Tomaszewski, Erin
(2021)
Skin Intrinsic Fluorescence in the Epidemiology of Diabetes and Complications Study: Predictors and Association with all-cause Mortality.
Doctoral Dissertation, University of Pittsburgh.
(Unpublished)
Abstract
Aims: The published literature suggests that higher skin intrinsic fluorescence (SIF), as a marker of advanced glycation endproducts (AGE), is associated with worse health status in type 1 diabetes (T1D). The first two aims of this dissertation test the relationship between traditional vascular disease risk factors as well as T1D-related complications, and SIF change among individuals with long-term T1D. The third aim assesses the association between SIF and all-cause mortality in T1D.
Methods: Data were from the 30-year longitudinal Epidemiology of Diabetes and Complications (EDC) study of individuals diagnosed with childhood-onset T1D at the Children’s Hospital of Pittsburgh, PA, USA, between 1950-80. EDC participants were followed for 30 years biennially providing medical history, lifestyle, demographic, and diabetes self-care survey information. SIF was collected from a convenience sample of EDC participants (n=245) between 2007-14. Mortality status was evaluated as of May 2020. Regression models were run to evaluate predictors of SIF scores; Cox regression was used evaluate SIF and all-cause mortality.
Results: We observed that modifiable T1D-related complication risk factors and markers at analytic baseline, such as worse blood glucose control and lower kidney function, were associated with increased SIF scores over a mean of 5.2 years follow up. Further, increased albuminuria at analytic baseline was associated with decreased SIF scores during follow-up. Body mass index change was marginally and inversely associated with SIF score change. SIF was univariately associated with all-cause mortality; this association remained significant after adjustment for multiple daily insulin shots/pump use, but not after adjustment for diabetes duration, A1c months, or estimated glomerular filtration rate.
Conclusion: The predictors of SIF change identified are aligned with known biological processes that occur during AGE formation, accumulation, and deposition on long lived proteins. Regarding all-cause mortality, this work builds on existing evidence that AGEs may play a role in ageing. Taken together, this work supports the existing evidence that AGEs may be a marker of complication status in T1D, and that AGEs may predict risk of accelerated ageing. Further work is needed to establish the meaningfulness of SIF scores.
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| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
|
| ETD Committee: |
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| Date: |
19 January 2021 |
| Date Type: |
Publication |
| Defense Date: |
14 October 2020 |
| Approval Date: |
19 January 2021 |
| Submission Date: |
10 December 2020 |
| Access Restriction: |
2 year -- Restrict access to University of Pittsburgh for a period of 2 years. |
| Number of Pages: |
161 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
School of Public Health > Epidemiology |
| Degree: |
PhD - Doctor of Philosophy |
| Thesis Type: |
Doctoral Dissertation |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
type 1 diabetes, skin intrinsic fluorescence, advanced glycation endproduct |
| Date Deposited: |
19 Jan 2021 20:02 |
| Last Modified: |
19 Jan 2023 06:15 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/40039 |
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