Effects of metformin exposure on neurodegenerative diseases in elderly patients with type 2 diabetes mellitus

Kuan, Yi Chun; Huang, Kai; Lin, Cheng Li; Hu, Chaur Jong; Kao, Chia Hung

doi:10.1016/j.pnpbp.2017.06.002

Cited by 135 publications

(123 citation statements)

References 26 publications

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“…Recent studies suggest that a hypoglycemic effect may induce neuroprotection in addition to reducing cognitive impairment in elderly adults diagnosed with T2DM and AD simultaneously (Chen, Zhang, Zhang, & Gong, ; Kuan, Huang, Lin, Hu, & Kao, ). The in vivo models, with transgenic animals to study AD, strengthen this proposal, because chronic treatment with metformin reduces levels of Aβ, in addition to that the death of neurons of the cortex and hippocampus could be smaller, in comparison to animals that did not receive this drugs (Asadbegi, Yaghmaei, Salehi, Ebrahim‐Habibi, & Komaki, ).…”

Section: Alzheimer Diseasementioning

confidence: 99%

Alzheimer's disease and metabolic syndrome: A link from oxidative stress and inflammation to neurodegeneration

Rojas-Gutierrez

Muñoz-Arenas

Treviño

et al. 2017

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149

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Alzheimer's disease (AD) is the most common cause of dementia and one of the most important causes of morbidity and mortality among the aging population. AD diagnosis is made post-mortem, and the two pathologic hallmarks, particularly evident in the end stages of the illness, are amyloid plaques and neurofibrillary tangles. Currently, there is no curative treatment for AD. Additionally, there is a strong relation between oxidative stress, metabolic syndrome, and AD. The high levels of circulating lipids and glucose imbalances amplify lipid peroxidation that gradually diminishes the antioxidant systems, causing high levels of oxidative metabolism that affects cell structure, leading to neuronal damage. Accumulating evidence suggests that AD is closely related to a dysfunction of both insulin signaling and glucose metabolism in the brain, leading to an insulin-resistant brain state. Four drugs are currently used for this pathology: Three FDA-approved cholinesterase inhibitors and one NMDA receptor antagonist. However, wide varieties of antioxidants are promissory to delay or prevent the symptoms of AD and may help in treating the disease. Therefore, therapeutic efforts to achieve attenuation of oxidative stress could be beneficial in AD treatment, attenuating Aβ-induced neurotoxicity and improve neurological outcomes in AD. The term inflammaging characterizes a widely accepted paradigm that aging is accompanied by a low-grade chronic up-regulation of certain pro-inflammatory responses in the absence of overt infection, and is a highly significant risk factor for both morbidity and mortality in the elderly.

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Section: Alzheimer Diseasementioning

confidence: 99%

Alzheimer's disease and metabolic syndrome: A link from oxidative stress and inflammation to neurodegeneration

Rojas-Gutierrez

Muñoz-Arenas

Treviño

et al. 2017

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149

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“…Recent studies have suggested that metformin might have neuroprotective effect in several neurologic diseases such as Alzheimer's disease (Chen et al, 2009) and Parkinson's disease (Kuan et al, 2017). Furthermore, activated microglial cells release pro-inflammatory cytokines such as TNF-α and IL-6 in chronic neurodegenerative diseases (Hanisch, 2002).…”

Section: Discussionmentioning

confidence: 99%

Anti-inflammatory Effects of Metformin on Neuro-inflammation and NLRP3 Inflammasome Activation in BV-2 Microglial Cells

Yeom

Jang

et al. 2019

BSL

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Metformin is a drug used for the treatment of diabetes and is associated with anti-inflammatory reaction, but the underlying mechanism is unclear. In this study, we investigated the effect of metformin on the inflammatory response in BV-2 microglial cells induced by lipopolysaccharide (LPS) and S100 calcium-binding protein A8 (S100A8). The results revealed that metformin significantly attenuated several inflammatory responses in BV-2 microglial cells, including the secretion of pro-inflammatory cytokines, such as tumor necrosis factor-α and interleukin (IL)-6, involved in the activation of Beclin-1, a crucial regulator of autophagy. In addition, metformin inhibited the LPS-induced phosphorylation of ERK. Metformin also suppressed the activation of NOD-like receptor pyrin domain containing 3 inflammasomes composed of NLRP3, caspase-1, and apoptosis-associated speck like protein containing a caspase recruitment domain, which are involved in the innate immune response. Notably, metformin decreased the secretion of S100A8-induced IL-6 production. These findings suggest that metformin alleviates the neuroinflammatory response via autophagy activation.

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“…Однако следует отметить, что в одном из исследований, не включенных в метаанализ, использование препаратов сульфонилмочевины было статистически значимо ассоциировано с повышенным риском развития деменции в сравнении с терапией метформином (ОШ 1,24; 95% ДИ 1,10−1,40) [60]. Риск развития деменции на фоне лечения метформином (оценивался в 3 исследованиях, включенных в метаанализ [61,62,63]) статистически значимо не повышался (ОР 1,08; 95% ДИ 0,49−2,36). Представляет интерес тот факт, что в одном из исследований (H.W.…”

Section: A R T I C L E I N P R E S Sunclassified

Hypoglycemia and the risk of cognitive impairment and dementia in elderly and senile patients with type 2 diabetes

Остроумова¹,

Суркова²,

Васильевна³

et al. 2020

Diabetes mellitus

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Research results show that poor glycemic control and recurrent episodes of severe hypoglycaemia are associated with a decrease in cognitive function in elderly people with type 2 diabetes mellitus (T2DM). On the other hand, patients with diabetes mellitus associated with cognitive impairment/dementia are most at risk of developing hypoglycaemic conditions. It is obvious that the relationship between hypoglycaemia and dementia is very complex and has a mutually aggravating nature. Studies also show that individuals of older age groups with diabetes and cognitive impairment have a high risk of developing hypoglycaemic conditions, such as unwanted side effects from glucose-lowering therapy. In this case, of particular interest is the question that is being actively studied at the present time, which is concerning the effect of different groups of glucose-lowering antidiabetic drugs on the cognitive status and the rate of cognitive decline in diabetic patients with cognitive impairment. In this review, we attempted to summarise, systematise, and present data available in the literature concerning the effect of hypoglycaemia on the risk of cognitive impairment and dementia in elderly and senile patients with type-2 diabetes, as well as the degree of participation in this process of of various groups of sugar-lowering antidiabetic drugs.

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Effects of metformin exposure on neurodegenerative diseases in elderly patients with type 2 diabetes mellitus

Cited by 135 publications

References 26 publications

Alzheimer's disease and metabolic syndrome: A link from oxidative stress and inflammation to neurodegeneration

Alzheimer's disease and metabolic syndrome: A link from oxidative stress and inflammation to neurodegeneration

Anti-inflammatory Effects of Metformin on Neuro-inflammation and NLRP3 Inflammasome Activation in BV-2 Microglial Cells

Hypoglycemia and the risk of cognitive impairment and dementia in elderly and senile patients with type 2 diabetes

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