Dementia in Diabetes: The Role of Hypoglycemia

Abstract

Hypoglycemia, a common consequence of diabetes treatment, is associated with severe morbidity and mortality and has become a major barrier to intensifying antidiabetic therapy. Severe hypoglycemia, defined as abnormally low blood glucose requiring the assistance of another person, is associated with seizures and comas, but even mild hypoglycemia can cause troubling symptoms such as anxiety, palpitations, and confusion. Dementia generally refers to the loss of memory, language, problem-solving, and other cognitive functions, which can interfere with daily life, and there is growing evidence that diabetes is associated with an increased risk of both vascular and non-vascular dementia. Neuroglycopenia resulting from a hypoglycemic episode in diabetic patients can lead to the degeneration of brain cells, with a resultant cognitive decline, leading to dementia. In light of new evidence, a deeper understating of the relationship between hypoglycemia and dementia can help to inform and guide preventative strategies. In this review, we discuss the epidemiology of dementia among patients with diabetes, and the emerging mechanisms thought to underlie the association between hypoglycemia and dementia. Furthermore, we discuss the risks of various pharmacological therapies, emerging therapies to combat hypoglycemia-induced dementia, as well as risk minimization strategies.

Alterations in Brain Morphometric Networks and Their Relationship with Memory Dysfunction in Patients with Type 2 Diabetes Mellitus

“…While HbA1c levels reflect glycemic control over the previous three months, and insulin resistance is a key aspect of T2DM pathophysiology, a more robust marker for long-term glycemic control, such as lifetime cumulative glycemic control levels [ 50 ], might be required to elucidate the exact metabolic mechanisms underlying T2DM-related brain alterations. This suggestion stems from the understanding that the brain’s susceptibility to diabetes-related alterations could result from the cumulative impact of the condition over an extended period, which current HbA1c levels may not adequately represent [ 51 ].…”

Editorial: The crosstalk of different mechanisms in cognitive impairment associated with aging, Alzheimer's disease, and related dementias

“…The mechanisms and implications underlying cognitive decline, mild cognitive impairment (MCI), and dementia in Type 2 diabetes mellitus (T2DM) have attracted significant attention in recent years since a large number of studies have found that T2DM may increase their incidence rate (Biessels and Despa, 2018;Husain et al, 2023). In this Research Topic, two works addressed interesting aspects of this issue.…”

Glucose Transport and Utilization in the Hippocampus: From Neurophysiology to Diabetes-Related Development of Dementia

“…Since then, the concept that neuroglycopenia in DM subjects-resulting from a hypoglycemic episode-leads to neuronal degeneration with cognitive decline and dementia, has been consolidated. That must be considered not only in insulin-treated T1D, but also in several cases of some drugand insulin-treated T2D (for a review, see [93]).…”

“…Since then, DM microvascular disease has contributed to the recognition of DM as a risk factor mainly of VD; however, the mechanisms underlying this association are not completely understood [93]. The homology of cerebral and retinal microvasculature, probably due to their similar embryological origin, provides some insight that, like retinopathy, cerebral small vessel disease (SVD) should also develop in DM (for a review, see [127]).…”