Inducing elevated glucose levels in vitro: A model to simulate prediabetes (preDBT) states in primary cultures

Abstract

There is increasing evidence suggesting a relationship between prediabetes (preDBT, the early stage of Type 2 Diabetes or DBT2) and neurodegenerative disorders (NDDs) such as Alzheimer´s disease. The preDBT stage, characterized by impaired fasting glucose (IFG), may represent an early risk factor for cognitive decline and the onset of NDDs. However, the underlying mechanisms connecting preDBT to cognitive impairment and neurodegeneration remain poorly understood. This study aims to explore the effects of IFG on central nervous system (CNS) cells by developing an in vitro model of preDBT using sera from individuals with IFG. Our results demonstrate that exposure of astrocyte-neuron mixed cultures to IFG sera induced hyperglycemia, increased oxidative levels and astrogliosis that would lead to cognitive impairment observed in the analyzed cohort, as evidenced by a battery of cognitive tests. These findings suggest that the early stages of preDBT may trigger changes in CNS cells that correlate with cognitive decline. The study underscores the importance of early diagnosis and intervention in preDBT to prevent progression to DBT2 and associated NDDs.