Gregory E. Gilbert

Risk Factors Related to Inflammation and Endothelial Dysfunction in the DCCT/EDIC Cohort and Their Relationship With Nephropathy and Macrovascular Complications

OBJECTIVE—Because endothelial cell dysfunction and inflammation are key contributors to the development of complications in type 1 diabetes, we studied risk factors related to endothelial dysfunction and inflammation (C-reactive protein and fibrinogen, soluble vascular cell adhesion molecule-1, intracellular adhesion molecule-1, and E-selectin, and fibrinolytic markers) in a subgroup of patients from the Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Intervention and Complications (EDIC) study cohort. RESEARCH DESIGN AND METHODS—We determined which of these risk factors or clusters thereof are associated with the presence of and subsequent development of nephropathy and macrovascular complications (reflected by carotid intima-media thickness [IMT]). RESULTS—After adjustment for conventional risk factors (age, sex, DCCT treatment group, diabetes duration, A1C, systolic blood pressure, waist-to-hip ratio, total and HDL cholesterol, and smoking status), fibrinogen remained strongly associated with progression of internal and common carotid IMT (P < 0.01) and soluble E-selectin had a strong association with nephropathy (P < 0.01). CONCLUSIONS—The best predictor for IMT progression in the DCCT/EDIC cohort was plasma fibrinogen, and the levels of soluble E-selectin discriminate patients with albuminuria better than conventional risk factors.

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 HbA1c. 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 HbA1c levels (as continuous and dichotomized at ≥8.0%). RESULTS Relative to non-Hispanic whites (NHWs), HbA1c 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 HbA1c being lowest in the South and highest in the Mid-Atlantic. Rural/urban location of residence was not associated with HbA1c 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 HbA1c levels and HbA1c 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.

Delayed Prenatal Care and the Risk of Low Birth Weight Delivery

To determine if the timing of prenatal care is associated with low birth weight delivery after adjusting for sociodemographic and behavioral risk factors, we performed a retrospective cross-sectional study of singleton births to white (2,945,595) or African-American (552,068) women in the United States in 1996. When adjusted for race, maternal age, educational level attained, and the use of alcohol and tobacco during pregnancy, women beginning care in the 2nd (adjusted RR = 0.85; 95% CI: 0.83–0.86) and 3rd trimesters (RR = 0.87; 95% CI: 0.84–0.91) had a reduced risk of low birth weight compared to women beginning care in the 1st trimester. Our findings suggest that no benefit exists for early initiation of prenatal care for reducing the risk of low birth weight. Findings related to differences in low birth weight among women who start prenatal care later are likely due to sociodemographic differences that may influence access to early care.

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.

Undergraduate Institutional MCAT Scores as Predictors of USMLE Step 1 Performance

Medical schools using formal undergrad-uate selectivity measures do so to compensate for the psychometricinadequacies of college grade-point averages, believing that moremeaning can be derived from the GPA if it is attached to a measureof institutional performance (academic rigor) or selectivity (strin-gent admission standards).Researchers have reported mixed results on whether formal mea-sures of undergraduate institution selectivity are useful contributorsto predicting medical student performance.

Does institutional selectivity aid in the prediction of medical school performance

Various factors are considered in the decision to offer an admission interview to a medical school applicant, including Medical College Admission Test (MCAT) scores, undergraduate grade-point average (GPA), and the selectivity of the degree-granting undergraduate institution. Admission officers view MCAT scores, undergraduate GPA, and institutional selectivity as having high or moderate importance. Research has indicated that these factors, most notably the MCAT scores and the undergraduate GPA, are reliable in helping predict medical school performance. The strongest association has been shown between MCAT scores and performance on the United States Medical Licensing Examination, Step 1. Institutional selectivity data are used to help control for differences in grading stringency across undergraduate institutions. Previous reports have examined the role of institutional selectivity, or a specific undergraduate institution, as a predictor of performance in the first two years of medical school. With the exception of the study of Zelesnik et al., which examined ten specific undergraduate institutions, these reports have used the Higher Education Research Institute (HERI) Index, also called the ‘‘Astin Index,’’ as a measure of institutional selectivity. Other measures of institutional selectivity or categorization that schools of medicine may employ include the Barron’s Profiles of American Colleges Admissions Selector Rating and the Carnegie Classification from the Carnegie Foundation for the Advancement of Teaching. (These measures are explained in the next section.) Institutional validity studies of admission decision-making data help to determine which characteristics should be accorded highest importance in applicant selection. Given the reliance upon institutional selectivity as an important admission characteristic and the different types of selectivity classifications available for medical schools to use, the purpose of this study was to examine how well three measures of institutional selectivity could predict medical students’ performances, specifically their performances on the USMLE Step 1 and Step 2 and their final medical school GPAs.

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

BackgroundMany 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.MethodsA 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).ResultsQuantile-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.ConclusionQuantile 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.

Comparison of Cardiovascular Risk Factors for High Brachial Pulse Pressure in Blacks versus Whites (Charleston Heart Study, Evans County Study, NHANES I and II Studies)

We examined whether the risk factors for increased brachial pulse pressure (PP) are similar for blacks and whites. Many studies have reported the strong association of increased brachial PP and the prevalence of cardiovascular disease. Participants were from 4 major epidemiologic studies in the United States (26,083 subjects): Charleston Heart Study, Evans County Heart Study, the National Health and Nutrition Examination Survey (NHANES) I study, and the NHANES II study. At baseline, there was no history or clinical evidence of coronary heart disease (CHD). The CHD mortality as a function of brachial PP and the association of traditional risk factors for CHD with PP were analyzed for each of the 4 studies and for the 4 studies combined. Multiple regression analysis showed that the most significant predictors of high brachial PP are body mass index > or =30 kg/m(2) (regression coefficient 3.79, p <0.0001), diabetes mellitus (5.14, p <0.0001), serum total cholesterol > or =240 mg/dl (0.51, p <0.0157), age (0.60, p <0.0001), gender (-1.77, p <0.0001), and race (3.75, p <0.0001). In conclusion, the same risk factors for CHD (namely, increase in body mass index > or =30 kg/m(2), diabetes mellitus, hypercholesterolemia, and age) are significantly associated with high brachial PP for blacks and whites. These risk factors were stronger in whites compared with blacks. However, female gender and age variables were even more associated with brachial PP in blacks. Smoking was significant but not reflected in peripheral brachial PP as it is in aortic PP.

Thirty-year survival for black and white hypertensive individuals in the Evans County Heart Study and the Hypertension Detection and Follow-up Program

The Evans County Heart Study (ECHS), initiated in 1960, was one of the first major studies to document cardiovascular disease (CVD) risks for African Americans and Caucasians with elevated blood pressures. In the early 1970s, the Hypertension Detection and Follow-up Program (HDFP), with a site in Georgia (HDFP-GA) was one of the first major studies to demonstrate that treating hypertension with stepped care (SC), versus referred care (RC), has better short-term outcomes. With this background, study objectives were to evaluate 30-year survival and cardiovascular outcomes of the HDFP-GA and to compare outcomes of these patients with 1619 hypertensive individuals (30-69 years of age) from the ECHS. HDFP-GA patients included 688 individuals (black [n=267]; white [n=421]) randomized to RC (n=341) and SC (n=347). The ECHS was comprised of 733 black and 886 white hypertensives. All-cause mortality and CVD mortality were assessed in the HDFP-GA and compared to the ECHS hypertensives. After 30-years of follow-up, 65.7% of the HDFP-GA cohort had died compared with a similar 65.8% of the ECHS hypertensives. However, CVD mortality rates, while similar for the SC and RC arms, were lower than in the HDFP-GA total study group than the hypertensive participants of ECHS (32.6% vs. 40.3% p<.001). CVD survival rates for both SC and RC HDFP-GA arms were significantly better than population-based hypertensive individuals in the ECHS, with consistent benefits in all four race-sex groups. These results identify the importance of long-term follow-up of individuals in hypertension studies and trials that include CVD outcomes.

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.