Effects of Diabetes Mellitus-Related Dysglycemia on the Functions of Blood-Brain Barrier and the Risk of Dementia

Diabetes mellitus is one of the most common metabolic diseases worldwide, and its long-term complications include neuropathy, referring both to the peripheral and to the central nervous system. Detrimental effects of dysglycemia, especially hyperglycemia, on the structure and function of the blood-brain barrier (BBB), seem to be a significant backgrounds of diabetic neuropathy pertaining to the central nervous system (CNS). Effects of hyperglycemia, including excessive glucose influx to insulin-independent cells, may induce oxidative stress and secondary innate immunity dependent inflammatory response, which can damage cells within the CNS, thus promoting neurodegeneration and dementia. Advanced glycation end products (AGE) may exert similar, pro-inflammatory effects through activating receptors for advanced glycation end products (RAGE), as well as some pattern-recognition receptors (PRR). Moreover, long-term hyperglycemia can promote brain insulin resistance, which may in turn promote A & beta; aggregate accumulation and tau hyperphosphorylation. This review is focused on a detailed analysis of the effects mentioned above towards the CNS, with special regard to mechanisms taking part in the pathogenesis of central long-term complications of diabetes mellitus initiated by the loss of BBB integrity.

Automated summary

Diabetes mellitus is a common metabolic disease that can lead to neuropathy in both the peripheral and central nervous systems. Hyperglycemia, oxidative stress, and inflammation are the main factors contributing to the damage of cells in the central nervous system, causing neurodegeneration and dementia. Advanced glycation end products and brain insulin resistance are also involved in the pathogenesis of long-term complications of diabetes mellitus. This review focuses on the effects of dysglycemia on the central nervous system and the mechanisms underlying the loss of blood-brain barrier integrity.