in the united states , diabetes mellitus affects 26 million people   and its chronic vascular complications are associated with significant morbidity [ 2 , 3 ] , disability , and mortality .
chronic complications from diabetes account for approximately $ 58 billion in excess medical expenditures per year .
common risk factors for microvascular and macrovascular diabetic complications include age , duration of diabetes , hyperglycemia [ 79 ] , and high blood pressure ; therefore multiple complications commonly develop in the same patient [ 5 , 6 ] .
in addition to the management of cardiovascular risk factors , prevention of diabetes complications also involves diabetes self - care such as diet , exercise , self - monitoring of blood glucose , and self - foot examination . as a result
, the american diabetes association ( ada ) has established clinical practice guidelines regarding standard diabetes care , which include recommendations for diabetes process of care measures ( frequency of laboratory testing , clinical goals , and recommended medications ) and self - care .
a few studies have suggested that adherence with these diabetes clinical practice guidelines varies by sex .
women with diabetes have been reported to have worse blood pressure , lipid , and glycemic control compared to men , even amongst those known to have cardiovascular disease [ 13 , 14 ] .
however , sex differences in laboratory testing and other self - care behaviors have not been explored in detail , nor is it known whether these sex disparities persist in high - risk patients , such as those who already have a history of a diabetic complication .
identification of modifiable factors related to diabetes outcomes is imperative if the rate of adverse outcomes is to be decreased , and evaluation of sex - specific differences provides an opportunity to develop strategies to reduce sex - related health disparities in diabetes care .
this study examined the associations between sex and selected diabetes process of care measures and self - care activities in a cohort of primary care patients with diabetes .
this study also examined whether sex differences in diabetes process of care measures and self - care activities were detectable in the subgroup of subjects with a history of diabetic complications , a particularly high - risk group for adverse outcomes .
we conducted a cross - sectional analysis of baseline data from the pathways study , which has been described previously [ 16 , 17 ] . in brief , the pathways study is a prospective , observational cohort of the prevalence and impact of depression on patients with diabetes at group health ( gh ) , a large nonprofit health maintenance organization ( hmo ) in washington and idaho , usa .
nine primary care clinics were chosen for patient recruitment based on the number of diabetic patients , ethnic diversity , and proximity to seattle , wa , usa .
for the study , 9,063 potential candidates were identified from the gh diabetes registry ( figure 1 ) . in 2001 - 2002 , surveys were sent to these patients regarding demographic information , diabetes characteristics , diabetic complications , and self - care .
diabetic complications included retinopathy , nephropathy , neuropathy , cerebrovascular , cardiovascular , peripheral vascular disease , or metabolic ( hypoglycemia , diabetic ketoacidosis , or hyperosmolar nonketotic coma ) . of those identified , 1,222 patients were excluded from the study due to no diabetes , gestational diabetes , cognitive impairment , severe illness , deceased , disenrollment from gh , language or hearing problems , or other reasons . of
the remaining 7,842 eligible patients for the study , 4,839 ( 61.7% ) returned the survey of which 4,467 ( 92.3% ) gave permission to link survey data with automated data from gh regarding laboratory tests , pharmacy records , hospitalizations , and outpatient visits .
baseline hemoglobin a1c and low - density lipoprotein ( ldl ) were ascertained closest to the date of the baseline epidemiologic survey , up to 12 months prior to study enrollment .
microalbuminuria was defined as a urine albumin to creatinine ratio ( uacr ) > 17  mg / g for women and > 25  mg / g for men , based on sex - specific cutoffs ; given the large proportion of missing data , microalbuminuria was ascertained up to 24 months prior to study enrollment . 
estimated glomerular filtration rate ( egfr ) was calculated using chronic kidney disease - epidemiology ( ckd - epi ) equations . chronic kidney disease ( ckd ) stage was determined by egfr and microalbuminuria , using the national kidney foundation kidney disease outcomes quality initiative classification system .
computerized pharmacy records were used to identify patients who were prescribed any insulin , oral diabetic medication , hmg - coa reductase inhibitor ( statin ) , angiotensin - converting enzyme ( ace ) inhibitor , or angiotensin receptor blocker ( arb ) in the 12 months prior to study enrollment . for simplicity we will use the generic term ace inhibitor to refer to either an ace inhibitor or arb .
self - care activities were assessed using the summary of diabetes self - care activities ( sdsca ) , which is a brief questionnaire that asks how many days per week an activity was performed .
the sdsca has been shown to be a reliable and valid measure of adherence to diabetes self - care in observational and interventional studies .
for this study , investigators selected five sdsca questions regarding diet , exercise , blood glucose testing , and foot care that were considered the most clinically relevant for analysis ( table 1 ) .  
the primary outcomes of interest were sex - specific differences in the following diabetes process of care measures and self - care activities : ( 1 ) history of recommended laboratory testing ( hemoglobin a1c , ldl , and microalbuminuria ) , ( 2 ) attainment of clinical targets ( hemoglobin  a1c < 7% and ldl < 130  mg / dl ) , ( 3 ) medication use ( statins in all subjects and in those with ldl > 130  mg / dl , ace inhibitors in all subjects and in those with microalbuminuria ) , and ( 4 ) compliance with self - care ( diet , exercise , and foot examination at least 3 times per week ; blood glucose testing at least 3 times a week if on oral hypoglycemic agents only or 5 times a week if on insulin ) .  
statistical analyses were performed using stata version 12 ( college station , tx , usa ) .
significant sex differences in diabetes clinical process of care measures and self - care activities were determined using t - tests for continuous data and  tests for categorical data .
logistic regression models were used to calculate adjusted odds ratios ( aors ) to determine if there were adjusted sex differences in compliance with diabetes process of care measures and self - care activities .
models regarding process of care measures were adjusted for age , race / ethnicity , marital status , education , smoking , body mass index , hemoglobin a1c ( except for models where hemoglobin a1c testing and achievement of hemoglobin a1c <
7% were outcomes of interest ) , history of hypertension , and ckd stage ( except the model for microalbuminuria testing ) .
models regarding self - care activities were additionally adjusted for a history of major depression , which was strongly associated with both sex and self - care outcomes .
analyses were also performed on the subgroup of patients with a known history of at least one diabetic complication ( n = 3,045 ) , since these patients are at high risk for adverse outcomes .
sensitivity analyses demonstrated similar results in this subgroup as with subgroups of patients with specific diabetic complications ( cardiovascular , cerebrovascular , or nephropathy ) .
of the 4,839 subjects in the total cohort , 48.8% were women ( table 2 ) .
men tended to be older , more frequently married , and had higher levels of education and income compared to women .
women had higher mean bmi and greater prevalence of hypertension ( 45.0% versus 41.0% ) and major depression ( 14.1% versus 9.6% ) than men .
men had a greater prevalence of microalbuminuria ( 46.7% versus 34.4% ) and higher mean number of diabetic complications ( 1.4  1.4 versus 1.3  1.3 ) compared to women .
there were similar patterns of sex differences in cohort characteristics amongst the subset of subjects known to have diabetic complications .
approximately 86.7% of subjects had previous hemoglobin a1c testing and 61.4% had urine microalbuminuria screening ; these test frequencies did not vary significantly by sex .
in contrast , ldl testing was less frequent in women compared to men ; only 52.6% of women had their ldl checked in the previous year compared to 59.0% of men ( p < 0.001 ) .
both men and women had a mean hemoglobin a1c of 7.8% , and a similar proportion of subjects achieved a hemoglobin a1c < 7% .
mg / dl ) than in men ( 107.8  33.6  mg / dl , p < 0.001 ) , and a lower proportion of women achieved a target ldl of < 130  mg / dl ( 67.3% versus 75.3% in men , p < 0.001 ) .
statins were prescribed less frequently to women than men overall ( 26.5% versus 35.4% , p < 0.001 ) and in those with ldl levels above 130  mg / dl ( 24.2% versus 31.3% , p = 0.02 ) .
there were no sex differences in ace inhibitor use overall or in the subset with microalbuminuria . in
adjusted multivariable logistic regression models ( table 3 ) , a greater proportion of women were more likely to be guideline discordant than men for ldl testing ( aor 0.73 , 95% ci 0.620.85 ) , achievement of ldl target < 130  mg / dl ( aor 0.70 , 95% ci 0.580.86 ) , any statin prescription ( aor 0.69 , 95% ci 0.580.81 ) , or statin prescription if ldl was greater than 130  mg / dl ( aor 0.61 , 95% ci 0.410.91 ) compared to men .
women were more likely to achieve hemoglobin a1c target ( aor 1.19 , 95% ci 1.021.41 )
. there were no differences in the odds of hemoglobin a1c testing , microalbuminuria screening , or ace inhibitor prescription by sex .
women reported more frequent consumption of 5 servings of fruits or vegetables per day and less frequent consumption of high fat foods compared with men . in the week prior to study assessment , a lower proportion of women ( 55.3% ) exercised at least 3 times a week compared to men ( 63.9% , p < 0.001 ) .
in adjusted logistic regression models of self - care activities ( figure 2(a ) ) , women were more likely to report high fruit and vegetable consumption ( aor 1.36 , 95% ci 1.151.61 ) , blood glucose testing ( 1.27 , 95% ci 1.041.55 ) , and self - foot examination ( aor 1.32 , 95% ci 1.111.57 ) but less likely to report fatty food consumption ( aor 0.69 , 95% ci 0.590.80 ) and regular exercise ( aor 0.72 , 95% ci 0.620.85 ) compared to men . based on adjusted logistic regression models of 3,045 patients with at least one known diabetic complication , men and women had similar odds of hemoglobin a1c and microalbuminuria testing ( table 4 ) .
women in this subgroup had decreased odds of ldl testing ( aor 0.65 , 95% ci 0.540.77 ) , achievement of ldl goal < 130  mg / dl ( aor 0.63 , 95% ci 0.510.78 ) , statin use overall ( aor 0.67 , 95% ci 0.560.79 ) , and statin use if serum ldl was > 130  mg / dl ( aor 0.64 , 95% ci 0.420.97 ) .
women with at least one diabetic complication had greater odds of achieving target hemoglobin a1c < 7% compared to their male counterparts . there were no sex - specific differences in ace inhibitor use . amongst those with at least one diabetic complication , women had greater odds of high fruit and vegetable consumption ( aor 1.61 , 95% ci 1.341.93 ) , blood glucose monitoring ( aor 1.26 , 95% ci 1.011.55 ) , and self - foot examination ( aor 1.31 , 95% ci 1.081.58 ) compared to men ( figure 2(b ) ) .
women in this subgroup were less likely to consume fatty foods ( aor 0.69 , 95% ci 0.580.81 ) or to exercise ( aor 0.69 , 95% ci 0.590.82 ) compared to their male counterparts .
this analysis found significant sex differences in diabetes process of care measures and self - care activities , even amongst the high - risk subgroup of subjects who were known to have chronic complications of diabetes .
in general , women tended to have better glycemic control and adherence to recommended self - care compared to men .
however , despite having higher ldl levels , women were less likely to be screened for dyslipidemia or to be prescribed statins compared to men .
this is the first study to report sex disparities in diabetes processes of care and self - care behaviors in the subgroup of patients with a history of at least one diabetic complication , which is surprising since these patients are at high - risk for additional diabetic complications and warrant aggressive diabetes care .
our results are congruent with previous findings of sex differences in diabetes process of care measures , particularly with respect to management of dyslipidemia . in a cross - sectional study of 3,849 patients with diabetes from five academic medical centers , wexler et al . found that women had higher cholesterol levels , were less likely to receive lipid lowering therapy , and when receiving lipid lowering therapy , were less likely to reach ldl targets compared to men .
found that , compared to men , diabetic women without cardiovascular disease received less frequent lipid testing and diabetic women with cardiovascular disease were treated less frequently with lipid lowering agents . although other studies have reported worse glycemic control in diabetic women compared to men [ 12 , 14 ] , we found that women had better glycemic control than men .  
diabetic women tended to be more physically inactive than men , which is consistent with findings from the third national health and nutrition examination survey ( nhanes iii ) .
this study builds on previous reports by demonstrating sex differences in other diabetes self - care activities .
diabetic men were consistently less adherent to recommendations regarding diet , blood glucose monitoring , and foot care than women .
likewise , these sex differences in diabetes self - care persisted in patients with known diabetic complications .
the observed sex differences in diabetes process of care measures and self - care activities are likely multifactorial and may be related to both provider and patient factors .
providers may perceive diabetic women to have a lower risk of cardiovascular disease and other diabetic complications compared to men , which may result in less aggressive monitoring and treatment in women .
whether sex influences management of diabetic patients has not been investigated ; however , research in cardiovascular disease revealed that sex influenced how physicians managed chest pain , coronary heart disease , and cardiovascular disease prevention . since public awareness of cardiovascular disease in women remains suboptimal
[ 29 , 30 ] , female patients may themselves underestimate their risk for diabetic complications and either fail to inquire about or decline routine diabetes care .
moreover , men and women may have differing beliefs in the benefit of self - care . in a survey of new patients to a diabetes education center ,
women were more likely than men to have a history of previous diabetes education and had higher expectations that self - management would improve health outcomes ; this may explain our finding that women had better glycemic control and overall better adherence to self - care than men .
finally , biologic differences between men and women , due to estrogen or lack thereof , may result in differential outcomes in care .
sex hormones are associated with glucose tolerance , lipid metabolism , albuminuria , and coronary heart disease .
diabetes has a greater adverse effect on serum triglyceride and ldl levels in women compared to men , and a recent meta - analysis of statin therapy for secondary cardiovascular prevention found that statins reduced all - cause mortality and stroke risk men but not in women .  
it is important to recognize that the results of this study present an opportunity to improve the quality of diabetes care not only for women , but for men as well .
although women had less adequate screening and management of dyslipidemia and poorer adherence to exercise , they tended to have better glycemic control and adherence to other recommended self - care activities compared to men .
health care providers should pay particular attention to ordering recommended laboratory tests and medications in women and targeting patient education interventions regarding self - care to men .
all patients should be encouraged to follow a regular exercise program and this should be heavily emphasized among women .
the strengths of this study include the large sample size of study subjects with comparable access to care .
the study surveyed patients directly for variables related to diabetes self - care and we were able to adjust for several known confounding variables , including major depression . however , this study does have several limitations that are important to consider .
the cross - sectional nature of this study is subject to unmeasured confounding and can not establish causal relationships .
we did not have access to actual blood pressure measurements and therefore could not adjust for the degree of control of hypertension .
there was a large proportion of missing data for laboratory test results , particularly for ldl and microalbuminuria , which affects the validity and generalizability of these results .
pharmacy records could only capture medications prescribed within the gh system and do not reflect actual patient usage .
self - care activities were ascertained by self - reported measures rather than actual measurements .
although the sdsca has been shown to be a reliable and valid measure of diabetes self - management , differential misclassification could occur if there were systematic differences in how men and women recall or report self - care .
finally , this study could not account for several factors that may contribute to the observed sex differences , such as differences in patient visit frequency , provider styles of care , or patient preferences by sex .
in conclusion , sex is associated with significant differences in diabetes process of care measures and self - care activities , even amongst subjects known to have chronic complications from diabetes .
women may benefit from more attention to dyslipidemia screening , lipid lowering treatment , and regular exercise , whereas men may require more encouragement in diabetes self - care including healthy diet , self - blood glucose monitoring , and self - foot examination .
the findings from this study indicate an opportunity for intervention to reduce sex - related disparities in diabetes care .
although further studies are needed to elucidate the causes for these sex disparities , it is important for primary health care providers to be aware of the existence of sex differences in diabetes care such that these disparities may be eliminated .
 patients with chronic diabetic complications experience high morbidity and mortality . 
 sex disparities in modifiable factors such as processes of care or self - care activities have not been explored in detail , particularly in these high - risk patients . 
 sex differences in processes of care and self - care activities were assessed in a cross - sectional analysis of the pathways study , an observational cohort of primary care diabetic patients from a managed care organization ( n = 4,839 ) . compared to men , 
 women had decreased odds of dyslipidemia screening ( adjusted odds ratio ( aor ) 0.73 , 95% ci 0.620.85 ) , reaching low - density lipoprotein goal ( aor 0.70 , 95% ci 0.580.86 ) , and statin use ( aor 0.69 , 95% ci 0.580.81 ) ; women had 19% greater odds of reaching hemoglobin a1c < 7% ( 95% ci 1.021.41 ) . there were no sex differences in hemoglobin a1c testing , microalbuminuria screening , or angiotensin - converting enzyme inhibitor use . 
 women were less likely to report regular exercise but had better adherence to healthy diet , glucose monitoring , and self - foot examination compared to men . 
 patterns of sex differences were consistent in subjects with diabetic complications . 
 significant sex disparities exist in diabetes process of care measures and self - care , even amongst patients known to have chronic diabetic complications . 