Cognitive impairment and type 2 diabetes mellitus: Focus of SGLT2 inhibitors treatment

Rizzo, Maria Rosaria; Meo, Irene Di; Polito, Rita; Auriemma, Maria Chiara; Gambardella, A.; Mauro, Gabriella di; Capuano, Annalisa; Paolisso, Giuseppe

doi:10.1016/j.phrs.2022.106062

Cited by 67 publications

(50 citation statements)

References 86 publications

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“…Emerging reports show that SGLT-2 inhibitors protect neurovascular units (Pawlos et al, 2021). In addition, SGLT-2 inhibition ameliorates cognitive dysfunction in obese and type 2 diabetic mice (Rizzo et al, 2022). An interesting study showed that empagliflozin alleviated neuronal apoptosis induced cerebral ischemia/reperfusion injury and reduced the size of brain infarctions in a murine model, through up-regulation of hypoxia-inducible factor 1-alpha and its downstream mediator VEGF (Abdel-Latif et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

Sodium-Glucose Cotransporter-2 Inhibition Exacerbates Hepatic Encephalopathy in Biliary Cirrhotic Rats

Hsu

Huang

Pun

et al. 2022

J Pharmacol Exp Ther

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In liver cirrhosis, hepatic inflammation and abundant portal-systemic collaterals are indicated for the development of hepatic encephalopathy. Sodium-glucose cotransporter-2 (SGLT-2) inhibitors are a type of anti-diabetic agent, which exert pleiotropic and anti-inflammatory effects. Diabetes and chronic liver disease often coexist but the influence of SGLT-2 inhibition on liver cirrhosis and hepatic encephalopathy remains unknown. This study investigated the effect of SGLT-2 inhibition on cirrhotic rats. Biliary cirrhosis was induced in Sprague-Dawley rats via common bile duct ligation. A total of 2-weeks treatment with the SGLT-2 inhibitor, empagliflozin 30 mg/kg/day, was applied. The motor activities, hemodynamics, biochemistry parameters, plasma levels of vascular endothelial growth factor (VEGF) and the severity of portal-systemic collateral shunts were measured. The hepatic histopathology and protein expressions were examined. We found that empagliflozin treatment did not affect hemodynamics, liver biochemistry or blood glucose levels in cirrhotic rats. Empagliflozin did not affect hepatic inflammation and fibrosis. The protein expression of factors related to liver injury were not influenced by empagliflozin.However, empagliflozin decreased motor activities in cirrhotic rats and increased portal-systemic collateral shunts and VEGF plasma levels. In summary, SGLT-2 inhibition by empagliflozin did not ameliorate portal hypertension and hepatic This article has not been copyedited and formatted. The final version may differ from this version. JPET Fast Forward.

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Section: Discussionmentioning

confidence: 99%

Sodium-Glucose Cotransporter-2 Inhibition Exacerbates Hepatic Encephalopathy in Biliary Cirrhotic Rats

Hsu

Huang

Pun

et al. 2022

J Pharmacol Exp Ther

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“…Various diabetes-specific risk factors and comorbid conditions have been linked to cognitive dysfunction in T2DM. Duration of diabetes may be a potential contributing factor, with studies suggesting a higher occurrence of cognitive dysfunction associated with a longer duration of diabetes [20,21]. This, however, may be because of the prevalence of both conditions rising with age [4].…”

Section: Diabetes-specific Risk Factorsmentioning

confidence: 99%

Type 2 diabetes mellitus and cognitive function: understanding the connections

Dao¹,

Choi

Freeby³

2022

Current Opinion in Endocrinology, Diabetes &Amp; Obesity

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Purpose of reviewTo review the connection between type 2 diabetes and cognitive dysfunction, including its epidemiology, potential mechanisms of pathophysiology, risk factors, possible prevention, and treatment considerations.Recent findingsDiabetes is a risk factor for mild cognitive decline, in addition to Alzheimer's disease and vascular dementia. Duration of diabetes, concomitant vascular or associated co-morbidities, hyper- and hypoglycemia may lead to worsening cognitive dysfunction. Unfortunately, there is a lack of evidence-based guidance on the prevention of cognitive dysfunction in the diabetes population. Studies of diabetes medications, including metformin, glucagon-like peptide-1 (GLP-1) receptor agonists, and sodium-glucose cotransporter-2 inhibitors (SGLT2) have shown some benefit with cardiovascular morbidity and may affect cognition. In the absence of clearly defined preventive tools, diabetes practice guidelines recommend annual cognitive screening as standard of care in adults with diabetes aged 65 years or older.SummaryPeople living with diabetes are at risk for significant decline in cognitive function. Epidemiology and risk factors are well defined. Prevention and treatment strategies are limited and require further study.

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“…Particularly, it has been observed that T2DM may accelerate the effects of aging on some brain structures, as a form of neurodegeneration, and may therefore contribute to the higher prevalence of cognitive impairment observed in T2DM patients ( Abbatecola et al, 2006 ; Rizzo et al, 2010 ; Riederer et al, 2017 ). Emerging evidence indicates that insulin resistance and hyperinsulinemia are shared features between T2DM and Alzheimer’s disease (AD), suggesting a potential counteracting role of some antidiabetic drugs ( Rizzo et al, 2014 , 2022 ), such as also metformin, on several neurodegenerative mechanisms ( Sanati et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

Neurovascular coupling in patients with type 2 diabetes mellitus

Canna

Esposito

Tedeschi

et al. 2022

Front. Aging Neurosci.

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Functional and metabolic neural changes in Type 2 diabetes mellitus (T2DM) can be associated with poor cognitive performances. Here we analyzed the functional-metabolic neurovascular coupling (NVC) in the brain of T2DM patients. Thirty-three patients (70 ± 6 years, 15 males) with recent T2DM diagnosis and 18 healthy control (HC) subjects (65 ± 9 years, 9 males) were enrolled in a brain MRI study to identify the potential effects of T2DM on NVC. T2DM patients were either drug-naive (n = 19) or under treatment with metformin (n = 14) since less than 6 months. Arterial spin labeling and blood oxygen level dependent resting-state functional MRI (RS-fMRI) images were combined to derive NVC measures in brain regions and large-scale networks in a standard brain parcelation. Altered NVC values in T2DM patients were correlated with cognitive performances spanning several neurological domains using Spearman correlation coefficients. Compared to HC, T2DM patients had reduced NVC in the default mode network (DMN) and increased NVC in three regions of the dorsal (DAN) and salience-ventral (SVAN) attention networks. NVC abnormalities in DAN and SVAN were associated with reduced visuo-spatial cognitive performances. A spatial pattern of NVC reduction in the DMN, accompanied by isolated regional NVC increases in DAN and SVAN, could reflect the emergence of (defective) compensatory processes in T2DM patients in response to altered neurovascular conditions. Overall, this pattern is reminiscent of neural abnormalities previously observed in Alzheimer’s disease, suggesting that similar neurobiological mechanisms, secondary to insulin resistance and manifesting as NVC alterations, might be developing in T2DM pathology.

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Cognitive impairment and type 2 diabetes mellitus: Focus of SGLT2 inhibitors treatment

Cited by 67 publications

References 86 publications

Sodium-Glucose Cotransporter-2 Inhibition Exacerbates Hepatic Encephalopathy in Biliary Cirrhotic Rats

Sodium-Glucose Cotransporter-2 Inhibition Exacerbates Hepatic Encephalopathy in Biliary Cirrhotic Rats

Type 2 diabetes mellitus and cognitive function: understanding the connections

Neurovascular coupling in patients with type 2 diabetes mellitus

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