Longitudinal effects of medication nonadherence on glycemic control.

BACKGROUND: Medication nonadherence is known to worsen glycemic control. Few studies have examined this relationship over several years. OBJECTIVE: The aim of this study was to examine the longitudinal effect of medication nonadherence on glycemic control among a large cohort of veterans. METHODS: Analysis was performed on a cohort of 11 272 veterans with type 2 diabetes followed from April 1994 to May 2006. The primary outcome measures were mean glycosylated hemoglobin A1c (A1C) and proportion in poor control (A1C > 8%) over time. The main predictor was medication nonadherence based on medication possession ratio (MPR). Other covariates included sociodemographics and ICD-9 coded medical and psychiatric comorbidities. Generalized linear mixed models (GLMMs) were used to assess the relationship between MPR and A1C after adjusting for covariates. RESULTS: Mean follow-up was 5.4 years. In the linear mixed model, after adjusting for baseline A1C and other confounding variables, mean A1C decreased by 0.24 (P < 0.001) for each 10% increase in MPR (95% CI = -0.27, -0.21). In the fully adjusted GLMM, each percentage increase in MPR was associated with a 48% lower likelihood of having poor glycemic control (odds ratio = 0.52; 95% CI = 0.4, 0.6). In both continuous and dichotomized A1C analyses, average A1C showed a decreasing trend over the study period (P < 0.001). CONCLUSIONS: In patients with type 2 diabetes, glycemic control worsens over time in the presence of medication nonadherence. Future studies need to take into account the complexity of patient- and system-level factors affecting long-term medication adherence to improve diabetes-related outcomes.

Impact of diabetes control on mortality by race in a national cohort of veterans.

PURPOSE: The association between glycated hemoglobin (HbA1c), medication use/adherence, and mortality stratified by race/ethnicity was examined in a national cohort of veterans with type 2 diabetes. METHODS: A total of 892,223 veterans with diabetes in 2002 were followed through 2006. HbA1c category was the main exposure (i.e., HbA1c <7%, HbA1c 7%-8% [reference], HbA1c 8%-9%, and HbA1c >9%). Covariates included age, sex, marital status, rural/urban residence, geographic region, number of comorbidities, and diabetes medication use/adherence (i.e., adherent, medication possession ratio ≥80%; nonadherent; and nonusers). HbA1c and medication use/adherence varied over time, and Cox regression models accounting for time-varying variables were used. RESULTS: In nonmedication users, HbA1c greater than 9% predicted higher mortality risk relative to HbA1c of 7%-8% in non-Hispanic whites (hazard ratio [HR], 1.55; 95% confidence interval [95% CI], 1.43-1.69), non-Hispanic blacks (NHB) (HR, 1.58; 95% CI, 1.34-1.87), and Hispanics (HR, 2.22; 95% CI, 1.75-2.82). In contrast, in nonadherent medication users, HbA1c less than 7% predicted higher mortality risk in NHB (HR, 1.12; 95% CI, 1.05-1.20), whereas HbA1c greater than 9% only predicted mortality in non-Hispanic whites (HR, 1.11; 95% CI, 1.06-1.16). In adherent medication users, HbA1c less than 7% predicted higher mortality in NHB (HR, 1.18; 95% CI, 1.07-1.31), whereas HbA1c greater than 9.0% predicted higher mortality risk across all race/ethnic groups. CONCLUSION: We found evidence for racial/ethnic differences in the association between glycemic control and mortality, which varied by medication use/adherence.

Differential impact of longitudinal medication non-adherence on mortality by race/ethnicity among veterans with diabetes.

OBJECTIVE: To examine the differential effect of medication non-adherence over time on all-cause mortality by race/ethnicity. RESEARCH DESIGN AND METHODS: Data on a longitudinal cohort of veterans with type 2 diabetes was examined. The main outcome was time to death. Primary independent variables were race/ethnicity and mean medication possession ratio (MPR) categorized into quintiles over the study period. Cox regression was used to model the association between time to death and MPR quintiles and race/ethnicity, adjusting for relevant covariates. RESULTS: The cohort of 629,563 veterans was followed for 5 years. After adjusting for all covariates, the hazard ratios (HR) for subjects in the lowest versus highest MPR quintile was 12.21 (95 % CI 11.89, 12.55) for non-Hispanic white (NHW), 10.01 (95 % CI 9.18, 10.91) for non-Hispanic black (NHB), 12.65 (95 % CI 11.10, 14.43) for Hispanic and 10.41 (95 % CI 9.06, 11.96) for Other race veterans. Furthermore, type of diabetes therapy (oral versus insulin) maintained a significant relationship with mortality that varied by racial/ethnic group. CONCLUSIONS: This study demonstrates the differential impact of medication non-adherence on mortality by race. It also demonstrates that type of diabetes therapy (insulin with or without oral agents) is associated with mortality and varies by racial/ethnic group.

Racial/Ethnic disparities in mortality risk among US veterans with traumatic brain injury.

OBJECTIVES: We examined the association of race/ethnicity with mortality risk in a national cohort of US veterans clinically diagnosed with traumatic brain injury. METHODS: Between January 1, 2006 and December 31, 2006, we obtained data from a national cohort study of 7885 non-Hispanic White, 1748 Non-Hispanic Black, 314 Hispanic, and 4743 other or missing race/ethnicity veterans clinically diagnosed with traumatic brain injury in Veterans Affairs medical centers and community-based outpatient clinics. RESULTS: Overall mortality at 48 months was 6.7% in Hispanic, 2.9% in non-Hispanic White, and 2.7% in non-Hispanic Black veterans. Compared with non-Hispanic White, Hispanic ethnicity was positively associated with a higher mortality risk (hazard ratio [HR] = 2.33; 95% confidence interval [CI] = 1.49, 3.64) in the race/ethnicity-only adjusted model. After adjusting for sociodemographic characteristics and comorbidities, Hispanic ethnicity continued to be positively associated (HR = 1.61; 95% CI = 1.00, 2.58) with a higher mortality risk relative to non-Hispanic White ethnicity. CONCLUSIONS: Hispanic ethnicity is positively associated with higher mortality risk among veterans clinically diagnosed with traumatic brain injury. More research is needed to understand the reasons for this disparity.

Longitudinal ethnic differences in multiple cardiovascular risk factor control in a cohort of US adults with diabetes.

AIM: To examine longitudinal differences in multiple cardiovascular risk factor control (glycemia, blood pressure, and lipids) by race/ethnicity. METHODS: Data were analyzed on a cohort of 11,203 veterans with type 2 diabetes. Primary outcome was odds of none of the risk factors out of control vs. having at least one out of control (HbA1c>8.0%, BP>140/90 mmHg, and LDL>100mg/dL). Secondary outcome was odds of having none out of control vs. having one, two or three risk factors out of control, respectively. Generalized linear mixed models assessed the relationship between race/ethnicity and multiple risk factor control adjusted for covariates. RESULTS: Adjusted models for primary outcome showed that NHB had two-fold (95%CI 1.8-2.3) and Hispanics had 48% higher (95%CI 1.3-1.7) odds of multiple risk factors out of control over time compared to NHW. Adjusted models for secondary outcome showed that NHB and Hispanics also had higher odds of having one, two, and three risk factors out of control over time compared to NHW. CONCLUSIONS: Ethnic minority veterans with diabetes are less likely to have multiple cardiovascular risk factor control over time compared to whites. Thus, greater risk reduction efforts are needed to reduce the heavier disease burden among ethnic minorities.

Using quantile regression to investigate racial disparities in medication non-adherence.

BACKGROUND: Many studies have investigated racial/ethnic disparities in medication non-adherence in patients with type 2 diabetes using common measures such as medication possession ratio (MPR) or gaps between refills. All these measures including MPR are quasi-continuous and bounded and their distribution is usually skewed. Analysis of such measures using traditional regression methods that model mean changes in the dependent variable may fail to provide a full picture about differential patterns in non-adherence between groups. METHODS: A retrospective cohort of 11,272 veterans with type 2 diabetes was assembled from Veterans Administration datasets from April 1996 to May 2006. The main outcome measure was MPR with quantile cutoffs Q1-Q4 taking values of 0.4, 0.6, 0.8 and 0.9. Quantile-regression (QReg) was used to model the association between MPR and race/ethnicity after adjusting for covariates. Comparison was made with commonly used ordinary-least-squares (OLS) and generalized linear mixed models (GLMM). RESULTS: Quantile-regression showed that Non-Hispanic-Black (NHB) had statistically significantly lower MPR compared to Non-Hispanic-White (NHW) holding all other variables constant across all quantiles with estimates and p-values given as -3.4% (p = 0.11), -5.4% (p = 0.01), -3.1% (p = 0.001), and -2.00% (p = 0.001) for Q1 to Q4, respectively. Other racial/ethnic groups had lower adherence than NHW only in the lowest quantile (Q1) of about -6.3% (p = 0.003). In contrast, OLS and GLMM only showed differences in mean MPR between NHB and NHW while the mean MPR difference between other racial groups and NHW was not significant. CONCLUSION: Quantile regression is recommended for analysis of data that are heterogeneous such that the tails and the central location of the conditional distributions vary differently with the covariates. QReg provides a comprehensive view of the relationships between independent and dependent variables (i.e. not just centrally but also in the tails of the conditional distribution of the dependent variable). Indeed, without performing QReg at different quantiles, an investigator would have no way of assessing whether a difference in these relationships might exist.

Racial and ethnic differences in longitudinal blood pressure control in veterans with type 2 diabetes mellitus.

BACKGROUND: Few studies have examined racial/ethnic differences in blood pressure (BP) control over time, especially in an equal access system. We examined racial/ethnic differences in longitudinal BP control in Veterans with type 2 diabetes. METHODS: We collected data on a retrospective cohort of 5,319 Veterans with type 2 diabetes and initially uncontrolled BP followed from 1996 to 2006 at a Veterans Administration (VA) facility in the southeastern United States. The mean blood pressure value for each subject for each year was used for the analysis with BP control defined as <140/<90 mmHg. The primary outcome measure was proportion with controlled BP. The main predictor variable was race/ethnicity categorized as non-Hispanic White (NHW), non-Hispanic Black (NHB), or Hispanic/Other (H/O). Other covariates included age, gender, employment, marital status, service connectedness, and ICD-9 coded medical and psychiatric comorbidities. Generalized linear mixed models were used to assess the relationship between race/ethnicity and BP control after adjusting for covariates. RESULTS: Mean follow-up was 5.0 years. The sample was 46% NHW, 26% NHB, 19% H/O, and 9% unknown. The average age was 68 years. In the final model, after adjusting for covariates, NHB race (OR = 1.38, 95%CI: 1.2, 1.6) and H/O race (OR = 1.57, 95% CI: 1.3, 1.8) were associated with increased likelihood of poor BP control (>140/>90 mmHg) over time compared to NHW patients. CONCLUSION: Ethnic minority Veterans with type 2 diabetes have significantly increased odds of poor BP control over ∼5 years of follow-up compared to their non-Hispanic White counterparts independent of sociodemographic factors and comorbidity patterns.

Regional, geographic, and racial/ethnic variation in glycemic control in a national sample of veterans with diabetes.

OBJECTIVE: We performed a retrospective analysis of a national cohort of veterans with diabetes to better understand regional, geographic, and racial/ethnic variation in diabetes control as measured by HbA(1c). RESEARCH DESIGN AND METHODS: A retrospective cohort study was conducted in a national cohort of 690,968 veterans with diabetes receiving prescriptions for insulin or oral hypoglycemic agents in 2002 that were followed over a 5-year period. The main outcome measures were HbA(1c) levels (as continuous and dichotomized at ≥8.0%). RESULTS: Relative to non-Hispanic whites (NHWs), HbA(1c) levels remained 0.25% higher in non-Hispanic blacks (NHBs), 0.31% higher in Hispanics, and 0.14% higher in individuals with other/unknown/missing racial/ethnic group after controlling for demographics, type of medication used, medication adherence, and comorbidities. Small but statistically significant geographic differences were also noted with HbA(1c) being lowest in the South and highest in the Mid-Atlantic. Rural/urban location of residence was not associated with HbA(1c) levels. For the dichotomous outcome poor control, results were similar with race/ethnic group being strongly associated with poor control (i.e., odds ratios of 1.33 [95% CI 1.31-1.35] and 1.57 [1.54-1.61] for NHBs and Hispanics vs. NHWs, respectively), geographic region being weakly associated with poor control, and rural/urban residence being negligibly associated with poor control. CONCLUSIONS: In a national longitudinal cohort of veterans with diabetes, we found racial/ethnic disparities in HbA(1c) levels and HbA(1c) control; however, these disparities were largely, but not completely, explained by adjustment for demographic characteristics, medication adherence, type of medication used to treat diabetes, and comorbidities.

Regional, Geographic, and Ethnic Differences in Medication Adherence Among Adults with Type 2 Diabetes.

BACKGROUND: Medication adherence, a critical component of glycemic control for patients with type 2 diabetes, differs by race/ethnicity. However, few studies have examined regional and rural/urban differences in medication adherence and whether racial/ethnic differences persist after controlling for these differences. OBJECTIVE: To examine regional, rural/urban, and racial/ethnic differences in medication adherence in a national sample of veterans with type 2 diabetes. METHODS: We performed a cohort study of a national sample of veterans with diabetes (N = 690,968) receiving prescriptions for insulin or oral hypoglycemic agents in 2002. Patients were followed until death, loss to follow-up, or through December 2006. We calculated the annual medication possession ratio (MPR) for each veteran across 4 groups of medication users: individuals using (1) insulin only, (2) oral hypoglycemic agents only, (3) insulin combined with hypoglycemic agents, and (4) insulin or oral hypoglycemic agents (primary analysis). RESULTS: In longitudinal models for the primary analysis, adjusting for relevant covariates and time trends, MPR was significantly lower among non-Hispanic blacks (NHBs), Hispanics, and individuals with other/missing/unknown race/ethnicity (6.07%, 1.76%, and 2.83% lower, respectively) relative to non-Hispanic whites (NHWs). MPR was also 2.0% higher in rural versus urban veterans and 1.28% higher in the mid-Atlantic, 2.04% higher in the Midwest, and 0.76% lower in the West, relative to the South. There was a significant race/ethnicity and urban/rural interaction. In NHWs and NHBs, MPR was 1.91% and 2.00% higher, respectively, in rural versus urban veterans; in contrast, in Hispanics, MPR was 1.0% lower in rural veterans relative to urban veterans. CONCLUSIONS: In a national longitudinal cohort of veterans with type 2 diabetes, we found significant regional, rural/urban, and racial/ethnic differences in MPR. Rural/urban residence modified the effect of race/ethnicity on MPR. Recognition of these differences can enable clinicians to better allocate resources and target quality improvement programs.

Impact of psychiatric comorbidity on mortality in veterans with type 2 diabetes.

BACKGROUND: particular psychiatric disorders, such as depression, have a significant and negative effect on diabetes outcomes. However, we know very little about the impact of other psychiatric disorders, and of the effect of multiple psychiatric comorbidities, on the clinical course of diabetes. As such, the present study examined the impact of a wide range of psychiatric comorbidities on all-cause mortality in individuals with type 2 diabetes. METHODS: retrospective follow-up was conducted of 15,065 veterans with type 2 diabetes enrolled in hospital care between 1997 and 2006. Clinical diagnoses from patient records were used to construct four psychiatric disorder scales: internalizing (i.e., depression and anxiety); externalizing (i.e., alcohol and drug abuse); psychotic; and bipolar. Longitudinal relationships were examined between these scales and mortality using Cox regression. RESULTS: only externalizing disorders were significantly associated with mortality: hazard ratio = 1.22 (95% confidence interval = 1.02-1.47). In other words, each additional diagnosed externalizing disorder increased an individual's chance of dying over the follow-up period by 22%. This association remained significant when demographics and medical comorbidities were statistically controlled, but was rendered nonsignificant when medication adherence was introduced to the regression model. CONCLUSIONS: the results provide evidence that among individuals with diabetes, alcohol and drug abuse/dependence have a significant impact on mortality. This increased risk of mortality may have been due to the association between psychiatric disorders and adherence to antidiabetes medications observed in the present study. Individuals with co-occurring diabetes and alcohol or drug abuse should be targeted for intensive interventions given their acute increased risk of mortality.

Racial disparities in all-cause mortality among veterans with type 2 diabetes.

BACKGROUND: Racial differences in mortality among veterans with diabetes are less well characterized than those in the general population. OBJECTIVE: To examine racial differences in all-cause mortality in a large sample of veterans with diabetes. DESIGN: A retrospective cohort. PARTICIPANTS: Participants comprised 8,812 veterans with type 2 diabetes. MEASUREMENTS: The main outcome measure was time to death. The main predictor was race/ethnicity. Other risk factors (or covariates) included age, gender, marital status, employment, glycosylated hemoglobin (HgbA1c), and several ICD-9 coded physical and mental health comorbidities. RESULTS: Average follow-up was 4.5 years; 64% of veterans were non-Hispanic whites (NHW), 97% male, and 84% at least 50 years old. The overall mortality rate was 15% and was significantly lower for non-Hispanic blacks (NHB). Baseline HgbA1c values also differed for NHW (mean = 7.05) and NHB (mean = 7.65) (p < 0.001). In sequentially-built models NHB race was associated with a lower risk of mortality with HR ranging 0.80-0.92. After adjusting for all significant covariates, the risk of mortality remained lower for NHB (HR = 0.84, 95% CI: 0.75, 0.94). Increased mortality risk was associated with age, not being employed or retired, poor glycemic control, cancer, Coronary Heart Disease (CHD), and anxiety disorder; while a lower risk was associated with being female and ever being married. CONCLUSIONS: The risk of death among NHB veterans with diabetes remained significantly lower than that of NHW after controlling for important confounding variables. Future studies in the VA need to examine detailed contributions of patient, provider and system-level factors on racial differences in mortality in adults with diabetes, especially if the findings of this study are replicated at other sites or using national VA data.

Longitudinal differences in glycemic control by race/ethnicity among veterans with type 2 diabetes.

OBJECTIVE: To examine longitudinal differences in glycemic control between non-Hispanic white and non-Hispanic black veterans with type 2 diabetes. DESIGN: Retrospective cohort study. SETTING: VA facility in the Southeastern United States. PARTICIPANTS: A 3-month person-period dataset was created for 8813 veterans with type 2 diabetes between June 1997 and May 2006. MAIN OUTCOME MEASURES: Primary outcome was mean change in hemoglobin A1c (HbA1c) over time. Secondary outcome was the odds of poor glycemic control over time (HbA1c >8%). For the primary outcome, a linear mixed model (LMM) approach was used to model the relationship of HbA1c levels and race/ethnicity over time. For the secondary outcome, generalized LMMs were used to assess whether glycemic control changed over time and whether change in glycemic control varied by racial/ethnic group. RESULTS: Mean age was 66.3 years, 36% were non-Hispanic black (NHB), 98% were male, 65% were married, and 50% were unemployed. Mean follow-up time was 4.4 years. Least square mean HbA1c levels from LMM adjusted for time and relevant confounders showed that NHBs had higher HbA1c values over time (mean difference of 0.54% [P < 0.001]). The final model with poor versus good glycemic control as the dependent variable, race/ethnicity as primary independent variable adjusted for time, and relevant confounders showed that NHBs were likely to have poor control compared with NHWs (OR: 1.8, 95% CI, 1.7; 2.0, P < 0.0001). CONCLUSIONS: NHB veterans were more likely to have higher mean HbA1c values and less likely to have good glycemic control over time compared with NHW veterans.

Effect of trajectories of glycemic control on mortality in type 2 diabetes: a semiparametric joint modeling approach.

Data on the effect of trajectories in long-term glycemia and all-cause mortality are lacking. The authors studied the effect of trajectories in long-term glycemic control on all-cause mortality in patients with type 2 diabetes. A cohort of 8,812 veterans with type 2 diabetes was assembled retrospectively using Veterans Affairs registry data. For each veteran in the cohort, a 3-month person-period data set was created from April 1997 to May 2006. The average duration of follow-up was 4.5 years. The overall mortality rate was 15.3%. Using a novel approach for joint modeling of time to death and longitudinal measurements of hemoglobin A1c (HbA1c) level, after adjustment for all significant baseline covariates, baseline HbA1c was found to be significantly associated with mortality (hazard ratio = 2.1, 95% confidence interval: 1.3, 3.6) (i.e., a 1% increase in baseline HbA1c level was associated with an average 2-fold increase in mortality risk). Similarly, the slope of the HbA1c trajectory was marginally significantly associated with mortality (hazard ratio = 7.3, 95% confidence interval: 0.9, 57.1) after adjustment for baseline covariates (i.e., a 1% increase in HbA1c level over 3 months was associated with a 22% increase in mortality risk). The authors conclude that a positive trajectory of long-term hyperglycemia is associated with increased mortality.

Longitudinal effects of depression on glycemic control in veterans with Type 2 diabetes.

OBJECTIVES: To examine the longitudinal effects of depression on glycemic control in veterans with Type 2 diabetes. METHODS: Data on 11,525 veterans with Type 2 diabetes were analyzed. A person-period dataset for each subject to cover 3-month intervals (36 time intervals) from April 1997 to March 2006 was created. Subjects were classified as depressed based on ICD-9 codes for depression. General linear mixed model regression was used to examine changes over time in HbA(1c) levels and whether the changes from baseline were different in depressed and nondepressed diabetic veterans, sequentially adjusting for baseline age, demographic variables and comorbidities (coronary heart disease, stroke and hypertension). Pooled t-tests were used to compare unadjusted mean HbA(1c) at each time point across the depressed and nondepressed groups. SAS was used for statistical analysis. RESULTS: Ninety-seven percent were men, 48% were white, 27% were blacks and 25% were other. Mean age was 66 years and mean follow-up period was 4.1 years. Six percent (696/11,525) of the sample had diagnosed depression. Unadjusted mean HbA(1c) values were significantly higher in depressed vs. nondepressed subjects at all time points. The adjusted mean HbA(1c) values over time in the final mixed model were significantly higher in depressed vs. nondepressed subjects (mean difference of 0.13; 95% CI [0.03; 0.22]; P=.008). In all adjusted models, differences in mean HbA(1c) values were significantly higher in depressed vs. nondepressed subjects with Type 2 diabetes. CONCLUSION: This study of veterans with Type 2 diabetes demonstrates that there is a significant longitudinal relationship between depression and glycemic control as measured by HbA(1c) and that depression is associated with persistently higher HbA(1c) levels over time.