the clinical population , melbourne pathology ( mp ) group , included all patients referred by medical practitioners for an ogtt in 20032008 to a state - wide private pathology service ( mp services , australia ) ; the ausdiab population comes from a national population - based study ( 20042005 ausdiab follow - up ) ( 5 ) . only people with concurrent a1c and ogtt results are included here ( mp group : n = 2,494 ; ausdiab : n = 6,014 ) . a1c was determined either by diabetes control and complications trial ( dcct)-aligned ( 7 ) cation - exchange chromatography ( mp population ) or by boronate affinity chromatography with values converted to dcct - aligned a1c ( 5 ) ( ausdiab ) . among those with undiagnosed diabetes ( 34.6% ) by ogtt criteria in the mp population , a1c at the 2.5th percentile was 5.6% . for those without diabetes ( 65.4% ) , a1c at the 97.5th percentile was 6.9% . a1c 7.0% was thus chosen to rule in ( diagnose ) diabetes . applying the above cut offs , a total 1a ) , while the remaining 64.8% had an impaired a1c of 5.66.9% . from those with impaired a1c a1c at 5.5% provided high sensitivity ( 97.8% ) and high negative predictive value ( npv ) ( 95.8% ) , while a1c at 7.0% gave high specificity ( 98.2% ) and high positive predictive value ( ppv ) ( 92.9% ) . using the recommended cut off of 6.5% ( 3 ) , application of the a1c cut offs to screen or diagnose diabetes in a clinical group ( mp population , n = 2,494 , undiagnosed diabetes 34.6% ) ( a ) and in a national population - based group ( ausdiab population , n = 6,014 , undiagnosed diabetes 4.6% ) ( b ) . applying the same cut offs , a total 75.9% of the ausdiab population had diabetes ruled in or ruled out ( fig . 1b ) , while the remaining 24.1% had impaired a1c . from those with impaired a1c , 69.3% had abnormal glucose status . for diabetes , a1c at 5.5% provided moderate sensitivity ( 83.5% ) but high npv ( 99.0% ) , since diabetes prevalence was lower in the ausdiab than in the mp population . a1c at 7.0% gave 100% specificity and 100% ppv . by dropping the cut off to 6.5% , specificity remained 99.9% , with ppv near 100% . among those with undiagnosed diabetes ( 34.6% ) by ogtt criteria in the mp population , a1c at the 2.5th percentile was 5.6% . for those without diabetes ( 65.4% ) , a1c at the 97.5th percentile was 6.9% . applying the above cut offs , a total 35.2% of the mp population had diabetes ruled in or ruled out ( fig . 1a ) , while the remaining 64.8% had an impaired a1c of 5.66.9% . from those with impaired a1c a1c at 5.5% provided high sensitivity ( 97.8% ) and high negative predictive value ( npv ) ( 95.8% ) , while a1c at 7.0% gave high specificity ( 98.2% ) and high positive predictive value ( ppv ) ( 92.9% ) . using the recommended cut off of 6.5% ( 3 ) , application of the a1c cut offs to screen or diagnose diabetes in a clinical group ( mp population , n = 2,494 , undiagnosed diabetes 34.6% ) ( a ) and in a national population - based group ( ausdiab population , n = 6,014 , undiagnosed diabetes 4.6% ) ( b ) . applying the same cut offs , a total 75.9% of the ausdiab population had diabetes ruled in or ruled out ( fig . 1b ) , while the remaining 24.1% had impaired a1c . from those with impaired a1c a1c at 5.5% provided moderate sensitivity ( 83.5% ) but high npv ( 99.0% ) , since diabetes prevalence was lower in the ausdiab than in the mp population . a1c at 7.0% gave 100% specificity and 100% ppv . by dropping the cut off to 6.5% , specificity remained 99.9% , with ppv near 100% . our study supports recommendations to use a1c for diabetes screening and diagnosis ( 2,3 ) . using two , rather than one , cut off values for a1c achieved high sensitivity for screening plus optimal specificity for diabetes diagnosis . we also show the high probability that those with impaired a1c have abnormal glucose status . single a1c cut offs have limited clinical utility in identifying those people with abnormal blood glucose levels . the most commonly reported single a1c cut off obtained from reported receiver - operated characteristic ( roc ) curves was 6.1% , which gives sensitivities of 7881% , with specificities of 7984% ( 8) . in our mp population , the roc curve  identified optimal a1c of 6.2% gave a sensitivity of 82.2% and specificity of 78.8% ( z.x.l , unpublished data ) but yielded a reduced ppv ( 67.2% ) and npv ( 89.3% ) . the lower was chosen for its high npv , as diabetes is ruled out with high confidence ( with a1c 5.5% , npv was > 95% in both clinical and population settings ) . applying an a1c of 5.5% to national health and nutrition examination survey ( nhanes ) data generated a sensitivity of 92% and specificity of 30% from the published roc curve ( 9 ) . this gave an npv of 99% ( assuming 3.4% undiagnosed diabetes ) and agrees with our finding that diabetes is very unlikely in individuals with a1c 5.5% . our 7.0% cut off for diabetes diagnosis is higher than the 6.5% recommended cut off ( 2,3 ) but was chosen to optimize specificity . for those with impaired a1c , the prevalence of diabetes increases as a1c increases . a1c is a continuous variable for diabetes and any cut off values chosen are somewhat arbitrary . from our data , people with a1c 5.66.0% were more likely to have either normoglycemia or pre - diabetes ( impaired fasting glucose and/or impaired glucose tolerance ) than diabetes , consistent with nhanes , where a1c 5.56.0% excluded diabetes in moderate but not high - risk individuals ( 10 ) . thus , those with an a1c of 5.66.0% would probably require education and lifestyle modification to prevent progression to diabetes ( 11 ) plus retesting every 612 months . also in our study , people with an a1c of 6.16.4% were more likely to have pre - diabetes or diabetes than normoglycemia , while among those with a a1c of 6.56.9% , diabetes was highly probable . thus , individuals with an a1c of 6.16.9% may require an ogtt to confirm their glycemic status plus lifestyle education and regular monitoring as for people with pre - diabetes . for those with an a1c 6.5% , screening for retinopathy is also necessary ( 2 ) . a1c the main issues are method bias , which is now being addressed by internation federation of clinical chemistry standardization ( 12 ) and certain confounding medical conditions ( hemoglobinopathies and anemia ) . while a1c analysis , per se , is more expensive than for glucose , the overall differences are small once the costs for blood collection are accounted for . from our own estimates , total costs are aud $ 10.20 for a1c compared with aud $ 8.80 for fpg and aud $ 12.10 for a two - point collection of ogtt . further , the time and inconvenience to patients in having to fast for an ogtt can not be ignored . 5.5% and 7.0% predicts with 97.5% confidence the absence or presence of type 2 diabetes using the ogtt as a reference . many with impaired a1c have pre - diabetes , while diabetes is highly probable when a1c reaches 6.56.9% . although the cost of a1c is slightly higher than for fpg , the overall efficiency of using a1c as a first line for diabetes screening may facilitate early diagnosis and reduce the health burden associated with diabetes complications .
objectiveto evaluate a1c for screening and diagnosis of undiagnosed type 2 diabetes defined by oral glucose tolerance testing in clinical and general populations.research design and methodsa1c cut offs ( 5.5% to rule out diabetes ; 7.0% to rule in diabetes ) were derived from a clinical group ( melbourne pathology [ mp ] group : n = 2,494 ; undiagnosed diabetes 34.6% ) and then evaluated in a population - based sample ( ausdiab group : n = 6,015 ; undiagnosed diabetes 4.6%).resultsfor diabetes in the mp and ausdiab groups , a1c at 5.5% gave sensitivities of 98.7 and 83.5% , while a1c at 7.0% gave specificities of 98.2 and 100% , respectively . 
 many ( 61.969.3% ) with impaired a1c ( 5.66.9% ) in both populations had abnormal glucose status.conclusionsa1c 5.5% and 7.0% predicts absence or presence of type 2 diabetes , respectively , while at a1c 6.56.9% diabetes is highly probable in clinical and population settings . 
 a high proportion of people with impaired a1c have abnormal glucose status requiring follow - up .