Recurrent non-severe hypoglycemia aggravates cognitive decline in diabetes and induces mitochondrial dysfunction in cultured astrocytes

Gao, Ruonan; Ren, Lingjia; Zhou, Yu; Wang, Lijing; Xie, Yunzhen; Zhang, Mengjun; Li, Xiaoying; Ke, Sujie; Wu, Kejun; Zheng, Jiaping; Liu, Xiaohong; Zhou, C.; Liu, Libin

doi:10.1016/j.mce.2021.111192

Cited by 19 publications

(11 citation statements)

References 70 publications

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“…Most studies have shown that hypoglycemia promotes oxidative stress-induced brain damage in diabetes patients [ 21 , 23 , 43 ]. We believe that such events are mainly related to vascular damage.…”

Section: Discussionmentioning

confidence: 99%

“…Hypoglycemia is a common clinical event in diabetes patients, especially those with intensive glycemic control and using insulin or other hypoglycemic agents [4,7,43]. Most studies of diabetic hypoglycemia have focused on cognitive dysfunction [23,[43][44][45]. As glucose is the primary the energy source of the adult human brain, severe hypoglycemia, a blood glucose of <2.3 mM, can lead to coma, permanent brain damage, or death.…”

Section: Discussionmentioning

confidence: 99%

“…Current studies of the complications of hypoglycemia in diabetes have primarily focused on brain injury induced by hypoglycemia [23,[43][44][45]. Studies of the effects of severe hypoglycemia in humans have yielded conflicting results.…”

Section: Discussionmentioning

confidence: 99%

“…Diabetic hypoglycemia promotes mitochondrial dysfunction in vascular cells that consequently increases the levels of reactive oxygen species (ROS) [20][21][22][23]. Increased expression of proinflammatory cytokines stimulates inducible nitric oxide synthase (iNOS) expression, which results in the aggravation of oxidative stress and worsening of chronic inflammation and endothelial dysfunction in diabetes [24,25].…”

Section: Introductionmentioning

confidence: 99%

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Recurrent Hypoglycemia Impaired Vascular Function in Advanced T2DM Rats by Inducing Pyroptosis

Luo

et al. 2022

Oxidative Medicine and Cellular Longevity

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Background. Hypoglycemia is a dangerous side effect of intensive glucose control in diabetes. Even though it leads to adverse cardiovascular events, the effects of hypoglycemia on vascular biology in diabetes have not been adequately studied. Methods. Aged Sprague-Dawley rats were fed a high-fat diet and given streptozotocin to induce type 2 diabetes mellitus (T2DM). Acute and recurrent hypoglycemia were then induced by glucose via insulin administration. Vascular function, oxidative stress, and pyroptosis levels in aortic tissue were assessed by physiological and biochemical methods. Results. Hypoglycemia was associated with a marked decrease in vascular function, elevated oxidative stress, and elevated pyroptosis levels in the thoracic aorta. The changes in oxidative stress and pyroptosis were greater in rats with recurrent hypoglycemia than in those with acute hypoglycemia. Conclusions. Hypoglycemia impaired vascular function in aged rats with T2DM by inducing pyroptosis. The extent of injury increased with the duration of blood glucose fluctuation.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Recurrent Hypoglycemia Impaired Vascular Function in Advanced T2DM Rats by Inducing Pyroptosis

Luo

et al. 2022

Oxidative Medicine and Cellular Longevity

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“…People with T2DM are at risk of life-threatening acute and chronic complications, especially T2DM-caused central nervous system damage, which can cause functional and structural changes in the brain that lead to cognitive impairment and behavioral de cits [1]. Chronic hyperglycemia, recurrent hypoglycemic episodes and glycemic excursions have been implicated as potential causative factors of cognitive impairment [2][3][4], and for this reason, continuous glucose monitoring (CGM) has evolved as an essential part of diabetes management for diabetic patients with cognitive impairment. With the development of CGM technology, ash glucose monitoring (FGM) systems have increased in popularity in recent years because of the highly detailed information and enhanced accuracy that they provide.…”

Section: Introductionmentioning

confidence: 99%

Relationship between key continuous glucose monitoring-derived metrics and specific cognitive domains in patients with type 2 diabetes mellitus

Dong

Wang

Zhao

et al. 2023

Preprint

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Objective Continuous glucose monitoring (CGM)-derived time in range (TIR) is closely associated with micro- and macro-vascular complications in type 2 diabetes mellitus (T2DM). This study was performed to investigate the relationship between key CGM metrics and specific cognitive domains in patients with T2DM. Methods A total of 96 outpatients with T2DM were recruited in this study. A battery of neuropsychological tests was performed to evaluate cognitive function, including memory, executive functioning, visuospatial ability, attention, and language. Participants wore a blinded flash glucose monitor (FGM) for 72 h. The key FGM metrics were calculated, including TIR, time below range (TBR), and time above range (TAR). Furthermore, the glycemia risk index (GRI) was also calculated by the GRI formula. Binary logistic regression was used to assess risk factors for TBR, and we further analyzed the associations between neuropsychological test results and TBR/TAR/TIR/GRI with multiple linear regressions. Results A total of 45.8% of patients with T2DM had hypoglycemia (TBR < 3.9) measured by FGM. The Spearman analysis results revealed that a higher TBR < 3.9 was correlated with worse performance on trail making test A (TMTA), clock drawing test (CDT) and cued recall scores (P < 0.05). The logistic regression analysis results revealed that TMTA (OR = 1.010, P = 0.036) and CDT (OR = 0.429, P = 0.016) scores were independent factors influencing the occurrence of TBR < 3.9. Multiple linear regressions revealed that TBR < 3.9 (β = -0.214, P = 0.033), TAR > 13.9 (β = -0.216, P = 0.030) and TAR 10.1–13.9 (β = 0.206, P = 0.042) were significantly correlated with cued recall scores after adjusting for confounding factors. TIR and GRI had no correlation with neuropsychological test results (P > 0.05). Conclusion A higher TBR < 3.9 and TAR > 13.9 were associated with worse cognitive functions (memory, visuospatial ability, and executive functioning). A higher TAR of 10.1–13.9 was associated with better memory performance. For patients with T2DM, glycemic targets can be relaxed to 10.1–13.9 mmol/L, which may slow the decline in cognitive function.

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Sharma

2025

The Charnolosome as a Novel Nanothereranostic Biomarker

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Recurrent non-severe hypoglycemia aggravates cognitive decline in diabetes and induces mitochondrial dysfunction in cultured astrocytes

Cited by 19 publications

References 70 publications

Recurrent Hypoglycemia Impaired Vascular Function in Advanced T2DM Rats by Inducing Pyroptosis

Recurrent Hypoglycemia Impaired Vascular Function in Advanced T2DM Rats by Inducing Pyroptosis

Relationship between key continuous glucose monitoring-derived metrics and specific cognitive domains in patients with type 2 diabetes mellitus

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