years , we believed some , if not all , have attended the program . therefore , we analyzed the agreement in patients younger and older than 45  years . in patients younger than 45  years , an a1c cutoff of 6.5% showed a higher agreement with ogtt criteria ( kappa 0.83 ) than that in those older than 45  years ( kappa 0.60 ; supporting information table  s2 ) . the performance of using ada criteria to find patients with ifg or igt was poor . the kappa statistics , sensitivity and specificity were 0.19 , 65 and 71% for ifg , and 0.19 , 54 and 72% for igt ( table  2 ) . diabetes was defined as fasting plasma glucose    7  mmol / l or oral glucose tolerance test ( ogtt ) 2h plasma glucose    11.1 impaired fasting glucose was defined as fasting plasma glucose 5.66.9  mmol / l .  impaired glucose tolerance was defined as ogtt 2h pg 7.811.0 ci , confidence interval ; lr+ , positive likelihood ratio ; lr , negative likelihood ratio ; npv , negative prediction value ; ppv , positive prediction value . there was no difference in age , sex , bmi , blood pressure and lipid profile between patients with dm diagnosed by ogtt criteria ( n  =  101 ) and by a1c    6.5% criteria , but not by ogtt criteria ( n  =  34 ) . however , patients with dm by a1c criteria had lower fpg ( 5.5    0.5 vs 7.4    2.6 mmol / l , p  <  0.001 ) and 2h pg ( 7.9    2.1 vs 15.0    4.8  mmol / l , p  < tables  35 show the prevalence , ppv , npv , false positive and false negative percentages by using different cutoffs of fpg , a1c and fpg with a1c to screen dm by ogtt . in finding criteria to rule out dm , in contrast , as the a1c cutoff increased , the prevalence and false negative percentage increased . in other words , as the a1c cutoff increased , there were fewer people who had to receive the ogtt , in the expanse of a higher false negative percentage . in finding criteria to rule in dm , the main concern was ppv , as these subjects might be treated as having dm . false negative values among patients with diabetes by oral glucose tolerance test fasting plasma glucose ( fpg )  <  5.56  mmol / l and a1c  <  cutoff . fpg    5.56  mmol / l and a1c    cutoff . npv , negative predictive value ; ppv , positive predictive value . based on these data , using ifg criteria ( fpg  <  5.56  mmol / l to rule out dm and fpg    7  mmol / l to rule in dm ) , dm could be excluded in 83.3% , confirmed in 3.2 , and 13.5% of the whole population required ogtt ( figure  2a ) . although the npv to rule out dm was high ( 98.3% ) , there were 18.8% of diabetic patients who were missed ( false negative ) . the sensitivity and specificity of this strategy to diagnose dm by ogtt were 77.2% and 100% , respectively . in figure  2b , a1c  <  5.9% was chosen to be the cutoff to rule out dm , in order to reduce the false negative percentage to an acceptable range ( 10.9% ) , with good npv ( 98.8% ) . a1c    7.0% was used to rule in dm to maximize ppv ( 96% ) . by these criteria , there were 26.5% of the patients who had to receive the ogtt to confirm dm . the sensitivity and specificity to diagnose dm by ogtt were 89.1 and 99.8% , respectively . in figure  2c , both fpg and a1c were applied to screen dm . fpg  <  5.56  mmol / l and a1c  <  6.1% were used to exclude dm , in order to reduce the false negative percentage ( 10.9% ) while having good npv ( 99% ) . fpg    5.56  mmol / l and a1c    7% were used to rule in dm , with high ppv ( 96% ) and a very low percentage of false positive percentages ( 0.2% of total nondiabetic subjects ) . the sensitivity and specificity to diagnose dm by ogtt were 85.2 and 100% , respectively . the performance of combining fpg    5.56  mmol / l and a1c    7% to rule in dm is identical to that of a1c alone , suggesting that hba1c    7% alone did rule in diabetes , regardless of fpg levels . ( a ) by impaired fasting glucose criteria , that is , fasting plasma glucose ( fpg ) 5.567.0  mmol / l . ( c ) by fpg cutoff at 5.56  mmol / l and a1c cutoffs at 6.1 and 7% . in the present study , the agreement between ogtt and a1c criteria to diagnose dm was poor ; neither the adaproposed cutoff of 6.5% nor the optimal cutoff of 6.1% derived from our population . in the korean and chinese population , similar to the present results , the sensitivity and specificity for a1c were not good enough to find dm by ogtt ( korean population 81.8 and 84.9% , chinese population 81 and 81% ) . these observations suggest that a1c criteria identified different groups of people with dm . in the present report , the agreement between ogtt with a1c cutoff of 6.5% to diagnose dm is higher ( kappa 0.83 ) in those younger than 45  years than that in those older than 45  years . consistently , mannucci et  al . motta et  al . also found that the performance of a1c to diagnose dm is poorer than fpg in the elderly . taken together , these results show that a1c can not replace ogtt to diagnose dm , although its use in a younger population might be acceptable . we found that a1c could be used as a screening tool for the diagnosis of dm . two different strategies were provided ( figure  2 ) . if fasting is the main obstacle in screening dm , a1c followed by ogtt strategy is recommended ( figure  2b ) . compared with ifg criteria , use of a1c cutoffs at 5.9 and 7.0% improved overall sensitivity and reduced the false negative percentage , from 18.8 to 10.9% , with similar false positive and false negative percentages ( figure  2a , b ) . however , more people will be recommended to receive ogtt ( ifg criteria 13.5% , a1c criteria 26.5% ) . in the australian population , lu et  al . suggested cutoffs of a1c    7.0% to rule in dm and 5.5% to exclude dm . following their criteria , up to 65.2% of patients who had a1c values between 5.5 and 7.0% were recommended to have ogtt , which can be practically difficult and might be not costeffective . in contrast , if fasting is not a concern , the present results showed that a1c could improve the performance of fpg as the firststep screening tool ( figure  2c ) . compared with ifg criteria ( figure  2a ) , fpg and a1c criteria improved overall sensitivity , reduced the false negative percentage from 18.8 to 10.9% , had similarly good ppv and npv , and had a little more ogtt required ( ifg criteria 13.5% , fpg and a1c criteria 18.9% ) . similarly , combining fpg and a1c as a screening tool has been suggested to improve the diagnostic performance and to reduce the need of ogtt . in the chinese population , ko et  al . suggested that patients with a fpg range of 5.67.7  mmol / l and a1c    5.5% should receive ogtt to confirm dm . in a multiethnic study , fpg    5.7  mmol / l and a1c    5.9% yielded a sensitivity of 78.6% and a specificity of 95.9% for the chinese population ( n  =  307 ) . hu et  al . also reported a high specificity of 96.3% combining fpg    6.1  mmol / l or a1c    6.1% to screen dm . most previous studies provided a single cutoff of a1c instead of using two different cutoffs to rule in and rule out dm . in the uk and the australian populations , manley et  al . provided an algorithm to diagnose dm using fpg and a1c as initial screening tools . those with fpg  <  7  mmol / l and a1c    6.0% were recommended to receive the ogtt . these criteria are similar to our suggestions in figure  2c . in the present study , patients who met the a1c criteria , but not the ogtt criteria , had lower fpg and 2h pg , suggesting that the addition of a1c criteria helps to identify people with hyperglycemia earlier in their time course . although adding a1c criteria as screening costs more money , early identification of these patients and subsequent early intervention might reduce diabetic complications . the cost  benefit issue should be studied in longitudinal followup studies . a very low agreement among a1c ranged 5.76.4% , ifg and igt the test performance of a1c criteria against ifg or igt was also poor , which is consistent with previous studies in the usa , australian   and chinese populations . therefore , the a1c criteria of 5.76.4% might identify a different population at risk of dm from ifg and igt criteria , and should not be viewed as a replacement for ogtt . first , there were differences in the distribution of age and sex between the present study subjects and whole taiwanese population . although age , but not sex , is a risk factor for isolated postprandial hyperglycemia , using only one criterion is more practical than using different criteria in different age groups . indeed , there is only one criterion for the diagnosis of diabetes and prediabetes , by both the ada and the easd . therefore , we think it s acceptable to use current cutoffs and the flow charts in the present report . if age and other risk factors are of concern , we have also provided four different risk scores to determine if ogtt is needed in a previous report . second , we did not assess if the subjects had hemoglobinopathies in the present study . although this is more likely to be the real clinical situation , care should be taken in applying the findings of the present study . in conclusion , using a1c  <  5.9% to exclude and a1c    7.0% to diagnose dm by ogtt is more sensitive than using fpg  <  5.56  mmol / l to exclude and fpg    7.0  mmol / <  6.1% plus fpg  <  5.56  mmol / l to exclude and a1c    7.0% to diagnose dm by ogtt reduced the number of ogtt needed with acceptable sensitivity . however , there is no single cutoff for a1c to replace ogtt to diagnose dm , ifg and igt . table s1 comparison of different criteria to diagnose diabetes , impaired fasting glucose , and impaired glucose tolerance in male and female subjects table s2 comparison of different criteria to diagnose diabetes , impaired fasting glucose , and impaired glucose tolerance in subjects older or younger than 45 years old click here for additional data file .
abstractaims / introduction :   to evaluate if hemoglobin a1c ( a1c ) can replace the use of the oral glucose tolerance test ( ogtt ) to diagnose diabetes in chinese patients.materials and methods :   subjects without preexisting diabetes were included in this communitybased study . 
 each participant received a 75g ogtt and a1c tests.results :   a total of 1362 subjects , 512 men and 850 women , aged 1888  years , were enrolled . 
 the prevalence of diabetes was 7.4 and 7.3% by ogtt and by a1c    6.5% criteria , respectively . 
 the optimal a1c cutoff for diabetes defined by ogtt was 6.1% . 
 the performance of a1c    6.1% to find diabetes by ogtt was poor , with a kappa 0.50 , sensitivity 80% and specificity 91% . using current criteria of fasting plasma glucose ( fpg )  <  5.56  mmol / l to exclude and 7  mmol / l to diagnose diabetes ( fpg criterion ) , the sensitivity , specificity and ogtt required were 77.2 , 100 and 13.5% , respectively . using a1c  < 
 5.9% to exclude and 7.0% to diagnose diabetes ( a1c criterion ) , the sensitivity , specificity and ogtt required were 89.1 , 99.8 and 26.5% , respectively . 
 however , using fpg  <  5.56  mmol / l and a1c  <  6.1% to exclude , and a1c    7.0% to diagnose diabetes ( a1c plus fpg criterion ) , the sensitivity , specificity and ogtt required were 85.2 , 100 and 18.9% , respectively.conclusions :   to screen for diabetes , the a1c criterion is more sensitive than the fpg criterion , with more ogtt needed . 
 the a1c plus fpg criterion reduced the number of ogtt needed with acceptable sensitivity . 
 a1c can guide , but can not replace , ogtt to diagnose diabetes . 
 ( j diabetes invest , doi : 10.1111/j.20401124.2011.00181.x , 2011 )