Diabetes and Alzheimer's Disease: Mechanisms and Nutritional Aspects

Abstract

Blood glucose homeostasis is well maintained by coordinated control of various hormones including insulin and glucagon as well as cytokines under normal conditions. However, chronic exposure to diabetic environment with high fat/high sugar diets and physical/mental stress can cause hyperglycemia, one of main characteristics of insulin resistance, metabolic syndrome, and diabetes. Hyperglycemia impairs organogenesis and induces organ abnormalities such as cardiac defect in utero. It is a risk factor for the development of metabolic diseases in adults. Resulting glucotoxicity affects peripheral tissues and vessels, causing pathological complications including diabetic neuropathy, nephropathy, vessel damage, and cardiovascular diseases. Moreover, chronic exposure to hyperglycemia can deteriorate cognitive function and other aspects of mental health. Recent reports have demonstrated that hyperglycemia is closely related to the development of cognitive impairment and dementia, suggesting that there may be a cause-effect relationship between hyperglycemia and dementia. With increasing interests in aging-related diseases and mental health, diabetes-related cognitive impairment is attracting great attention. It has been speculated that glucotoxicity can result in structural damage and functional impairment of brain cells and nerves, hemorrhage of cerebral blood vessel, and increased accumulation of amyloid beta. These are potential mechanisms underlying diabetes-related dementia. Nutrients and natural food components have been investigated as preventive and/or intervention strategy. Among candidate components, resveratrol, curcumin, and their analogues might be beneficial for the prevention of diabetes-related cognitive impairment. The purposes of this review are to discuss recent experimental evidence regarding diabetes and cognitive impairment and to suggest potential nutritional intervention strategies for the prevention and/or treatment of diabetes-related dementia.

Bridelia speciosa Müll.Arg. Stem bark Extracts as a Potential Biomedicine: From Tropical Western Africa to the Pharmacy Shelf

“…The inhibition of cholinesterases, namely acetylcholinesterase and butyrylcholinesterase, remains the main focus for the management of Alzheimer's disease. Besides, an increasing number of publications and clinical studies substantiates that Alzheimer's disease and type 2 diabetes might share some pathophysiological similarities [42,43]. As such, type 2 diabetes has been identified as a risk factor for Alzheimer's disease based on multiple connections [44].…”

Metabolic Endotoxemia: A Potential Underlying Mechanism of the Relationship between Dietary Fat Intake and Risk for Cognitive Impairments in Humans?

“…Moreover, adopting this fat-rich dietary pattern can lead to metabolic disorders such as obesity or Type 2 Diabetes Mellitus (T2DM), these latter being associated with a higher risk of developing dementia in later life [9,10].Nutritional strategies represent a promising area to prevent neurocognitive impairments and subsequent dementia. While the precise mechanisms underlying the relationships between these dietary habits on age-related cognitive disorders are not yet completely understood (for instance, inflammatory pathways, vascular factors, oxidative stress or amyloidogenesis [11][12][13][14]), we suggest that the activation of the innate immune system by endotoxins-which are still poorly described-could be considered as one potential cellular mechanism involved in these relationships.Endotoxins (Lipopolysaccharides, LPS), a major component of the outer membrane of Gram-negative bacteria, are now well as contributors to the inflammation [15]. Although LPS may originate from skin and mucous membranes or local sites of bacterial infection for instance, the gut microbiota is considered the main natural reservoir of pro-inflammatory endotoxins in the body [16].…”

“…Nutritional strategies represent a promising area to prevent neurocognitive impairments and subsequent dementia. While the precise mechanisms underlying the relationships between these dietary habits on age-related cognitive disorders are not yet completely understood (for instance, inflammatory pathways, vascular factors, oxidative stress or amyloidogenesis [11][12][13][14]), we suggest that the activation of the innate immune system by endotoxins-which are still poorly described-could be considered as one potential cellular mechanism involved in these relationships.…”

Advance of sporadic Alzheimer's disease animal models

“…Streptozotocin (STZ), a naturally occurring alkylating antineoplastic agent that is particularly toxic to the insulin‐producing β cells of the pancreas in mammals, is structurally similar to glucose and N ‐acetyl glucosamine and can induce peripheral insulin resistance in animals by inhibiting N‐acetyl amino glycosidase enzymes and destroying islet β cells . It has been reported that the cognitive decline of diabetic patients complicated with AD is significantly severer than patients who only suffer from the pathologies of AD . In addition, the dysfunctions of insulin/insulin‐like growth factor‐1 signal pathway may cause neurodegeneration in center nerve system .…”

“…44 It has been reported that the cognitive decline of diabetic patients complicated with AD is significantly severer than patients who only suffer from the pathologies of AD. 45 In addition, the dysfunctions of insulin/insulin-like growth factor-1 signal pathway may cause neurodegeneration in center nerve system. 46 STZ simulates characteristic pathology of sAD such as lowed glucose metabolism, glycogen synthase kinase-3β activation, Aβ deposition, Tau hyperphosphorylation, synaptic dysfunction, and neuronal apoptosis.…”