diabetes is a growing epidemic affecting more than 346 million people worldwide ( 13 ) .
the metabolic abnormalities associated with diabetes lead to altered platelet , endothelial cell , and smooth muscle cell function ( 47 ) .
together , these changes promote systemic atherosclerosis and lead to the traditional micro- and macrovascular complications commonly observed in diabetes .
morbidity and mortality in the population with diabetes are largely due to complications of atherosclerosis .
furthermore , vascular disease in one arterial bed increases the risk for concomitant vascular disease in other arterial territories ( 8,9 ) .
vascular disease in the peripheral arteries presents a significant burden to health care expenditure and represents a major cause of myocardial infarction , stroke , and limb morbidity ( 1012 ) .
in addition , both diabetes and disease in the peripheral vasculature are associated with increased long - term mortality ( 1316 ) .
however , the peripheral neuropathy associated with diabetes masks symptoms of atherosclerosis , making the true prevalence of disease in the peripheral arteries difficult to ascertain without additional testing and presenting a challenge to early identification and prevention of disease progression ( 12,17 ) .
given the known clustering of traditional cardiovascular risk factors and coronary heart disease with diabetes , this study sought to investigate the independent association between diabetes and the presence and severity of vascular disease in the peripheral arteries . while several studies have evaluated the association between diabetes and lower extremity peripheral artery disease ( pad ) , few studies have explored carotid artery stenosis ( cas ) or abdominal aortic aneurysms ( aaa ) in populations with and without diabetes , and no study to date has evaluated the association between diabetes and all three major vascular disease subtypes in a large unselected population . in this study , we aim to evaluate the association between diabetes and the presence and severity of pad , cas , and aaa in more than 3 million subjects .
a total of 3,696,778 primarily self - referred people participated in the life line screening ( lls ; independence , ohio ) vascular survey at more than 20,000 screening sites , representing all 50 states and broad geographical and socioeconomic characteristics , between 2003 and 2008 .
as noted previously , the prevalence of different cardiovascular risk factors in this population database is similar to that of the general u.s .
census data linked by the subject s zip code , we categorized individuals based on income and education and found fairly good representation across different levels of socioeconomic status ( 19 ) .
a variety of costs was incurred by the individuals based on the package of tests purchased .
all lls sites use identical protocols and are subject to a quality control program ( 18 ) . in accord with the office for human research protections , this study is exempt from review by an institutional review board ( 20 ) .
participants completed a two - page questionnaire , providing their demographic information , height and weight , and medical and surgical history , including cardiovascular risk factors , physical activity , nutrition , and family history of cardiovascular disease .
obesity was identified as bmi 30 kg / m , and tobacco use was defined as use of at least 100 cigarettes during their lifetime and currently smoking ( current ) or not currently smoking ( former ) .
hypertension was defined as systolic blood pressure of 140 mmhg in either upper extremity or self - reported physician diagnosis or medication use .
history of coronary artery disease was defined as having a history of myocardial infarction , percutaneous coronary intervention , or coronary artery bypass graft .
presence of pad was assessed with the bilateral ankle - brachial pressure index ( abi ) , defined as systolic blood pressure in the left and right ankle ( measured in the posterior tibial artery or dorsalis pedis artery if a posterior tibial artery doppler signal was inaudible ) divided by the highest of the two systolic blood pressures in the left or right arm ( brachial artery ) . in the overall population , 5.6% ( n = 207,818 )
pad was defined as either left or right abi 0.9 or history of peripheral arterial intervention .
pad was defined as symptomatic if participants had a prior revascularization procedure or answered yes to ,  do you have aching or pain in the legs that is worse with walking or running  or 
 degree of pad was categorized as normal ( abi 0.911.4 ) , mild ( abi 0.810.90 ) , moderate ( abi 0.610.80 ) , severe ( abi 0.60 ) , or unable to compress artery ( abi > 1.4 ) ( 17 ) . presence of cas was assessed using duplex ultrasound , and in the population of interest , 2.9% ( n = 107,318 ) did not have carotid ultrasound results recorded .
symptomatic cas was defined as participants with a prior stroke , transient ischemic attack , or operation on the carotid arteries .
the degree of cas was categorized as moderate for 5069% stenosis or severe for 70% stenosis .
all participants had abdominal aortic ultrasound results recorded , and aaa was defined as presence of an infrarenal abdominal aortic diameter of 3 cm on ultrasound ( the greater of the anteroposterior or transverse measurement was used ) or prior surgical or special procedure to repair an aaa .
each individual was assigned a unique identifier , and the investigators had access only to de - identified data .
baseline characteristics and the presence of pad , cas , and aaa between participants with and without diabetes were compared using the  test for proportions and a two - sided independent sample t test for continuous variables .
odds ratios ( ors ) and 95% cis were assessed using a logistic regression model to examine the strength of association between diabetes and pad , cas , and aaa .
in addition to unadjusted or , model 1 adjusted for age , sex , and race , whereas model 2 adjusted for age , sex , race , bmi , hypertension , hyperlipidemia , tobacco use , coronary artery disease , and stroke or transient ischemic attack . in sex - specific analysis ,
the strength of association between diabetes and pad , cas , and aaa was evaluated using the logistic regression model in model 2 .
the wald test was used for testing interaction between the presence of diabetes and sex for the presence of each of the vascular disease subtypes .
chicago , il ) , sas ( version 9.12 ; sas institute inc . , cary , nc ) , and the r package ( r development core team ; available from http://www.r-project.org/ ) .
a total of 3,696,778 primarily self - referred people participated in the life line screening ( lls ; independence , ohio ) vascular survey at more than 20,000 screening sites , representing all 50 states and broad geographical and socioeconomic characteristics , between 2003 and 2008 .
as noted previously , the prevalence of different cardiovascular risk factors in this population database is similar to that of the general u.s .
census data linked by the subject s zip code , we categorized individuals based on income and education and found fairly good representation across different levels of socioeconomic status ( 19 ) .
a variety of costs was incurred by the individuals based on the package of tests purchased .
all lls sites use identical protocols and are subject to a quality control program ( 18 ) . in accord with the office for human research protections , this study is exempt from review by an institutional review board ( 20 ) .
participants completed a two - page questionnaire , providing their demographic information , height and weight , and medical and surgical history , including cardiovascular risk factors , physical activity , nutrition , and family history of cardiovascular disease .
obesity was identified as bmi 30 kg / m , and tobacco use was defined as use of at least 100 cigarettes during their lifetime and currently smoking ( current ) or not currently smoking ( former ) .
hypertension was defined as systolic blood pressure of 140 mmhg in either upper extremity or self - reported physician diagnosis or medication use .
history of coronary artery disease was defined as having a history of myocardial infarction , percutaneous coronary intervention , or coronary artery bypass graft .
presence of pad was assessed with the bilateral ankle - brachial pressure index ( abi ) , defined as systolic blood pressure in the left and right ankle ( measured in the posterior tibial artery or dorsalis pedis artery if a posterior tibial artery doppler signal was inaudible ) divided by the highest of the two systolic blood pressures in the left or right arm ( brachial artery ) . in the overall population , 5.6% ( n = 207,818 )
pad was defined as either left or right abi 0.9 or history of peripheral arterial intervention .
pad was defined as symptomatic if participants had a prior revascularization procedure or answered yes to ,  do you have aching or pain in the legs that is worse with walking or running  or 
 degree of pad was categorized as normal ( abi 0.911.4 ) , mild ( abi 0.810.90 ) , moderate ( abi 0.610.80 ) , severe ( abi 0.60 ) , or unable to compress artery ( abi > 1.4 ) ( 17 ) .
presence of cas was assessed using duplex ultrasound , and in the population of interest , 2.9% ( n = 107,318 ) did not have carotid ultrasound results recorded .
symptomatic cas was defined as participants with a prior stroke , transient ischemic attack , or operation on the carotid arteries .
the degree of cas was categorized as moderate for 5069% stenosis or severe for 70% stenosis .
all participants had abdominal aortic ultrasound results recorded , and aaa was defined as presence of an infrarenal abdominal aortic diameter of 3 cm on ultrasound ( the greater of the anteroposterior or transverse measurement was used ) or prior surgical or special procedure to repair an aaa .
each individual was assigned a unique identifier , and the investigators had access only to de - identified data .
baseline characteristics and the presence of pad , cas , and aaa between participants with and without diabetes were compared using the  test for proportions and a two - sided independent sample t test for continuous variables .
odds ratios ( ors ) and 95% cis were assessed using a logistic regression model to examine the strength of association between diabetes and pad , cas , and aaa .
in addition to unadjusted or , model 1 adjusted for age , sex , and race , whereas model 2 adjusted for age , sex , race , bmi , hypertension , hyperlipidemia , tobacco use , coronary artery disease , and stroke or transient ischemic attack . in sex - specific analysis ,
the strength of association between diabetes and pad , cas , and aaa was evaluated using the logistic regression model in model 2 .
the wald test was used for testing interaction between the presence of diabetes and sex for the presence of each of the vascular disease subtypes .
chicago , il ) , sas ( version 9.12 ; sas institute inc . , cary , nc ) , and the r package ( r development core team ; available from http://www.r-project.org/ ) .
consistent with prior observations , participants with diabetes were older , more frequently male , less frequently white , and more likely to have other cardiovascular risk factors .
subjects with vascular disease had a higher prevalence of risk factors than subjects without vascular disease .
subjects with aaa were more likely to be men and had a higher prevalence of heart disease and stroke than subjects with pad or cas ( supplementary table 1 ) . among the 3,696,778 participants in the study , 422,501 participants had any vascular disease ; 233,958 participants had pad , 193,734 participants had cas , and 73,443 participants had aaa .
participants with diabetes had a higher prevalence of any vascular disease ( unadjusted or 1.98 [ 95% ci 1.962.00 ] ; p < 0.0001 ) ( fig .
1 ) . diabetes was associated with a higher odds of pad ( unadjusted or 1.96 [ 95% ci 1.941.98 ] ; p < 0.0001 ) , cas ( unadjusted or 2.13 [ 95% ci 2.112.16 ] ; p < 0.0001 ) , and aaa ( unadjusted or 1.40 [ 95% ci 1.371.43 ] ; p < 0.0001 ) compared with those without diabetes ( table 1 ) . vascular disease in more than one peripheral vascular bed was also more common in participants with diabetes . compared with participants without diabetes ,
participants with diabetes were more likely to have peripheral vascular disease in one territory ( 15.1% vs. 9.0% ; p < 0.0001 ) , two territories ( 2.9% vs. 1.2% ; p
< 0.0001 ) , or three territories ( 0.7% vs. 0.4% ; p < 0.0001 ) ( supplementary fig .
1 ) . proportion of survey participants with lower extremity pad , cas , and aaa in the populations with and without diabetes ( dm ) .
odds of vascular disease by degree of severity in the presence of diabetes after adjustment for age , sex , race , hypertension , hyperlipidemia , smoking status , bmi , coronary artery disease , and stroke or transient ischemic attack , diabetes was significantly associated with increased odds of any vascular disease ( adjusted or 1.41 [ 95% ci 1.391.42 ] ; p < 0.0001 ) .
a significant interaction existed between diabetes and vascular disease phenotype ( p < 0.0001 ) ; diabetes was significantly associated with increased odds of pad ( adjusted or 1.42 [ 95% ci 1.411.44 ] ; p < 0.0001 ) and cas ( adjusted or 1.45 [ 95% ci 1.431.47 ] ; p < 0.0001 ) .
in contrast , after multivariable adjustment , diabetes was significantly associated with lower odds of aaa ( adjusted or 0.86 [ 95% ci 0.840.88 ] ; p < 0.001 ) ( table 1 ) .
the relationship between severity of vascular disease and diabetes across the spectrum of vascular phenotypes is shown in table 1 and fig .
the association between diabetes and pad became more pronounced with severity of disease ( adjusted ors : mild pad , 1.37 ; moderate pad , 1.77 ; severe pad , 2.16 ; p for trend < 0.001 ) .
although less striking , a similar observation was noted in cas ; the association between diabetes and cas increased with severity of disease ( adjusted or 1.53 [ 95% ci 1.501.56 ] ; p < 0.001 for moderate cas and adjusted or 1.60 [ 95% ci 1.561.63 ] ; p < 0.001 for severe cas ) . for the end point of aaa , diabetes was associated with a 20% and 25% lower odds of smaller and larger aaa , respectively ( adjusted or 0.80 [ 95% ci 0.770.83 ] ; p < 0.001 for 3- to 5-cm - diameter aneurysm and adjusted or 0.75 [ 95% ci 0.660.85 ] ; p < 0.001 for > 5-cm - diameter aneurysm ) . proportion of survey participants with lower extremity pad ( a ) , cas ( b ) , and aaa ( c ) by disease severity in the population with and without diabetes ( dm ) .
2 shows the prevalence of vascular disease stratified by symptoms in participants with and without diabetes .
participants with diabetes were more likely to have both asymptomatic disease and symptomatic disease . to minimize recall bias in our analysis , we excluded subjects with symptomatic disease .
results were not greatly altered , with increased odds of pad ( adjusted or 1.54 [ 95% ci 1.501.57 ] ; p < 0.0001 ) and cas ( adjusted or 1.57 [ 95% ci 1.551.60 ] ; p < 0.0001 ) and decreased odds of aaa ( adjusted or 0.80 [ 95% ci 0.770.83 ] ; p < 0.0001 ) .
we further investigated the association between diabetes and different phenotypes of vascular disease in women and men ( table 2 ) .
a significant association between diabetes and pad and cas was present in women and men , respectively .
diabetes was associated with a 21% decreased odds of aaa in men , but no significant association between diabetes and aaa was noted among women ( adjusted or 0.99 [ 95% ci 0.961.03 ] ; p = 0.76 ) .
consistent with prior observations , participants with diabetes were older , more frequently male , less frequently white , and more likely to have other cardiovascular risk factors .
subjects with vascular disease had a higher prevalence of risk factors than subjects without vascular disease .
subjects with aaa were more likely to be men and had a higher prevalence of heart disease and stroke than subjects with pad or cas ( supplementary table 1 ) .
among the 3,696,778 participants in the study , 422,501 participants had any vascular disease ; 233,958 participants had pad , 193,734 participants had cas , and 73,443 participants had aaa .
participants with diabetes had a higher prevalence of any vascular disease ( unadjusted or 1.98 [ 95% ci 1.962.00 ] ; p < 0.0001 ) ( fig .
diabetes was associated with a higher odds of pad ( unadjusted or 1.96 [ 95% ci 1.941.98 ] ; p < 0.0001 ) , cas ( unadjusted or 2.13 [ 95% ci 2.112.16 ] ; p < 0.0001 ) , and aaa ( unadjusted or 1.40 [ 95% ci 1.371.43 ] ; p < 0.0001 ) compared with those without diabetes ( table 1 ) .
vascular disease in more than one peripheral vascular bed was also more common in participants with diabetes . compared with participants without diabetes ,
participants with diabetes were more likely to have peripheral vascular disease in one territory ( 15.1% vs. 9.0% ; p < 0.0001 ) , two territories ( 2.9% vs. 1.2% ; p < 0.0001 ) , or three territories ( 0.7% vs. 0.4% ; p
1 ) . proportion of survey participants with lower extremity pad , cas , and aaa in the populations with and without diabetes ( dm ) .
odds of vascular disease by degree of severity in the presence of diabetes after adjustment for age , sex , race , hypertension , hyperlipidemia , smoking status , bmi , coronary artery disease , and stroke or transient ischemic attack , diabetes was significantly associated with increased odds of any vascular disease ( adjusted or 1.41 [ 95% ci 1.391.42 ] ; p < 0.0001 ) .
a significant interaction existed between diabetes and vascular disease phenotype ( p < 0.0001 ) ; diabetes was significantly associated with increased odds of pad ( adjusted or 1.42 [ 95% ci 1.411.44 ] ; p < 0.0001 ) and cas ( adjusted or 1.45 [ 95% ci 1.431.47 ] ; p < 0.0001 ) .
in contrast , after multivariable adjustment , diabetes was significantly associated with lower odds of aaa ( adjusted or 0.86 [ 95% ci 0.840.88 ] ; p < 0.001 ) ( table 1 ) .
the relationship between severity of vascular disease and diabetes across the spectrum of vascular phenotypes is shown in table 1 and fig .
2 . subjects with diabetes were more likely to have more severe pad than subjects without diabetes .
the association between diabetes and pad became more pronounced with severity of disease ( adjusted ors : mild pad , 1.37 ; moderate pad , 1.77 ; severe pad , 2.16 ; p for trend < 0.001 ) .
although less striking , a similar observation was noted in cas ; the association between diabetes and cas increased with severity of disease ( adjusted or 1.53 [ 95% ci 1.501.56 ] ; p < 0.001 for moderate cas and adjusted or 1.60 [ 95% ci 1.561.63 ] ; p < 0.001 for severe cas ) . for the end point of aaa
, diabetes was associated with a 20% and 25% lower odds of smaller and larger aaa , respectively ( adjusted or 0.80 [ 95% ci 0.770.83 ] ; p < 0.001 for 3- to 5-cm - diameter aneurysm and adjusted or 0.75 [ 95% ci 0.660.85 ] ; p < 0.001 for > 5-cm - diameter aneurysm ) . proportion of survey participants with lower extremity pad ( a ) , cas ( b ) , and aaa ( c ) by disease severity in the population with and without diabetes ( dm ) .
2 shows the prevalence of vascular disease stratified by symptoms in participants with and without diabetes .
participants with diabetes were more likely to have both asymptomatic disease and symptomatic disease . to minimize recall bias in our analysis , we excluded subjects with symptomatic disease .
results were not greatly altered , with increased odds of pad ( adjusted or 1.54 [ 95% ci 1.501.57 ] ; p < 0.0001 ) and cas ( adjusted or 1.57 [ 95% ci 1.551.60 ] ; p < 0.0001 ) and decreased odds of aaa ( adjusted or 0.80 [ 95% ci 0.770.83 ] ; p < 0.0001 ) .
we further investigated the association between diabetes and different phenotypes of vascular disease in women and men ( table 2 ) .
a significant association between diabetes and pad and cas was present in women and men , respectively .
diabetes was associated with a 21% decreased odds of aaa in men , but no significant association between diabetes and aaa was noted among women ( adjusted or 0.99 [ 95% ci 0.961.03 ] ; p = 0.76 ) .
in this large population - based analysis , all three major forms of vascular disease were significantly higher in people with diabetes compared with those without diabetes .
however , after adjustment for baseline demographics and traditional risk factors , diabetes was significantly associated with an increased odds of pad and cas but lower odds of aaa . in support of this observation , the strength of association was more pronounced with increasing severity of disease in each of the three vascular phenotypes . moreover , the positive association between diabetes and pad and cas , as well as the negative association between diabetes and aaa , remained robust in subjects with asymptomatic disease .
finally , the increased association between diabetes and pad and cas was similar in women and men ; however , diabetes was associated with lower odds of aaa in men , which was not observed in women .
the results of this study are consistent with a recent analysis of more than 40,000 men without a history of cardiovascular disease at baseline who were followed for 25 years in the prospective health professionals follow - up study , which demonstrated an independent association between diabetes and pad ( 21 ) . another study using national health and nutrition examination survey ( nhanes ) data demonstrated almost double the proportion of individuals with pad in the population with diabetes compared with the overall population ( 22 ) .
in contrast to the current study , though , the abi in the nhanes was measured using systolic blood pressure in only the right upper extremity , and the diagnosis of pad did not include history of prior lower extremity revascularization ( 22 ) . furthermore , the authors noted an increase in the proportion of individuals with pad in the elderly , non - hispanic black , and mexican american populations but did not perform adjusted analyses ( 22 ) .
our results demonstrating a significant positive association between diabetes and cas are consistent with those reported in prior smaller cohorts .
one study evaluating 1,058 patients referred for doppler ultrasonography of the carotid arteries reported a significant association between diabetes and severe cas ( or 2.77 ) in a multivariate logistic regression analysis that included age , sex , and ischemic heart disease ( 23 ) .
another small prospective study evaluated 782 subjects ( 14% with diabetes ) with high - resolution b - mode ultrasound and demonstrated a nonsignificant association between the presence of diabetes without cardiovascular disease and cas ( adjusted for age and sex : or 2.16 [ 95% ci 0.964.86 ] ; adjusted for age , sex , and cardiovascular risk factors : or 2.19 [ 95% ci 0.925.20 ] ) ( 24 ) .
unlike pad and cas , however , the odds of aaa in participants with diabetes significantly decrease after multivariate adjustment .
similar to our findings , a cross - sectional screening study of 73,451 veterans with no history of aaa demonstrated a negative association between the presence of diabetes and aaa in a multivariable model accounting for demographics and traditional cardiovascular risk factors ( or 0.68 [ 95% ci 0.600.77 ] for aaa 3.03.9 cm and or 0.54 [ 95% ci 0.440.65 ] for aaa 4.0 cm , compared with < 3.0 cm ) ( 25 ) .
consistent with these results , a report of 6,142 veterans screened for aaa demonstrated that the presence of diabetes was associated with a normal aortic size ( 26 ) .
another international , prospective , observational outpatient registry of 68,236 patients 45 years of age with established coronary , cerebral , or peripheral arterial disease or at least three vascular disease risk factors also demonstrated an inverse relationship between diabetes and aaa in a multivariate analysis ( or 0.59 [ 95% ci 0.520.66 ] ) ( 27 ) . although these studies demonstrate a lower or then that presented in the current study , the populations studied are different .
for example , the studies from the veterans affairs system consisted almost entirely of men , and we found sex differences in the association between diabetes and aaa , whereas the international registry represents a highly selective population with established vascular disease or at high risk for vascular disease .
although aaa is considered an atherosclerotic disease process ( similar to pad and cas ) , an experimental mouse model demonstrated elevated glucose concentrations to be associated with increased plasminogen activator inhibitor-1 concentrations ( concomitant with increased aneurysmal aortic pai-1 gene expression ) , reduced plasmin generation , and reduced abdominal aortic diameter , suggesting a role for the fibrinolytic pathway in aaa pathophysiology and a possible mechanism of inhibition of aaa disease in the presence of diabetes ( 28 ) .
a prospective cohort study of predominately men demonstrated the development of thicker aortic walls in diabetes , a reduction in the secretion of matrix metalloproteinase , and , thereby , reduced aortic wall stress and subsequent development of aaa ( 29 ) .
this is consistent with a recent report of 360 patients ( 96% men ) with small aaa ; the study demonstrated an inverse correlation between diabetes and aneurysm growth ( 30 ) .
it is interesting that we note a neutral association between diabetes and aaa in women .
the current study is one of the few with a large number of women ( > 2 million ) .
one report of 9,342 women did demonstrate a six - times lower prevalence of aaa in women than men but did not comment on the prevalence of aaa by diabetes status ( 31 ) .
in addition , one meta - analysis of more than 15,000 patients from 18 studies , the majority of which consisted of more than 80% men , demonstrated that female sex was not associated with aneurysm growth ; however , it did not comment on the association between female sex and the prevalence of aaa ( 32 ) .
the underlying mechanism for the sex disparities noted in the prevalence of aaa , and particularly in subjects with diabetes , needs further elucidation .
there are several limitations to this study , including those inherent to a retrospective observational study design .
first , participants were provided access to the lls measures for a fee ; therefore the cohort may underrepresent people from lower socioeconomic backgrounds .
second , the diagnosis of diabetes was based on participant self - report and was not verified by medical records .
nonetheless , we found that the prevalence of diabetes was 10.8% , which is similar to the prevalence of diabetes noted in more representative populations ( e.g. , nhanes [ 9.7% ] and 2013 american heart association heart disease and stroke statistics [ 11.8% ] ) .
third , while abi was measured during pad screening in this survey , the toe brachial pressure index could be used to establish the diagnosis of pad in people in whom pad is clinically suspected , but abi tests are unreliable because of noncompressible vessels , such as in people with long - standing diabetes or advanced age . however , this population comprises only 1.2% of the total cohort with available abi data and is therefore unlikely to have a significant effect on the differences detected .
in addition , in this study , abi was measured using the posterior tibial artery ; the dorsalis pedis artery was used only when the posterior tibial artery was inaudible .
the highest of the dorsalis pedis or posterior tibial artery pressures at the ankle traditionally is used to form the calculation ( 17 ) . however , a recent report compared this traditional method with an alternative method using the lower of the two ankle artery pressures , and both methods had similar diagnostic and predictive accuracy for all - cause and cardiovascular mortality , suggesting the utility of the alternate method in identifying a clinically meaningful population with pad ( 33 ) .
fourth , severe pad is defined in this study as abi 0.6 , whereas some definitions use abi 0.4 to define severe pad .
we did evaluate the population with abi < 0.4 and demonstrated similar results ( adjusted or 2.23 [ 95% ci 2.072.41 ] ; p < 0.001 ) .
finally , while a small percentage ( 7.5% ) of individuals did not have abi calculated , did not receive carotid ultrasound screenings , or both , subjects excluded because of incomplete data were similar to the subjects included in the final analyses . despite these limitations , this is the largest evaluation of the relationship between vascular disease in the peripheral arteries and diabetes , as well as the only study to examine all three major vascular subtypes in one cohort . in a large contemporary survey , after adjustment of demographics and traditional risk factors , the presence of diabetes is associated with higher odds of pad and cas but lower odds of aaa .
future studies exploring this difference in vascular subtype and assessing the risks versus benefits of screening for pad and cas in asymptomatic people with diabetes are needed .
there are several limitations to this study , including those inherent to a retrospective observational study design .
first , participants were provided access to the lls measures for a fee ; therefore the cohort may underrepresent people from lower socioeconomic backgrounds .
second , the diagnosis of diabetes was based on participant self - report and was not verified by medical records .
nonetheless , we found that the prevalence of diabetes was 10.8% , which is similar to the prevalence of diabetes noted in more representative populations ( e.g. , nhanes [ 9.7% ] and 2013 american heart association heart disease and stroke statistics [ 11.8% ] ) .
third , while abi was measured during pad screening in this survey , the toe brachial pressure index could be used to establish the diagnosis of pad in people in whom pad is clinically suspected , but abi tests are unreliable because of noncompressible vessels , such as in people with long - standing diabetes or advanced age . however , this population comprises only 1.2% of the total cohort with available abi data and is therefore unlikely to have a significant effect on the differences detected .
in addition , in this study , abi was measured using the posterior tibial artery ; the dorsalis pedis artery was used only when the posterior tibial artery was inaudible .
the highest of the dorsalis pedis or posterior tibial artery pressures at the ankle traditionally is used to form the calculation ( 17 ) . however , a recent report compared this traditional method with an alternative method using the lower of the two ankle artery pressures , and both methods had similar diagnostic and predictive accuracy for all - cause and cardiovascular mortality , suggesting the utility of the alternate method in identifying a clinically meaningful population with pad ( 33 ) .
fourth , severe pad is defined in this study as abi 0.6 , whereas some definitions use abi 0.4 to define severe pad .
we did evaluate the population with abi < 0.4 and demonstrated similar results ( adjusted or 2.23 [ 95% ci 2.072.41 ] ; p < 0.001 ) .
finally , while a small percentage ( 7.5% ) of individuals did not have abi calculated , did not receive carotid ultrasound screenings , or both , subjects excluded because of incomplete data were similar to the subjects included in the final analyses . despite these limitations , this is the largest evaluation of the relationship between vascular disease in the peripheral arteries and diabetes , as well as the only study to examine all three major vascular subtypes in one cohort .
in a large contemporary survey , after adjustment of demographics and traditional risk factors , the presence of diabetes is associated with higher odds of pad and cas but lower odds of aaa .
future studies exploring this difference in vascular subtype and assessing the risks versus benefits of screening for pad and cas in asymptomatic people with diabetes are needed .
 objectivethe aim of this study was to investigate the relationship between diabetes and different phenotypes of peripheral vascular disease ( lower extremity peripheral artery disease [ pad ] , carotid artery stenosis [ cas ] , and abdominal aortic aneurysm [ aaa]).research design and methodsprevalence of vascular disease was evaluated in 3,696,778 participants of the life line screening survey between 2003 and 2008 . 
 pad was defined as ankle - brachial pressure index < 0.90 or prior revascularization , cas as 50% stenosis or prior revascularization , and aaa as infrarenal aortic diameter 3 cm or prior repair . 
 odds ratios ( ors ) and 95% cis were assessed using logistic regression modeling.resultsdiabetes mellitus was present in 10.8% of participants ( n = 399,884 ) . 
 prevalence of pad , cas , and aaa was significantly higher ( p < 0.0001 ) in participants with compared with those without diabetes . 
 after multivariate adjustment for baseline demographics and clinical risk factors , a significant interaction existed between diabetes and vascular disease phenotype ( p < 0.0001 ) . 
 diabetes was associated with increased odds of pad ( or 1.42 [ 95% ci 1.411.4 ] ; p < 0.0001 ) and cas ( 1.45 [ 1.431.47 ] ; p < 0.0001 ) but decreased odds of aaa ( 0.86 [ 0.840.88 ] ; p < 0.0001 ) 
 . the strength of association increased with increasing severity of disease in each vascular phenotype , and this association persisted in the population with asymptomatic vascular disease.conclusionsin a large population - based study , the association between diabetes and vascular disease differed according to vascular phenotype . 
 future studies exploring the mechanism for these vascular - specific differences are needed . 
Introduction
Research Design and Methods
Study Population
Covariates
Vascular Disease Outcomes
Statistical Analysis
Results
Baseline Characteristics
Prevalence of Vascular Disease
Vascular Disease Severity
Sex Differences
Conclusions
Limitations
Conclusion