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 #
1R01DK089174-01A1
Application #
8050235
Study Section
Special Emphasis Panel (ZDK1-GRB-B (O1))
Program Officer
Garfield, Sanford A
Project Start
2011-01-18
Project End
2015-12-31
Budget Start
2011-01-18
Budget End
2011-12-31
Support Year
1
Fiscal Year
2011
Total Cost
$678,509
Indirect Cost
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
Rebholz, Casey M; Yu, Bing; Zheng, Zihe et al. (2018) Serum metabolomic profile of incident diabetes. Diabetologia 61:1046-1054
Fretz, Anna; McEvoy, John W; Rebholz, Casey M et al. (2018) 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 121:430-436
George, Kristen M; Selvin, Elizabeth; Pankow, James S et al. (2018) George et al. Respond to ""Diabetes and Cardiovascular Disease"". Am J Epidemiol 187:415-416
Rebholz, Casey M; Selvin, Elizabeth; Liang, Menglu et al. (2018) Plasma galectin-3 levels are associated with the risk of incident chronic kidney disease. Kidney Int 93:252-259
Gupte, A N; Mave, V; Meshram, S et al. (2018) Trends in HbA1c levels and implications for diabetes screening in tuberculosis cases undergoing treatment in India. Int J Tuberc Lung Dis 22:800-806
West, Nancy A; Tingle, Jonathan V; Simino, Jeannette et al. (2018) The PPARG Pro12Ala Polymorphism and 20-year Cognitive Decline: Race and Sex Heterogeneity. Alzheimer Dis Assoc Disord 32:131-136
Deal, Jennifer A; Sharrett, A Richey; Rawlings, Andreea M et al. (2018) Retinal signs and 20-year cognitive decline in the Atherosclerosis Risk in Communities Study. Neurology 90:e1158-e1166
Walker, Keenan A; Windham, B Gwen; Brown, Charles H et al. (2018) The Association of Mid- and Late-Life Systemic Inflammation with Brain Amyloid Deposition: The ARIC-PET Study. J Alzheimers Dis 66:1041-1052
Mondul, Alison M; Joshu, Corinne E; Barber, John R et al. (2018) Longer-term Lipid-lowering Drug Use and Risk of Incident and Fatal Prostate Cancer in Black and White Men in the ARIC Study. Cancer Prev Res (Phila) 11:779-788
Schneider, Andrea L C; Zhao, Di; Lutsey, Pamela L et al. (2018) Serum Vitamin D Concentrations and Cognitive Change Over 20 Years: The Atherosclerosis Risk in Communities Neurocognitive Study. Neuroepidemiology 51:131-137

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