Epidemiology of Retinopathy and Other Complications in Long Term Type 1 DiabetesProject Summary / Abstract Persons with long term type 1 diabetes mellitus (T1DM) are at high risk of developing severecomplications, presenting a pressing need to prevent these outcomes. It is, therefore, the goal of thisepidemiological study to determine the relationship of specific underexamined risk factors for thesecomplications that hold promise of diminishing these risks beyond the improvements achieved with currentstrategies. This study aims to measure advanced glycation endproducts (AGEs), receptors for AGEs (RAGE),carotid intimal-medial thickness, markers of antioxidant stress, and related candidate genes and theirrelationships to diabetic retinopathy, diabetic nephropathy, diabetic neuropathy, myocardial infarction, stroke,and cognitive dysfunction outcomes. In addition, the study will determine the relationship of retinal vesseldiameters and severity of diabetic retinopathy to diabetic nephropathy, diabetic neuropathy, MI, stroke, andcognitive dysfunction. This proposal builds on a longitudinal representative cohort study of persons with longduration of T1DM participating in the Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR, fundedby NEI grants R01 EY03083 and R01 EY016379). The study included all insulin-taking persons with type 1diabetes who were receiving primary medical care in an 11-county area of southwestern Wisconsin in 1979-1980. They were examined in 1980-1982 and approximately every 5 years thereafter. Objective recording ofretinopathy from stereoscopic fundus photography combined with a standardized grading, refraction and visualacuity, carotid artery ultrasound, electrocardiogram, measurement of skin intrinsic fluorescence, tests ofcognition, and measurement of serum (e.g., AGEs [carboxymethyl lysine, pentosidine], soluble RAGE, oxidizedlow density lipoprotein cholesterol, creatinine) according to standardized protocols will be obtained in theproposed examination. In addition, we will measure AGEs, RAGE and oxidized low density lipoproteincholesterol from frozen serum from previous exams to determine longitudinal associations with PDR and othercomplications. The new data from this study will provide a unique opportunity to determine why, independentof glycemic and blood pressure control, and despite long duration of T1DM, some persons have minimal tomild diabetic retinopathy, diabetic nephropathy, diabetic neuropathy, cognitive dysfunction, and less severecardiovascular disease, while others have more severe complications. These data will be important to patientsand their physicians in developing new interventions for managing type 1 diabetes and to public healthpractitioners charged with delivering preventive care.

Public Health Relevance

Epidemiology of Retinopathy and Other Complications in Long Term Type 1 Diabetes Project Narrative Persons with long term type 1 diabetes mellitus are at high risk of developing severe complications of type 1 diabetes, presenting a pressing need to prevent these outcomes. The new data from this study will provide a unique opportunity to determine why, independent of glycemic and blood pressure control, and despite long duration of type 1 diabetes, some persons have minimal to mild diabetic retinopathy, diabetic nephropathy, cognitive dysfunction and less severe cardiovascular disease, while others have more severe complications. These data will be important to patients and their physicians in managing type 1 diabetes and to public health practitioners charged with delivering preventive care.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
2R01EY016379-05A1
Application #
8294242
Study Section
Special Emphasis Panel (ZEY1-VSN (10))
Program Officer
Wideroff, Louise
Project Start
2005-09-01
Project End
2017-03-31
Budget Start
2012-05-01
Budget End
2013-03-31
Support Year
5
Fiscal Year
2012
Total Cost
$1,543,937
Indirect Cost
$407,240
Name
University of Wisconsin Madison
Department
Type
Schools of Medicine
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
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Ryan, Christopher M; Klein, Barbara E K; Lee, Kristine E et al. (2016) Associations between recent severe hypoglycemia, retinal vessel diameters, and cognition in adults with type 1 diabetes. J Diabetes Complications 30:1513-1518
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Klein, Barbara E K; Myers, Chelsea E; Howard, Kerri P et al. (2015) Serum Lipids and Proliferative Diabetic Retinopathy and Macular Edema in Persons With Long-term Type 1 Diabetes Mellitus: The Wisconsin Epidemiologic Study of Diabetic Retinopathy. JAMA Ophthalmol 133:503-10
Hosseini, S Mohsen; Boright, Andrew P; Sun, Lei et al. (2015) The association of previously reported polymorphisms for microvascular complications in a meta-analysis of diabetic retinopathy. Hum Genet 134:247-57
Lecaire, Tamara J; Klein, Barbara E K; Howard, Kerri P et al. (2014) Risk for end-stage renal disease over 25 years in the population-based WESDR cohort. Diabetes Care 37:381-8

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