Diabetes
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BACKGROUND: Type 2 Diabetes (T2D) and other chronic diseases are caused by a complex combination of many genetic and environmental factors. Few methods are available to comprehensively associate specific physical environmental factors with disease. We conducted a pilot Environmental-Wide Association Study (EWAS), in which epidemiological data are comprehensively and systematically interpreted in a manner analogous to a Genome Wide Association Study (GWAS).

METHODS AND FINDINGS: We performed multiple cross-sectional analyses associating 266 unique environmental factors with clinical status for T2D defined by fasting blood sugar (FBG) concentration > or =126 mg/dL. We utilized available Centers for Disease Control (CDC) National Health and Nutrition Examination Survey (NHANES) cohorts from years 1999 to 2006. Within cohort sample numbers ranged from 503 to 3,318. Logistic regression models were adjusted for age, sex, body mass index (BMI), ethnicity, and an estimate of socioeconomic status (SES). As in GWAS, multiple comparisons were controlled and significant findings were validated with other cohorts. We discovered significant associations for the pesticide-derivative heptachlor epoxide (adjusted OR in three combined cohorts of 1.7 for a 1 SD change in exposure amount; p<0.001), and the vitamin gamma-tocopherol (adjusted OR 1.5; p<0.001). Higher concentrations of polychlorinated biphenyls (PCBs) such as PCB170 (adjusted OR 2.2; p<0.001) were also found. Protective factors associated with T2D included beta-carotenes (adjusted OR 0.6; p<0.001).

CONCLUSIONS AND SIGNIFICANCE: Despite difficulty in ascertaining causality, the potential for novel factors of large effect associated with T2D justify the use of EWAS to create hypotheses regarding the broad contribution of the environment to disease. Even in this study based on prior collected epidemiological measures, environmental factors can be found with effect sizes comparable to the best loci yet found by GWAS.

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Journal Articles
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PLoS One
Authors
Patel CJ
Jay Bhattacharya
Jay Bhattacharya
Butte AJ
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The nation's leading sources of morbidity and health disparities (eg, preterm birth, obesity, chronic lung disease, cardiovascular disease, type 2 diabetes, mental health disorders, and cancer) require an evidence-based approach to the delivery of effective preventive care across the life course (eg, prenatal care, primary preventive care, immunizations, physical activity, nutrition, smoking cessation, and early diagnostic screening). Health literacy may be a critical and modifiable factor for improving preventive care and reducing health disparities. Recent studies among adults have established an independent association between lower health literacy and poorer understanding of preventive care information and poor access to preventive care services. Children of parents with higher literacy skills are more likely to have better outcomes in child health promotion and disease prevention. Adult studies in disease prevention have suggested that addressing health literacy would be an efficacious strategy for reducing health disparities. Future initiatives to reduce child health inequities should include health-promotion strategies that meet the health literacy needs of children, adolescents, and their caregivers.

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Journal Articles
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Pediatrics
Authors
Lee M. Sanders
Lee M. Sanders
Shaw, J. S.
Guez, G.
Baur, C.
Rudd, R.
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Background.  The net value of increased health care spending remains unclear, especially for chronic diseases.

Objective. To assess value for money spent on medical care for patients with type 2 diabetes, using a “cost-of-living” approach.

Setting. Mayo Clinic Rochester, a not-for-profit integrated health care delivery system. 

Patients. 613 patients with type 2 diabetes: 36 diagnosed before 1985; 186 in 1985-96; 181 in 1997-99; and 210 in 2000-02.

Design. We compare the increase in inflation-adjusted annual health care spending with the value of changes in health status between 1997 and 2005.

Measurements. Measures of health status are (1) cardiovascular risk based on the United Kingdom Prospective Diabetes Study (UKPDS) equations, holding age and diabetes duration constant (“modifiable risk”); and (2) simulated outcomes for all diabetes complications using the UKPDS Outcomes Model. The present discounted value of improved survival and avoided treatment spending for coronary heart disease (CHD), net of the increase in annual spending per patient, yields net value.

Results. We estimate a total value of $20,824 per patient for quality improvement ($17,392 from reduction in modifiable risk of fatal CHD and fatal stroke, $3,432 from avoided CHD treatment spending), and a value net of cost of $10,911 per patient (95% confidence interval -$8,480, $33,402). A second approach to assessing value, using the UKPDS Outcomes Model, yields a net value of $6,931 per patient.

Conclusions. Our estimates of net value are positive, indicating that value for money has improved, although confidence intervals bracket zero. The increase in spending thus appears “worth it” on average, but there remains considerable room for enhancing value for money in care for patients with diabetes.

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Journal Articles
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Journal Publisher
Annals of Internal Medicine
Authors
Karen Eggleston
Karen Eggleston
Nilay D. Shah
Steven A. Smith
Amy E. Wagie
Arthur R. Williams
Jerome H. Grossman
Ernst R. Berndt
Kirsten Hall Long
Ritesh Banerjee
Joseph P. Newhouse
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Abstract

Objectives. We assessed the potential health and economic benefits of reducing common risk factors in older Americans.
Methods. A dynamic simulation model tracked a national cohort of persons 51 and 52 years of age to project their health and medical spending in prevention scenarios for diabetes, hypertension, obesity, and smoking.
Results. The gain in life span from successful treatment of a person aged 51 or 52 years for obesity would be 0.85 years; for hypertension, 2.05 years; and for diabetes, 3.17 years. A 51- or 52-year-old person who quit smoking would gain 3.44 years. Despite living longer, those successfully treated for obesity, hypertension, or diabetes would have lower lifetime medical spending, exclusive of prevention costs. Smoking cessation would lead to increased lifetime spending. We used traditional valuations for a life-year to calculate that successful treatments would be worth, per capita, $198018 (diabetes), $137964 (hypertension), $118946 (smoking), and $51750 (obesity).
Conclusions. Effective prevention could substantially improve the health of older Americans, and—despite increases in longevity—such benefits could be achieved with little or no additional lifetime medical spending.

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Journal Articles
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American Journal of Public Health
Authors
Dana P. Goldman
Yuhui Zheng
Federico Girosi
Pierre-Carl Michaud
Jay Olshansky
David Cutler
John (Jack) W. Rowe
John (Jack) Rowe
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BACKGROUND: The burden of hypertension and related health care needs among Mexican Americans will likely increase substantially in the near future.

OBJECTIVES: In a nationally representative sample of U.S. Mexican American adults we examined: 1) the full range of blood pressure categories, from normal to severe; 2) predictors of hypertension awareness, treatment and control and; 3) prevalence of comorbidities among those with hypertension.

DESIGN: Cross-sectional analysis of pooled data from the National Health and Nutrition Examination Surveys (NHANES), 1999-2004. PARTICIPANTS: The group of participants encompassed 1,359 Mexican American women and 1,421 Mexican American men, aged 25-84 years, who underwent a standardized physical examination.

MEASUREMENTS: Physiologic measures of blood pressure, body mass index, and diabetes. Questionnaire assessment of blood pressure awareness and treatment.

RESULTS: Prevalence of Stage 1 hypertension was low and similar between women and men ( approximately 10%). Among hypertensives, awareness and treatment were suboptimal, particularly among younger adults (65% unaware, 71% untreated) and those without health insurance (51% unaware, 62% untreated). Among treated hypertensives, control was suboptimal for 56%; of these, 23% had stage >/=2 hypertension. Clustering of CVD risk factors was common; among hypertensive adults, 51% of women and 55% of men were also overweight or obese; 24% of women and 23% of men had all three chronic conditions-hypertension, overweight/obesity and diabetes.

CONCLUSION: Management of hypertension in Mexican American adults fails at multiple critical points along an optimal treatment pathway. Tailored strategies to improve hypertension awareness, treatment and control rates must be a public health priority.

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Journal Articles
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Journal of General Internal Medicine
Authors
Bersamin A
Randall Stafford
Winkleby MA
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Aims The prevalence of Type 2 diabetes mellitus (DM) has grown rapidly, but little is known about the drivers of inpatient spending in low- and middle-income countries. This study aims to compare the clinical presentation and expenditure on hospital admission for inpatients with a primary diagnosis of Type 2 DM in India, China, Thailand and Malaysia.

Methods We analysed data on adult, Type 2 DM patients admitted between 2005 and 2008 to five tertiary hospitals in the four countries, reporting expenditures relative to income per capita in 2007.

Results Hospital admission spending for diabetic inpatients with no complications ranged from 11 to 75% of per-capita income. Spending for patients with complications ranged from 6% to over 300% more than spending for patients without complications treated at the same hospital. Glycated haemoglobin was significantly higher for the uninsured patients, compared with insured patients, in India (8.6 vs. 8.1%), Hangzhou, China (9.0 vs. 8.1%), and Shandong, China (10.9 vs. 9.9%). When the hospital admission expenditures of the insured and uninsured patients were statistically different in India and China, the uninsured always spent less than the insured patients.

Conclusions With the rising prevalence of DM, households and health systems in these countries will face greater economic burdens. The returns to investment in preventing diabetic complications appear substantial. Countries with large out-of-pocket financing burdens such as India and China are associated with the widest gaps in resource use between insured and uninsured patients. This probably reflects both overuse by the insured and underuse by the uninsured.

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Journal Articles
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Journal Publisher
Diabetic Medicine
Authors
Jeremy Goldhaber-Fiebert
Jeremy Goldhaber-Fiebert
Ratanawijitrasin S
Vidyasagar S
Wang XY
Aljunid S Aljunid S
Shah N Shah N
Wang Z
Hirunrassamee S
Bairy KL
Wang J
Saperi S
Nur AM
Karen Eggleston
Karen Eggleston
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Context: Fetuin-A inhibits the insulin receptor in vitro. Higher serum fetuin-A concentrations are associated with type 2 diabetes longitudinally and greater adiposity in cross-sectional analyses. Whether higher fetuin-A concentrations are associated with accumulation of adiposity over time is unknown.

Objective: To determine the association of fetuin-A levels with changes in body composition over 5 yr.

Study Design: Observational cohort study nested in the Health Aging and Body Composition Study.

Predictor: Serum fetuin-A levels.

Outcomes: Visceral adipose tissue (VAT), abdominal sc adipose tissue, and thigh muscle area by computed tomography, and waist circumference and body mass index were measured at baseline and again after 5 yr. Percent change and extreme change (>1.5 SDs) in each measure were calculated.

Results: Over 5 yr, subjects lost body mass in each measure, including 6% decline in VAT. Yet each SD (0.42 g/liter) higher fetuin-A concentration was associated with a 5.5% increase in VAT over 5 yr (95% confidence interval 1.9-9.2%; P = 0.003) in models adjusted for age, sex, race, clinical site, diabetes, physical activity, triglycerides, kidney function, and the baseline VAT score. Similarly, higher fetuin-A concentrations were associated with extreme VAT gain (relative risk 1.70, 95% confidence interval 1.12-2.60, P = 0.01). Fetuin-A concentrations were not statistically significant associated with change in any other measures of body composition (P > 0.20).

Conclusions: Higher fetuin-A concentrations are associated with the accumulation of VAT in well-functioning, community-living older persons. The mechanisms linking fetuin-A, VAT, and insulin resistance remain to be determined.

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Journal Articles
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Journal Publisher
Journal of Clinical Endocrinology and Metabolism
Authors
Ix JH
Wassel CL
Glenn M. Chertow
Koster A
Johnson KC
Tylavsky FA
Cauley JA
Cummings SR
Harris TB
Harris TB
Shilpak MG
Shilpak MG
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Background: An increasing number of people suffer from chronic illness. Processes exist to provide better chronic illness care and yet for the most part, they are not used.

Objective: To examine the change in use of commonly recommended chronic illness care management processes (CMPs) in large medical groups between 2000 and 2006 and the factors associated with the change.

Design and Measures: Cohort analysis of data from a national telephone survey in year 2000 and again in 2006. Participants provided information on their organizations' ownership, size, use of defined chronic illness CMPs, financial incentives, quality improvement involvement, profitability, and use of electronic medical records.

Setting: Medical groups and independent practice associations of 20 physicians or more (N = 369) that treat patients with asthma, congestive heart failure, depression, and diabetes, and that responded to the survey in 2000 and 2006.

Results: Use of CMP increased from 6.25 to 7.67 (of a total of 17; P ≤ 0.001), that is, by 23%, between 2000 and 2006. Increases were greatest for those practices receiving financial rewards for quality; those participating in quality improvement activities; and those practices that were profitable. Most of the increase was in use of registries and in patient self-management support services.

Conclusions: There is significant opportunity for improving chronic illness care even in larger physician organizations. Public policies that promote financial rewards for improving quality and that encourage quality improvement initiatives are likely to be associated with improved chronic illness care.

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Journal Articles
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Journal Publisher
Medical Care
Authors
Stephen M. Shortell
Gillies R
Siddique J
Casalino LP
Rittenhouse D
Robinson JC
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Background Optimal treatment for patients with both type 2 diabetes mellitus and stable ischemic heart disease has not been established.

Methods We randomly assigned 2368 patients with both type 2 diabetes and heart disease to undergo either prompt revascularization with intensive medical therapy or intensive medical therapy alone and to undergo either insulin-sensitization or insulin-provision therapy. Primary end points were the rate of death and a composite of death, myocardial infarction, or stroke (major cardiovascular events). Randomization was stratified according to the choice of percutaneous coronary intervention (PCI) or coronary-artery bypass grafting (CABG) as the more appropriate intervention.

Results At 5 years, rates of survival did not differ significantly between the revascularization group (88.3%) and the medical-therapy group (87.8%, P=0.97) or between the insulin-sensitization group (88.2%) and the insulin-provision group (87.9%, P=0.89). The rates of freedom from major cardiovascular events also did not differ significantly among the groups: 77.2% in the revascularization group and 75.9% in the medical-treatment group (P=0.70) and 77.7% in the insulin-sensitization group and 75.4% in the insulin-provision group (P=0.13). In the PCI stratum, there was no significant difference in primary end points between the revascularization group and the medical-therapy group. In the CABG stratum, the rate of major cardiovascular events was significantly lower in the revascularization group (22.4%) than in the medical-therapy group (30.5%, P=0.01; P=0.002 for interaction between stratum and study group). Adverse events and serious adverse events were generally similar among the groups, although severe hypoglycemia was more frequent in the insulin-provision group (9.2%) than in the insulin-sensitization group (5.9%, P=0.003).

Conclusions Overall, there was no significant difference in the rates of death and major cardiovascular events between patients undergoing prompt revascularization and those undergoing medical therapy or between strategies of insulin sensitization and insulin provision. (ClinicalTrials.gov number, NCT00006305.)

The members of the writing group (Robert L. Frye, M.D., Mayo Clinic, Rochester, MN; Phyllis August, M.D., M.P.H., New York Hospital Queens, Queens, NY; Maria Mori Brooks, Ph.D., Regina M. Hardison, M.S., Sheryl F. Kelsey, Ph.D., Joan M. MacGregor, M.S., and Trevor J. Orchard, M.B., B.Ch., University of Pittsburgh, Pittsburgh; Bernard R. Chaitman, M.D., Saint Louis University, St. Louis; Saul M. Genuth, M.D., Case Western Reserve University, Cleveland; Suzanne H. Goldberg, R.N., M.S.N., National Heart, Lung, and Blood Institute, Bethesda, MD; Mark A. Hlatky, M.D., Stanford University, Palo Alto, CA; Teresa L.Z. Jones, M.D., National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD; Mark E. Molitch, M.D., Feinberg School of Medicine, Northwestern University, Chicago; Richard W. Nesto, M.D., Lahey Clinic Medical Center, Burlington, MA; Edward Y. Sako, M.D., Ph.D., University of Texas Health Science Center, San Antonio; and Burton E. Sobel, M.D., University of Vermont, Burlington) assume responsibility for the overall content and integrity of the article.

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Publication Type
Working Papers
Publication Date
Journal Publisher
New England Journal of Medicine
Authors
(The BARI 2D Study Group)
Robert L. Frye
Phyllis August
Maria Mori Brooks
Regina M. Hardison
Sheryl F. Kelsey
Joan M. MacGregor
Trevor J. Orchard
Bernard R. Chaitman
Saul M. Genuth
Suzanne H. Goldberg
Mark A. Hlatky
Mark A. Hlatky
Teresa L.Z. Jones
Mark E. Molitch
Richard W. Nesto
Edward Y. Sako
Burton E. Sobel
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Background

Coronary artery bypass graft (CABG) and percutaneous coronary intervention (PCI) are alternative treatments for multivessel coronary disease. Although the procedures have been compared in several randomised trials, their long-term effects on mortality in key clinical subgroups are uncertain. We undertook a collaborative analysis of data from randomised trials to assess whether the effects of the procedures on mortality are modified by patient characteristics.

Methods

We pooled individual patient data from ten randomised trials to compare the effectiveness of CABG with PCI according to patients' baseline clinical characteristics. We used stratified, random effects Cox proportional hazards models to test the effect on all-cause mortality of randomised treatment assignment and its interaction with clinical characteristics. All analyses were by intention to treat.

Findings

Ten participating trials provided data on 7812 patients. PCI was done with balloon angioplasty in six trials and with bare-metal stents in four trials. Over a median follow-up of 5·9 years (IQR 5·0—10·0), 575 (15%) of 3889 patients assigned to CABG died compared with 628 (16%) of 3923 patients assigned to PCI (hazard ratio [HR] 0·91, 95% CI 0·82—1·02; p=0·12). In patients with diabetes (CABG, n=615; PCI, n=618), mortality was substantially lower in the CABG group than in the PCI group (HR 0·70, 0·56—0·87); however, mortality was similar between groups in patients without diabetes (HR 0·98, 0·86—1·12; p=0·014 for interaction). Patient age modified the effect of treatment on mortality, with hazard ratios of 1·25 (0·94—1·66) in patients younger than 55 years, 0·90 (0·75—1·09) in patients aged 55—64 years, and 0·82 (0·70—0·97) in patients 65 years and older (p=0·002 for interaction). Treatment effect was not modified by the number of diseased vessels or other baseline characteristics.

Interpretation

Long-term mortality is similar after CABG and PCI in most patient subgroups with multivessel coronary artery disease, so choice of treatment should depend on patient preferences for other outcomes. CABG might be a better option for patients with diabetes and patients aged 65 years or older because we found mortality to be lower in these subgroups.

Funding

Agency for Healthcare Research and Quality.
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Publication Type
Journal Articles
Publication Date
Journal Publisher
The Lancet
Authors
Mark A. Hlatky
Mark A. Hlatky
Boothroyd DB
Dena M. Bravata
Boersma E
Booth J
Brooks MM
Carrie MD
Clayton TC
Danchin N
Flather M
Hamm CW
Hueb WA
Kahler J
Kelsey SF
King SB
Kosinski AS
Lopes N
Kathryn M. McDonald
Rodriguez A
Serruys P
Sigwart P
Stables RH
Douglas K. Owens
Douglas K. Owens
Pocock SJ
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