Disparities in A1C Levels Between Hispanic and Non-Hispanic White Adults with Diabetes a Meta-Analysis

Epidemiology/Health Services Research ORIGINAL ARTICLE

Disparities in A1C Levels Between Hispanic and Non-Hispanic White Adults With Diabetes A meta-analysis

1 2 JULIENNE K. KIRK, PHARMD, CDE RALPH B. D’AGOSTINO,JR., PHD group in the U.S., and Hispanics have a 2 1 LEAH V. PASSMORE, MS THOMAS A. ARCURY, PHD higher lifetime risk of diabetes than do 3 3 RONNY A. BELL, PHD SARA A. QUANDT, PHD non-Hispanic whites (2,3). Diabetes has a K.M. VENKAT NARAYAN, MD, MSC, MBA, major adverse impact on life years and FRCP4 quality-adjusted life years in all U.S. sub- populations, with an even greater impact among minority individuals including OBJECTIVE — Hispanics have higher rates of diabetes and diabetes-related complications Hispanics (3). Specifically, Hispanics than do non-Hispanic whites. A meta-analysis was conducted to estimate the difference between have higher rates of many diabetes com- the mean values of A1C for these two groups. plications such as retinopathy, neuropathy, and lower leg amputations than do RESEARCH DESIGN AND METHODS — We executed a PubMed search of articles non-Hispanic whites (4–9). published from 1993 through July 2007. Data sources included PubMed, Web of Science, Cumulative Index to Nursing and Allied Health, the Cochrane Library, Combined Health Infor- Improvements in glycemic control mation Database, and Education Resources Information Center. Data on sample size, age, sex, have been shown to prevent microvascu- A1C, geographical location, and study design were extracted. Cross-sectional data and baseline lar complications, and large trials have data from clinical trials and cohort studies for Hispanics and non-Hispanic whites with diabetes demonstrated the need for glucose con- were included. Studies were excluded if they included individuals Ͻ18 years of age or patients trol among patients with diabetes with pre-diabetes or gestational diabetes. (10,11). Literature reviews have sug- gested that A1C is higher among minority RESULTS — A total of 495 studies were reviewed, of which 73 contained data on A1C for populations than among nonminority Hispanics and non-Hispanic whites, and 11 met the inclusion criteria. Meta-analysis revealed a populations, and a previous meta- statistically significant mean difference (P Ͻ 0.0001) of Ϫ0.46 (95% CI Ϫ0.63 to Ϫ0.33), correlating to an ϳ0.5% higher A1C for Hispanics. Grouping studies by design (cross-sectional analysis confirmed higher levels of A1C or cohort), method of data collection for A1C (chart review or blood sampling), and care type among African Americans than among (managed or nonmanaged) yielded similar results. non-Hispanic whites (12,13). Factors that may underlie lack of A1C control in- CONCLUSIONS — In this meta-analysis, A1C was ϳ0.5% higher in Hispanic patients with clude language barriers, inadequate ac- diabetes than in non-Hispanic patients. Understanding the reasons for this disparity should be a cess to care, lack of insurance coverage, focus for future research. low socioeconomic status, quality-of-care factors, self-care behaviors, and biological Diabetes Care 31:240–246, 2008 differences (14,15). Variance in A1C between populations may be due to poor thnic minorities in the U.S. are dis- abetes is 10.5% for Hispanic or Latino in- control and/or biological differences proportionately affected by diabetes dividuals compared with 6.8% for non- across ethnic groups. Ն E (1). For adults 18 years of age, the Hispanic whites (1). The Hispanic Although a number of studies varying age-adjusted prevalence of diagnosed di- population is the fastest growing minority in size and design have shown ethnic dif- ●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●● ferences in glycemic control between His- From the 1Department of Family and Community Medicine, Wake Forest University School of Medicine, panics and non-Hispanic whites, to date Winston-Salem, North Carolina; the 2Division of Public Health Sciences, Department of Biostatical Sciences, there has not been a systematic analysis of Wake Forest University School of Medicine, Winston-Salem, North Carolina; the 3Division of Public Health these data. We reviewed the literature Sciences, Department of Epidemiology and Prevention, Wake Forest University School of Medicine, Win- (1993–July 2007) for studies in which ston-Salem, North Carolina; and the 4Hubert Department of Global Health, Emory University and Division of Diabetes Translation, Centers for Disease Control and Prevention, Atlanta Georgia. comparisons between these populations Address correspondence and reprint requests to Julienne K. Kirk, PharmD, CDE, Associate Professor, were made and conducted a meta- Department of Family and Community Medicine, Wake Forest University School of Medicine, Medical analysis using standardized statistical Center Boulevard, Winston-Salem, NC 27157-1084. E-mail: [email protected]. methods. This time period was selected Received for publication 23 February 2007 and accepted in revised form 19 October 2007. because the A1C measurement, a marker Published ahead of print at http://care.diabetesjournals.org on 31 October 2007. DOI: 10.2337/dc07- 0382. of attachment of glucose to the erythro- Abbreviations: MeSH, Medical Subject Heading. cyte over the previous 3 months, became The contents of this article are the responsibility of the authors and do not necessarily reflect the official more standardized over the past 10–15 views of Centers for Disease Control and Prevention or Association of Teachers of Preventive Medicine. years. Hispanic refers to populations who © 2008 by the American Diabetes Association. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby trace their origin to Spain or a Spanish- marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. speaking country. We used this criterion

240 DIABETES CARE, VOLUME 31, NUMBER 2, FEBRUARY 2008 Kirk and Associates for defining Hispanic populations in this abetes and contain comparative data for of potential selection bias in patient re- article and restricted our focus to such both Hispanics (of any area) and non- cruitment. If there was more than one populations residing in the U.S. Hispanic whites. We rejected abstracts publication from the same database, we that included patients with gestational di- accepted the most recent data file that was published. RESEARCH DESIGN AND abetes or pre-diabetes. However, we ac- METHODS cepted studies that included both type 1 and type 2 diabetes. We collected addi- Data extraction Identification of studies tional references from bibliographies of Two investigators (J.K.K. and R.A.B.) in- We conducted a MEDLINE search in reviews, original research articles, and other articles of interest. Web of Science, dependently reviewed each study for the PubMed, using Medical Subject Heading following data: 1) sample size (N), 2) (MeSH) terms and restricted the search to Cumulative Index to Nursing and Allied Health, the Cochrane Library, Combined mean and SD of participants’ age, 3) num- entries from 1993 through July 2007. We ber of men and women, 4) A1C mean and used the search terms “Diabetes Mellitus” Health Information Database, and Educa- tion Resources Information Center were SD, 5) geographic location of the re- (MeSH) or “Diabetes Mellitus, type 2” search, and 6) study design. Figure 1 (MeSH) and “Hemoglobin A, Glycosy- databases that we also searched. A total of 495 abstracts were applicable to the shows a flow diagram of the literature related” (MeSH) and “Hispanic Americans” view. Eleven studies (16–26) contained (MeSH) or “Mexican Americans” (MeSH). project. A variety of study designs were found glycemia-related data for Hispanics and The MeSH term “Hispanic Americans” non-Hispanic whites including A1C when exploded includes Hispanic Amer- (Table 1). If the SD of the A1C was not reported or could not be obtained from mean value and SD (Table 1). For three of icans, Spanish Americans, Cuban Ameri- the studies (15,17,18) included in this cans, Hispanics, Latinos, and Puerto the authors, we did not include the study in the meta-analysis. We accepted author- meta-analysis, the authors personally Ricans. We applied the limits “All Adult, provided A1C data or SDs. Ն18 years of age,” and “English lan- reported data only if we were assured by guage.” We initially retrieved 1,271 ab- written communication that the information was obtained from the original com- stracts and evaluated them for Statistical analysis puterized dataset. If a study was an applicability to the project. Publications A primary meta-analysis was conducted accepted had to include patients with di- intervention trial, it was excluded because on the 11 studies (16–26). Six individual meta-analyses were conducted on subsets including study type (cohort and cross- sectional studies), method of data collection (chart review and blood sampling), and care type (managed or nonmanaged). Baseline data are summarized in Table 1 for the 11 studies that met the inclusion criteria. Individual meta-analyses were conducted on the subsets to judge the sensitivity of the results and justify the conclusions of the primary analysis. In addition to the meta-analyses performed in the subsets, two additional analyses were done to further examine the effect of age or BMI on A1C differences between Hispanics and non-Hispanic whites. Without patient-level data, the summary meta-analysis could not be adjusted for possible confounding effects of age and BMI. The first of these two additional meta-analyses was done on the subset of studies in which there were no differences in age between the two groups. The second analysis was done on the subset of studies in which there was no difference in BMI between the two groups (Table 1). A mean difference in A1C was calculated between Hispanics and non-Hispanic whites. For each study, a 95% CI was calculated. Homogeneity of the effect sizes across studies was first assessed using a ␹2 test to determine whether a fixed- or random- effects approach should be implemented. Figure 1—Flow diagram of systematic review of literature. A fixed-effects approach treats the set of

DIABETES CARE, VOLUME 31, NUMBER 2, FEBRUARY 2008 241 Hispanic disparities in A1C

Figure 2—Mean A1C (%) differences between Hispanics and non-Hispanic whites. *Cross-sectional study; †prospective cohort study; ‡data obtained from chart review; §A1C sample from study-initiated blood draw; ʈmanaged care; ¶nonmanaged care. studies as homogeneous and considers dom-effects models were used in all seven tion as Hispanic, three as Mexican Amer- them representative of all potential stud- cases. All tests of effect were two sided, ican, and two as Latino. Four studies were ies of interest, whereas the random-effects and P Ͻ 0.05 was considered to be statis- done in a managed care setting; five used approach treats the studies as heteroge- tically significant. chart review, and six used blood sampling neous and considers them to be a sample to obtain A1C data (Table 1). BMI and age from a population of comparable studies. were reported for 10 of the 11 studies. The homogeneity test results indicated RESULTS — Differences existed in the Statistical comparison of mean age be- the use of random-effects models in five of age of participants across studies, but tween non-Hispanic whites and Hispan- the seven meta-analyses. As the more con- most included patients Ͼ50 of age (Table ics showed no difference in age in five of servative approach to meta-analyses, ran- 1). Four studies designated the popula- the studies. The same comparison for BMI

Figure 3—Summary of mean A1C (%) differences between Hispanics and non-Hispanic whites.

242 DIABETES CARE, VOLUME 31, NUMBER 2, FEBRUARY 2008 243 Kirk and Associates

Table 1—Characteristics of studies among Hispanics and non-Hispanic whites*

Non-Hispanic whites Hispanic Age BMI A1C Age BMI A1C Study n (years)* (kg/m2 )† (%) n (years)* (kg/m2 )† (%) Site Study design Boltri et al., 2005 (16) 157 59 Ϯ 1.7 32.8 Ϯ 9.8 7.6 Ϯ 2.5 202 56.5 Ϯ 1.6 31.0 Ϯ 5.16 8.2 Ϯ 4.2 1999–2000 NHANES Cross-sectional national sample Bonds et al., 2003 (17)*‡ 144 62 Ϯ 8 30.8 Ϯ 6 7.4 Ϯ 1.8 156 61.4 Ϯ 9.1 30.7 Ϯ 5.7 7.9 Ϯ 2.1 IRAS cohort in CO and TX Prospective cohort Brown et al., 2005 (18)*‡ 2,787 61 Ϯ 13 31.6 Ϯ 7.3 7.8 Ϯ 1.7 1,207 60.9 Ϯ 12.7 30.9 Ϯ 6.8 8.2 Ϯ 1.9 TRIAD study of diabetes in Prospective cohort managed care (MI, NJ, PA, TX, CA, HI, and IN) Chesla et al., 2000 (19)† 116 48.4 Ϯ 8.9 31.0 Ϯ 7.2 8.2 Ϯ 1.6 76 51.7 Ϯ 7.7 31.8 Ϯ 5.3 9.0 Ϯ 2.1 11 private and public health Cross-sectional facilities in CA Dunbar et al., 2005 (20) 599 51 Ϯ 1.9 31.4 Ϯ 7.6 8.7 Ϯ 2.2 257 46 Ϯ 1.9 29.5 Ϯ 5.5 9.3 Ϯ 2.9 Urban outpatient diabetes Cross-sectional clinic in GA Harris et al., 1999 (21) 486 Ն20 NA 7.6 Ϯ 1.9 399 Ն20 NA 8.0 Ϯ 2.0 NHANES III Cross-sectional Karter et al., 2002 (22)‡ 40,025 61 Ϯ 13 30.0 Ϯ 6.6 8.4 Ϯ 1.8 6,279 56.7 Ϯ 12.3 30.3 Ϯ 6.1 8.8 Ϯ 2.0 Northern CA Kaiser Prospective cohort Permanente patients Lindeman et al., 1998 (23)*† 70 72.9 Ϯ 5.5 27.7 Ϯ 4.0 8.4 Ϯ 2.5 118 74.1 Ϯ 5.6 27.8 Ϯ 4.7 8.9 Ϯ 2.9 Medicare recipients from Cross-sectional Health Care Financing Authority in NM Sharma and Pavlik, 2001 (24)*† 111 63.2 Ϯ 12.7 31.4 Ϯ 8.1 9.4 Ϯ 2.9 132 60.6 Ϯ 13 30.6 Ϯ 6.3 10.2 Ϯ 2.1 Community clinic patients Retrospective chart review 2008 in TX Wendel et al. 2006 (26)*† 226 65,5 Ϯ 9.4 32.3 Ϯ 6.2 7.9 Ϯ 1.4 72 64.9 Ϯ 10.1 30.9 Ϯ 5.7 8.2 Ϯ 1.6 3 Veterans Affairs Medical Cross-sectional

Centers in Southwest EBRUARY Ϯ Ϯ Ϯ Ϯ Ϯ Ϯ Young et al., 2005 (25)† 2,197 60.9 12.3 31.9 7.5 7.8 1.6 98 55.5 11.9 31.1 7.8 8.0 1.8 9 primary care clinics in Cross-sectional 2, F western WA Data are means Ϯ SD. *t test for differences in age (NS). †t test for differences in BMI (NS). ‡A1C provided by the author via written communication. IRAS, Insulin Resistance Atherosclerosis Study; NA, not available; NHANES, National Health and Nutrition Examination Survey; TRIAD, Translating Research into Action for Diabetes. NUMBER 31, VOLUME , ARE C IABETES D Hispanic disparities in A1C resulted in no difference between the inclusion of a variety of study designs, the relationship between A1C and com- groups in six of the studies. Two separate the ability to examine A1C differences plications related to medical costs has additional meta-analyses were performed by study type, data collection methods, been investigated using a computer- including only these five and six studies, and care type, and the use of previously simulated model in individuals with type respectively. unpublished data (15,17,18). 2 diabetes developed by the National In- One of the 11 studies indicated signif- The reasons for the disparity in A1C stitutes of Health (38). Using this model, icantly higher A1C levels in Hispanics found in this meta-analysis are not well Hispanics had the highest predicted com- than in non-Hispanic whites (Fig. 2). established in the literature. Hispanic pa- plication rates and the highest predicted Each meta-analysis resulted in statistically tients with diabetes have been reported to costs for eye disease, renal disease, and significant differences in A1C levels be- have a higher prevalence of cardiovascu- neuropathy/lower extremity amputation. tween Hispanics and non-Hispanic lar disease risk factors than non-Hispanic Although the studies included in our whites. The summary mean A1C (%) dif- whites (4–6). Differences in biology, ac- analysis used a variety of designs, a con- Ϫ Ϫ ference size was 0.46 (95% CI 0.54 to cess to care, insurance status, and adher- sistency in the degree of disparity of gly- Ϫ 0.39), which indicated that non- ence to diabetes treatment regimens cemic control was found regardless of Hispanic whites had A1C values that were (medication, nutrition, behavior, and study type. Multiple separate meta- ϳ 0.5% below those of Hispanics (Fig. 3). others) are all plausible explanations of analyses were conducted across study The mean differences were similar regard- the disparity. Beliefs about diabetes com- types (prospective cohort, cross- less of study design. The estimated mean mon among Hispanics may also result in sectional, or retrospective chart review). difference for cross-sectional studies was behaviors that limit diabetes self- Ϫ Ϫ Additional meta-analyses were also per- 0.52 ( 0.71 to 0.32) and for prospec- management (33–35). A recent compari- formed according to whether A1C data tive cohort studies was Ϫ0.40 (Ϫ0.42 to son of 2004 Behavioral Risk Factor Ϫ were collected by blood sampling or ob- 0.37). Similarly, when studies were di- Surveillance System data for Hispanics tained post hoc from medical chart review vided into two groups according to data and non-Hispanic whites indicates that and by sex, with all resulting in the same collection type, the mean A1C (percent) Hispanics have lower quality of diabetes outcome. Hispanics with diabetes have an differences were consistent with the re- care (36). ϳ0.5% higher A1C across studies. Of sults from the summary analysis. Studies A limitation to the analysis is publi- note is the fact that a 1% reduction in A1C in which the A1C values were collected cation bias. However, we performed nu- has been correlated with an estimated from chart reviews had a mean difference merous searches on this topic and of Ϫ0.45 (Ϫ0.55 to Ϫ0.35), and studies contacted multiple investigators to re- 21% reduction in vascular complications in which the values were obtained from trieve unpublished data on A1C means (39). For this meta-analysis, an estimated baseline blood sampling had a mean dif- and SDs. The heterogeneity of the stud- reduction would correspond to about a ference of Ϫ0.55 (Ϫ0.59 to Ϫ0.51). For ies adds to the limitations of the analysis 10.5% decreased risk. The reported find- managed care studies the mean difference in that individuals classified as Hispanic ings are significant because ethnic dispar- was Ϫ0.38 (0.43 to Ϫ0.33), and for non- have a variety of places of origin. In ities in glycemic control may be directly managed care it was Ϫ0.57 (Ϫ0.78 to some studies, Hispanics (20) were likely related to vascular outcomes. Ϫ0.36). The supporting analysis, includ- to be recent migrants from Mexico and Future researchers should focus not ing only studies in which there was no Central America, whereas others (17) only on discovering the source of dispar- difference in age, had a mean difference of included Spanish-speaking populations ities in glycemic control that exist be- Ϫ0.48 (Ϫ0.63 to Ϫ0.33). Likewise, the who have been in the U.S. for a consid- tween minority populations and non- analysis including only studies in which erable length of time. Nevertheless, re- Hispanic whites but also on reducing there was no difference in BMI had a mean sults are probably generalizable to these disparities—specifically, how much difference of Ϫ0.50 (Ϫ0.70 to Ϫ0.30). Hispanic and non-Hispanic white adult of these disparities is due to biological dif- Both results support the primary meta- patients with type 2 diabetes because ferences, types of lifestyles, health care ac- analysis and indicate that despite differ- the data included a broad range of pa- cess and utilization, or socioeconomic ences in age or BMI between non- tient ages, geographic settings, and factors. Although an overall 0.5% differ- Hispanic whites and Hispanics in some study types. Another limitation to this ence in A1C among studies between His- studies included in this analysis, the dif- meta-analysis is that despite the com- panics and non-Hispanic whites was ferences in A1C are persistent. prehensive review of abstracts, the po- found, the largest difference in A1C was tential for omission exists if an abstract among the nonmanaged care group of CONCLUSIONS — This meta-analy- initially reviewed through our search studies. These data suggest that Hispanic sis shows that, in general, A1C is higher in process did not specifically address ra- patients with diabetes in nonmanaged Hispanics than in non-Hispanic whites cial disparities. care settings are different with regard to with an overall mean A1C difference of The results of this meta-analysis, A1C values. Potential fragmented care, 0.5%. The consistency of the findings is however, depend in part on the accuracy, access to care, and quality of care should notable. This meta-analysis combined 11 standardization, and reliability of the A1C be further evaluated in this population. studies to evaluate the overall mean dif- measurement across studies. A recent ference. For the studies that were ex- evaluation of ethnic differences in A1C cluded but that reported A1C above among patients in the Diabetes Preven- Acknowledgments— This publication was Ͼ target thresholds (i.e., 7%), glycemic tion Program with impaired glucose tol- made possible through a cooperative agree- control was worse among Hispanics erance indicated that hemoglobin ment between the Centers for Disease Control than among non-Hispanic whites (27– glycation or red cell survival may differ and Prevention and the Association of Teach- 32). The strengths of this analysis are its among ethnic groups (37). Additionally, ers of Preventive Medicine (Award TS-0778).

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