Welch Center for Prevention

Baltimore, MD, United States

Welch Center for Prevention

Baltimore, MD, United States

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Selvin E.,Welch Center for Prevention | Rawlings A.M.,Welch Center for Prevention | Hoogeveen R.C.,Baylor College of Medicine | Ballantyne C.M.,Baylor College of Medicine | And 2 more authors.
Diabetes | Year: 2013

Advanced glycation end products (AGEs) and their receptors are strongly implicated in the development of diabetes complications. When stimulated by AGEs, the receptors for AGEs (RAGEs) induce in flammation and are thought to fuel disease progression. Soluble circulating RAGE (sRAGE) may counteract the detrimental effects of RAGE. We measured sRAGE in stored plasma from a random sample of 1,201 participants in the Atherosclerosis Risk in Communities (ARIC) Study who were aged 47-68 years, had normal kidney function, and had no history of cardiovascular disease. In cross-sectional analyses, black race, male sex, higher BMI, and higher C-reactive protein were independently associated with low sRAGE. The racial difference was striking, with blacks approximately three times more likely to have low sRAGE compared with whites even after adjustment. During ∼18 years of follow-up, there were 192 incident coronary heart disease events, 53 ischemic strokes, 213 deaths, and 253 cases of diabetes (among the 1,057 persons without diabetes at baseline). In multivariable Cox models comparing risk in the first quartile with that in the fourth quartile of baseline sRAGE, low levels of sRAGE were significantly associated with risk of diabetes (hazard ratio 1.64 [95% CI 1.10-2.44]), coronary heart disease (1.82 [1.17-2.84]), and mortality (1.72 [1.11-2.64]) but not ischemic stroke (0.78 [0.34-1.79]). In conclusion, we found that low levels of sRAGE were a marker of future chronic disease risk and mortality in the community and may represent an inflammatory state. Racial differences in sRAGE deserve further examination. © 2013 by the American Diabetes Association.


Pickett-Blakely O.,Johns Hopkins University | Cooper L.A.,Johns Hopkins University | Cooper L.A.,Welch Center for Prevention
Patient Education and Counseling | Year: 2011

Methods: We analyzed cross-sectional clinical encounter data. Obese adults were obtained from the 2005 National Ambulatory Medical Care Survey (N = 2458). Results: A third of obese adults received an obesity diagnosis (28.9%) and approximately a fifth received counseling for weight reduction (17.6%), diet (25.2%), or exercise (20.5%). Women (OR = 1.54; 95% CI: 1.14, 2.09), young adults ages 18-29 (OR = 2.61; 95% CI: 1.37, 4.97), and severely/morbidly obese individuals (class II: OR 2.08; 95% CI: 1.53, 2.83; class III: OR 4.36; 95% CI: 3.09, 6.16) were significantly more likely to receive an obesity diagnosis. One of the biggest predictors of weight-related counseling was an obesity diagnosis (weight reduction: OR = 5.72; 95% CI: 4.01, 8.17; diet: OR = 2.89; 95% CI: 2.05, 4.06; exercise: OR = 2.54; 95% CI: 1.67, 3.85). Other predictors of weight-related counseling included seeing a cardiologist/other internal medicine specialist, a preventive visit, or spending more time with the doctor (p< 0.05). Conclusions: Most obese patients do not receive an obesity diagnosis or weight-related counseling. Practice implications: Preventive visits may provide a key opportunity for obese patients to receive weight-related counseling from their physician. © 2010 Elsevier Ireland Ltd.


Selvin E.,Welch Center for Prevention | Selvin E.,Johns Hopkins University | Steffes M.W.,University of Minnesota | Matsushita K.,Welch Center for Prevention | And 6 more authors.
New England Journal of Medicine | Year: 2010

BACKGROUND: Fasting glucose is the standard measure used to diagnose diabetes in the United States. Recently, glycated hemoglobin was also recommended for this purpose. METHODS: We compared the prognostic value of glycated hemoglobin and fasting glucose for identifying adults at risk for diabetes or cardiovascular disease. We measured glycated hemoglobin in whole-blood samples from 11,092 black or white adults who did not have a history of diabetes or cardiovascular disease and who attended the second visit (occurring in the 1990-1992 period) of the Atherosclerosis Risk in Communities (ARIC) study. RESULTS: The glycated hemoglobin value at baseline was associated with newly diagnosed diabetes and cardiovascular outcomes. For glycated hemoglobin values of less than 5.0%, 5.0 to less than 5.5%, 5.5 to less than 6.0%, 6.0 to less than 6.5%, and 6.5% or greater, the multivariable-adjusted hazard ratios (with 95% confidence intervals) for diagnosed diabetes were 0.52 (0.40 to 0.69), 1.00 (reference), 1.86 (1.67 to 2.08), 4.48 (3.92 to 5.13), and 16.47 (14.22 to 19.08), respectively. For coronary heart disease, the hazard ratios were 0.96 (0.74 to 1.24), 1.00 (reference), 1.23 (1.07 to 1.41), 1.78 (1.48 to 2.15), and 1.95 (1.53 to 2.48), respectively. The hazard ratios for stroke were similar. In contrast, glycated hemoglobin and death from any cause were found to have a J-shaped association curve. All these associations remained significant after adjustment for the baseline fasting glucose level. The association between the fasting glucose levels and the risk of cardiovascular disease or death from any cause was not significant in models with adjustment for all covariates as well as glycated hemoglobin. For coronary heart disease, measures of risk discrimination showed significant improvement when glycated hemoglobin was added to models including fasting glucose. CONCLUSIONS: In this community-based population of nondiabetic adults, glycated hemoglobin was similarly associated with a risk of diabetes and more strongly associated with risks of cardiovascular disease and death from any cause as compared with fasting glucose. These data add to the evidence supporting the use of glycated hemoglobin as a diagnostic test for diabetes. Copyright © 2010 Massachusetts Medical Society.


Selvin E.,Welch Center for Prevention | Selvin E.,Johns Hopkins University
Diabetes Care | Year: 2016

Studies that have compared HbA1c levels by race have consistently demonstrated higher HbA1c levels in African Americans than in whites. These racial differences in HbA1c have not been explained by measured differences in glycemia, sociodemographic factors, clinical factors, access to care, or quality of care. Recently, a number of nonglycemic factors and several genetic polymorphisms that operate through nonglycemic mechanisms have been associated with HbA1c. Their distributions across racial groups and their impact on hemoglobin glycation need to be systematically explored. Thus, on the basis of evidence for racial differences in HbA1c, current clinical guidelines from the American Diabetes Association state: "It is important to take⋯race/ethnicity⋯into consideration when using the A1C to diagnose diabetes." However, it is not clear from the guidelines how this recommendation might be actualized. So, the critical question is not whether racial differences in HbA1c exist between African Americans and whites; the important question is whether the observed differences in HbA1c level are clinically meaningful. Therefore, given the current controversy, we provide a Point-Counterpoint debate on this issue. In the preceding point narrative, Dr. Herman provides his argument that the failure to acknowledge that HbA1c might be a biased measure of average glycemia and an unwillingnessto rigorously investigate this hypothesis will slow scientific progress and has the potential to do great harm. In the counterpoint narrative below, Dr. Selvin argues that there is no compelling evidence for racial differences in the validity of HbA1c as a measure of hyperglycemia and that race is a poor surrogate for differences in underlying causes of disease risk. © 2016 by the American Diabetes Association.


Kalyani R.R.,Johns Hopkins University | Saudek C.D.,Johns Hopkins University | Brancati F.L.,Welch Center for Prevention | Brancati F.L.,Johns Hopkins University | And 2 more authors.
Diabetes Care | Year: 2010

OBJECTIVE - To examine the relationship of diabetes and functional disability in older adults and the possible mediating roles of comorbidities and A1C. RESEARCH DESIGN AND METHODS - We analyzed data from a nationally representative sample of 6,097 participants aged ≥60 years in the National Health and Nutrition Examination Survey, 1999-2006. Diabetes was defined by self-report. Disability was defined as difficulty performing a physical task. We evaluated disability by grouping 19 physical tasks into five functional groups: lower-extremity mobility (LEM), general physical activities (GPA), activities of daily living (ADL), instrumental activities of daily living (IADL), and leisure and social activities (LSA). RESULTS - Older U.S. adults with diabetes had the greatest disability in GPA (prevalence 73.6% [95% CI 70.2-76.9]), followed by LEM (52.2% [48.5-55.9]), IADL (43.6% [40.1-47.2]), ADL (37.2% [33.1-41.3]), and LSA groups (33.8% [30.8-36.9]). Diabetes was associated with two to three times increased odds of disability across functional groups (all P < 0.05). Comorbidities, mostly cardiovascular disease and obesity, and poor glycemic control (A1C ≥8%) together explained up to 85% of the excess odds of disability associated with diabetes, whereas poor glycemic control alone explained only ∼10% of the excess odds. Adjustment for comorbidities, A1C, and diabetes duration fully attenuated the associations of diabetes with disability in all functional groups (all P > 0.05). CONCLUSIONS - Older adults with diabetes have a high prevalence of disabilities with variable associations attributable to comorbidities and A1C. Aggressive management of cardiovascular risk factors and obesity may significantly reduce the burden of disability in this population. © 2010 by the American Diabetes Association.


Selvin E.,Welch Center for Prevention | Steffes M.W.,University of Minnesota | Ballantyne C.M.,Baylor College of Medicine | Hoogeveen R.C.,Baylor College of Medicine | And 2 more authors.
Annals of Internal Medicine | Year: 2011

Background: Although differences between black and white persons in hemoglobin A1c (HbA1c) values are well established, recent studies suggest that this might not reflect differences in glycemia. Objective: To investigate racial disparities in glycemic markers, including those that reflect biological processes independent of hemoglobin glycation and erythrocyte turnover. Design: Cross-sectional. Setting: Community-based. Participants: 1376 nondiabetic and 343 diabetic adults in a substudy of the Atherosclerosis Risk in Communities Study. Measurements: Hemoglobin A1c, fasting glucose, glycated albumin, fructosamine, and 1,5-anhydroglucitol levels. Results: Among persons with and without diabetes, black persons had significantly higher HbA1c, glycated albumin, and fructosamine levels than white persons before and after adjustment for covariates and fasting glucose concentration. Serum 1,5-anhydroglucitol levels, which are reduced in the setting of hyperglycemia-induced glycosuria, were lower in black persons than in white persons, although this difference was statistically significant only in nondiabetic adults. Limitation: The design was cross-sectional, a limited number of participants with a history of diabetes was included, and the study did not include integrated measures of circulating nonfasting glycemia. Conclusion: Differences between black and white persons in glycated albumin, fructosamine, and 1,5-anhydroglucitol levels parallel differences between these groups in HbA1c values. Racial differences in hemoglobin glycation and erythrocyte turnover cannot explain racial disparities in these serum markers. The possibility that black persons have systematically higher levels of nonfasting glycemia warrants further study. Primary Funding Source: National institutes of health, National institute of diabetes and digestive and kidney diseases. © 2011 American College of Physicians.


Bower J.K.,Welch Center for Prevention | Brancati F.L.,Welch Center for Prevention | Brancati F.L.,Johns Hopkins University | Selvin E.,Welch Center for Prevention
Diabetes Care | Year: 2013

OBJECTIVEdCurrent recommendations for the use of hemoglobin A1c (HbA1c) in diabetes screening and diagnosis aim to identify those at greatest risk for diabetic microvascular complications. However, there is current controversy regarding the clinical implications of ethnic differences in HbA1c values. The objective of this study was to determine whether the association between HbA1c and retinopathy differs by ethnic group in a representative sample of U.S. adults. RESEARCH DESIGN AND METHODSdThe study was a cross-sectional analysis of 2,945 non-Hispanic white, 1,046 non-Hispanic black, and 1,231 Hispanic American participants aged 40 years from the 2005-2008 National Health and Nutrition Examination Survey. RESULTSdAmong nondiabetic adults, the mean HbA1c was 5.5% in non-Hispanic whites, 5.7% in non-Hispanic blacks, and 5.6% in Hispanic Americans. Among those with diagnosed diabetes, mean HbA1c was 6.9% in non-Hispanic whites, 7.5% in non-Hispanic Blacks, and 7.7% in Hispanic Americans. Overall, non-Hispanic blacks had the highest prevalence of retinopathy. In multivariable logistic models, HbA1c clinical categories were strongly associated with prevalent retinopathy. However, the magnitude of the association did not differ by ethnic group (all P values for interaction 0.7). Similar results were observed with HbA1c modeled continuously (per one percentage point) and stratified by diabetes status (all P for interactions . 0.3). CONCLUSIONSdWe observed no ethnic differences in the association of HbA1c with retinopathy. These data do not support ethnic-specific cut points for HbA1c for diagnosis or screening of diabetes mellitus. Copyright © 2013 by the American Diabetes Association.


Selvin E.,Welch Center for Prevention | Parrinello C.M.,Welch Center for Prevention | Sacks D.B.,U.S. National Institutes of Health | Coresh J.,Welch Center for Prevention
Annals of Internal Medicine | Year: 2014

Background: Trends in the prevalence and control of diabetes defined by hemoglobin A1c (HbA1c) levels are important for health care policy and planning. Objective: To update trends in the prevalence of diabetes, prediabetes, and glycemic control. Design: Cross-sectional. Setting: NHANES (National Health and Nutrition Examination Survey) in 1988-1994 and 1999-2010. Participants: Adults aged 20 years or older. Measurements: We used calibrated HbA1c levels to define undiagnosed diabetes (≥6.5%); prediabetes (5.7% to 6.4%); and, among persons with diagnosed diabetes, glycemic control (<7.0% or <8.0%). Trends in HbA1c categories were compared with fasting glucose levels (≥7.0 mmol/L [≥126 mg/dL] and 5.6 to 6.9 mmol/L [100 to 125 mg/dL]). Results: In 2010, approximately 21 million U.S. adults aged 20 years or older had total confirmed diabetes (self-reported diabetes or diagnostic levels for both fasting glucose and calibrated HbA1c). During 2 decades, the prevalence of total confirmed diabetes increased, but the prevalence of undiagnosed diabetes remained fairly stable, reducing the proportion of total diabetes cases that are undiagnosed to 11% in 2005-2010. The prevalence of prediabetes was lower when defined by calibrated HbA1c levels than when defined by fasting glucose levels but has increased from 5.8% in 1988-1994 to 12.4% in 2005-2010 when defined by HbA1c levels. Glycemic control improved overall, but total diabetes prevalence was greater and diabetes was less controlled among non-Hispanic blacks and Mexican Americans compared with non-Hispanic whites. Limitation: Cross-sectional design. Conclusion: Over the past 2 decades, the prevalence of total diabetes has increased substantially. However, the proportion of undiagnosed diabetes cases decreased, suggesting improvements in screening and diagnosis. Among the growing number of persons with diagnosed diabetes, glycemic control improved but remains a challenge, particularly among non-Hispanic blacks and Mexican Americans. © 2014 American College of Physicians.


Levey A.S.,Tufts University | Inker L.A.,Tufts University | Coresh J.,Welch Center for Prevention
American Journal of Kidney Diseases | Year: 2014

Estimating glomerular filtration rate (GFR) is essential for clinical practice, research, and public health. Appropriate interpretation of estimated GFR (eGFR) requires understanding the principles of physiology, laboratory medicine, epidemiology, and biostatistics used in the development and validation of GFR estimating equations. Equations developed in diverse populations are less biased at higher GFRs than equations developed in chronic kidney disease (CKD) populations and are more appropriate for general use. Equations that include multiple endogenous filtration markers are more precise than equations including a single filtration marker. The CKD-EPI (CKD Epidemiology Collaboration) equations are the most accurate GFR estimating equations that have been evaluated in large diverse populations and are applicable for general clinical use. The 2009 CKD-EPI creatinine equation is more accurate in estimating GFR and prognosis than the 2006 MDRD (Modification of Diet in Renal Disease) Study equation and provides lower estimates of prevalence of decreased eGFR. It is useful as a "first test" for decreased eGFR and should replace the MDRD Study equation for routine reporting of serum creatinine-based eGFR by clinical laboratories. The 2012 CKD-EPI cystatin C equation is as accurate as the 2009 CKD-EPI creatinine equation in estimating GFR, does not require specification of race, and may be more accurate in patients with decreased muscle mass. The 2012 CKD-EPI creatinine-cystatin C equation is more accurate than the 2009 CKD-EPI creatinine and 2012 CKD-EPI cystatin C equations and is useful as a confirmatory test for decreased eGFR as determined by serum creatinine-based eGFR. Further improvement in GFR estimating equations will require development in more broadly representative populations, including diverse racial and ethnic groups, use of multiple filtration markers, and evaluation using statistical techniques to compare eGFR to "true GFR." © 2014 by the National Kidney Foundation, Inc.


Cook N.R.,Harvard University | Appel L.J.,Welch Center for Prevention | Whelton P.K.,Tulane University
Circulation | Year: 2014

BACKGROUND-: Recent studies have raised the possibility of adverse effects of low sodium, particularly <2300 mg/d, on cardiovascular disease; however, these paradoxical findings might have resulted from suboptimal measurement of sodium and potential biases related to indication or reverse causation. METHODS AND RESULTS-: Phases 1 and 2 of the Trials of Hypertension Prevention (TOHP) collected multiple 24-hour urine specimens among prehypertensive individuals. During extended posttrial surveillance, 193 cardiovascular events or cardiovascular disease deaths occurred among 2275 participants not in a sodium reduction intervention with 10 (TOHP II) or 15 (TOHP I) years of posttrial follow-up. Median sodium excretion was 3630 mg/d, with 1.4% of the participants having intake <1500 mg/d and 10% <2300 mg/d, consistent with national levels. Compared with those with sodium excretion of 3600 to <4800 mg/d, risk for those with sodium <2300 mg/d was 32% lower after multivariable adjustment (hazard ratio, 0.68; 95% confidence interval, 0.34-1.37; P for trend=0.13). There was a linear 17% increase in risk per 1000 mg/d increase in sodium (P=0.05). Spline curves supported a linear association of sodium with cardiovascular events, which continued to decrease from 3600 to 2300 and 1500 mg/d, although the data were sparse at the lowest levels. Controlling for creatinine levels had little effect on these results. CONCLUSIONS-: Results from the TOHP studies, which overcome the major methodological challenges of prior studies, are consistent with overall health benefits of reducing sodium intake to the 1500 to 2300 mg/d range in the majority of the population, in agreement with current dietary guidelines. © 2014 American Heart Association, Inc.

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