Plasma homocysteine and cerebral small vessel disease as possible mediators between kidney and cognitive functions in patients with diabetes mellitus

Sonoda, Mika; Shoji, Tetsuo; Kuwamura, Yukinobu; Okute, Yujiro; Naganuma, Takeshi; Shima, Hideaki; Motoyama, Koka; Morioka, Tomoaki; Mori, Katsuhito; Fukumoto, Shinya; Shioi, Atsushi; Shimono, Taro; Fujii, Hisako; Kabata, Daijiro; Shintani, Ayumi; Emoto, Masanori; Inaba, Masaaki

doi:10.1038/s41598-017-04515-w

Cited by 15 publications

(8 citation statements)

References 48 publications

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“…These studies suggest that the brain may be a target organ for T2DM microangiopathy, similar to other classical target organs, such as the retina or kidney. Interestingly, Mika Sonoda et al ( 54 ) conducted a cross-sectional study of 143 patients with T2DM who were not diagnosed with dementia or stroke. In multiple regression models adjusted for 12 potential confounders, eGFR was not significant in the presence of any type of WMH.…”

Section: Resultsmentioning

confidence: 99%

Relationship Between Type 2 Diabetes and White Matter Hyperintensity: A Systematic Review

Wang

Wei

et al. 2020

Front. Endocrinol.

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White matter (WM) disease is recognized as an important cause of cognitive decline and dementia. White matter lesions (WMLs) appear as white matter hyperintensities (WMH) on T2-weighted magnetic resonance imaging (MRI) scans of the brain. Previous studies have shown that type 2 diabetes (T2DM) is associated with WMH. In this review, we reviewed the literature on the relationship between T2DM and WMH in PubMed and Cochrane over the past five years and explored the possible links among the presence of T2DM, the course or complications of diabetes, and WMH. We found that: (1) Both from a macro- and micro-scopic point of view, most studies support the relationship of a larger WMH and a decrease in the integrity of WMH in T2DM; (2) From the relationship between brain structural changes and cognition in T2DM, the poor performance in memory, attention, and executive function tests associated with abnormal brain structure is consistent; (3) Diabetic microangiopathy or peripheral neuropathy may be associated with WMH, suggesting that the brain may be a target organ for T2DM microangiopathy; (4) Laboratory markers such as insulin resistance and fasting insulin levels were significantly associated with WMH. High HbA1c and high glucose variability were associated with WMH but not glycemic control.

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Section: Resultsmentioning

confidence: 99%

Relationship Between Type 2 Diabetes and White Matter Hyperintensity: A Systematic Review

Wang

Wei

et al. 2020

Front. Endocrinol.

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“…The pathological changes of blood vessels including the arterioles with a diameter of 30-300 μm, namely, cerebellar vessels, including those capillaries supplying gray matter nuclei and deep white matter, and small brain stems. The wall of these small arteries is mainly composed of endothelial cells and a small number of smooth muscle cells and is in direct contact with astrocyte synapses, but these capillaries generally have no collateral anastomosis [13,14]. The incidence of CSVD is largely unknown and has various clinical manifestations.…”

Section: Discussionmentioning

confidence: 99%

Serum Homocysteine as One of the Risk Factors of Cerebral Small Vessel Disease in Chinese Patients

2019

JMN

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Objective: This study aimed to determine the risk factors of cerebral small vessel disease (CSVD) from different variables including serum homocysteine (Hcy) in a group of Chinese patients. Methods: A total of 139 patients with CSVD admitted to the affiliated hospital of Xuzhou Medical University from July 2017 to July 2018 were enrolled. Fifty healthy individuals were selected as controls. According to the diagnostic criteria, the CSVD patients were divided into three groups, namely, lacunar infarction (LI) group (n=59), white matter lesion (WML) group (n=46), and LI+WML group (n=34). The serum Hcy levels of the three groups were observed and compared. Multivariate logistic regression was performed to determine whether a number of variables including serum Hcy level are the risk factors of CSVD. Results: Hypertension, systolic blood pressure (SBP), diastolic blood pressure (DBP), low-density lipoprotein cholesterol (LDL-C), triglycerides (TGs), fasting blood glucose (FBG), and Hcy were significantly higher in CSVD group than the control group (P < 0.05). The age, gender, SBP, platelet, TG, and Hcy were significantly different between the LI group, WML group, and LI+WML groups (P<0.05). The age and Hcy level of patients in LI+WML group were higher than those of the LI group and WML group, and the difference was statistically significant (P < 0.05). The level of SBP was higher in the LI group than the WML group (P < 0.05). The Hcy level of patients in the LI group was higher than that in the WML group, but there was no significant difference (P > 0.05). The platelet and TG were significantly higher in WML group than LI group and LI+WML group (P < 0.05). Controlling the influence of sex and age, multivariate logistic regression analysis revealed that the Hcy levels were correlated with the incidence of the CSVD. Conclusion: Serum Hcy level is a risk factor for CSVD. Regular detection of serum Hcy level and timely intervention may effectively prevent and control the occurrence and development of CSVD.

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“…This study was comprised of two parts. The first was a cross-sectional study using clinical data derived from our previous study of 143 patients with type 2 diabetes mellitus [39], while the second part was an in vitro study of the effect of increased zinc concentration on T 50 assay findings, which was conducted using separately pooled serum samples obtained from healthy volunteers and patients with hemodialysis. Such pooled serum samples are routinely measured as a quality control for the T 50 assay.…”

Section: Methodsmentioning

confidence: 99%

“…The inclusion and exclusion criteria for the clinical study were previously described [39]. Patients with type 1 diabetes or other types of diabetes were not included in this study.…”

Section: Participants Of the Cross Sectional Studymentioning

confidence: 99%

Association between Serum Zinc and Calcification Propensity (T50) in Patients with Type 2 Diabetes Mellitus and In Vitro Effect of Exogenous Zinc on T50

et al. 2020

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Zinc inhibits vascular calcification in vivo and in vitro. Patients with type 2 diabetes mellitus show hypozincemia and are at an elevated risk of cardiovascular events. Recently, an in vitro test (T50-test) was developed for determination of serum calcification propensity and a shorter T50 means a higher calcification propensity. This cross-sectional study investigated the association between serum zinc and T50 in 132 type 2 diabetes mellitus patients with various kidney functions. Furthermore, the effect of exogenous zinc on T50 was also investigated in vitro using separately pooled serum samples obtained from healthy volunteers and patients with hemodialysis. We measured T50 levels using the established nephelometric method. The median (interquartile range) levels of T50 and serum zinc were 306 (269 to 332) min, and 80.0 (70.1 to 89.8) µg/dL, respectively. Serum zinc level showed a weak, but positive correlation with T50 (rs = 0.219, p = 0.012). This association remained significant in multivariable-adjusted analysis, and was independent of known factors including phosphate, calcium, and magnesium. Kidney function and glycemic control were not significantly associated with T50. Finally, in vitro experiments showed that addition of a physiological concentration of exogenous zinc chloride significantly increased serum T50. Our results indicate that serum zinc is an independent factor with a potential role in suppressing calcification propensity in serum.

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Plasma homocysteine and cerebral small vessel disease as possible mediators between kidney and cognitive functions in patients with diabetes mellitus

Cited by 15 publications

References 48 publications

Relationship Between Type 2 Diabetes and White Matter Hyperintensity: A Systematic Review

Relationship Between Type 2 Diabetes and White Matter Hyperintensity: A Systematic Review

Serum Homocysteine as One of the Risk Factors of Cerebral Small Vessel Disease in Chinese Patients

Association between Serum Zinc and Calcification Propensity (T50) in Patients with Type 2 Diabetes Mellitus and In Vitro Effect of Exogenous Zinc on T50

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