Glucose regulation, cognition, and brain MRI in type 2 diabetes: a systematic review

Summary Type 2 diabetes is associated with cognitive dysfunction and structural brain changes. Abnormalities in glucose regulation are involved in several complications related to type 2 diabetes, but their role in these cerebral complications is unclear. We systematically reviewed studies of the association between glucose regulation (glycaemia, hypoglycaemic events, insulin concentration, insulin resistance, and glucose-lowering treatment) and cognitive function and brain abnormalities on MRI in people with type 2 diabetes. The 86 papers included showed that glycaemia, particularly high HbA1c concentration and glucose variability, are negatively associated with cognitive function in people with type 2 diabetes without dementia. However, the strength of this association is weak, and HbA1c generally accounted for less than 10% of the variance in cognition. Importantly, few studies have measured long-term cerebral outcomes, such as dementia and structural brain changes on MRI, and the effect of glucose-lowering treatment on these outcomes. More randomised controlled trials are needed to establish the effect of glucose-lowering treatment on long-term cognitive function in people with type 2 diabetes.