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diabetes_mellitus

Diabetes mellitus

Diabetes mellitus is a crucial risk factor for stroke and is associated with increased frequency and poor prognosis. Although endothelial dysfunction is a known contributor of stroke, the underlying mechanisms have not been elucidated.


The prevalence of both Alzheimer disease (AD) and vascular dementia (VaD) is increasing with the aging of the population. Studies from the last several years have shown that people with diabetes have an increased risk for dementia and cognitive impairment. Therefore, the authors of this consensus review tried to elaborate on the role of diabetes, especially diabetes type 2 (T2DM) in both AD and VaD. Based on the clinical and experimental work of scientists from 18 countries participating in the International Congress on Vascular Disorders and on literature search using PUBMED, it can be concluded that T2DM is a risk factor for both, AD and VaD, based on a pathology of glucose utilization. This pathology is the consequence of a disturbance of insulin-related mechanisms leading to brain insulin resistance. Although the underlying pathological mechanisms for AD and VaD are different in many aspects, the contribution of T2DM and insulin resistant brain state (IRBS) to cerebrovascular disturbances in both disorders cannot be neglected. Therefore, early diagnosis of metabolic parameters including those relevant for T2DM is required. Moreover, it is possible that therapeutic options utilized today for diabetes treatment may also have an effect on the risk for dementia. T2DM/IRBS contribute to pathological processes in AD and VaD 1).


Data suggest that diabetes in Chinese patients with intracerebral hemorrhage (ICH) is not associated with increased mortality or functional outcome. Future studies are needed to clarify possible confounders affecting prognosis after ICH 2).

Mishiro et al. examined the effect of hyperglycemia on hemorrhagic transformation at 24 hours after middle cerebral artery occlusion (MCAO) in streptozotocin (STZ) -induced diabetic mice.

They also examined the effects of high-glucose exposure for 6 days on cell death, mitochondrial functions and morphology in human brain microvascular endothelial cells (HBMVECs) or human endothelial cells derived from induced pluripotent stem cells (iCell endothelial cells). Hyperglycemia aggravated hemorrhagic transformation, but not infarction following stroke. High-glucose exposure increased apoptosis, capase-3 activity, and release of apoptosis inducing factor (AIF) and cytochrome c in HBMVECs as well as affected mitochondrial functions (decreased cell proliferation, ATP contents, mitochondrial membrane potential, and increased matrix metalloproteinase (MMP)-9 activity, but not reactive oxygen species production). Furthermore, morphological aberration of mitochondria was observed in diabetic cells (a great deal of fragmentation, vacuolation, and cristae disruption). A similar phenomena were seen also in iCell endothelial cells. In conclusion, chronic hyperglycemia aggravated hemorrhagic transformation after stroke through mitochondrial dysfunction and morphological alteration, partially via MMP-9 activation, leading to caspase-dependent apoptosis of endothelial cells of diabetic mice. Mitochondria-targeting therapy may be a clinically innovative therapeutic strategy for diabetic complications in the future 3).

1)
Riederer P, Korczyn AD, Ali SS, Bajenaru O, Choi MS, Chopp M, Dermanovic-Dobrota V, Grünblatt E, Jellinger KA, Kamal MA, Kamal W, Leszek J, Sheldrick-Michel TM, Mushtaq G, Meglic B, Natovich R, Pirtosek Z, Rakusa M, Salkovic-Petrisic M, Schmidt R, Schmitt A, Sridhar GR, Vécsei L, Wojszel ZB, Yaman H, Zhang ZG, Cukierman-Yaffe T. The diabetic brain and cognition. J Neural Transm (Vienna). 2017 Aug 1. doi: 10.1007/s00702-017-1763-2. [Epub ahead of print] Review. PubMed PMID: 28766040.
2)
Wang Q, Wang D, Liu M, Fang Y, You C, Dong W, Chang X, Lei C, Zhang J, Chen Y. Is diabetes a predictor of worse outcome for spontaneous intracerebral hemorrhage? Clin Neurol Neurosurg. 2015 Feb 12;134:67-71. doi: 10.1016/j.clineuro.2015.01.020. [Epub ahead of print] PubMed PMID: 25950926.
3)
Mishiro K, Imai T, Sugitani S, Kitashoji A, Suzuki Y, Takagi T, Chen H, Oumi Y, Tsuruma K, Shimazawa M, Hara H. Diabetes Mellitus Aggravates Hemorrhagic Transformation after Ischemic Stroke via Mitochondrial Defects Leading to Endothelial Apoptosis. PLoS One. 2014 Aug 18;9(8):e103818. doi: 10.1371/journal.pone.0103818. eCollection 2014. PubMed PMID: 25133692.
diabetes_mellitus.txt · Last modified: 2017/08/03 16:47 by administrador