Brain functions and cognition on transient insulin deprivation in type 1 diabetes
Ana L. Creo, … , John D. Port, K. Sreekumaran Nair
Ana L. Creo, … , John D. Port, K. Sreekumaran Nair
Published February 9, 2021
Citation Information: JCI Insight. 2021;6(5):e144014. https://doi.org/10.1172/jci.insight.144014.
View: Text | PDF
Clinical Medicine Endocrinology

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

Abstract

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.TRIAL REGISTRATION ClinicalTrials.gov NCT03392441.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.

Authors

Ana L. Creo, Tiffany M. Cortes, Hang Joon Jo, Andrea R.S. 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

×

Figure 1

Study design.

Options: View larger image (or click on image) Download as PowerPoint
Study design. Both study groups (nondiabetic [ND] and T1D) started the s...
Both study groups (nondiabetic [ND] and T1D) started the study with a fasting blood sampling. Participants with T1D were then started on a continuous insulin infusion titrated to maintain blood glucose between 5 and 6.7 mmol/l (Time 1). Following a 3-hour insulin infusion in the T1D group or the corresponding time course for the ND group, participants had cognitive testing. Following this, the participants were taken to radiology, and MR studies were performed. The insulin infusion was continued during both cognitive testing and MR studies. Then, blood sampling was performed, and immediately after the insulin infusion was discontinued in the participants with T1D. Four hours following after a period of insulin withdrawal (Time 2), or at the corresponding time course for the control participants, the cognitive testing (4–4.5 hours) and then MR studies were performed (5 ± 0.6 hours). Time 1 represents the insulin-treated period in T1D, and Time 2 represents the period following insulin deprivation in T1 D. Both times represent no intervention but specifically address time-related changes in the ND group.