TY - JOUR
T1 - Brain functions and cognition on transient insulin deprivation in type 1 diabetes
AU - Creo, Ana L.
AU - Cortes, Tiffany M.
AU - Jo, Hang Joon
AU - Huebner, Andrea R.S.
AU - Dasari, Surendra
AU - Tillema, Jan-Mendelt
AU - Lteif, Aida N.
AU - Klaus, Katherine A.
AU - Ruegsegger, Gregory N.
AU - Kudva, Yogish C
AU - Petersen, Ronald C.
AU - Port, John D.
AU - Sreekumaran Nair, K.
N1 - Funding Information:
FUNDING. Clinical and Translational Science Award (UL1 TR002377) from the National Center for Advancing Translational Science; NIH grants (R21 AG60139 and R01 AG62859); the Mayo Foundation.
Funding Information:
We acknowledge Peter D. Kollasch and Venkata V. Chebrolu, (our 2 Siemens site scientists who helped us create the imaging protocol) and Mandie J. Maroney (our MRI technologist who did an amazing job with the image acquisition). We also acknowledge the diabetes nurses Janet L. Hansen, Mary L. Heyrman, and Rebecca N. Spee, for their help in patient recruitment. This publication was supported by Clinical and Translational Science Award (grant UL1 TR002377) from the National Center for Advancing Translational Science. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. KSN is supported by NIH grants R21 AG60139 and R01 AG62859 as well as the Mayo Foundation.
Publisher Copyright:
Copyright: © 2021, Creo et al.
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/3/8
Y1 - 2021/3/8
N2 - BACKGROUND. Type 1 diabetes (T1D) is a risk factor for dementia and structural brain changes. It remains to be determined whether transient insulin deprivation that frequently occurs in insulin-treated individuals with T1D alters brain function. METHODS. We therefore performed functional and structural magnetic resonance imaging, magnetic resonance spectroscopy, and neuropsychological testing at baseline and following 5.4 ± 0.6 hours of insulin deprivation in 14 individuals with T1D and compared results with those from 14 age-, sex-, and BMI-matched nondiabetic (ND) participants with no interventions. RESULTS. Insulin deprivation in T1D increased blood glucose, and β-hydroxybutyrate, while reducing bicarbonate levels. Participants with T1D showed lower baseline brain N-acetyl aspartate and myo-inositol levels but higher cortical fractional anisotropy, suggesting unhealthy neurons and brain microstructure. Although cognitive functions did not differ between participants with T1D and ND participants at baseline, significant changes in fine motor speed as well as attention and short-term memory occurred following insulin deprivation in participants with T1D. Insulin deprivation also reduced brain adenosine triphosphate levels and altered the phosphocreatine/adenosine triphosphate ratio. Baseline differences in functional connectivity in brain regions between participants with T1D and ND participants were noted, and on insulin deprivation further alterations in functional connectivity between regions, especially cortical and hippocampus-caudate regions, were observed. These alterations in functional connectivity correlated to brain metabolites and to changes in cognition. CONCLUSION. Transient insulin deprivation therefore caused alterations in executive aspects of cognitive function concurrent with functional connectivity between memory regions and the sensory cortex. These findings have important clinical implications, as many patients with T1D inadvertently have periods of transient insulin deprivation.
AB - BACKGROUND. Type 1 diabetes (T1D) is a risk factor for dementia and structural brain changes. It remains to be determined whether transient insulin deprivation that frequently occurs in insulin-treated individuals with T1D alters brain function. METHODS. We therefore performed functional and structural magnetic resonance imaging, magnetic resonance spectroscopy, and neuropsychological testing at baseline and following 5.4 ± 0.6 hours of insulin deprivation in 14 individuals with T1D and compared results with those from 14 age-, sex-, and BMI-matched nondiabetic (ND) participants with no interventions. RESULTS. Insulin deprivation in T1D increased blood glucose, and β-hydroxybutyrate, while reducing bicarbonate levels. Participants with T1D showed lower baseline brain N-acetyl aspartate and myo-inositol levels but higher cortical fractional anisotropy, suggesting unhealthy neurons and brain microstructure. Although cognitive functions did not differ between participants with T1D and ND participants at baseline, significant changes in fine motor speed as well as attention and short-term memory occurred following insulin deprivation in participants with T1D. Insulin deprivation also reduced brain adenosine triphosphate levels and altered the phosphocreatine/adenosine triphosphate ratio. Baseline differences in functional connectivity in brain regions between participants with T1D and ND participants were noted, and on insulin deprivation further alterations in functional connectivity between regions, especially cortical and hippocampus-caudate regions, were observed. These alterations in functional connectivity correlated to brain metabolites and to changes in cognition. CONCLUSION. Transient insulin deprivation therefore caused alterations in executive aspects of cognitive function concurrent with functional connectivity between memory regions and the sensory cortex. These findings have important clinical implications, as many patients with T1D inadvertently have periods of transient insulin deprivation.
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U2 - 10.1172/jci.insight.144014
DO - 10.1172/jci.insight.144014
M3 - Article
C2 - 33561011
AN - SCOPUS:85102477145
VL - 6
JO - JCI insight
JF - JCI insight
SN - 2379-3708
IS - 5
M1 - e144014
ER -