Poster presented at Obesity Week 2018 meeting in Nashville, TN

1. @jennyrsadler
www.NIBLunc.org
jenny_sadler@unc.edu
This work was supported by R01 DK112317
Jennifer R Sadler, Grace E Shearrer, Kyle S Burger
Department of Nutrition, Gillings School of Global Public Health, University of North Carolina, Chapel Hill NC
• Type 2 diabetes mellitus (T2D) is related to symptoms of
cognitive decline (Nolan et al, 2011) including decreased
information processing speed, and impaired attention.
• Cognitive decline appears early in T2D progression (Biessels et
al, 2014) and is associated with decreased functional
connectivity within the default mode network (DMN), a brain
network important for basal brain function (Musen et al, 2012)
• Prediabetes is a condition characterized by impaired
glycemic control, and is on the path to T2D.
• The impact of prediabetes on cognitive function and brain
network connectivity in prediabetes is under-studied.
AIM: Test for differences in functional connectivity before the
onset of T2D between individuals with prediabetes and healthy
individuals. We hypothesized that prediabetes would be
associated with disruptions in DMN connectivity.
Introduction:
Methods:
Sample
• Data from the Human Connectome Project (Van Essen et al, 2012)
Of the sample, n=825 with hemoglobin A1c measurement.
• N=44 prediabetes group; A1c > 5.7%
• N=44 healthy A1c group; A1c < 5.7%; matched on BMI & sex
Measures
• 4 resting state functional MRI runs = 58 minutes
• NIH Toolbox’s cognitive function test battery (9 tests)
Analysis
• Resting state network (RSN) connectivity tested in FSLNets
(FMRIB, Oxford, UK)
• Per participant, activity in 15 RSNs over time correlated to make
network connectivity matrix.
• Paired samples t-test performed on the matrices to identify
stronger connectivity in each group
• Applied FSL’s Randomise tool with 10,000 permutations for non-
parametric statistical thresholding.
Alterations to Orbitofrontal Cortex Functional Connectivity in
Individuals With Prediabetes
Results:
• Prediabetes group and healthy A1c group showed differential
connectivity of the ventral attention network (orbitofrontal cortex and
middle temporal gyrus)
• Groups showed significant differences in 2 cognitive tests, but
differences are not clinically meaningful.
• Dimensional Change Card Sort Test (µ-prediabetes: 115.4, µ-
healthy: 100.6, t=6.4, p < 0.0001)
• Picture Vocabulary Test (µ-prediabetes: 102.7, µ-healthy: 112.5,
t=2.9, pFWE < 0.0049).
Figure 1. Stronger Connectivity in Prediabetes
Table 1: Sample Characteristics
Healthy A1c Prediabetes p-value a
Sex M: 18, F: 26 M: 18, F: 26 1.0
Age (years) 28.3 ± 3.6 29.0 ± 4.4 0.37
Body Mass Index (kg/m2) 26.6 ± 3.3 28.1 ± 5.8 0.13
Race
Caucasian 37 (84.1%) 22 (50.0%)
0.013*
African American 3 (6.8%) 13 (29.5%)
Asian or Pacific Islander 1 (2.3%) 5 (11.4%)
Native American/American Indian 0 (0%) 1 (2.3%)
More than One Race 2 (4.5%) 1 (2.3%)
Unknown 1 (2.3%) 2 (4.5%)
Ethnicity
Hispanic 2 (4.5%) 6 (13.6%)
0.21Non-Hispanic 41 (93.2%) 38 (86.4%)
Unknown 1 (2.3%) 0 (0%)
Hemoglobin A1c (%) 4.7 ± 0.2 5.8 ± 0.2 < 0.0001*
a significant testing between groups was completed using Welch’s two sample t-test or
Pearson’s chi-squares test. Significance is considered at p < 0.05. Significant differences
are denoted with an asterisk (*)
A) Prediabetes was associated with stronger connectivity of the orbitofrontal
cortex/middle temporal gyrus with 1) a somatosensory network containing precentral
and postcentral gyrus; and 2) a visual network comprising the occipital pole; compared
to individuals with healthy A1c. B) Simplified representation of network connectivity
associated with prediabetes.
Figure 2. Stronger Connectivity in Healthy A1c
Table 2: Significant Network Connectivity Differences
Prediabetes Group > Healthy A1c Group (Figure 1)
Connected RSNs t-value p-value
Ventral Attention Network & Visual Network 4.28 0.0001
Ventral Attention Network & Somatosensory Network 4.20 0.0027
Healthy A1c Group > Prediabetes Group (Figure 2)
Connected RSNs t-value p-value
Ventral Attention Network & Cingular-Operecular Task Control
Network
4.15 0.0024
Ventral Attention Network & Thalamic Striatal, Visual Network 4.38 0.0011
A) Compared to the prediabetes group, healthy A1c was associated with stronger
connectivity of OFC/middle temporal gyrus with 1) the insula, cingulate, middle frontal
gyrus, superior temporal gyrus and with 2) a network including the thalamus, ventral
striatum, and visual cortex. B) Simplified representation of network connectivity
associated with healthy A1c.
Conclusions:
• Prediabetes is associated with a shift in ventral attention
network connectivity away from self-regulating brain areas
and towards sensory regions, as evidenced by:
• Lack of connectivity of ventral attention network to the
cingular-operecular task control network in the
prediabetes group
• Stronger connectivity of ventral attention network to
sensory regions.
• Healthy A1c was associated with stronger ventral attention
network and thalamic-striatal connectivity. This is
representative of a cortical-striatal-thalamic loop implicated in
cognitive control, decision-making, and reversal learning (Peters
et al, 2016).
• Similarity in DMN connectivity between the groups may
indicate that degradation of the DMN seen in T2D (Musen et al
2012) occurs with worse glycemic control or longer disease
duration. The present prediabetes sample showed no signs of
cognitive decline.