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Changes in brain structure and function: under-recognized complications of type 1 diabetes

Nunley, Karen (2014) Changes in brain structure and function: under-recognized complications of type 1 diabetes. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Abstract

Type 1 diabetes (T1D) develops in genetically susceptible individuals due to an auto-immune mediated destruction of pancreatic beta-cells. Disproportionately affecting non-Hispanic Caucasians, it is becoming more common among other races/ethnicities. With improvements in T1D management, patients can expect to live almost as long as people without T1D. Consequently, these patients will live longer with diabetes-associated complications, causing higher healthcare costs and reduced quality of life. When taken in consideration with a projected 3-5% annual increase in T1D incidence, preventing or delaying the onset and progression of diabetes complications deserves immediate public health attention.
While most T1D-related complications are well researched, its deleterious effects on the brain have received less attention. Because the majority of T1D brain studies have focused on pediatric and young adult populations, the complex interplay between increasing age and T1D-related brain abnormalities remains unclear. The goal of this research is to bring attention to the effects of childhood-onset T1D on brain structure and function in middle-aged adults who are also experiencing aging-induced cerebral insults. Data from a subset of middle-aged adults participating in the Pittsburgh Epidemiology of Diabetes Complications Study (EDC), diagnosed with childhood-onset T1D between 1950-80, baseline 1986-88 and who underwent brain imaging and neuropsychological testing between 2010 and 2013 was used to address this goal, yielding some novel results.
First, the presence and severity of white matter hyperintensities was dramatically greater in those with vs. without T1D. These lesions developed at a younger-than-expected age and were independent of traditional cardiovascular risk factors. Skin intrinsic fluorescence and smoking were identified as risk factors deserving further exploration. Second, the prevalence of cognitive dysfunction was three times greater in adults with vs. without T1D. Chronic hyperglycemia, proliferative retinopathy and polyneuropathy were related cognitive dysfunction in those with T1D, suggesting a shared pathophysiology of chronic hyperglycemia having systemic vascular effects. Third, among those with T1D, reduced blood flow to the prefrontal cortex and superior parietal lobes was related to cognitive dysfunction; these regions are important for information processing and executive function, tasks highly affected by cognitive dysfunction. As a whole, these results suggest that altered brain structure and function should be considered a T1D complication with important public health relevance.


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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Nunley, Karenkan62@pitt.eduKAN62
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Thesis AdvisorRosano, Caterinacar2350@pitt.eduCAR2350
Committee ChairZgibor, Janice C.edcjan@pitt.eduEDCJAN
Committee MemberAizenstein, Howard Jaizensteinhj@upmc.eduAIZEN
Committee MemberCostacou, Tinacostacout@edc.pitt.eduCOSTACOU
Committee MemberBoudreau, Robert Mrob21@pitt.eduROB21
Date: 29 September 2014
Date Type: Publication
Defense Date: 30 May 2014
Approval Date: 29 September 2014
Submission Date: 7 July 2014
Access Restriction: 2 year -- Restrict access to University of Pittsburgh for a period of 2 years.
Number of Pages: 206
Institution: University of Pittsburgh
Schools and Programs: Graduate School of Public Health > Epidemiology
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: Type 1 diabetes; white matter hyperintensities; brain; cognitive dysfunction; MRI;
Date Deposited: 29 Sep 2014 21:36
Last Modified: 19 Dec 2016 14:41
URI: http://d-scholarship.pitt.edu/id/eprint/22233

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