echocardiographic measurements were performed in 19992001 ( baseline ) and 20072009 ( follow - up ) examinations of the hoorn study .
the hoorn study is a population - based cohort study on glucose metabolism and cardiovascular diseases , previously described in detail ( 10 ) . at baseline , 290 individuals with normal glucose metabolism ( ngm ) , 187 with impaired glucose metabolism ( igm ) , and 345 with type 2 diabetes participated . at follow - up ,
167 ( 20% ) individuals were excluded a priori because of incomplete baseline data ( n = 26 ) , mental incompetence to participate ( n = 12 ) , or death ( n = 129 ) . of the remaining 655 individuals , 441 ( 67% ) participated .
thirteen ( 3% ) of those were excluded in the present analyses because of missing echocardiography data at follow - up . to restrict the study population to individuals at risk of developing lv
systolic and/or diastolic dysfunction , we also excluded 34 individuals ( 8% ) with an lv ejection fraction < 50% or an la volume index > 40 ml / m at baseline .
the local ethics committee approved the study , and written informed consent was obtained from all participants .
echocardiography was performed at baseline and follow - up with the use of an hp sonos 5500 echocardiography system ( 24 mhz transducer ) according to a standardized protocol consisting of two - dimensional , m - mode , and pulsed wave doppler assessments as previously described ( 13 ) . at follow - up , this protocol was expanded with tissue doppler assessments of mitral annular velocities .
a set of three markers of lv diastolic dysfunction was determined : la volume index , lv mass indexed to height to the power of 2.7 ( 14 ) , and the ratio of early ( e ) mitral valve flow to early ( e ) diastolic lengthening velocity ( e / e ) using tissue and pulsed wave doppler assessments .
incident heart failure was considered present if signs and symptoms were accompanied by lv systolic ( lv ejection fraction < 35% ) and/or diastolic dysfunction ( 15 ) .
presence of incident lv diastolic dysfunction ( grade 2 or 3 ) was assessed according to international recommendations ( 16 ) . in the present analyses ,
we primarily focused on previously described ultrasound - derived distensibility coefficients of carotid , brachial , and femoral arteries to assess stiffness of the arterial wall ( 10 ) .
additionally , systemic arterial compliance was determined according to the time - decay method and by calculating the ratio of stroke volume to aortic pulse pressure ( 17 ) .
augmentation index was determined using applanation tonometry . in a subset of the study population ,
carotid - femoral pulse wave velocity was approached by measuring carotid - femoral transit time , adjusted for height in the statistical analyses .
reproducibility of arterial ultrasound measurements at baseline was assessed by calculating intraobserver intersession coefficients of variation as previously described ( 10 ) . at follow - up ,
intraobserver intersession coefficients of variation in 10 individuals ( aged 70.3  3.6 years ) were comparable : 4.2 , 13.1 , 4.1 , and 6.1% for lv ejection fraction , la volume , lv mass , and e / e , respectively .
for assessment of glucose status , all participants except those with previously diagnosed diabetes underwent a standard 75-g oral glucose tolerance test and were classified into ngm , igm ( impaired fasting glucose and/or impaired glucose tolerance ) , and type 2 diabetes groups according to the 1999 world health organization criteria ( 18 ) .
health status , medical history , medication use , and smoking habits were assessed by questionnaires ( 10 ) .
waist circumference , blood pressures ( systolic , mean arterial , and pulse pressures ) , and levels of cholesterol , insulin , hba1c , and c - reactive protein were determined as previously described ( 10 ) .
descriptive statistics are presented as means  sd or , in the case of a skewed distribution , as median ( interquartile range ) .
the f test for anova in the case of continuous variables or  tests in the case of proportions were performed to test for differences between groups of glucose status . in the case of skewed distributions ,
the above tests were done on log - transformed data . for every variable that had >
10% missing data , the number missing is presented in the legends of tables 13 .
linear regression analyses , adjusted for age and sex , were performed to assess associations of glucose status and arterial stiffness with markers of lv systolic and diastolic dysfunction at follow - up .
regression models with arterial stiffness as an independent variable were subsequently adjusted for mean arterial pressure to investigate to what extent these associations were explained by elevated blood pressure .
for investigation of changes in markers , lv systolic and diastolic dysfunction according to glucose status or arterial stiffness , we adjusted all models for baseline values of these markers ( models assessing e / e adjusted for baseline la volume index ) .
lv systolic and diastolic dysfunction in type 2 diabetes and arterial stiffness might partially be due to underlying factors , like overweight , hypertension , insulin resistance , or previous cardiovascular events ( 19 ) .
therefore , we additionally analyzed which potentially underlying or mediating factors contribute to these associations and to what extent by adding these factors one by one or simultaneously to the models ( supplementary data ) .
a secondary purpose of these analyses was to investigate potential residual confounding by these factors .
product terms were entered to test for effect modification by sex or medication use at follow - up and for interactions of glucose status with arterial stiffness or prior cardiovascular disease .
associations of arterial distensibility coefficients , systemic arterial compliance , and arterial compliance coefficients were shown per lower unit to reflect associations with greater arterial stiffness .
additional analyses , adjusted for age and sex , were performed to investigate whether diabetes duration had an effect on markers of lv systolic and diastolic function .
p values < 0.05 , or < 0.10 in case of interaction analyses , were considered statistically significant .
statistical analyses were performed with spss for windows ( version 15.0 ; spss , chicago , il ) .
echocardiography was performed at baseline and follow - up with the use of an hp sonos 5500 echocardiography system ( 24 mhz transducer ) according to a standardized protocol consisting of two - dimensional , m - mode , and pulsed wave doppler assessments as previously described ( 13 ) . at follow - up , this protocol was expanded with tissue doppler assessments of mitral annular velocities .
a set of three markers of lv diastolic dysfunction was determined : la volume index , lv mass indexed to height to the power of 2.7 ( 14 ) , and the ratio of early ( e ) mitral valve flow to early ( e ) diastolic lengthening velocity ( e / e ) using tissue and pulsed wave doppler assessments .
incident heart failure was considered present if signs and symptoms were accompanied by lv systolic ( lv ejection fraction < 35% ) and/or diastolic dysfunction ( 15 ) .
presence of incident lv diastolic dysfunction ( grade 2 or 3 ) was assessed according to international recommendations ( 16 ) .
in the present analyses , we primarily focused on previously described ultrasound - derived distensibility coefficients of carotid , brachial , and femoral arteries to assess stiffness of the arterial wall ( 10 ) .
additionally , systemic arterial compliance was determined according to the time - decay method and by calculating the ratio of stroke volume to aortic pulse pressure ( 17 ) .
augmentation index was determined using applanation tonometry . in a subset of the study population ,
carotid - femoral pulse wave velocity was approached by measuring carotid - femoral transit time , adjusted for height in the statistical analyses .
reproducibility of arterial ultrasound measurements at baseline was assessed by calculating intraobserver intersession coefficients of variation as previously described ( 10 ) . at follow - up ,
intraobserver intersession coefficients of variation in 10 individuals ( aged 70.3  3.6 years ) were comparable : 4.2 , 13.1 , 4.1 , and 6.1% for lv ejection fraction , la volume , lv mass , and e / e , respectively .
for assessment of glucose status , all participants except those with previously diagnosed diabetes underwent a standard 75-g oral glucose tolerance test and were classified into ngm , igm ( impaired fasting glucose and/or impaired glucose tolerance ) , and type 2 diabetes groups according to the 1999 world health organization criteria ( 18 ) .
health status , medical history , medication use , and smoking habits were assessed by questionnaires ( 10 ) .
waist circumference , blood pressures ( systolic , mean arterial , and pulse pressures ) , and levels of cholesterol , insulin , hba1c , and c - reactive protein were determined as previously described ( 10 ) .
descriptive statistics are presented as means  sd or , in the case of a skewed distribution , as median ( interquartile range ) . the f test for anova in the case of continuous variables or  tests in the case of proportions
were performed to test for differences between groups of glucose status . in the case of skewed distributions ,
the above tests were done on log - transformed data . for every variable that had >
10% missing data , the number missing is presented in the legends of tables 13 .
linear regression analyses , adjusted for age and sex , were performed to assess associations of glucose status and arterial stiffness with markers of lv systolic and diastolic dysfunction at follow - up .
regression models with arterial stiffness as an independent variable were subsequently adjusted for mean arterial pressure to investigate to what extent these associations were explained by elevated blood pressure . for investigation of changes in markers , lv systolic and diastolic dysfunction according to glucose status or arterial stiffness , we adjusted all models for baseline values of these markers ( models assessing e / e adjusted for baseline la volume index ) .
lv systolic and diastolic dysfunction in type 2 diabetes and arterial stiffness might partially be due to underlying factors , like overweight , hypertension , insulin resistance , or previous cardiovascular events ( 19 ) .
therefore , we additionally analyzed which potentially underlying or mediating factors contribute to these associations and to what extent by adding these factors one by one or simultaneously to the models ( supplementary data ) .
a secondary purpose of these analyses was to investigate potential residual confounding by these factors .
product terms were entered to test for effect modification by sex or medication use at follow - up and for interactions of glucose status with arterial stiffness or prior cardiovascular disease .
associations of arterial distensibility coefficients , systemic arterial compliance , and arterial compliance coefficients were shown per lower unit to reflect associations with greater arterial stiffness .
additional analyses , adjusted for age and sex , were performed to investigate whether diabetes duration had an effect on markers of lv systolic and diastolic function .
p values < 0.05 , or < 0.10 in case of interaction analyses , were considered statistically significant .
statistical analyses were performed with spss for windows ( version 15.0 ; spss , chicago , il ) .
a total of 394 individuals in the age range of 5087 years were included in the present analyses , 87 ( 22% ) of whom had igm and 128 ( 32% ) of whom had type 2 diabetes . compared with individuals who were not included ,
these individuals were younger and less likely to have type 2 diabetes and had more favorable levels of arterial stiffness and lv systolic and diastolic dysfunction at baseline ( data not shown ) .
individuals with type 2 diabetes were younger , had higher bmi and blood pressure , and had greater arterial stiffness and more severe lv systolic and diastolic dysfunction at baseline compared with individuals without type 2 diabetes ( table 1 ) .
heart failure incidence was not significantly different : 23 ( 21% ) in type 2 diabetes versus 15 ( 19% ) in igm and 24 ( 15% ) in ngm .
incidence of lv diastolic dysfunction grade 2 or 3 was higher with deteriorating glucose status : 88 ( 72% ) in type 2 diabetes versus 52 ( 61% ) in igm and 55 ( 31% ) in ngm .
characteristics according to glucose status the presence of type 2 diabetes was associated with more severe levels of all markers of lv systolic and diastolic dysfunction : lv ejection fraction , la volume index , lv mass index , and e / e ( table 2 ) .
after adjustment for age and sex , lv ejection fraction at follow - up was 2.98% lower in individuals with type 2 diabetes at baseline compared with that in subjects with ngm .
individuals with type 2 diabetes had a 3.71 ml / m higher la volume index , 5.86 g / m higher lv mass index , and 1.64 higher e / e. these associations were attenuated after adjustment for baseline markers of lv systolic and diastolic dysfunction , but type 2 diabetes was still significantly associated with a higher lv mass index ( 3.41 g / m ) and e / e ( 1.43 ) .
individuals with igm compared with those with ngm had a 2.93 g / m higher lv mass index , independent of baseline lv mass index .
markers of lv systolic and diastolic dysfunction at follow - up according to baseline glucose status ( ngm = reference ) associations of type 2 diabetes with markers of lv systolic and diastolic dysfunction were largely independent of blood pressure , lipid levels , renal function , c - reactive protein , and coronary artery disease ( supplementary data table a ) .
adjustment for hba1c levels or insulin resistance diminished the associations of type 2 diabetes with lv ejection fraction and la volume index .
associations between type 2 diabetes and lv mass index were attenuated after adjustment for waist circumference .
interaction analyses showed that type 2 diabetes was particularly associated with a lower lv ejection fraction in individuals with prior cvd . a longer diabetes duration ( per year )
was associated with a 0.59 ml / m higher la volume index at follow - up but not with other markers of lv systolic and diastolic function .
greater stiffness of carotid , brachial , and femoral arteries , measured as lower distensibility coefficients , was associated with higher levels of la volume index , lv mass index , and e / e ( table 3 ) .
after adjustment for age and sex , every 10  kpa lower carotid artery distensibility coefficient was associated with a 0.31 ml / m higher la volume index and a 0.58 g / m higher lv mass index .
every 10  kpa lower brachial artery distensibility coefficient was associated with a 0.43 ml / m higher la volume index and a 0.09 higher e / e. every 10  kpa lower femoral artery distensibility coefficient was associated with a 0.80 ml / m higher la volume index , a 0.91 g / m higher lv mass index , and a 0.09 higher e / e. these associations were independent of mean arterial pressure , except for associations with e / e. after adjustment for baseline markers of lv diastolic dysfunction , 10  kpa lower distensibility coefficients of carotid , brachial , and femoral arteries remained significantly associated with a 0.29 , 0.38 , and 0.73 ml / m higher la volume index , respectively .
markers of lv systolic and diastolic dysfunction at follow - up according to baseline arterial distensibility coefficients associations of femoral distensibility coefficients with markers of lv systolic and diastolic dysfunction were partly dependent on body weight and systolic blood pressure ( supplementary data table a ) .
lower compliance coefficients of brachial and femoral arteries , as well as a higher young elastic modulus or pulse pressure , were similarly associated with more severe lv diastolic dysfunction ( supplementary data table b ) .
a higher aortic augmentation index was the only marker of arterial stiffness that was significantly associated with lv systolic dysfunction : lv ejection fraction was 0.21% lower with every percentage point higher aortic augmentation index .
carotid - femoral transit time was measured in a subset of 178 individuals , and lv ejection fraction was 0.14% lower with every second shorter carotid - femoral transit time , though not significantly ( p = 0.13 ) .
there was no interaction between glucose status and arterial distensibility coefficients in their associations with lv systolic and diastolic dysfunction ( p values for interaction > 0.10 ) .
figure 1 shows the associations of glucose status and sd scores of arterial stiffness ( measured as femoral artery distensibility coefficients ) with sd scores for all four markers of lv systolic and diastolic dysfunction , adjusted for age and sex .
the right half of each histogram shows that  values hardly changed if glucose status and arterial stiffness were combined in one model .
for instance , the presence of type 2 diabetes was associated with a 0.26 sd lower lv ejection fraction after adjustment for age and sex .
after subsequent adjustment for arterial stiffness , this  value remained similar , despite a loss of statistical significance : 0.25 ( p = 0.08 ) .
associations of glucose status with la volume index , lv mass index , and e / e hardly changed either after adjustment for arterial stiffness .
furthermore , each sd higher arterial stiffness score was associated with a 0.14 sd higher la volume index after adjustment for age and sex .
after subsequent adjustment for glucose status , this  value was 0.12 ( p = 0.02 ) .
associations of arterial stiffness with lv mass index and e / e did not change significantly either after adjustment for glucose status , despite a loss of statistical significance .
standardized associations of impaired glucose metabolism ( black bars ) , type 2 diabetes ( light gray bars ) , and lower femoral artery distensibility coefficients ( dark gray bars ) with markers of lv systolic and diastolic dysfunction , adjusted for age and sex ( left half of each histogram ) and , additionally , for each other ( right half of each histogram ) . *
there was no significant effect modification by sex , use of ace inhibitors , or lipid - lowering , glucose - lowering , or blood pressure  lowering medication at follow - up on the associations of glucose status or arterial stiffness with markers of lv systolic and diastolic dysfunction ( p > 0.10 , data not shown ) .
the presence of type 2 diabetes was associated with more severe levels of all markers of lv systolic and diastolic dysfunction : lv ejection fraction , la volume index , lv mass index , and e / e ( table 2 ) .
after adjustment for age and sex , lv ejection fraction at follow - up was 2.98% lower in individuals with type 2 diabetes at baseline compared with that in subjects with ngm .
individuals with type 2 diabetes had a 3.71 ml / m higher la volume index , 5.86 g / m higher lv mass index , and 1.64 higher e / e. these associations were attenuated after adjustment for baseline markers of lv systolic and diastolic dysfunction , but type 2 diabetes was still significantly associated with a higher lv mass index ( 3.41 g / m ) and e / e ( 1.43 ) . individuals with igm compared with those with ngm had a 2.93 g / m higher lv mass index , independent of baseline lv mass index .
markers of lv systolic and diastolic dysfunction at follow - up according to baseline glucose status ( ngm = reference ) associations of type 2 diabetes with markers of lv systolic and diastolic dysfunction were largely independent of blood pressure , lipid levels , renal function , c - reactive protein , and coronary artery disease ( supplementary data table a ) .
adjustment for hba1c levels or insulin resistance diminished the associations of type 2 diabetes with lv ejection fraction and la volume index . associations between type 2 diabetes and lv mass index were attenuated after adjustment for waist circumference .
interaction analyses showed that type 2 diabetes was particularly associated with a lower lv ejection fraction in individuals with prior cvd .
a longer diabetes duration ( per year ) was associated with a 0.59 ml / m higher la volume index at follow - up but not with other markers of lv systolic and diastolic function .
greater stiffness of carotid , brachial , and femoral arteries , measured as lower distensibility coefficients , was associated with higher levels of la volume index , lv mass index , and e / e ( table 3 ) .
after adjustment for age and sex , every 10  kpa lower carotid artery distensibility coefficient was associated with a 0.31 ml / m higher la volume index and a 0.58 g / m higher lv mass index .
every 10  kpa lower brachial artery distensibility coefficient was associated with a 0.43 ml / m higher la volume index and a 0.09 higher e / e. every 10  kpa lower femoral artery distensibility coefficient was associated with a 0.80 ml / m higher la volume index , a 0.91 g / m higher lv mass index , and a 0.09 higher e / e. these associations were independent of mean arterial pressure , except for associations with e / e. after adjustment for baseline markers of lv diastolic dysfunction , 10  kpa lower distensibility coefficients of carotid , brachial , and femoral arteries remained significantly associated with a 0.29 , 0.38 , and 0.73 ml / m higher la volume index , respectively .
markers of lv systolic and diastolic dysfunction at follow - up according to baseline arterial distensibility coefficients associations of femoral distensibility coefficients with markers of lv systolic and diastolic dysfunction were partly dependent on body weight and systolic blood pressure ( supplementary data table a ) .
lower compliance coefficients of brachial and femoral arteries , as well as a higher young elastic modulus or pulse pressure , were similarly associated with more severe lv diastolic dysfunction ( supplementary data table b ) .
a higher aortic augmentation index was the only marker of arterial stiffness that was significantly associated with lv systolic dysfunction : lv ejection fraction was 0.21% lower with every percentage point higher aortic augmentation index .
carotid - femoral transit time was measured in a subset of 178 individuals , and lv ejection fraction was 0.14% lower with every second shorter carotid - femoral transit time , though not significantly ( p = 0.13 ) .
there was no interaction between glucose status and arterial distensibility coefficients in their associations with lv systolic and diastolic dysfunction ( p values for interaction > 0.10 ) .
figure 1 shows the associations of glucose status and sd scores of arterial stiffness ( measured as femoral artery distensibility coefficients ) with sd scores for all four markers of lv systolic and diastolic dysfunction , adjusted for age and sex .
the right half of each histogram shows that  values hardly changed if glucose status and arterial stiffness were combined in one model .
for instance , the presence of type 2 diabetes was associated with a 0.26 sd lower lv ejection fraction after adjustment for age and sex .
after subsequent adjustment for arterial stiffness , this  value remained similar , despite a loss of statistical significance : 0.25 ( p = 0.08 ) .
associations of glucose status with la volume index , lv mass index , and e / e hardly changed either after adjustment for arterial stiffness . furthermore , each sd higher arterial stiffness score was associated with a 0.14 sd higher la volume index after adjustment for age and sex .
after subsequent adjustment for glucose status , this  value was 0.12 ( p = 0.02 ) .
associations of arterial stiffness with lv mass index and e / e did not change significantly either after adjustment for glucose status , despite a loss of statistical significance .
standardized associations of impaired glucose metabolism ( black bars ) , type 2 diabetes ( light gray bars ) , and lower femoral artery distensibility coefficients ( dark gray bars ) with markers of lv systolic and diastolic dysfunction , adjusted for age and sex ( left half of each histogram ) and , additionally , for each other ( right half of each histogram ) .
there was no significant effect modification by sex , use of ace inhibitors , or lipid - lowering , glucose - lowering , or blood pressure  lowering medication at follow - up on the associations of glucose status or arterial stiffness with markers of lv systolic and diastolic dysfunction ( p > 0.10 , data not shown ) .
this study shows that both glucose status and arterial distensibility coefficients were prospectively associated with more severe lv diastolic dysfunction .
furthermore , associations of glucose status and arterial stiffness with lv diastolic dysfunction were largely independent of each other and indicated a deterioration of lv diastolic dysfunction compared with baseline .
strengths include the population - based design and comprehensive assessment of glucose status , arterial stiffness , and lv systolic and diastolic dysfunction .
these data provide a unique insight into many different aspects of arterial stiffness and their influence on lv systolic and diastolic dysfunction .
lv diastolic dysfunction at baseline was therefore based on la volume index only , and this might have been subject to some misclassification .
furthermore , differences between attendees and nonattendees suggest that a  healthy cohort bias  may have occurred in this study .
we also had missing data for some echocardiographic markers , predominantly in individuals with high bmi .
our findings that lv systolic and diastolic dysfunction was more severe in type 2 diabetic patients than in individuals with ngm are in line with previous data reporting associations between glucose metabolism and lv systolic and diastolic dysfunction ( 20,21 ) . the type 2 diabetes  associated lv diastolic dysfunction at follow - up could not completely be explained by an already more severe lv diastolic dysfunction at baseline .
these results imply that lv diastolic dysfunction deteriorates more in individuals with than in those without type 2 diabetes .
there was a trend toward more severe lv systolic and diastolic dysfunction in individuals with igm as well , but this was not statistically significant .
individuals with a longer duration of type 2 diabetes appeared to have a higher la volume index at follow - up .
peripheral markers of arterial stiffness , like arterial distensibility and compliance coefficients , and brachial pulse pressure were most consistently associated with markers of lv diastolic dysfunction .
associations of arterial distensibility coefficients with lv diastolic dysfunction were not due to elevated blood pressure , since adjustment for mean arterial pressure only resulted in a small reduction of the associations .
associations of arterial distensibility coefficients with la volume index and e / e at follow - up were largely independent of baseline la volume index .
this might imply that 1 ) arterial stiffness precedes deterioration of lv diastolic dysfunction or 2 ) stiffening of arteries and lv walls occurs simultaneously .
the first might be due to arterial wave reflections that lead to an increased lv load and decreased coronary perfusion ( 6 ) .
the second might be due to coinciding structural changes in arterial and lv walls ( 9 ) . in the current study
, wave reflections seemed especially harmful to lv systolic function , since augmentation index was the only marker of arterial stiffness that was significantly associated with lv ejection fraction , followed by carotid - femoral transit time .
lv diastolic dysfunction seemed to be more coherent to peripheral artery stiffening than to central artery stiffness .
this might support the second theory : that stiffening of arteries and lv walls occurs simultaneously .
type 2 diabetes and arterial stiffness were largely independently associated with lv systolic and diastolic dysfunction in the current study .
more severe lv systolic and diastolic dysfunction in type 2 diabetes therefore can not be explained or can or just partly be explained by increased arterial stiffness
. other mechanisms that might play a role in the development of lv systolic and diastolic dysfunction in type 2 diabetes include an altered cardiac metabolism or increased stiffening of the lv due to myocardial fibrosis or an elevated cardiomyocyte resting tension ( 11,2224 ) .
this might be reflected by the lowered associations between type 2 diabetes and markers of lv systolic and diastolic dysfunction after adjustment for hba1c .
overweight and obesity are known to be associated with a higher lv mass index , and indeed , waist circumference seemed to play a role in type 2 diabetes  related higher lv mass index ( 25 ) .
lv systolic function was particularly worsened in type 2 diabetic patients with prior cardiovascular disease . since individuals with type 2 diabetes already had a worse cardiovascular profile at baseline , the influence of changes in cardiovascular risk factors earlier in life on lv systolic and diastolic dysfunction may also be worth examining .
to conclude , the presence of type 2 diabetes and the presence of arterial stiffness are both associated with deterioration of lv diastolic dysfunction .
it is likely that type 2 diabetes and arterial stiffness relate to lv diastolic dysfunction through different pathways , since these associations were independent of each other .
a better understanding of the mechanisms behind those different pathways in changes in lv diastolic dysfunction could help identify targets for prevention of heart failure .
our findings that lv systolic and diastolic dysfunction was more severe in type 2 diabetic patients than in individuals with ngm are in line with previous data reporting associations between glucose metabolism and lv systolic and diastolic dysfunction ( 20,21 ) . the type 2 diabetes  associated lv diastolic dysfunction at follow - up could not completely be explained by an already more severe lv diastolic dysfunction at baseline .
these results imply that lv diastolic dysfunction deteriorates more in individuals with than in those without type 2 diabetes .
there was a trend toward more severe lv systolic and diastolic dysfunction in individuals with igm as well , but this was not statistically significant .
individuals with a longer duration of type 2 diabetes appeared to have a higher la volume index at follow - up .
peripheral markers of arterial stiffness , like arterial distensibility and compliance coefficients , and brachial pulse pressure were most consistently associated with markers of lv diastolic dysfunction .
associations of arterial distensibility coefficients with lv diastolic dysfunction were not due to elevated blood pressure , since adjustment for mean arterial pressure only resulted in a small reduction of the associations .
associations of arterial distensibility coefficients with la volume index and e / e at follow - up were largely independent of baseline la volume index .
this might imply that 1 ) arterial stiffness precedes deterioration of lv diastolic dysfunction or 2 ) stiffening of arteries and lv walls occurs simultaneously .
the first might be due to arterial wave reflections that lead to an increased lv load and decreased coronary perfusion ( 6 ) .
the second might be due to coinciding structural changes in arterial and lv walls ( 9 ) . in the current study
, wave reflections seemed especially harmful to lv systolic function , since augmentation index was the only marker of arterial stiffness that was significantly associated with lv ejection fraction , followed by carotid - femoral transit time .
lv diastolic dysfunction seemed to be more coherent to peripheral artery stiffening than to central artery stiffness .
this might support the second theory : that stiffening of arteries and lv walls occurs simultaneously .
type 2 diabetes and arterial stiffness were largely independently associated with lv systolic and diastolic dysfunction in the current study .
more severe lv systolic and diastolic dysfunction in type 2 diabetes therefore can not be explained or can or just partly be explained by increased arterial stiffness
. other mechanisms that might play a role in the development of lv systolic and diastolic dysfunction in type 2 diabetes include an altered cardiac metabolism or increased stiffening of the lv due to myocardial fibrosis or an elevated cardiomyocyte resting tension ( 11,2224 ) .
this might be reflected by the lowered associations between type 2 diabetes and markers of lv systolic and diastolic dysfunction after adjustment for hba1c .
overweight and obesity are known to be associated with a higher lv mass index , and indeed , waist circumference seemed to play a role in type 2 diabetes  related higher lv mass index ( 25 ) .
lv systolic function was particularly worsened in type 2 diabetic patients with prior cardiovascular disease . since individuals with type 2 diabetes already had a worse cardiovascular profile at baseline , the influence of changes in cardiovascular risk factors earlier in life on lv systolic and diastolic dysfunction may also be worth examining .
to conclude , the presence of type 2 diabetes and the presence of arterial stiffness are both associated with deterioration of lv diastolic dysfunction .
it is likely that type 2 diabetes and arterial stiffness relate to lv diastolic dysfunction through different pathways , since these associations were independent of each other .
a better understanding of the mechanisms behind those different pathways in changes in lv diastolic dysfunction could help identify targets for prevention of heart failure .
 objectiveto investigate relative contributions of glucose status and arterial stiffness to markers of left ventricular ( lv ) systolic and diastolic dysfunction after 8 years of follow-up.research design and methodsin the population - based prospective hoorn study , 394 individuals with preserved lv systolic and diastolic function participated , of whom 87 had impaired glucose metabolism and 128 had type 2 diabetes . 
 measurements including arterial ultrasound and echocardiography were performed according to standardized protocols.resultsthe presence of type 2 diabetes was associated with more severe lv systolic and diastolic dysfunction 8 years later : lv ejection fraction was 2.98% ( 95% ci 0.465.51 ) lower , and left atrial ( la ) volume index , lv mass index , and tissue doppler - derived e / e were 3.71 ml / m2 ( 1.206.22 ) , 5.86 g / m2.7 ( 2.948.78 ) , and 1.64 units ( 0.952.33 ) higher , respectively . 
 furthermore , presence of impaired glucose metabolism or type 2 diabetes was associated with 8-year increases in lv mass index . 
 more arterial stiffness ( measured as a lower distensibility ) was associated with lv diastolic dysfunction 8 years later : la volume index , lv mass index , and e / e at follow - up were higher . 
 subsequent adjustments for baseline mean arterial pressure and/or lv diastolic dysfunction did not eliminate these associations . 
 associations of type 2 diabetes and arterial stiffness with markers of lv diastolic dysfunction were largely independent of each other.conclusionsboth glucose status and arterial distensibility are independently associated with more severe lv diastolic dysfunction 8 years later and with deterioration of lv diastolic dysfunction . 
 therefore , type 2 diabetes and arterial stiffness may relate to lv diastolic dysfunction through different pathways . 