Design of a novel ex vivo murine brain slice model for analysis of pericyte morphology in diabetes; An Autoethnographic Perspective on Type 1 Diabetes Burnout

Author:
Johannsen, Garrett, School of Engineering and Applied Science, University of Virginia
Advisors:
Peirce-Cottler, Shayn, Biomedical Engineering, University of Virginia
Seabrook, Bryn, Engineering and Society, University of Virginia
Abstract:

Type 1 diabetes (T1D) is a persistent and complex medical problem that poses many
unique challenges to millions of people in the United States. Of these challenges, two of the most pressing are the somewhat abstract emotional toll that blood glucose management takes on a
diabetic and the much more concrete physical repercussions that arise as a result of inconsistent
personal care. Awareness of the diabetic experience and the resiliency that diabetes management
requires needs to be raised because prevalence of diabetes is increasing (Wild et al., 2004). The
STS Research Paper, “An Autoethnographic Perspective on Type 1 Diabetes,” and the technical
report, “Design of a novel ex vivo murine brain slice model for analysis of pericyte morphology
in diabetes” provide the general audience necessary information to understand the emotional and
physical complications of diabetes, respectively.
T1D is an autoimmune disease in which the pancreas no longer produces enough insulin
to regulate blood glucose (BG) levels, resulting in chronic high BG (hyperglycemia) that is
treated with exogenous insulin delivery. Patients affected with this condition must do manually
what a healthy body does autonomously, and the attention required to maintain healthy BG
levels can cause overwhelming feelings of exhaustion and frustration in response to the
challenging requirements of BG management, defined by the term “diabetes burnout.” Diabetes
burnout is associated with suboptimal BG management and severe hyperglycemia, leading to
increased risk of blood vessel damage, organ damage, and hospitalization. The prevalence of
T1D is increasing in the United States and there is no standardized treatment for patients who
suffer from diabetes burnout; therefore, it is important to explore the pathology and experience
of burnout patients, and offer potential solutions. Thus, the STS research question, “What are
societal, physical, and emotional consequences of diabetes burnout, and what are the potential
solutions for those who struggle with this condition?” will be conducted through the framework
of wicked problems. This framework will be utilized to emphasize the scope of diabetes burnout
and its main contributors. An autoethnographic analysis describing the author’s personal
experiences with diabetes burnout will be paired with wicked problem framing to offer palliative
care to burnout patients. The analysis conducted here proposes novel alternatives to patients who
struggle to live with and manage a difficult disease.
In addressing the vast medical problem of microvascular complications of diabetes, a
disease complication that affects more than 30 million Americans (CDC, 2020), the Technical
Report is a design project that proposes a novel extracellular vesicle (EV) therapy to stabilize
brain microvessels in diabetes. During periods of chronic high blood glucose (hyperglycemia) as
seen in diabetes, cells of the microvasculature called pericytes (PC) that communicate and signal
to the structural cells of blood vessels called endothelial cells (EC) begin to detach from blood
vessels and lose functional capabilities. Also referred to as PC dropout, this disease state can
result in blood vessel necrosis and the progression of diabetic microvascular complications such
as retinopathy, neuropathy, and nephropathy. EVs are lipid-based particles produced by most
cells in the body that contain proteins, DNA, and RNA, and show promise as a regenerative
medicine candidate (van Niel et al., 2018). After isolation from urine, plasma, or cell cultures,
these vesicles contain highly specific contents that can be used as a signaling method upon
delivery to EC and PC to reduce detachment and return to expected interactions observed in
normoglycemic environments. The research team, composed of Garrett Johannsen, Stephen
Muzyka, and Connor McKechnie, hypothesizes that the use of EVs to target tissues in
hyperglycemic environments will restore healthy PC/EC interactions. If successful, the
downstream implementation of this therapy could serve as a direct treatment for microvascular
complications of the brain, and a successful EV protocol could initiate similar therapies for
related complications of diabetes. An EV treatment would improve quality of life for diabetic
patients and reduce the high medical expenditures each year due to diabetic microvascular
complications.
The field of biomedical research proposes novel alternatives and innovative solutions to
complex human health problems, and this cannot be done without having an understanding of the
biomedical problem at hand and how it affects patients. Through writing the STS Research
Paper, and while analyzing my personal experience of living with T1D, it became clear that the
problems of diabetes are far beyond the scope of physiological consequences that the disease
poses on its patients. The future implementation of the Capstone project would hopefully provide
a source of relief to the physiological complications of diabetes, but how would it affect the
livelihood of a T1D patient suffering from diabetes burnout? Questions like this one are very
important to consider when designing engineering solutions, and the patients should always be at
the center of the design process. The STS Research Paper emphasizes the importance of creating
medical technology that improves convenience and quality of life for the patient, whether this is
in the form of a smaller, cordless insulin pump, or a novel treatment option that every diabetic
patient can afford, to name two examples. When a biomedical expert considers the psychosocial,
socioeconomic, emotional, mental, and physical state of the patient, the resulting innovation is
more likely to accurately address an aspect of a wicked problem, and more compassion is
brought into the field of engineering.

Degree:
BS (Bachelor of Science)
Keywords:
Peirce-Cottler Lab, diabetes, diabetes burnout, microvascular engineering, pericytes, hyperglycemia, insulin, wicked problem
Notes:

School of Engineering and Applied Science
Bachelor of Science in Biomedical Engineering
Technical Advisor: Shayn Peirce-Cottler
STS Advisor: Bryn Seabrook
Technical Team Members: Connor McKechnie, Stephen Muzyka

Language:
English
Rights:
All rights reserved (no additional license for public reuse)
Issued Date:
2022/05/08