this retrospective observational study was conducted using electronic medical records from the south central veterans affairs health care network ( visn 16 ) , one of the largest of the 23 visns in the veterans health administration ( vha ) .
the vha is a national integrated health care system providing a set of comprehensive services to veterans . as of 2010
the visn 16 data warehouse is an integrated , de - identified , individual - level database representing 7.8% of u.s .
veterans and covers a geographic region of 170,000 square miles , including the states of arkansas , louisiana , mississippi , and oklahoma , and parts of alabama , florida , missouri , and texas .
it includes records for > 445,000 veterans from 10 medical centers and 40 outpatient clinics , with information regarding demographics , vital signs , laboratory results , diagnoses , procedures , inpatient and outpatient services ( e.g. , admission date , length of stay , and emergency room visits ) , drug prescriptions , and database enrollment history .
as in the national vha population , patients in visn 16 are predominantly male ( 90.1% ) .
the study protocol was approved by the institutional review board and research and development committee of the southeast louisiana veterans health care systems .
adult patients ( 18 years of age ) were included in the study if they had two or more diagnoses of t2 dm between 1 january 2004 and 30 june 2010 .
patients had at least one measurement of hba1c and ldl - c within 30 days of each other ( paired measurements ) after the first diabetes diagnosis ; the earlier date of the hba1c or ldl - c measurement was defined as the index date .
all patients were further required to have at least one more measurement of hba1c and ldl - c within 1 year after the index date , irrespective of the gap between the measurements .
the final sample included patients who were enrolled in the database for at least 12 months after the index date .
average hba1c and ldl - c levels were estimated for each cycle using the area under the curve method ( 24,25 ) . for each cycle , these estimated averages were used to stratify patients into one of four goal achievement categories : dual goal ( average hba1c < 7% [ 53 mmol / mol ] and average ldl - c < 100 mg / dl ) , hba1c only ( average hba1c < 7% [ 53 mmol / mol ] and average ldl - c 100 mg / dl ) , ldl - c only ( average ldl - c < 100 mg / dl and average hba1c 7% [ 53 mmol / mol ] ) , or no goal ( average hba1c 7% [ 53 mmol / mol ] and average ldl - c 100 mg / dl ) .
patient characteristics as of the first cycle were summarized for the overall population , as well as stratified according to goal achievement status .
demographic information included age on index date , sex , race , bmi , and year of index date .
the history of diabetes - related complications ( microvascular , macrovascular , and other ) , comorbidities , and surgical procedures was identified as of the first cycle using icd-9 , clinical modification ( icd-9-cm ) codes .
medication use during the first cycle was categorized by drug therapeutic class ; health care resource utilization during the first cycle was categorized by hospitalization days and outpatient visits .
characteristics were compared across the four groups according to goal achievement status using the anova method for continuous variables and  tests for categorical variables .
clinical outcomes were selected a priori and comprised 1 ) a composite cardiovascular - related end point ( cerebrovascular disease [ stroke ] , acute myocardial infarction , or cardiovascular death [ defined by a diagnosis of coronary artery disease or cerebrovascular disease on the day of death ] ) , 2 ) a composite end point for microvascular complications ( diabetic retinopathy , nephropathy , or neuropathy ) , 3 ) acute coronary syndromes ( acs ; acute myocardial infarction or unstable angina ) , and 4 ) cardiovascular procedures ( percutaneous coronary intervention [ pci ] or coronary artery bypass graft [ cabg ] ) .
for each clinical outcome , goal achievement and patient characteristics were measured in a given cycle and outcomes were assessed for the following cycle .
the time to the first clinical event was evaluated using a cox proportional hazards model , with goal achievement status as a time - dependent variable , controlling for patient demographics and other potential confounding factors such as cumulative comorbidity history , resource utilization , and medication use .
all clinical outcomes were measured from the start of the second cycle until the first event , death , or end of data ; for the analyses of specific clinical outcomes , patients were excluded from the analysis if any clinical event defining the particular outcome occurred before the end of the first cycle .
the numbers of diabetes - related hospitalization days and outpatient visits were estimated for each 6-month cycle .
diabetes - related medical service costs were measured in each cycle using the average cost method ( 26 ) .
dollars according to the medical care services component of the consumer price index ( 27,28 ) . utilization and costs were considered diabetes related if they were associated with diagnoses of any of the following : diabetes , macrovascular complications , or microvascular complications .
the associations between goal achievement status in a given study cycle and utilization in the following cycle were assessed using generalized linear regression models ( glms ) with a poisson distribution ; results are reported as adjusted incidence rate ratios with 95% cis .
the associations between goal achievement status in a given cycle and costs in the following cycle were assessed using glms with a  distribution , and adjusted results are reported as annualized incremental cost differences .
all longitudinal glms accounted for within - patient correlation using a generalized estimating equation approach and controlled for demographics and time - dependent variables such as cumulative comorbidity history , resource utilization , and medication use .
sas software version 9.2 was used to conduct statistical analyses , and a two - tailed  level of 0.05 was used to determine statistical significance .
this retrospective observational study was conducted using electronic medical records from the south central veterans affairs health care network ( visn 16 ) , one of the largest of the 23 visns in the veterans health administration ( vha ) .
the vha is a national integrated health care system providing a set of comprehensive services to veterans . as of 2010
the visn 16 data warehouse is an integrated , de - identified , individual - level database representing 7.8% of u.s .
veterans and covers a geographic region of 170,000 square miles , including the states of arkansas , louisiana , mississippi , and oklahoma , and parts of alabama , florida , missouri , and texas .
it includes records for > 445,000 veterans from 10 medical centers and 40 outpatient clinics , with information regarding demographics , vital signs , laboratory results , diagnoses , procedures , inpatient and outpatient services ( e.g. , admission date , length of stay , and emergency room visits ) , drug prescriptions , and database enrollment history .
as in the national vha population , patients in visn 16 are predominantly male ( 90.1% ) .
the study protocol was approved by the institutional review board and research and development committee of the southeast louisiana veterans health care systems .
adult patients ( 18 years of age ) were included in the study if they had two or more diagnoses of t2 dm between 1 january 2004 and 30 june 2010 .
patients had at least one measurement of hba1c and ldl - c within 30 days of each other ( paired measurements ) after the first diabetes diagnosis ; the earlier date of the hba1c or ldl - c measurement was defined as the index date .
all patients were further required to have at least one more measurement of hba1c and ldl - c within 1 year after the index date , irrespective of the gap between the measurements .
the final sample included patients who were enrolled in the database for at least 12 months after the index date .
average hba1c and ldl - c levels were estimated for each cycle using the area under the curve method ( 24,25 ) . for each cycle , these estimated averages were used to stratify patients into one of four goal achievement categories : dual goal ( average hba1c < 7% [ 53 mmol / mol ] and average ldl - c < 100 mg / dl ) , hba1c only ( average hba1c < 7% [ 53 mmol / mol ] and average ldl - c 100 mg / dl ) , ldl - c only ( average ldl - c < 100 mg / dl and average hba1c 7% [ 53 mmol / mol ] ) , or no goal ( average hba1c 7% [ 53 mmol / mol ] and average ldl - c 100 mg / dl ) .
patient characteristics as of the first cycle were summarized for the overall population , as well as stratified according to goal achievement status .
demographic information included age on index date , sex , race , bmi , and year of index date .
the history of diabetes - related complications ( microvascular , macrovascular , and other ) , comorbidities , and surgical procedures was identified as of the first cycle using icd-9 , clinical modification ( icd-9-cm ) codes .
medication use during the first cycle was categorized by drug therapeutic class ; health care resource utilization during the first cycle was categorized by hospitalization days and outpatient visits .
characteristics were compared across the four groups according to goal achievement status using the anova method for continuous variables and  tests for categorical variables .
clinical outcomes were selected a priori and comprised 1 ) a composite cardiovascular - related end point ( cerebrovascular disease [ stroke ] , acute myocardial infarction , or cardiovascular death [ defined by a diagnosis of coronary artery disease or cerebrovascular disease on the day of death ] ) , 2 ) a composite end point for microvascular complications ( diabetic retinopathy , nephropathy , or neuropathy ) , 3 ) acute coronary syndromes ( acs ; acute myocardial infarction or unstable angina ) , and 4 ) cardiovascular procedures ( percutaneous coronary intervention [ pci ] or coronary artery bypass graft [ cabg ] ) . for each clinical outcome , goal achievement and patient characteristics were measured in a given cycle and outcomes were assessed for the following cycle .
the time to the first clinical event was evaluated using a cox proportional hazards model , with goal achievement status as a time - dependent variable , controlling for patient demographics and other potential confounding factors such as cumulative comorbidity history , resource utilization , and medication use .
all clinical outcomes were measured from the start of the second cycle until the first event , death , or end of data ; for the analyses of specific clinical outcomes , patients were excluded from the analysis if any clinical event defining the particular outcome occurred before the end of the first cycle .
the numbers of diabetes - related hospitalization days and outpatient visits were estimated for each 6-month cycle .
diabetes - related medical service costs were measured in each cycle using the average cost method ( 26 ) .
dollars according to the medical care services component of the consumer price index ( 27,28 ) . utilization and costs were considered diabetes related if they were associated with diagnoses of any of the following : diabetes , macrovascular complications , or microvascular complications .
the associations between goal achievement status in a given study cycle and utilization in the following cycle were assessed using generalized linear regression models ( glms ) with a poisson distribution ; results are reported as adjusted incidence rate ratios with 95% cis .
the associations between goal achievement status in a given cycle and costs in the following cycle were assessed using glms with a  distribution , and adjusted results are reported as annualized incremental cost differences .
all longitudinal glms accounted for within - patient correlation using a generalized estimating equation approach and controlled for demographics and time - dependent variables such as cumulative comorbidity history , resource utilization , and medication use .
sas software version 9.2 was used to conduct statistical analyses , and a two - tailed  level of 0.05 was used to determine statistical significance .
of the 149,613 patients with at least two recorded diagnoses of t2 dm between 1 january 2004 and 30 june 2010 , a total of 75,646 patients met the selection criteria and were included in the analysis .
as shown in table 1 , as of the index date , most patients were older than 55 years ( 84.1% ; mean age 64.7 years ) and had an average bmi of 31.6 kg / m .
almost all patients were men ( 97.4% ) , and approximately two in three were white ( 67.4% ) . during the first cycle , 35.1% of patients achieved both goals ( dual - goal achievers ) , whereas 21.6% achieved only the ldl - c goal ( ldl - c achievers ) , 24.6% achieved only the hba1c goal ( hba1c achievers ) , and 18.6% did not achieve either goal ( no - goal achievers ) ( table 1 ) . compared with all other groups , dual - goal achievers were older ( 67.1 vs. 61.464.4 years ) .
rates of microvascular complications were lower for dual - goal ( 24.1% ) and hba1c achievers ( 22.4% ) than for ldl - c ( 33.0% ) and no - goal achievers ( 30.2% ) ; similar differences were observed for the usage of insulin ( 10.4 and 7.5% vs. 34.6 and 30.1% , respectively ) and oral antidiabetic drugs ( 67.4 and 64.0% vs. 82.2 and 82.7% , respectively ) . a higher rate of macrovascular complications was observed among dual - goal ( 47.4% ) and ldl - c achievers ( 45.6% ) than among hba1c ( 33.8% ) and no - goal achievers ( 33.9% ) ( table 1 ) .
patient baseline characteristics , demographics , comorbidities , complications , medications , and resource use the median duration of follow - up time was 4.5 years from the index date . after adjusting for demographics , diabetes - related complications , comorbidities , surgical procedures , diabetic medication use , and health care utilization , dual - goal achievement , when compared with achievement of ldl - c goal alone ,
was associated with a significantly reduced risk of microvascular complications ( adjusted hazard ratio 0.79 [ 95% ci 0.760.82 ] ) , acs ( 0.88 [ 0.810.96 ] ) , pci ( 0.78 [ 0.670.90 ] ) , and cabg ( 0.74 [ 0.600.92 ] ) , but not of the composite cardiovascular - related end point ( 1.00 [ 0.941.06 ] ) ( fig .
dual - goal achievement was associated with a lower risk of cabg ( 0.62 [ 0.490.79 ] ) and the composite cardiovascular end point ( 0.87 [ 0.810.93 ] ) .
dual , patients achieving both ldl - c and hba1c goals ; hba1c , patients achieving only the hba1c goal ; ldl - c , patients achieving only the ldl - c goal ; none , patients achieving neither goal ( see text for details ) . compared with no - goal achievers , dual - goal achievers had a significant 1930% lower hazard of the cardiovascular end point or diabetes - related microvascular or acs - related events , and a 4549% lower hazard of undergoing pci or cabg .
in addition , relative to no - goal achievers , both groups of single - goal achievers had significant reductions in hazard for all categories of complications and surgical procedures , except microvascular complications among ldl - c achievers . after controlling for demographics , diabetes - related complications , comorbidities , surgical procedures , diabetic medication use , and health care utilization ,
dual - goal achievers generally used less health care resources compared with single- or no - goal achievers ( fig .
2 ) . in particular , compared with ldl - c achievers , dual - goal achievers had significantly fewer hospitalization days ( adjusted incidence rate ratio 0.93 [ 95% ci 0.871.00 ] ) and outpatient visits ( 0.88 [ 0.870.89 ] ) . compared with hba1c achievers , dual - goal achievers had significantly fewer outpatient visits ( 0.98 [ 0.971.00 ] ) , but there was no statistical difference in the number of hospitalization days ( 0.98 [ 0.891.07 ] ) . compared with no - goal achievers , dual - goal achievers had significantly fewer hospitalization days ( 0.81 [ 0.720.90 ] ) and outpatient visits ( 0.86 [ 0.850.87 ] ) . similarly , both groups of single - goal achievers also had significantly fewer hospitalization days ( ldl - c achievers , 0.87 [ 0.780.96 ] ; hba1c achievers , 0.83 [ 0.730.94 ] ) and outpatient visits ( ldl - c achievers , 0.98 [ 0.960.99 ] ; hba1c achievers , 0.87 [ 0.860.89 ] ) than patients who did not achieve either goal .
dual , patients achieving both ldl - c and hba1c goals ; hba1c , patients achieving only the hba1c goal ; ldl - c , patients achieving only the ldl - c goal ; none , patients achieving neither goal . *
p < 0.05 ; * * p < 0.01 ; * * * p < 0.001 . after adjusting for demographics , diabetes - related complications , comorbidities , surgical procedures , diabetic medication use , and health care utilization , dual - goal achievers incurred significantly lower annualized diabetes - related medical service costs compared with those who achieved only the ldl - c goal ( $130.89 ; p = 0.016 ) , but no statistically significant difference was observed between dual - goal achievers and hba1c goal achievers ( $56.17 ; p = 0.404 ) ( fig .
diabetes - related medical service costs were significantly lower for dual - goal ( $376.50 ; p < 0.001 ) , ldl - c ( $245.61 ; p < 0.001 ) , and hba1c achievers ( $320.32 ; p < 0.001 ) compared with those who did not achieve either goal .
dual , patients achieving both ldl - c and hba1c goals ; hba1c , patients achieving only the hba1c goal ; ldl - c , patients achieving only the ldl - c goal ; none , patients achieving neither goal .
of the 149,613 patients with at least two recorded diagnoses of t2 dm between 1 january 2004 and 30 june 2010 , a total of 75,646 patients met the selection criteria and were included in the analysis .
as shown in table 1 , as of the index date , most patients were older than 55 years ( 84.1% ; mean age 64.7 years ) and had an average bmi of 31.6 kg / m .
almost all patients were men ( 97.4% ) , and approximately two in three were white ( 67.4% ) . during the first cycle , 35.1% of patients achieved both goals ( dual - goal achievers ) , whereas 21.6% achieved only the ldl - c goal ( ldl - c achievers ) , 24.6% achieved only the hba1c goal ( hba1c achievers ) , and 18.6% did not achieve either goal ( no - goal achievers ) ( table 1 ) . compared with all other groups , dual - goal achievers were older ( 67.1 vs. 61.464.4 years ) .
rates of microvascular complications were lower for dual - goal ( 24.1% ) and hba1c achievers ( 22.4% ) than for ldl - c ( 33.0% ) and no - goal achievers ( 30.2% ) ; similar differences were observed for the usage of insulin ( 10.4 and 7.5% vs. 34.6 and 30.1% , respectively ) and oral antidiabetic drugs ( 67.4 and 64.0% vs. 82.2 and 82.7% , respectively ) . a higher rate of macrovascular complications was observed among dual - goal ( 47.4% ) and ldl - c achievers ( 45.6% ) than among hba1c ( 33.8% ) and no - goal achievers ( 33.9% ) ( table 1 ) .
the median duration of follow - up time was 4.5 years from the index date . after adjusting for demographics , diabetes - related complications , comorbidities , surgical procedures , diabetic medication use , and health care utilization , dual - goal achievement , when compared with achievement of ldl - c goal alone ,
was associated with a significantly reduced risk of microvascular complications ( adjusted hazard ratio 0.79 [ 95% ci 0.760.82 ] ) , acs ( 0.88 [ 0.810.96 ] ) , pci ( 0.78 [ 0.670.90 ] ) , and cabg ( 0.74 [ 0.600.92 ] ) , but not of the composite cardiovascular - related end point ( 1.00 [ 0.941.06 ] ) ( fig .
dual - goal achievement was associated with a lower risk of cabg ( 0.62 [ 0.490.79 ] ) and the composite cardiovascular end point ( 0.87 [ 0.810.93 ] ) .
dual , patients achieving both ldl - c and hba1c goals ; hba1c , patients achieving only the hba1c goal ; ldl - c , patients achieving only the ldl - c goal ; none , patients achieving neither goal ( see text for details ) . compared with no - goal achievers , dual - goal achievers had a significant 1930% lower hazard of the cardiovascular end point or diabetes - related microvascular or acs - related events , and a 4549% lower hazard of undergoing pci or cabg .
in addition , relative to no - goal achievers , both groups of single - goal achievers had significant reductions in hazard for all categories of complications and surgical procedures , except microvascular complications among ldl - c achievers .
after controlling for demographics , diabetes - related complications , comorbidities , surgical procedures , diabetic medication use , and health care utilization , dual - goal achievers generally used less health care resources compared with single- or no - goal achievers ( fig .
2 ) . in particular , compared with ldl - c achievers , dual - goal achievers had significantly fewer hospitalization days ( adjusted incidence rate ratio 0.93 [ 95% ci 0.871.00 ] ) and outpatient visits ( 0.88 [ 0.870.89 ] ) . compared with hba1c achievers , dual - goal achievers had significantly fewer outpatient visits ( 0.98 [ 0.971.00 ] ) , but there was no statistical difference in the number of hospitalization days ( 0.98 [ 0.891.07 ] ) . compared with no - goal achievers , dual - goal achievers had significantly fewer hospitalization days ( 0.81 [ 0.720.90 ] ) and outpatient visits ( 0.86 [ 0.850.87 ] ) .
similarly , both groups of single - goal achievers also had significantly fewer hospitalization days ( ldl - c achievers , 0.87 [ 0.780.96 ] ; hba1c achievers , 0.83 [ 0.730.94 ] ) and outpatient visits ( ldl - c achievers , 0.98 [ 0.960.99 ] ; hba1c achievers , 0.87 [ 0.860.89 ] ) than patients who did not achieve either goal .
dual , patients achieving both ldl - c and hba1c goals ; hba1c , patients achieving only the hba1c goal ; ldl - c , patients achieving only the ldl - c goal ; none , patients achieving neither goal .
* p < 0.05 ; * * p < 0.01 ; * * * p < 0.001 .
after adjusting for demographics , diabetes - related complications , comorbidities , surgical procedures , diabetic medication use , and health care utilization , dual - goal achievers incurred significantly lower annualized diabetes - related medical service costs compared with those who achieved only the ldl - c goal ( $130.89 ; p = 0.016 ) , but no statistically significant difference was observed between dual - goal achievers and hba1c goal achievers ( $56.17 ; p = 0.404 ) ( fig .
diabetes - related medical service costs were significantly lower for dual - goal ( $376.50 ; p < 0.001 ) , ldl - c ( $245.61 ; p < 0.001 ) , and hba1c achievers ( $320.32 ; p < 0.001 ) compared with those who did not achieve either goal .
dual , patients achieving both ldl - c and hba1c goals ; hba1c , patients achieving only the hba1c goal ; ldl - c , patients achieving only the ldl - c goal ; none , patients achieving neither goal . *
the study results showed that , compared with the achievement of only the ldl - c goal , achievement of both hba1c and ldl - c goals is associated with a lower risk of microvascular complications , acs , and cardiovascular surgeries ( pci or cabg ) , lower utilization of health care resources , and lower costs of care , but no additional effect was observed for the composite cardiovascular - related end point .
in addition , dual - goal achievement relative to hba1c goal achievement is associated with a lower risk of the composite cardiovascular - related end point , cabg , and outpatient visits . to our knowledge , this is the first study that was designed to quantify the differences in clinical and economic outcomes between dual - goal and single - goal achievement in patients with t2 dm . the results from our study are generally consistent with findings from previous studies designed to assess the benefits of treatment paradigms aimed at achieving more than one clinical goal in diabetes . in steno-2 , a danish open - label ,
randomized , parallel - group study of patients with established t2 dm , patients assigned to receive an intensive treatment targeting tighter goals for blood pressure ( systolic < 130140 mmhg ; diastolic < 8085 mmhg ) , hba1c ( < 6.5% [ 48 mmol / mol ] ) , total cholesterol ( < 175190 mg / dl ) , and triglycerides ( < 150 mg / dl ) had a significantly lower risk of cardiovascular disease and microvascular complications over an average follow - up of 7.8 years , compared with patients assigned to antidiabetic treatment in accordance with national guidelines ( 21 ) .
a 5.5-year extension of that same study demonstrated that the multifactorial therapy was associated with sustained lower risk of cardiovascular events or death ( 20 ) . in the steno-2 study ,
lipid - lowering treatments were suggested to have had the greatest contribution to cardiovascular risk reduction , whereas antiglycemic and antihypertensive treatments were considered to have accounted for the greatest reduction in microvascular complications ( 29 ) .
these results are in alignment with our findings that suggest that there are additional cardiovascular benefits associated with the achievement of both ldl - c and hba1c goals when compared with only hba1c goal achievement , while there are additional microvascular benefits associated with the achievement of both hba1c and ldl - c goals when compared with only ldl - c goal achievement .
in contrast to the steno-2 study ( 21 ) , we did not assess the impact of multiple interventions or goal achievements other than hba1c and ldl - c .
the blood pressure level cutoff recommended by major national and international guidelines for patients with diabetes ( < 130/80 mmhg ) may be difficult to achieve , and the benefits of achieving this blood pressure goal are unclear ( 30 ) .
we decided to await final consensus on the optimal blood pressure goal for patients with diabetes before creating appropriate models to account for blood pressure goal achievements .
current lipid and glycemic goals , however , are relatively easy to achieve , as can be seen from our study , and their effects are therefore easier to take into consideration .
our results are also consistent with findings from large randomized trials that evaluated situations analogous to the achievement of single metabolic goals .
the 10-year uk prospective diabetes study found that intensive glycemic control reduces the risk of microvascular complications but does not affect the risk of macrovascular disease ( 31 ) .
this lack of association between intensive glycemic control and macrovascular benefits has been observed in other large trials , such as action in diabetes and vascular disease : preterax and diamicron modified release controlled evaluation ( advance ) ( 4 ) , action to control cardiovascular risk in diabetes ( accord ) ( 2,3 ) , and veterans affairs diabetes trial ( vadt ) ( 32 ) , except in the case of patients with newly diagnosed diabetes ( 5,33 ) .
our study showed a 6% lower hazard of cardiovascular - related end point for hba1c achievers compared with no - goal achievers .
our findings are in agreement with the results from several large randomized trials that found that the treatments aimed at lowering ldl - c were associated with a reduced risk of cardiovascular events in patients with diabetes ( 610 ) . in our study ,
achievement of the hba1c goal alone and the ldl - c goal alone were each associated with a lower risk of cardiovascular surgeries , which is consistent with other research in patients with diabetes which has shown that patients who undergo cabg ( 3436 ) and pci ( 37,38 ) often have elevated hba1c levels , and that lowering ldl - c levels is also associated with lower risks of coronary events ( 6,7,39 ) .
this is the first study to examine the differences between dual- and single - goal achievement in terms of health care resource utilization and costs in patients with diabetes .
our results suggest that dual - goal achievement provides additional economic benefits . over ldl - c goal alone , but not over hba1c goal alone .
our results are consistent with previous studies that show that control of either ldl - c ( 40 ) or hba1c ( 15 ) is associated with cost savings . for example , a 2003 study designed to assess cost of statin therapy for the primary prevention of major coronary events in u.s .
patients with diabetes and ldl - c levels > 100 mg / dl found that among individuals with ldl - c levels of 100129 mg / dl and 130 mg / dl , the annual cost difference between patients with major coronary events with statin treatment versus without statin treatment was $ 480950 and $ 5901,920 , respectively ( 16 ) .
a 2005 analysis conducted to predict costs and outcomes for patients with uncontrolled t1 dm and t2 dm , compared with patients who remained at hba1c levels of 7% ( 53 mmol / mol ) or 6.5% ( 48 mmol / mol ) , found that efficient targeting of financial resources toward achievement of hba1c goals in the u.s . would result in $ 3572 billion savings over the subsequent 10 years ( 15 ) .
first , the data used for this study include laboratory measurements for patients over time .
second , this study used a longitudinal design that was able to capture the time - varying nature of laboratory measurements .
this allowed for better estimation of the association between goal achievement and risk of complications over time , compared with a simple cross - sectional design , which would use baseline laboratory values in regression models .
first , due to the retrospective observational design , the analysis may have been affected by unobserved factors that were not taken into account in the model .
second , the electronic medical records did not include information on disease severity , disease duration , lifestyle modifications , or other interventions .
third , although patients enrolled in the vha do not typically use services outside of the system , any health care services that were administered by a provider outside of the vha were not included in the electronic records .
fourth , because we used vha data , the patients in our study were predominantly male .
although our sample was representative of the vha population , gender imbalance may limit the generalization of our findings . as the vha population may have characteristics that are distinct from those in the general population , similar studies in the general population should be performed .
finally , studies on the clinical and economic benefits associated with triple goal achievement of hba1c , ldl - c , and blood pressure goals may shed additional light on the appropriate management of patients with t2 dm . in conclusion ,
veterans suggests that the achievement of both ldl - c and hba1c goals is associated with additional clinical and economic benefits , compared with the achievement of either goal alone
. these findings may facilitate decision making when considering the health and pharmacoeconomic benefits of various treatment strategies to target multiple treatment goals for individuals with diabetes .
to our knowledge , this is the first study that was designed to quantify the differences in clinical and economic outcomes between dual - goal and single - goal achievement in patients with t2 dm . the results from our study are generally consistent with findings from previous studies designed to assess the benefits of treatment paradigms aimed at achieving more than one clinical goal in diabetes . in steno-2 , a danish open - label ,
randomized , parallel - group study of patients with established t2 dm , patients assigned to receive an intensive treatment targeting tighter goals for blood pressure ( systolic < 130140 mmhg ; diastolic < 8085 mmhg ) , hba1c ( < 6.5% [ 48 mmol / mol ] ) , total cholesterol ( < 175190 mg / dl ) , and triglycerides ( < 150 mg / dl ) had a significantly lower risk of cardiovascular disease and microvascular complications over an average follow - up of 7.8 years , compared with patients assigned to antidiabetic treatment in accordance with national guidelines ( 21 ) .
a 5.5-year extension of that same study demonstrated that the multifactorial therapy was associated with sustained lower risk of cardiovascular events or death ( 20 ) . in the steno-2 study ,
lipid - lowering treatments were suggested to have had the greatest contribution to cardiovascular risk reduction , whereas antiglycemic and antihypertensive treatments were considered to have accounted for the greatest reduction in microvascular complications ( 29 ) .
these results are in alignment with our findings that suggest that there are additional cardiovascular benefits associated with the achievement of both ldl - c and hba1c goals when compared with only hba1c goal achievement , while there are additional microvascular benefits associated with the achievement of both hba1c and ldl - c goals when compared with only ldl - c goal achievement .
in contrast to the steno-2 study ( 21 ) , we did not assess the impact of multiple interventions or goal achievements other than hba1c and ldl - c .
the blood pressure level cutoff recommended by major national and international guidelines for patients with diabetes ( < 130/80 mmhg ) may be difficult to achieve , and the benefits of achieving this blood pressure goal are unclear ( 30 ) .
we decided to await final consensus on the optimal blood pressure goal for patients with diabetes before creating appropriate models to account for blood pressure goal achievements .
current lipid and glycemic goals , however , are relatively easy to achieve , as can be seen from our study , and their effects are therefore easier to take into consideration .
our results are also consistent with findings from large randomized trials that evaluated situations analogous to the achievement of single metabolic goals .
the 10-year uk prospective diabetes study found that intensive glycemic control reduces the risk of microvascular complications but does not affect the risk of macrovascular disease ( 31 ) .
this lack of association between intensive glycemic control and macrovascular benefits has been observed in other large trials , such as action in diabetes and vascular disease : preterax and diamicron modified release controlled evaluation ( advance ) ( 4 ) , action to control cardiovascular risk in diabetes ( accord ) ( 2,3 ) , and veterans affairs diabetes trial ( vadt ) ( 32 ) , except in the case of patients with newly diagnosed diabetes ( 5,33 ) .
our study showed a 6% lower hazard of cardiovascular - related end point for hba1c achievers compared with no - goal achievers .
our findings are in agreement with the results from several large randomized trials that found that the treatments aimed at lowering ldl - c were associated with a reduced risk of cardiovascular events in patients with diabetes ( 610 ) . in our study ,
achievement of the hba1c goal alone and the ldl - c goal alone were each associated with a lower risk of cardiovascular surgeries , which is consistent with other research in patients with diabetes which has shown that patients who undergo cabg ( 3436 ) and pci ( 37,38 ) often have elevated hba1c levels , and that lowering ldl - c levels is also associated with lower risks of coronary events ( 6,7,39 ) .
this is the first study to examine the differences between dual- and single - goal achievement in terms of health care resource utilization and costs in patients with diabetes .
our results suggest that dual - goal achievement provides additional economic benefits . over ldl - c goal alone , but not over hba1c goal alone .
our results are consistent with previous studies that show that control of either ldl - c ( 40 ) or hba1c ( 15 ) is associated with cost savings .
for example , a 2003 study designed to assess cost of statin therapy for the primary prevention of major coronary events in u.s .
patients with diabetes and ldl - c levels > 100 mg / dl found that among individuals with ldl - c levels of 100129 mg / dl and 130 mg / dl , the annual cost difference between patients with major coronary events with statin treatment versus without statin treatment was $ 480950 and $ 5901,920 , respectively ( 16 ) . a 2005 analysis conducted to predict costs and outcomes for patients with uncontrolled t1 dm and t2 dm ,
compared with patients who remained at hba1c levels of 7% ( 53 mmol / mol ) or 6.5% ( 48 mmol / mol ) , found that efficient targeting of financial resources toward achievement of hba1c goals in the u.s . would result in $ 3572 billion savings over the subsequent 10 years ( 15 ) .
first , the data used for this study include laboratory measurements for patients over time .
second , this study used a longitudinal design that was able to capture the time - varying nature of laboratory measurements .
this allowed for better estimation of the association between goal achievement and risk of complications over time , compared with a simple cross - sectional design , which would use baseline laboratory values in regression models .
first , due to the retrospective observational design , the analysis may have been affected by unobserved factors that were not taken into account in the model .
second , the electronic medical records did not include information on disease severity , disease duration , lifestyle modifications , or other interventions .
third , although patients enrolled in the vha do not typically use services outside of the system , any health care services that were administered by a provider outside of the vha were not included in the electronic records .
fourth , because we used vha data , the patients in our study were predominantly male .
although our sample was representative of the vha population , gender imbalance may limit the generalization of our findings . as the vha population may have characteristics that are distinct from those in the general population , similar studies in the general population should be performed . finally , studies on the clinical and economic benefits associated with triple goal achievement of hba1c
, ldl - c , and blood pressure goals may shed additional light on the appropriate management of patients with t2 dm . in conclusion , this retrospective study among u.s .
veterans suggests that the achievement of both ldl - c and hba1c goals is associated with additional clinical and economic benefits , compared with the achievement of either goal alone .
these findings may facilitate decision making when considering the health and pharmacoeconomic benefits of various treatment strategies to target multiple treatment goals for individuals with diabetes .
 objectivethis study compared the clinical and economic benefits associated with dual - goal achievement , glycated hemoglobin ( hba1c ) < 7% ( 53 mmol / mol ) and ldl cholesterol ( ldl - c ) < 100 mg / dl , with achievement of only the ldl - c goal or only the hba1c goal in veterans with type 2 diabetes mellitus ( t2dm).research design and methodsthis retrospective cohort analysis evaluated electronic medical records ( veterans integrated service network 16 ) in adult t2 dm patients with two or more measurements of ldl - c and hba1c between 1 january 2004 and 30 june 2010 ( n = 75,646 ) . 
 cox proportional hazards models were used to compare microvascular and cardiovascular outcomes by goal achievement status ; generalized linear regression models were used to assess diabetes - related resource utilization ( hospitalization days and number of outpatient visits ) and medical service costs.resultsrelative to achievement of only the ldl - c goal , dual - goal achievement was associated with lower risk of microvascular complications ( adjusted hazard ratio [ ahr ] 0.79 ) , acute coronary syndrome ( 0.88 ) , percutaneous coronary intervention ( 0.78 ) , and coronary artery bypass graft ( cabg ) ( 0.74 ) ; it was also associated with fewer hospitalization days ( adjusted incidence rate ratio [ airr ] 0.93 ) and outpatient visits ( 0.88 ) , as well as lower diabetes - related annual medical costs ( $130.89 ) . 
 compared with achievement of only the hba1c goal , dual - goal achievement was associated with lower risk of the composite cardiovascular - related end point ( ahr 0.87 ) and cabg ( ahr 0.62 ) , as well as fewer outpatient visits ( airr 0.98).conclusionsachieving both hba1c and ldl - c goals in diabetes care is associated with additional clinical and economic benefits , as compared with the achievement of either goal alone . 
RESEARCH DESIGN AND METHODS
Data source
Sample selection
Data preparation
Patient characteristics
Clinical outcomes
Economic outcomes
RESULTS
Patient characteristics
Clinical outcomes
Resource utilization
Medical service costs
CONCLUSIONS
Clinical outcomes: dual- vs. single-goal achievement
Clinical outcomes: single- vs. no-goal achievement
Economic outcomes