the current study was nested in an ongoing community - based cohort study that investigated associations between glucose dysregulation and cardiovascular complications .
the study design and protocol of baseline data collection of the cohort study were described previously ( 15 ) .
briefly , all the permanent residents aged 40 years or older in songnan community in shanghai were invited to participate in a screening examination for cardiometabolic diseases . among 10,185 participants , we randomly selected 5,250 subjects using a ratio of 1.0 [ diabetes diagnosed previously or fasting plasma glucose ( fpg ) 7.0
mmol / l ] to 1.2 ( no previous diabetes and 5.6  fpg < 7.0
mmol / l ) to 1.44 ( no previous diabetes and fpg < 5.6 mmol / l ) and oversampling people with lower glucose levels because they might have a lower participation rate than those with higher glucose levels , to undergo a much detailed and comprehensive evaluation including a standard 75-g oral glucose tolerance test .
we then reclassified the participating 4,012 subjects ( attendance rate , 76.4% ) into ngr , prediabetes , and diabetes groups based on their diabetes history and fpg and 2-h postload plasma glucose ( ppg ) levels according to the 1999 world health organization criteria .
there was no significant difference in age and sex distribution between those included and those not included in the cohort . for the current study
, we randomly selected 150 individuals from the diabetes group and 150 ngr group and 150 prediabetes group individuals matched for age and sex of diabetic participants , respectively , after excluding subjects with the following characteristics : 1 ) age older than 60 years ; 2 ) having symptoms of cad ( chest pain or shortness of breath ) ; 3 ) having a history of cardiovascular diseases ( myocardial infarction , unstable angina , percutaneous coronary intervention , or stroke ) ; 4 ) having abnormal q waves on resting electrocardiogram ( ecg ) ; 5 ) having a previous diagnosis of diabetes for > 5 years ; 6 ) having impaired liver or renal function [ alanine aminotransferease more than twice the upper limit of the normal range , serum creatinine level > 133 mol / l ( 1.5 mg / dl ) , or glomerular filtration rate < 60 ml / min ] ; 7 ) being pregnant or having significant medical comorbidities ; 8) having x - ray examination or ct scan within 1 year ; 9 ) having tachycardia ( a heart rate > 90 bpm ) or arrhythmia such as atrial fibrillation on ecg that causes coronary artifacts during cta examinations ; and 10 ) having a history of allergic reaction to iodine - containing contrast agent .
finally , a total of 420 individuals ( attendance rate , 93% ) participated in the current study .
the study protocol was approved by the institutional review board of rui - jin hospital and written informed consent was obtained from each participant after providing a full explanation of the protocol and procedure . during july 2009 and august 2010 , all participants underwent a comprehensive examination including a detailed questionnaire , anthropometric measurements , biochemical evaluation , and cta examination .
family history of cad in first - degree relatives was recorded and history of chronic diseases and current use of medication were acquired .
smoking status was defined as current if a subject smoked cigarettes regularly in the past 6 months .
the bmi was calculated as body weight in kilograms divided by body height in meters squared ( kg / m ) .
blood pressure was measured in the nondominant arm in a seated position three times consecutively at 1-min intervals after at least 5 min of rest using an automated electronic device ( omron model hem-752 ; omron company , dalian , china ) .
all participants were told to fast for at least 10 h before blood samples were collected .
plasma glucose , serum triglycerides , total cholesterol , hdl cholesterol , and ldl cholesterol were measured using an autoanalyser ( beckman cx-7 biochemical autoanalyser , beckman coulter , brea , ca ) . hemoglobin a1c
( hba1c ) was determined by high - performance liquid chromatography using the variant ii hemoglobin testing system ( bio - rad laboratories , berkeley , ca ) in a national glycohemoglobin standardization program  certified laboratory of shanghai institute of endocrine and metabolic diseases .
fasting serum insulin was measured by an electrochemiluminescence assay ( roche diagnostics ) . the single - void first morning
urinary albumin concentrations were determined by immunoturbidimetry and urinary creatinine concentrations were measured by a modified jaffe method on an automatic analyzer ( beckman lx-20 ) .
diabetes was defined either by a previous diagnosis and contemporary antidiabetic medication or by levels of plasma glucose during oral glucose tolerance test according to the 1999 world health organization criteria .
prediabetes was defined as fpg 6.1 mmol / l and < 7.0 mmol / l plus ppg < 7.8 mmol / l or fpg < 7.0 mmol / l plus ppg 7.8 mmol / l and < 11.1
the indexes of homeostasis model assessment ( homa ) of insulin resistance and homa -cell function were calculated according to the formulas : homa of insulin resistance = fasting insulin concentration ( miu / l )  fpg ( mmol / l ) / 22.5 ; homa -cell function = 20  fasting insulin concentration ( miu / l)/[fpg ( mmol / l )  3.5 ] .
urinary albumin - to - creatinine ratio was calculated by dividing the urinary albumin concentrations by the urinary creatinine concentrations and expressed in milligrams per gram .
microalbuminuria was defined as an albumin - to - creatinine ratio between 30 and 300 mg / g .
all examinations were performed on a dual - source ct scanner ( somatom definition ; siemens medical solutions , forchheim , germany ) .
a standard retrospectively ecg - gated scanning protocol was applied , with 0.6-mm slice collimation , 330-ms gantry rotation time , 120-kv tube voltage , and a maximum tube current of 400 mas / tube .
a bolus of 70 ml iohexol injection ( 350 mg / ml iodine ; omnipaque ; ge healthcare shanghai , shanghai , china ) was intravenously injected ( 4 ml / s ) via an 18-gauge catheter placed in the antecubital vein , followed by a 40-ml saline chaser .
the cta images were interpreted independently by an experienced senior radiologist , who was unaware of the clinical information of study participants , with an offline three - dimensional workstation ( adw 4.4 ; ge healthcare , waukesha , wi ) .
coronary arteries were divided into 15 segments according to the american heart association classification ( 16 ) .
the presence of atherosclerotic plaques and luminal narrowing were evaluated using axial images and curved multiplanar reconstructions .
coronary plaques were considered when structures > 1 mm were detected within or adjacent to the coronary artery lumen , which could be clearly distinguished from vessel lumen and the surrounding pericardial tissue .
given an estimated response rate of 75% , we calculated that a sample size of 140 participants for each of the 3 groups was needed to provide 90% power at a 2-tailed significance level of 0.05 to detect a difference from 5 to 20% of estimated prevalence of significant coronary stenosis assessed by cta among the groups .
all data were analyzed using sas 9.2 ( sas institute , cary , nc ) .
continuous variables were presented as means  sd or medians ( interquartile ranges ) for skewed variables .
demographic and metabolic features and characteristics of coronary arteries in ngr , prediabetes , and diabetes were described and compared using anova for continuous variables and logistic regression analysis for categorical variables , adjusted for age and sex .
the study population was reclassified into groups of increasing coronary stenosis ( participants without coronary stenosis , with < 50% coronary stenosis , and with significant coronary stenosis ) .
fpg , ppg , and hba1c levels and diabetes prevalence were then compared among these three groups . to investigate the associations of various cardiometabolic factors with significant coronary stenosis
, logistic regression models were used to assess the crude and multivariate - adjusted odds ratios ( or ) of advanced age ( age 53 years or older , representing the median cut - off value ) , female sex , family history of cad , ace inhibitor / angiotensin receptor blocker medication , current smoking , high school education or more , overweight / obesity , hypertension , high ldl , low hdl , prediabetes , and diabetes for risks of significant coronary stenosis . variables for multivariate regression analysis were chosen as confounding factors depending on their clinical plausibility and external evidence such as previous research and previous beliefs , i.e. , their well - recognized clinical relevance to both dysglycemia ( the independent variable of interest ) and cardiovascular diseases ( significant coronary stenosis , the dependent variable ) in this study , rather than internal statistical evidence from the data . to further elucidate the differences between diabetic participants with or without significant coronary stenosis , general characteristics were compared .
crude and multivariate - adjusted ors for significant coronary stenosis in diabetes by each 1-sd increase in levels of different glucose evaluations were calculated using logistic regression procedures .
the current study was nested in an ongoing community - based cohort study that investigated associations between glucose dysregulation and cardiovascular complications .
the study design and protocol of baseline data collection of the cohort study were described previously ( 15 ) .
briefly , all the permanent residents aged 40 years or older in songnan community in shanghai were invited to participate in a screening examination for cardiometabolic diseases . among 10,185 participants , we randomly selected 5,250 subjects using a ratio of 1.0 [ diabetes diagnosed previously or fasting plasma glucose ( fpg ) 7.0
mmol / l ] to 1.2 ( no previous diabetes and 5.6  fpg < 7.0
mmol / l ) to 1.44 ( no previous diabetes and fpg < 5.6 mmol / l ) and oversampling people with lower glucose levels because they might have a lower participation rate than those with higher glucose levels , to undergo a much detailed and comprehensive evaluation including a standard 75-g oral glucose tolerance test .
we then reclassified the participating 4,012 subjects ( attendance rate , 76.4% ) into ngr , prediabetes , and diabetes groups based on their diabetes history and fpg and 2-h postload plasma glucose ( ppg ) levels according to the 1999 world health organization criteria .
there was no significant difference in age and sex distribution between those included and those not included in the cohort . for the current study
, we randomly selected 150 individuals from the diabetes group and 150 ngr group and 150 prediabetes group individuals matched for age and sex of diabetic participants , respectively , after excluding subjects with the following characteristics : 1 ) age older than 60 years ; 2 ) having symptoms of cad ( chest pain or shortness of breath ) ; 3 ) having a history of cardiovascular diseases ( myocardial infarction , unstable angina , percutaneous coronary intervention , or stroke ) ; 4 ) having abnormal q waves on resting electrocardiogram ( ecg ) ; 5 ) having a previous diagnosis of diabetes for > 5 years ; 6 ) having impaired liver or renal function [ alanine aminotransferease more than twice the upper limit of the normal range , serum creatinine level > 133 mol / l ( 1.5 mg / dl ) , or glomerular filtration rate < 60 ml / min ] ; 7 ) being pregnant or having significant medical comorbidities ; 8) having x - ray examination or ct scan within 1 year ; 9 ) having tachycardia ( a heart rate > 90 bpm ) or arrhythmia such as atrial fibrillation on ecg that causes coronary artifacts during cta examinations ; and 10 ) having a history of allergic reaction to iodine - containing contrast agent .
finally , a total of 420 individuals ( attendance rate , 93% ) participated in the current study .
the study protocol was approved by the institutional review board of rui - jin hospital and written informed consent was obtained from each participant after providing a full explanation of the protocol and procedure .
during july 2009 and august 2010 , all participants underwent a comprehensive examination including a detailed questionnaire , anthropometric measurements , biochemical evaluation , and cta examination .
family history of cad in first - degree relatives was recorded and history of chronic diseases and current use of medication were acquired .
smoking status was defined as current if a subject smoked cigarettes regularly in the past 6 months .
the bmi was calculated as body weight in kilograms divided by body height in meters squared ( kg / m ) .
blood pressure was measured in the nondominant arm in a seated position three times consecutively at 1-min intervals after at least 5 min of rest using an automated electronic device ( omron model hem-752 ; omron company , dalian , china ) .
all participants were told to fast for at least 10 h before blood samples were collected .
plasma glucose , serum triglycerides , total cholesterol , hdl cholesterol , and ldl cholesterol were measured using an autoanalyser ( beckman cx-7 biochemical autoanalyser , beckman coulter , brea , ca ) . hemoglobin a1c ( hba1c ) was determined by high - performance liquid chromatography using the variant ii hemoglobin testing system ( bio - rad laboratories , berkeley , ca ) in a national glycohemoglobin standardization program  certified laboratory of shanghai institute of endocrine and metabolic diseases .
the single - void first morning urine samples were collected to assess urinary albumin - to - creatinine ratio .
urinary albumin concentrations were determined by immunoturbidimetry and urinary creatinine concentrations were measured by a modified jaffe method on an automatic analyzer ( beckman lx-20 ) .
diabetes was defined either by a previous diagnosis and contemporary antidiabetic medication or by levels of plasma glucose during oral glucose tolerance test according to the 1999 world health organization criteria .
prediabetes was defined as fpg 6.1 mmol / l and < 7.0 mmol / l plus ppg < 7.8 mmol / l or fpg < 7.0 mmol / l plus ppg 7.8 mmol / l and < 11.1
the indexes of homeostasis model assessment ( homa ) of insulin resistance and homa -cell function were calculated according to the formulas : homa of insulin resistance = fasting insulin concentration ( miu / l )  fpg ( mmol / l ) / 22.5 ; homa -cell function = 20  fasting insulin concentration ( miu / l)/[fpg ( mmol / l ) 
urinary albumin - to - creatinine ratio was calculated by dividing the urinary albumin concentrations by the urinary creatinine concentrations and expressed in milligrams per gram .
microalbuminuria was defined as an albumin - to - creatinine ratio between 30 and 300 mg / g .
all examinations were performed on a dual - source ct scanner ( somatom definition ; siemens medical solutions , forchheim , germany ) .
a standard retrospectively ecg - gated scanning protocol was applied , with 0.6-mm slice collimation , 330-ms gantry rotation time , 120-kv tube voltage , and a maximum tube current of 400 mas / tube .
all scans were performed using ecg - controlled tube current modulation . a bolus of 70 ml iohexol injection ( 350 mg / ml iodine ; omnipaque ; ge healthcare shanghai , shanghai , china )
was intravenously injected ( 4 ml / s ) via an 18-gauge catheter placed in the antecubital vein , followed by a 40-ml saline chaser .
the cta images were interpreted independently by an experienced senior radiologist , who was unaware of the clinical information of study participants , with an offline three - dimensional workstation ( adw 4.4 ; ge healthcare , waukesha , wi ) .
coronary arteries were divided into 15 segments according to the american heart association classification ( 16 ) .
the presence of atherosclerotic plaques and luminal narrowing were evaluated using axial images and curved multiplanar reconstructions .
coronary plaques were considered when structures > 1 mm were detected within or adjacent to the coronary artery lumen , which could be clearly distinguished from vessel lumen and the surrounding pericardial tissue .
given an estimated response rate of 75% , we calculated that a sample size of 140 participants for each of the 3 groups was needed to provide 90% power at a 2-tailed significance level of 0.05 to detect a difference from 5 to 20% of estimated prevalence of significant coronary stenosis assessed by cta among the groups .
all data were analyzed using sas 9.2 ( sas institute , cary , nc ) .
continuous variables were presented as means  sd or medians ( interquartile ranges ) for skewed variables .
demographic and metabolic features and characteristics of coronary arteries in ngr , prediabetes , and diabetes were described and compared using anova for continuous variables and logistic regression analysis for categorical variables , adjusted for age and sex .
the study population was reclassified into groups of increasing coronary stenosis ( participants without coronary stenosis , with < 50% coronary stenosis , and with significant coronary stenosis ) .
fpg , ppg , and hba1c levels and diabetes prevalence were then compared among these three groups . to investigate the associations of various cardiometabolic factors with significant coronary stenosis
, logistic regression models were used to assess the crude and multivariate - adjusted odds ratios ( or ) of advanced age ( age 53 years or older , representing the median cut - off value ) , female sex , family history of cad , ace inhibitor / angiotensin receptor blocker medication , current smoking , high school education or more , overweight / obesity , hypertension , high ldl , low hdl , prediabetes , and diabetes for risks of significant coronary stenosis .
variables for multivariate regression analysis were chosen as confounding factors depending on their clinical plausibility and external evidence such as previous research and previous beliefs , i.e. , their well - recognized clinical relevance to both dysglycemia ( the independent variable of interest ) and cardiovascular diseases ( significant coronary stenosis , the dependent variable ) in this study , rather than internal statistical evidence from the data . to further elucidate the differences between diabetic participants with or without significant coronary stenosis ,
crude and multivariate - adjusted ors for significant coronary stenosis in diabetes by each 1-sd increase in levels of different glucose evaluations were calculated using logistic regression procedures .
nineteen ( 4.5% ) patients with uninterpretable segments attributable to motion artifacts were excluded from analysis , which resulted in 135 with ngr , 132 with prediabetes , and 134 with diabetes participating for data analysis .
generally , percentages of individuals with a family history of cad , educated beyond high school level , or currently smoking were not significantly different among groups , whereas bmi , blood pressure , and triglycerides were elevated and hdl was decreased substantially in parallel with deteriorations in glucose levels , insulin sensitivity , and -cell function .
medications using ace inhibitors or angiotensin receptor blockers were basically similar among the three groups .
one was in the ngr group and the other was in the prediabetes group , and both were without coronary plaques .
statins were used by only one individual who was diabetic and had nonsignificant coronary stenosis .
general characteristics of study population by glycemic status as shown in table 1 , coronary plaques were found in 58 ( 43.0% ) participants with ngr , in 77 ( 58.3% ) with prediabetes , and in 74 ( 55.2% ) with diabetes ( p for trend = 0.081 ) , whereas plaques causing significant coronary stenosis were detected in 10 ( 7.4% ) , 10 ( 7.6% ) , and 22 ( 16.4% ) individuals with ngr , prediabetes , and diabetes , respectively ( p for trend = 0.029 ) .
therefore , a similar prevalence of cad detected by cta was found in prediabetes and diabetes , and it was relatively higher than that in ngr ; however , prevalence of significant coronary stenosis was doubled in diabetes and was substantially increased compared with that in ngr or prediabetes . when participants were reclassified
according to existence or extent of coronary stenosis , individuals with significant stenosis had dramatically elevated levels of fpg , ppg , and hba1c and had a significantly increased prevalence of diabetes compared with both groups of participants with < 50% coronary stenosis and without stenosis after controlling for a variety of confounding factors ( all p < 0.05 ; fig .
percentages of diabetes and levels of glucose evaluations in participants 1 ) without coronary stenosis , 2 ) with < 50% coronary stenosis , and 3 ) with significant coronary stenosis , respectively .
p values were adjusted for age , sex , family history of cad , history of ace inhibitor / angiotensin receptor blocker medication , smoking status , educational attainment , overweight or obesity , hypertension , high ldl cholesterol , and low hdl cholesterol .
women were strongly protected from significant coronary stenosis [ or , 0.33 ( 95% ci , 0.140.81 ) ; p = 0.016 ; table 2 ] .
prediabetes was not associated with an increased risk of significant coronary stenosis , whereas diabetes was associated with a significant 2.34-fold elevated risk [ 2.34 ( 1.015.43 ) ; p = 0.047 ] compared with ngr .
correlations of cardiometabolic factors with risks of significant coronary stenosis among 134 patients with diabetes for < 5 years , 22 ( 16.4% ) had significant coronary stenosis .
diabetic individuals with significant coronary stenosis were more likely to be males and had more deteriorated glucose metabolism and -cell function compared with those without significant coronary stenosis ( table 3 ) .
the presence of microalbuminuria tended to be increased in those with significant stenosis , but it failed to reach statistical significance . among all cases of diabetes , 104 ( 77.6% )
were newly diagnosed , but 14 ( 13.5% ) already had significant coronary stenosis . although newly diagnosed diabetes tended to occur more often in the group without significant coronary stenosis , the difference was not statistically significant .
comparison of characteristics by coronary artery status in diabetes in univariate and multivariate logistic analyses , glucose evaluation levels were independently and significantly associated with risks of significant coronary stenosis in diabetes .
each 1-sd increase in fpg , ppg , or hba1c conveyed 2.11-fold , 1.73-fold , or 1.81-fold higher risks of significant coronary stenosis , respectively , after controlling for other conventional cardiovascular risk factors ( all p < 0.05 ; table 4 ) .
characteristics of the study population according to glycemic status are shown in table 1 . generally , percentages of individuals with a family history of cad , educated beyond high school level , or currently smoking were not significantly different among groups , whereas bmi , blood pressure , and triglycerides were elevated and hdl was decreased substantially in parallel with deteriorations in glucose levels , insulin sensitivity , and -cell function .
medications using ace inhibitors or angiotensin receptor blockers were basically similar among the three groups .
one was in the ngr group and the other was in the prediabetes group , and both were without coronary plaques .
statins were used by only one individual who was diabetic and had nonsignificant coronary stenosis .
as shown in table 1 , coronary plaques were found in 58 ( 43.0% ) participants with ngr , in 77 ( 58.3% ) with prediabetes , and in 74 ( 55.2% ) with diabetes ( p for trend = 0.081 ) , whereas plaques causing significant coronary stenosis were detected in 10 ( 7.4% ) , 10 ( 7.6% ) , and 22 ( 16.4% ) individuals with ngr , prediabetes , and diabetes , respectively ( p for trend = 0.029 ) .
therefore , a similar prevalence of cad detected by cta was found in prediabetes and diabetes , and it was relatively higher than that in ngr ; however , prevalence of significant coronary stenosis was doubled in diabetes and was substantially increased compared with that in ngr or prediabetes . when participants were reclassified
according to existence or extent of coronary stenosis , individuals with significant stenosis had dramatically elevated levels of fpg , ppg , and hba1c and had a significantly increased prevalence of diabetes compared with both groups of participants with < 50% coronary stenosis and without stenosis after controlling for a variety of confounding factors ( all p < 0.05 ; fig .
percentages of diabetes and levels of glucose evaluations in participants 1 ) without coronary stenosis , 2 ) with < 50% coronary stenosis , and 3 ) with significant coronary stenosis , respectively .
p values were adjusted for age , sex , family history of cad , history of ace inhibitor / angiotensin receptor blocker medication , smoking status , educational attainment , overweight or obesity , hypertension , high ldl cholesterol , and low hdl cholesterol .
women were strongly protected from significant coronary stenosis [ or , 0.33 ( 95% ci , 0.140.81 ) ; p = 0.016 ; table 2 ] .
prediabetes was not associated with an increased risk of significant coronary stenosis , whereas diabetes was associated with a significant 2.34-fold elevated risk [ 2.34 ( 1.015.43 ) ; p = 0.047 ] compared with ngr .
among 134 patients with diabetes for < 5 years , 22 ( 16.4% ) had significant coronary stenosis .
diabetic individuals with significant coronary stenosis were more likely to be males and had more deteriorated glucose metabolism and -cell function compared with those without significant coronary stenosis ( table 3 ) .
the presence of microalbuminuria tended to be increased in those with significant stenosis , but it failed to reach statistical significance . among all cases of diabetes , 104 ( 77.6% ) were newly diagnosed , but 14 ( 13.5% ) already had significant coronary stenosis . although newly diagnosed diabetes tended to occur more often in the group without significant coronary stenosis , the difference was not statistically significant .
comparison of characteristics by coronary artery status in diabetes in univariate and multivariate logistic analyses , glucose evaluation levels were independently and significantly associated with risks of significant coronary stenosis in diabetes .
each 1-sd increase in fpg , ppg , or hba1c conveyed 2.11-fold , 1.73-fold , or 1.81-fold higher risks of significant coronary stenosis , respectively , after controlling for other conventional cardiovascular risk factors ( all p < 0.05 ; table 4 ) .
we used cta , which is a noninvasive diagnostic modality , to characterize subclinical cad in a community - dwelling adult population with ngr , prediabetes , or diabetes matched for age and sex .
we found that although coronary stenosis was more prevalent in both prediabetes and diabetes , the risk of significant stenosis was only elevated in diabetes , despite a short duration of < 5 years . additionally , glucose evaluation levels were significantly and independently associated with risks of significant coronary stenosis in diabetic participants
17 ) reported that the presence of diabetes alone confers risk of cardiovascular mortality similar to that in nondiabetic individuals with a previous myocardial infarction .
heart disease is the most frequent cause of death in those with diabetes , accounting for 70% of all deaths ( 18 ) .
coronary artery lesions in those with diabetes were often characterized as diffuse and multivessel , yet asymptomatic ( 19 ) .
in fact , silent myocardial ischemia is highly prevalent in the diabetic population . in the current study ,
74 out of 134 diabetic patients ( 55.2% ) were found to have a certain degree of coronary stenosis and 22 ( 16.4% ) had significant stenosis , which was relatively low compared with most studies using cta in asymptomatic patients with diabetes ( 1114 ) .
the variation in prevalence may well reflect the important differences regarding population characteristics between studies .
those with higher prevalence rates of significant stenosis , ranging between 26 and 41% , generally included a higher proportion of male participants ( for example , 66% in the study by rivera et al .
( 11 ) compared with 50% in the current study ) and more patients with hypertension ( 69 vs. 59% ) , dyslipidemia ( 78 vs. 32% ) , or family history of cad ( 30 vs. 19% ) .
another important and more relevant fact is that participants in those studies had much longer duration of diabetes ( mean duration , 710 years ) .
diabetes duration is thought to contribute significantly to cad risks , and the framingham heart study reported a 1.38-fold increased risk for cad and a 1.86-fold higher risk for cad death for each 10-year increase in diabetes duration ( 20 ) . in previous studies , much attention has been given to diabetes of an advanced stage and cad evaluation .
there is a paucity of data on coronary artery stenosis in asymptomatic diabetes that has been diagnosed for a relatively short period of time . in the current study ,
a majority of individuals in the diabetes group were newly diagnosed ( 104/134 ; 77.6% ) and the rest of diabetes cases were detected within 5 years .
these diabetic participants were found to have a 2.34-fold increased risk for significant coronary stenosis compared with ngr .
it is well - known that diabetes exists for several years before diagnosis , and thus an elevated risk of significant coronary stenosis in recently diagnosed diabetes may reflect a cumulative effect of glucose dysregulation that has been going on for years and for much longer than it had been noticed .
moreover , among diabetic patients in this study , those with significant coronary stenosis had much higher glucose and hba1c levels than those without .
glucose evaluations , i.e. , fpg , ppg , and hba1c , were found to be significant and independent risk markers for significant coronary stenosis in diabetes . although deterioration of glucose homeostasis is reflective of a longer diabetes duration , elevated levels of glucose evaluations still
were directly associated with increased risks of significant coronary stenosis in diabetes in that each 1-sd increment of glucose or hba1c level independently conveyed 1.73-fold to 2.11-fold elevated risks , adequately controlled for newly diagnosed cases and antidiabetic medications .
participants with prediabetes were found to have a significantly higher prevalence of any coronary plaques but a similar prevalence of plaques causing > 50% stenosis compared with ngr in this study .
the close relationship between prediabetes and future cad has been demonstrated by several studies ( 2123 ) .
the enhanced atherogenic risk profile in prediabetes , such as higher bmi values and greater prevalence of hypertension , together with a prediabetes glucose level , may contribute to the elevated cad prevalence in this study .
nevertheless , significant coronary stenosis as measured by cta was not increased in prediabetes and was statistically lower than that in diabetes ( 7.6 vs. 16.4% ; p = 0.027 ) .
studies investigating biomarker trajectories leading to diabetes diagnosis reported modest changes in insulin sensitivity and secretion from normal to impaired glucose tolerance but substantial decreases during further progression to diabetes , leading to abrupt and steep increases in fpg and ppg levels during the few years ( most likely 3 years ) immediately before diagnosis ( 24,25 ) .
this is consistent with our findings on homa of insulin resistance and homa -cell function in three groups with different glycemic status , and it might be one of the potential mechanisms of a markedly elevated risk for significant coronary stenosis in early diabetes compared with prediabetes .
in fact , despite glucose levels being within a normal range , 42% of these individuals were overweight or obese , 31% had hypertension , and 30% had dyslipidemia .
nearly 80% of these subjects had at least one cardiovascular risk factor , such as cigarette smoking , family history of cad , overweight / obesity , hypertension , or dyslipidemia , indicating a noteworthy overall cad risk profile in middle - aged chinese adults residing in metropolitan cities such as shanghai .
multislice ct coronary angiography recently has emerged as a powerful imaging modality for noninvasive assessment of cad . except for high diagnostic accuracy for detecting cad compared with the gold standard invasive coronary angiography ( 2628 ) , with a sensitivity of 89% , a specificity of 96% , and positive and negative predictive values of 78 and 98% , respectively ( 29 ) , cta also has been found useful in predicting future cardiac events in patients with known or suspected cad ( 3035 ) .
however , consistency is lacking regarding the use of cta in asymptomatic subjects , particularly in high - risk asymptomatic patients , such as those with diabetes .
the major concerns are unnecessary ct scan radiation , increased health care spending , and subsequent invasive cardiac procedures ( 36 ) .
however , recent advances in cta technology , such as dual - source ct coronary artery angiography , have dramatically improved spatial and temporal resolution , leading to substantial improvement in image quality and significant reduction in radiation dose and use of contrast material ( 37 )
currently , the american diabetes association consensus guidelines recommend cad screening in diabetic individuals with cardiovascular symptoms ( 38 ) .
however , our study showed a markedly increased risk for the presence of significant coronary stenosis in asymptomatic patients with diabetes , even soon after its diagnosis .
furthermore , evidence has indicated similar frequencies of cad in diabetic patients with and without angina symptoms ( 39,40 ) .
therefore , cardiac testing for asymptomatic patients with diabetes should not be considered unwarranted , especially with the latest development in ct technology , which provides satisfactory cardiac images while reducing radiation dose . meanwhile , although it could be somewhat premature to suggest that cta examination should be routinely used for patients with recently diagnosed diabetes , our findings may imply that cta screening should be used more aggressively in patients with diabetes , especially in those with additional risk factors such as dyslipidemia and hypertension .
nevertheless , whereas clinical effectiveness proves promising , cost - effectiveness is another important issue of concern before integrating cta into patient care algorithms .
it is possible that clinical outcomes may be sufficiently improved by use of cta , justifying the substantially higher spending associated with its use .
therefore , longitudinal studies comparing costs of downstream testing and treatment of cardiovascular complications in diabetes with and without use of cta are urgently needed . despite the findings and the clinical implications for cad management in asymptomatic early diabetes , this study suffers from several important limitations .
first , the sample size was relatively small and thus did not allow separate analyses by sex or stratification by cardiovascular risks and did not take menopause status into account .
second , although participants with ngr , prediabetes , or diabetes were well - matched for age and sex , other important cad risk factors such as hypertension were not considered when selecting participants .
third , coronary stenosis was classified as < 50% or 50% in this study , rather than a much detailed quantification to include severe stenosis , which is 75% narrowing of coronary artery lumen and is highly urgent for clinical intervention .
moreover , although many other cardiovascular risk factors such as smoking , hypertension , and dyslipidemia were adjusted for correlation of glucose dysregulation with significant coronary stenosis in the multivariate analyses , some residual or undetected confounding could not be ruled out . in conclusion , we used noninvasive diagnostic cta to anatomically assess subclinical cad in middle - aged community - dwelling chinese adults with different glycemic status .
we detected a markedly increased risk of significant coronary stenosis in early diabetes without clinical manifestation of myocardial ischemia .
although prediabetes is thought to be predictive of future cardiac events , it was not found to be associated with a higher risk of significant coronary stenosis .
follow - up studies are needed to investigate the long - term cardiovascular outcomes of cta - confirmed subclinical atherosclerosis in patients with diabetes .
 objective to evaluate coronary artery stenosis in early diabetes or prediabetes asymptomatic of myocardial ischemia in community - dwelling chinese adults.research design and methods age- and sex - matched participants with normal glucose regulation ( ngr ) , prediabetes , or diabetes diagnosed within 5 years , asymptomatic of coronary artery disease ( cad ) , were randomly selected from a community - dwelling chinese population aged 4060 years . 
 dual - source computed tomography coronary angiography was used to evaluate the existence and extent of coronary stenosis , which was considered significant if > 50% narrowing of vessel lumen was detected.results after excluding uninterpretable segments attributable to motion artifacts , a total of 135 participants with ngr , 132 with prediabetes , and 134 with diabetes participated in data analysis . 
 significant coronary stenosis was detected in 10 ( 7.4% ) , 10 ( 7.6% ) , and 22 ( 16.4% ) individuals with ngr , prediabetes , and diabetes , respectively ( p for trend = 0.029 ) . diabetes , rather than prediabetes , was associated with a significant 2.34-fold elevated risk [ odds ratio ( or ) 2.34 ( 95% ci 1.015.43 ) ; p = 0.047 ] of significant coronary stenosis as compared with that associated with ngr . 
 levels of glucose evaluation were independently and significantly associated with risks of significant coronary stenosis in diabetes . 
 each 1-sd increase in fasting plasma glucose , 2-h postload plasma glucose , and hba1c conveyed 2.11-fold , 1.73-fold , and 1.81-fold higher risks of significant coronary stenosis , respectively , after adjustment for other conventional cardiovascular risk factors.conclusionsusing a noninvasive cad diagnostic modality such as dual - source computed tomography coronary angiography , we detected a markedly elevated risk of significant coronary stenosis with early diabetes in asymptomatic chinese adults . 