BACKGROUND/RATIONALE:
Ethnic minority populations bear an inordinate burden from type 2 diabetes as reflected by the higher occurrence of disease sequelae such as amputations, loss of vision, and premature mortality. Effective control of diabetes requires treatment with multiple agents and adherence to these medications is critical to achieve target treatment goals. Evidence supports that up to 50% of people with diabetes are non-adherent to medications. Medication non-adherence (MNA) is highly correlated with poor metabolic control, increased health care cost, and increased mortality. Prior to our study, there were significant gaps in knowledge on the relationship between MNA, race/ethnicity and subsequent health care costs and mortality in veterans with type 2 diabetes.

OBJECTIVE(S):
Three aims addressed the primary study objectives, which determined: 1) racial/ethnic differences in MNA in elderly veterans with type 2 diabetes after controlling for relevant covariates, 2) the effect of MNA on healthcare costs across racial/ethnic groups over time, and 3) the effect of MNA on mortality across racial/ethnic groups over time. We hypothesized that, compared to non-Hispanic Whites (NHW), ethnic minorities (non-Hispanic Black-NHB, and Hispanic) would have higher MNA, and higher healthcare costs and mortality with increased MNA over time.

METHODS:
Study Population: A national cohort of veterans with type 2 diabetes was created by linking multiple patient and administrative files. The National Patient Care (NPC) database was the source data for the VHA Medical SAS Datasets, used to analyze veteran clinical data such as diagnosis and procedure codes for inpatient and outpatient visits. The Pharmacy Benefits Management (PBM) database included utilization information for every prescription filled in the VA by a site's pharmacy (new fill or refill) and by a Consolidated Mail Outpatient Pharmacy. Veterans were included in the cohort if they had type 2 diabetes defined by two or more International Classification of Diseases, Ninth Revision (ICD-9) codes for diabetes (250, 357.2, 362.0, and 366.41) in the previous 24 months (2000 and 2001) or during 2002 from inpatient stays and/or outpatient visits on separate days. Veterans were followed from time of entry until death, loss to follow-up, or through December 2006. The cohort included a total of 892,223 veterans of which 61.51% were NHW, 12.14% were NHB, 13.86% were Hispanic and 12.48% had either missing or unknown race/ethnicity information.

Primary Variables of Interest: Annual medication possession ratio (MPR) was defined as the number of days supply divided by 365 days over the study period for each veteran. MPR was also calculated for individuals using 1) insulin combined with hypoglycemic agents, 2) insulin only, and 3) hypoglycemic agents only. Additionally, a three-level variable classified individuals as medication-adherent (i.e., MPR 80%), non-adherent and no medication. Finally, HbA1c was calculated as post-entry (baseline) mean of all observations recorded within a year. Regression models were used to model relationships between exposures and outcomes of interest.

FINDINGS/RESULTS:
Several key findings have emerged from the study. Three articles have been published in peer-reviewed journals and five manuscripts are currently under review. In article #1 titled "Regional, Geographic, and Ethnic Differences in Medication Adherence Among Adults with Type 2 Diabetes" we reported significant regional, rural/urban, and racial/ethnic differences in MPR and that rural/urban residence modified the effect of race/ethnicity on MPR. In article #2 titled "Regional, geographic, and racial/ethnic variation in glycemic control in a national sample of veterans with diabetes", we found that NHB and Hispanics had higher HbA1c levels compared to NHW, but differences were largely explained by adjustment for covariates. In article #3 titled "Using quantile regression to investigate racial disparities in medication non-adherence", we focused on using quantile regression to investigate racial disparities in MNA. The five manuscripts currently under review examine (1) the relationship between MPR and mortality stratified by racial/ethnic group; (2) the relationship between HbA1c levels and mortality stratified by medication adherence and racial/ethnic group; (3) methodological considerations when working with large databases; (4) the economic impact of MNA in veterans with diabetes; and (5) methodological advances in examining the economic impact of MNA. The collective evidence from these manuscripts confirm our hypotheses that veterans have a substantially higher mortality risk and healthcare costs in the lowest MPR quintile relative to the highest quintile. Additionally, we found evidence for racial/ethnic differences in the association between glycemic control and mortality, which varied by medication adherence. Joint modeling analyses found annual pharmacy cost increased approximately 3% per year (p=0.001) while inpatient and outpatient costs remained stable during the 5-year study time period. Compared to adherent subjects, patients with MNA had 43% higher annual inpatient costs, 6% lower outpatient costs, and 36% lower pharmacy costs.

IMPACT:
These findings suggest that racial/ethnic variations in MPR, glycemic control, and mortality exist nationally and that there are racial/ethnic differences in the ability of MPR and glycemic control to predict outcomes. For example, race/ethnicity and medication status (i.e., medication use and adherence) appear to modify the association between HbA1c and mortality and may be important to consider when setting individualized HbA1c targets. Moreover, our economic analysis provides information on the financial impact to the VA of MNA among veterans with type 2 diabetes. Based on our estimations, extrapolating to the full Veteran population with diabetes, achieving 90% medication adherence (defined as MPR>=0.9) would result in an estimated mean savings of $1.79 billion per year in 2011 dollars.

In summary, quality improvement initiatives should target improvements in medication adherence, identification and early initiation of appropriate diabetes medications, and aggressive management of comorbid conditions in Veterans with diabetes. The strong association between MNA and mortality warrants further attention to multi-level interventions that increase ongoing and consistent use of medications. Aggressive strategies and policies should be implemented to achieve optimal medication adherence in patients with Type 2 diabetes.

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External Links for this Project

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PUBLICATIONS:

Journal Articles

1. Egede LE, Lynch CP, Gebregziabher M, Hunt KJ, Echols C, Gilbert GE, Mauldin PD. Differential impact of longitudinal medication non-adherence on mortality by race/ethnicity among veterans with diabetes. Journal of general internal medicine. 2013 Feb 1; 28(2):208-15. [view]
2. Egede LE, Gebregziabher M, Zhao Y, Dismuke CE, Walker RJ, Hunt KJ, Axon RN. Differential impact of mental health multimorbidity on healthcare costs in diabetes. The American journal of managed care. 2015 Aug 1; 21(8):535-44. [view]
3. Lynch CP, Gebregziabher M, Axon RN, Hunt KE, Payne E, Egede LE. Geographic and racial/ethnic variations in patterns of multimorbidity burden in patients with type 2 diabetes. Journal of general internal medicine. 2015 Jan 1; 30(1):25-32. [view]
4. Hunt KJ, Gebregziabher M, Lynch CP, Echols C, Mauldin PD, Egede LE. Impact of diabetes control on mortality by race in a national cohort of veterans. Annals of epidemiology. 2013 Feb 1; 23(2):74-9. [view]
5. Egede LE, Bishu KG, Walker RJ, Dismuke CE. Impact of diagnosed depression on healthcare costs in adults with and without diabetes: United States, 2004-2011. Journal of affective disorders. 2016 May 1; 195:119-26. [view]
6. Lynch CP, Gebregziabher M, Zhao Y, Hunt KJ, Egede LE. Impact of medical and psychiatric multi-morbidity on mortality in diabetes: emerging evidence. BMC endocrine disorders. 2014 Aug 20; 14:68. [view]
7. Egede LE, Gebregziabher M, Zhao Y, Dismuke CE, Walker RJ, Hunt KJ, Axon RN. Impact of mental health visits on healthcare cost in patients with diabetes and comorbid mental health disorders. PLoS ONE. 2014 Aug 1; 9(8):e103804. [view]
8. Gebregziabher MG, Zhao Y, Axon RN, Gilbert GE, Egede LE. Lessons learned in dealing with missing race data: an empirical investigation. Journal of biometrics & biostatistics. 2012 Apr 14; 3(138):1-5. [view]
9. Egede LE, Mueller M, Echols CL, Gebregziabher M. Longitudinal differences in glycemic control by race/ethnicity among veterans with type 2 diabetes. Medical care. 2010 Jun 1; 48(6):527-33. [view]
10. Egede LE, Gebregziabher M, Echols C, Lynch CP. Longitudinal effects of medication nonadherence on glycemic control. The Annals of pharmacotherapy. 2014 May 1; 48(5):562-70. [view]
11. Egede LE, Gebregziabher M, Lynch CP, Gilbert GE, Echols C. Longitudinal ethnic differences in multiple cardiovascular risk factor control in a cohort of US adults with diabetes. Diabetes research and clinical practice. 2011 Dec 1; 94(3):385-94. [view]
12. Egede LE, Gebregziabher M, Dismuke CE, Lynch CP, Axon RN, Zhao Y, Mauldin PD. Medication nonadherence in diabetes: longitudinal effects on costs and potential cost savings from improvement. Diabetes Care. 2012 Dec 1; 35(12):2533-9. [view]
13. Bishu KG, Gebregziabher M, Dismuke CE, Egede LE. Quantifying the Incremental and Aggregate Cost of Missed Workdays in Adults with Diabetes. Journal of general internal medicine. 2015 Dec 1; 30(12):1773-9. [view]
14. Hunt KJ, Gebregziabher M, Egede LE. Racial and ethnic differences in cardio-metabolic risk in individuals with undiagnosed diabetes: National Health and Nutrition Examination Survey 1999-2008. Journal of general internal medicine. 2012 Aug 1; 27(8):893-900. [view]
15. Axon RN, Gebregziabher M, Echols C, Msph GG, Egede LE. Racial and ethnic differences in longitudinal blood pressure control in veterans with type 2 diabetes mellitus. Journal of general internal medicine. 2011 Nov 1; 26(11):1278-83. [view]
16. Egede LE, Gebregziabher M, Hunt KJ, Axon RN, Echols C, Gilbert GE, Mauldin PD. Regional, Geographic, and Ethnic Differences in Medication Adherence Among Adults with Type 2 Diabetes. The Annals of pharmacotherapy. 2011 Feb 1; 45(2):169-78. [view]
17. Egede LE, Gebregziabher M, Hunt KJ, Axon RN, Echols C, Gilbert GE, Mauldin PD. Regional, geographic, and racial/ethnic variation in glycemic control in a national sample of veterans with diabetes. Diabetes Care. 2011 Apr 1; 34(4):938-43. [view]
18. Gebregziabher M, Lynch CP, Mueller M, Gilbert GE, Echols C, Zhao Y, Egede LE. Using quantile regression to investigate racial disparities in medication non-adherence. BMC medical research methodology. 2011 Jun 6; 11:88. [view]

Journal Other

1. Egede LE, Mueller M. Effects of Medication Adherence on Glycemic Control in Adults with Type 2 Diabetes. [Abstract]. Diabetes. 2008 Jan 1; 57(Suppl 1):A345. [view]

Book Chapters

1. Egede LE. Medical costs of depression and diabetes. In: Maj M, Sartorius N., Katon W, editors. Depression and Diabetes. Chichester, England: John Wiley & Sons, Ltd; 2010. Chapter 3. 63-79 p. [view]

Conference Presentations

1. Gebregziabher MG, Matthews L, Eckert M, Dubno J. A random effects approach for joint modeling of multivariate longitudinal hearing loss data ascertained at multiple frequencies. Paper presented at: Eastern North American Region / International Biometric Society Annual Meeting; 2013 Mar 1; Orlando, FL. [view]
2. Egede LE. Coordinated Care Approach to Improve Diabetes Care for Veterans. Poster session presented at: VA Rural Health State of the Science Conference; 2016 Sep 12; Washington, DC. [view]
3. Egede LE. Coordinated Care Approach to Improve Diabetes Care for Veterans. Poster session presented at: Diabetes Annual Fall Symposium for Primary Health Care Professionals; 2016 Sep 22; Charleston, SC. [view]
4. Hunt KJ, Gebregziabher MG, Lynch C, Egede LE. Differential Impact of Poorly Controlled Diabetes on Mortality by Race/Ethnicity and Medication Status in a National Cohort of Veterans with Diabetes. Poster session presented at: VA HSR&D / QUERI National Meeting; 2012 Jul 17; National Harbor, MD. [view]
5. Egede LE. Differential Relationships Between Diabetes Knowledge Scales and Diabetes Outcomes. Poster session presented at: Diabetes Annual Fall Symposium for Primary Health Care Professionals; 2016 Sep 22; Charleston, SC. [view]
6. Dismuke CE, Egede LE, Fakhry MD, Gebregziabher MG, Horner MD, Hunt KJ, Burgess J, Scanlon D. Dual Eligibility With Medicare: A Dual Problem For Veterans With Traumatic Brain Injury? Paper presented at: AcademyHealth Annual Research Meeting; 2013 Jun 23; Baltimore, MD. [view]
7. Egede LE, Dismuke CE. Estimating the Incidence of Diabetes in a Cohort of Veterans Diagnosed with Traumatic Brain Injury. Poster session presented at: Diabetes Annual Fall Symposium for Primary Health Care Professionals; 2016 Sep 22; Charleston, SC. [view]
8. Gebregziabher MG, Egede LE, Gilbert GE, Hunt KJ, Nietert PJ, Mauldin PD. Fitting parametric random effects models to very large data sets: case of VHA national data. Poster session presented at: Johns Hopkins Bloomberg School of Public Health Statistical Methods for Very Large Data Sets Conference; 2011 May 31; Baltimore, MD. [view]
9. Egede LE, Hunt KJ. Impact of Diabetes Control on Death by Race in a National Cohort of Veterans. Poster session presented at: National Institutes of Health Science of Eliminating Health Disparities Annual Summit; 2013 Oct 31; Baltimore, MD. [view]
10. Lynch C, Gebregziabher MG, Hunt KJ, Gilbert GE, Egede LE. Impact of Long-Term Medication Non-Adherence on Mortality Differs by Race/Ethnicity among Veterans with Diabetes. Poster session presented at: VA HSR&D / QUERI National Meeting; 2012 Jul 17; National Harbor, MD. [view]
11. Egede LE, Lynch C, Gebregziabher MG, Hunt KJ, Zhao Y, Gilbert GE. Impact of Medical and Psychiatric Comorbidity Burden and Mortality in Veterans with Type 2 Diabetes. Poster session presented at: Society of General Internal Medicine Annual Meeting; 2012 May 9; Orlando, FL. [view]
12. Egede LE. Independent Correlations of Chronic Kidney Disease Awareness Among Adults with Type 2 Diabetes. Paper presented at: Diabetes Annual Fall Symposium for Primary Health Care Professionals; 2016 Sep 22; Charleston, SC. [view]
13. Gebregziabher MG, Zhao Y, Dismuke CE, Hunt KJ, Egede LE. Jointly Modeling Multiple Cost Outcomes Using Multivariate Generalized Linear Mixed Models. Paper presented at: VA HSR&D National Meeting; 2012 Jul 18; Washington, DC. [view]
14. Gebregziabher MG, Zhao Y, Axon RN, Egede LE. Lessons Learned in Dealing with Missing Race Data: An Empirical Investigation. Poster session presented at: VA HSR&D National Meeting; 2010 Sep 13; Boston, MA. [view]
15. Dismuke CE, Walker RJ, Axon RN, Gebregziabher MG, Hunt KJ, Egede LE. Longitudinal Impact of Mental Health Outpatient Care on Healthcare Cost For Individuals with Type 2 Diabetes. Paper presented at: AcademyHealth Annual Research Meeting; 2013 Jun 23; Baltimore, MD. [view]
16. Gebregziabher MG, Egede LE, Dismuke CE, Hunt KJ, Axon RN, Walker RJ. Longitudinal Impact of Mental Health Outpatient Care on Healthcare Cost for Individuals with Type 2 Diabetes. Paper presented at: Medical University of South Carolina Student Research Day Annual Assembly; 2013 Nov 7; Charleston, SC. [view]
17. Egede LE. Quality of Diabetes Care Among Recent Immigrants to the United States. Poster session presented at: Diabetes Annual Fall Symposium for Primary Health Care Professionals; 2016 Sep 22; Charleston, SC. [view]
18. Hunt KJ, Gebregziabher MG, Lynch C, Axon RN, Gilbert GE, Green CE, Mauldin PD, Egede LE. Racial and ethnic differences in all-cause mortality in a national cohort of veterans with type 2 diabetes. Poster session presented at: VA HSR&D National Meeting; 2011 Feb 16; National Harbor, MD. [view]
19. Egede LE. Racial and Ethnic Differences in Out-of-Pocket Expenses among Adults with Diabetes. Poster session presented at: Diabetes Annual Fall Symposium for Primary Health Care Professionals; 2016 Sep 22; Charleston, SC. [view]
20. Egede LE. Racial Differences in Out-of-Pocket Medication Expenditures Overtime in US Adults with Diabetes: 2002-2011. Poster session presented at: Diabetes Annual Fall Symposium for Primary Health Care Professionals; 2016 Sep 22; Charleston, SC. [view]
21. Egede LE. Racial Differences in Spatial Patterns for Poor Glycemic Control in the Southeastern US. Poster session presented at: Diabetes Annual Fall Symposium for Primary Health Care Professionals; 2016 Sep 22; Charleston, SC. [view]
22. Egede LE. Relationship Between the Affordable Care Act and Insurance, Access, and Cost on the Quality of Care in Patients with Diabetes. Poster session presented at: Diabetes Annual Fall Symposium for Primary Health Care Professionals; 2016 Sep 22; Charleston, SC. [view]
23. Egede LE. Rural-Urban Differences in Quality of Care Indicators among Adults with Diabetes. Poster session presented at: Diabetes Annual Fall Symposium for Primary Health Care Professionals; 2016 Sep 22; Charleston, SC. [view]
24. Egede LE. Sex Differences in Quality of Care Indicators Among Adults with Diabetes. Poster session presented at: Diabetes Annual Fall Symposium for Primary Health Care Professionals; 2016 Sep 22; Charleston, SC. [view]
25. Gebregziabher MG, Zhao Y, Axon RN, Hunt KJ, Egede LE. Shared Parameter models for longitudinal multiple source cost data. Poster session presented at: Eastern North American Region / International Biometric Society Annual Meeting; 2012 Mar 30; Washington, DC. [view]
26. Egede LE, Gebregziabher MG. Telephone-delivered Behavioral Skills Intervention for African Americans with Type 2 Diabetes. Paper presented at: American Diabetes Association Annual Scientific Session; 2016 Jun 10; New Orleans, LA. [view]
27. Egede LE. The Association of Cumulative Discrimination on Quality of Care, Patient-Centered Care and Dissatisfaction with Care in Adults with Type 2 Diabetes. Paper presented at: Medical University of South Carolina Department of Medicine Annual Research Day; 2016 Feb 26; Charleston, SC. [view]
28. Gebregziabher MG, Lynch C, Mueller M, Gilbert GE, Green CE, Zhao Y, Egede LE. Using quantile regression to investigate racial disparities in medication non-adherence. Poster session presented at: VA HSR&D National Meeting; 2011 Feb 14; National Harbor, MD. [view]

DRA: Aging, Older Veterans' Health and Care, Diabetes and Other Endocrine Disorders
DRE: Treatment - Observational, Prognosis
Keywords: Adherence, Cost, Diabetes
MeSH Terms: none