Postprandial Hyperglycemia Is Associated With White Matter Hyperintensity and Brain Atrophy in Older Patients With Type 2 Diabetes Mellitus

Ogama, Noriko; Sakurai, Takashi; Kawashima, Shuji; Tanikawa, Takahisa; Tokuda, Harukuni; Satake, Shosuke; Miura, Hisayuki; Shimizu, Atsuya; Kokubo, Manabu; Niida, Shumpei; Toba, Kenji; Umegaki, Hiroyuki; Kuzuya, Masafumi

doi:10.3389/fnagi.2018.00273

Cited by 25 publications

(25 citation statements)

References 51 publications

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“…Because brain tissue of AD show increased oxidative stress during the course of the disease [39], AD patients are more likely to be susceptible to the influence of glucose fluctuations on the brain. In fact, our previous study showed that glucose fluctuations during postprandial periods were independently associated with frontal white matter hyperintensity (WMH) in diabetic patients with AD but not in patients with normal cognition [40]. Frontal WMH is known to play a predominant role in motor dysfunctions in AD/aMCI patients [41,42].…”

Section: Discussionmentioning

confidence: 99%

Association of Glucose Fluctuations with Sarcopenia in Older Adults with Type 2 Diabetes Mellitus

Ogama

Sakurai

Kawashima

et al. 2019

JCM

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Type 2 diabetes mellitus accelerates loss of muscle mass and strength. Patients with Alzheimer’s disease (AD) also show these conditions, even in the early stages of AD. The mechanism linking glucose management with these muscle changes has not been elucidated but has implications for clarifying these associations and developing preventive strategies to maintain functional capacity. This study included 69 type 2 diabetes patients with a diagnosis of cognitive impairment (n = 32) and patients with normal cognition (n = 37). We investigated the prevalence of sarcopenia in diabetes patients with and without cognitive impairment and examined the association of glucose alterations with sarcopenia. Daily glucose levels were evaluated using self-monitoring of blood glucose, and we focused on the effects of glucose fluctuations, postprandial hyperglycemia, and the frequency of hypoglycemia on sarcopenia. Diabetes patients with cognitive impairment displayed a high prevalence of sarcopenia, and glucose fluctuations were independently associated with sarcopenia, even after adjusting for glycated hemoglobin A1c (HbA1c) levels and associated factors. In particular, glucose fluctuations were significantly associated with a low muscle mass, low grip strength, and slow walking speed. Our observation suggests the importance of glucose management by considering glucose fluctuations to prevent the development of disability.

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Section: Discussionmentioning

confidence: 99%

Association of Glucose Fluctuations with Sarcopenia in Older Adults with Type 2 Diabetes Mellitus

Ogama

Sakurai

Kawashima

et al. 2019

JCM

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“…Patients with type 1 diabetes mellitus tend to develop WMH along with cognitive decline at a younger age than non-diabetic controls 27 . Ogama et al 28 found that postprandial hyperglycemia is related to WMH in diabetic patients with Alzheimer's disease while diabetic patients without dementia appeared to be less susceptible to the effects of hyperglycemia. Lacunar infarcts have been seen in patients with prediabetes and at an even higher number in patients with type 2 diabetes mellitus 29 , 30 .…”

Section: Discussionmentioning

confidence: 99%

The association between intraoperative hyperglycemia and cerebrovascular markers

Knaak¹,

Kant²,

Lammers-Lietz³

et al. 2021

Int. J. Med. Sci.

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BACKGROUND AND PURPOSE: Hyperglycemia can lead to an increased rate of apoptosis of microglial cells and to damaged neurons. The relation between hyperglycemia and cerebrovascular markers on MRI is unknown. Our aim was to study the association between intraoperative hyperglycemia and cerebrovascular markers. METHODS: In this further analysis of a subgroup investigation of the BIOCOG study, 65 older non-demented patients (median 72 years) were studied who underwent elective surgery of ≥ 60 minutes. Intraoperative blood glucose maximum was determined retrospectively in each patient. In these patients, preoperatively and at 3 months follow-up a MRI scan was performed and white matter hyperintensity (WMH) volume and shape, infarcts, and perfusion parameters were determined. Multivariable logistic regression analyses were performed to determine associations between preoperative cerebrovascular markers and occurrence of intraoperative hyperglycemia. Linear regression analyses were performed to assess the relation between intraoperative hyperglycemia and pre- to postoperative changes in WMH volume. Associations between intraoperative hyperglycemia and postoperative WMH volume at 3 months follow-up were also assessed by linear regression analyses. RESULTS: Eighteen patients showed intraoperative hyperglycemia (glucose maximum ≥ 150 mg/dL). A preoperative more smooth shape of periventricular and confluent WMH was related to the occurrence of intraoperative hyperglycemia [convexity: OR 33.318 (95 % CI (1.002 - 1107.950); p = 0.050]. Other preoperative cerebrovascular markers were not related to the occurrence of intraoperative hyperglycemia. Intraoperative hyperglycemia showed no relation with pre- to postoperative changes in WMH volume nor with postoperative WMH volume at 3 months follow-up. CONCLUSIONS: We found that a preoperative more smooth shape of periventricular and confluent WMH was related to the occurrence of intraoperative hyperglycemia. These findings may suggest that a similar underlying mechanism leads to a certain pattern of vascular brain abnormalities and an increased risk of hyperglycemia.

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“…Retinal and brain neurodegenerative diseases although affecting different parts of the CNS, appear to involve similar pathogenic mechanisms like oxidative stress, low-grade chronic neuroinflammation, disruption of blood-brain or blood-retinal barrier, and vascular abnormalities (London et al, 2013; Colligris et al, 2018). Increasing clinical and preclinical evidence points to associations between metabolic dysregulation and neurodegenerative brain disease (Weinstein et al, 2015; Arnold et al, 2018; Ogama et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

Adult Goat Retinal Neuronal Culture: Applications in Modeling Hyperglycemia

et al. 2019

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Culture of adult neurons of the central nervous system (CNS) can provide a unique model system to explore neurodegenerative diseases. The CNS includes neurons and glia of the brain, spinal cord and retina. Neurons in the retina have the advantage of being the most accessible cells of the CNS, and can serve as a reliable mirror to the brain. Typically, primary cultures utilize fetal rodent neurons, but very rarely adult neurons from larger mammals. Here, we cultured primary retinal neurons isolated from adult goat up to 10 days, and established an in vitro model of hyperglycemia for performing morphological and molecular characterization studies. Immunofluorescence staining revealed that approximately 30–40% of cultured cells expressed neuronal markers. Next, we examined the relative expression of cell adhesion molecules (CAMs) in adult goat brain and retina. We also studied the effect of different glucose concentrations and media composition on the growth and expression of CAMs in cultured retinal neurons. Hyperglycemia significantly enhances neurite outgrowth in adult retinal neurons in culture. Expression of CAMs such as Caspr1, Contactin1 and Prion is downregulated in the presence of high glucose. Hyperglycemia downregulates the expression of the transcription factor CCAAT/enhancer binding protein (C/EBP α), predicted to bind CAM gene promoters. Collectively, our study demonstrates that metabolic environment markedly affects transcriptional regulation of CAMs in adult retinal neurons in culture. The effect of hyperglycemia on CAM interactions, as well as related changes in intracellular signaling pathways in adult retinal neurons warrants further investigation.

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Postprandial Hyperglycemia Is Associated With White Matter Hyperintensity and Brain Atrophy in Older Patients With Type 2 Diabetes Mellitus

Cited by 25 publications

References 51 publications

Association of Glucose Fluctuations with Sarcopenia in Older Adults with Type 2 Diabetes Mellitus

Association of Glucose Fluctuations with Sarcopenia in Older Adults with Type 2 Diabetes Mellitus

The association between intraoperative hyperglycemia and cerebrovascular markers

Adult Goat Retinal Neuronal Culture: Applications in Modeling Hyperglycemia

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