ISSN 1849-9031 (Online)

ISSN 1849-8922    (Print)

Functional changes in the central nervous system: An early but unrecognized complication of type 1 diabetes mellitus.
Kristina Blaslov, Nikolina Brcina, Miroslav Ćaćić, Lora S. Kirigin Biloš, Lucija Ana Trtanj, Ivan Kruljac, Gorana Mirošević.


Purpose: Diabetic neuropathy is a chronic and disabling condition that affects a significant number of individuals with diabetes mellitus (DM). Long considered a disease of the peripheral nervous system, there is now increasing evidence of central nervous system (CNS) involvement. Recent advances in neuroimaging methods have improved our understanding of how diabetic neuropathy affects the CNS. The aim of this study was to explore the relationship between cerebrospinal fluid (CSF) concentration of polyols, plasma glucose, and 18-fluordeoxyglucose (18-FDG) uptake correlation in the CNS of Type 1 diabetes mice models.

Materials and Methods: We conducted a study using two different Type 1 DM mice models: Streptozotocin induced and non-obese diabetic (NOD) mice models. Positron emission tomography with 18-FDG was used to determine glucose uptake in the frontal cortex and hippocampus. CSF samples were taken from the cisterna magna, while polyol species in the CSF were determined using gas chromatographic/mass spectrometric assays by Sigma Aldrich.

Results: The concentration of CSF myoinositol was significantly higher in NOD mice compared to controls (P = 0.001). The 18-FDG uptake was significantly attenuated in NOD mice compared to controls. CSF-myoinositol negatively correlated with 18-FDG uptake in the hippocampal area (ρ = −0.571, P = 0.003) and frontal cortex (ρ = −0.521, P = 0.044).

Conclusion: We demonstrated that in the early course of Type 1 DM, there are functional changes in the CNS, precisely in the frontal cortex and hippocampal region, evidenced by elevated myoinositol, which might reflect the initiation of cerebral tissue damage. Whether this suggests that hyperglycemia is toxic for the brain needs further investigation.