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Creo AL, Cortes TM, Jo HJ, et al. Brain functions and cognition on transient insulin deprivation in type 1 diabetes. JCI Insight. 2021;6(5)doi: 10.1172/jci.insight.144014.
Creo, A. L., Cortes, T. M., Jo, H. J., Huebner, A. R., Dasari, S., Tillema, J. M., Lteif, A. N., Klaus, K. A., Ruegsegger, G. N., Kudva, Y. C., Petersen, R. C., Port, J. D., & Nair, K. S. (2021). Brain functions and cognition on transient insulin deprivation in type 1 diabetes. JCI insight, 6(5), . https://doi.org/10.1172/jci.insight.144014
Creo, Ana L, et al. "Brain functions and cognition on transient insulin deprivation in type 1 diabetes." JCI insight vol. 6,5 (2021). doi: https://doi.org/10.1172/jci.insight.144014
Creo AL, Cortes TM, Jo HJ, Huebner AR, Dasari S, Tillema JM, Lteif AN, Klaus KA, Ruegsegger GN, Kudva YC, Petersen RC, Port JD, Nair KS. Brain functions and cognition on transient insulin deprivation in type 1 diabetes. JCI Insight. 2021 Mar 08;6(5). doi: 10.1172/jci.insight.144014. PMID: 33561011; PMCID: PMC8021100.
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JCI Insight. 2021 Mar 08;6(5). doi: 10.1172/jci.insight.144014.

Brain functions and cognition on transient insulin deprivation in type 1 diabetes.

JCI insight

Ana L Creo, Tiffany M Cortes, Hang Joon Jo, Andrea Rs Huebner, Surendra Dasari, Jan-Mendelt Tillema, Aida N Lteif, Katherine A Klaus, Gregory N Ruegsegger, Yogish C Kudva, Ronald C Petersen, John D Port, K Sreekumaran Nair

Affiliations

  1. Division of Pediatric Endocrinology and Metabolism.
  2. Division of Endocrinology, Diabetes, Metabolism, and Nutrition.
  3. Department of Radiology.
  4. Division of Neurocognitive Disorders.
  5. Division of Biomedical Statistics and Informatics.
  6. Division of Child and Adolescent Neurology.
  7. Division of Behavioral Neurology, and.
  8. Division of Neuroradiology, Mayo Clinic, Rochester, Minnesota, USA.

PMID: 33561011 PMCID: PMC8021100 DOI: 10.1172/jci.insight.144014

Abstract

BACKGROUNDType 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.METHODSWe 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.RESULTSInsulin 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.CONCLUSIONTransient 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.TRIAL REGISTRATIONClinicalTrials.gov NCT03392441.FUNDINGClinical and Translational Science Award (UL1 TR002377) from the National Center for Advancing Translational Science; NIH grants (R21 AG60139 and R01 AG62859); the Mayo Foundation.

Keywords: Diabetes; Endocrinology; Insulin; Memory

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