This project will evaluate whether alternative glycemic markers add value to standard markers (fasting glucose and HbA1c) for long-term prognosis across a wide range of outcomes in a large representative cohort followed for 25-years from midlife to older age.
The aims are: 1) To assess the added prognostic value of novel glycemic markers to known measures for identifying populations and subgroups at high risk for microvascular and macrovascular outcomes;2) To investigate racial- and age-related differences in the associations of glycemic markers with health outcomes;3) To conduct a genome-wide association study of new glycemic markers to identify susceptibility genes important in glucose metabolism;and 4) To characterize the associations of hypo- and hyper-glycemic states with frailty, mood, and physical and cognitive impairment and dementia risk in the elderly. Design and Methods: We will analyze stored specimens and utilize data from the Atherosclerosis Risk in Communities (ARIC) Study, an ongoing NHLBI-funded community-based epidemiologic cohort of ~15,000 black and white adults followed for 25 years. The proposed research will build on the existing infrastructure of the parent study and utilize blood samples obtained during two phases of the participants'lifespan: during midlife (1990-92, 48-68 years old) and old age (2011-2013, 69-89 years old). The main outcomes of interest are microvascular disease (kidney and retinal disease), macrovascular (cardiovascular) disease, frailty, mood, physical and cognitive impairment, dementia, and all-cause mortality. Significance: If we demonstrate that novel markers of glycemia contribute additional prognostic information, our results will suggest the utility of these measures in clinical practice. Such results would challenge the definition of diabetes. We will also demonstrate whether documented racial disparities and age-related differences in levels of glycemia are clinically important. Our investigation of common genetic determinants will shed light on the biology of diabetes and the mechanisms by which glucose metabolism contributes to the development of complications. If this project is successful, our results will have direct relevance to clinical practice and inform strategies for the prevention of diabetes and its complications.

Public Health Relevance

This project will compare the effectiveness of alternative markers of glucose metabolism to current clinical measures (fasting glucose, hemoglobin A1c). We will assess whether these markers can improve prediction of health outcomes. We will also investigate racial and age-related disparities in diabetes risk and characterize genetic associations to inform the biology of diabetes. Our results should help prevent diabetes and its complications.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK089174-02
Application #
8213603
Study Section
Special Emphasis Panel (ZDK1-GRB-B (O1))
Program Officer
Leschek, Ellen W
Project Start
2011-01-18
Project End
2015-12-31
Budget Start
2012-01-01
Budget End
2012-12-31
Support Year
2
Fiscal Year
2012
Total Cost
$568,059
Indirect Cost
$157,490
Name
Johns Hopkins University
Department
Public Health & Prev Medicine
Type
Schools of Public Health
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Fretz, Anna; McEvoy, John W; Rebholz, Casey M et al. (2017) Relation of Lifestyle Factors and Life's Simple 7 Score to Temporal Reduction in Troponin Levels Measured by a High-Sensitivity Assay (from the Atherosclerosis Risk in Communities Study). Am J Cardiol :
Haring, Bernhard; Selvin, Elizabeth; Liang, Menglu et al. (2017) Dietary Protein Sources and Risk for Incident Chronic Kidney Disease: Results From the Atherosclerosis Risk in Communities (ARIC) Study. J Ren Nutr 27:233-242
Chatterjee, Ranee; Davenport, Clemontina A; Svetkey, Laura P et al. (2017) Serum potassium is a predictor of incident diabetes in African Americans with normal aldosterone: the Jackson Heart Study. Am J Clin Nutr 105:442-449
Jung, Molly; Warren, Bethany; Grams, Morgan et al. (2017) Performance of non-traditional hyperglycemia biomarkers by chronic kidney disease status in older adults with diabetes: Results from the Atherosclerosis Risk in Communities Study. J Diabetes :
Whelton, Seamus P; McEvoy, John W; Lazo, Mariana et al. (2017) High-Sensitivity Cardiac Troponin T (hs-cTnT) as a Predictor of Incident Diabetes in the Atherosclerosis Risk in Communities Study. Diabetes Care 40:261-269
Bancks, Michael P; Alonso, Alvaro; Gottesman, Rebecca F et al. (2017) Brain function and structure and risk for incident diabetes: The Atherosclerosis Risk in Communities Study. Alzheimers Dement 13:1345-1354
Warren, Bethany; Rawlings, Andreea M; Lee, Alexandra K et al. (2017) Increases in Biomarkers of Hyperglycemia With Age in the Atherosclerosis Risk in Communities (ARIC) Study. Diabetes Care 40:e96-e97
Pokharel, Yashashwi; Sun, Wensheng; Virani, Salim S et al. (2017) Myocardial Injury, Obesity, and the Obesity Paradox: The ARIC Study. JACC Heart Fail 5:56-63
Selvin, Elizabeth; Sacks, David B (2017) Monitoring Glycemic Control in End-Stage Renal Disease: What Should Be Measured? Clin Chem 63:447-449
Seidelmann, Sara B; Vardeny, Orly; Claggett, Brian et al. (2017) An NPPB Promoter Polymorphism Associated With Elevated N-Terminal pro-B-Type Natriuretic Peptide and Lower Blood Pressure, Hypertension, and Mortality. J Am Heart Assoc 6:

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