Sai Tian

Blood Pressure is Associated With Cerebral Blood Flow Alterations in Patients With T2DM as Revealed by Perfusion Functional MRI.

AbstractType 2 diabetes mellitus (T2DM) and hypertension are both associated with cognitive impairment and brain function abnormalities. We investigated whether abnormal cerebral blood flow (CBF) patterns exists in T2DM patients and possible relationships between aberrant CBF and cognitive performance. Furthermore, we examined the influence of hypertension on CBF alterations in T2DM patients.T2DM patients (n = 38) and non-T2DM subjects (n = 40) were recruited from clinics, hospitals, and normal community health screenings. Cerebral blood flow images were collected and analyzed using arterial spin labeling perfusion functional magnetic resonance imaging (fMRI). Regions with major CBF differences between T2DM patients and non-T2DM controls were detected via 1-way ANOVA. The interaction effects between hypertension and T2DM for CBF alterations were also examined. Correlation analyses illustrated the association between CBF values and cognitive performance and between CBF and blood pressure.Compared with non-T2DM controls, T2DM patients exhibited decreased CBF, primarily in the visual area and the default mode network (DMN); decreased CBF in these regions was correlated with cognitive performance. There was a significant interaction effect between hypertension and diabetes for CBF in the precuneus and the middle occipital gyrus. Additionally, blood pressure correlated negatively with CBF in T2DM patients.T2DM patients exhibited reduced CBF in the visual area and DMN. Hypertension may facilitate a CBF decrease in the setting of diabetes. T2DM patients may benefit from blood pressure control to maintain their brain perfusion through CBF preservation.

Diabetes mellitus as a risk factor for incident chronic kidney disease and end-stage renal disease in women compared with men: a systematic review and meta-analysis

Diabetes mellitus is a strong risk factor for chronic kidney disease and end-stage renal disease. Whether sex differences in chronic kidney disease and end-stage renal disease incidence exist among diabetic patients remains unclear. This systematic review and meta-analysis was conducted to evaluate the relative effect of diabetes on chronic kidney disease and end-stage renal disease risk in women compared with men. We systematically searched Embase, PubMed, and the Cochrane Library for both cohort and case–control studies until October 2015. Studies were selected if they reported a sex-specific relationship between diabetes mellitus and chronic kidney disease or end-stage renal disease. We generated pooled estimates across studies using random-effects meta-analysis after log transformation with inverse variance weighting. Ten studies with data from more than 5 million participants were included. The pooled adjusted risk ratio of chronic kidney disease associated with diabetes mellitus was 3.34 (95 % CI 2.27, 4.93) in women and 2.84 (95 % CI 1.73, 4.68) in men. The data showed no difference in diabetes-related chronic kidney disease risk between the sexes (pooled adjusted women-to-men relative risk ratio was 1.14 [95 % CI 0.97, 1.34]) except for end-stage renal disease—the pooled adjusted women-to men relative risk ratio was 1.38 (95 % CI 1.22, 1.55; p = 0.114, I² = 38.1 %). The study found no evidence of a sex difference in the association between diabetes mellitus and chronic kidney disease. However, the excess risk for end-stage renal disease was higher in women with diabetes than in men with the same condition, from which we assume that the female gender could accelerate the disease progression. Further studies are needed to support this notion and elucidate the underlying mechanisms.

Statins worsen glycemic control of T2DM in target LDL-c level and LDL-c reduction dependent manners: a meta-analysis

ABSTRACT Objective: Recent studies demonstrated that a low target low-density lipoprotein cholesterol (LDL-c) level, high LDL-c reduction and high dose of statin therapy increased incident diabetes. This study aimed to explore how statin therapy influences glycemic control in type 2 diabetes mellitus (T2DM). Methods: Medline, Embase, and Cochrane Central were searched for randomized control trials inT2DM. Trials with target LDL-c levels of ≤2.6 mmol/L or LDL-c reduction of ≥30% were analyzed. Then, we calculated mean differences in glycosylated hemoglobin (HbA1c) and fasting blood glucose via stratified LDL-c level, relative LDL-c reduction and statin dose. Results: In total, trials involving 6,875 participants (3,619 statins, 3,256 controls) were included. Meta-analysis showed that detrimental effect of intensive LDL-c lowering statin therapy on HbA1c (SMD 0.10%; 95% CI 0.05, 0.15; p = 0.000) was more severe than all statin trials analyzed together (SMD 0.07%; 95% CI 0.02, 0.12; p = 0.005). Stratified analyses revealed that the effects on HbA1c became increasingly significant as target LDL-c level decreased and LDL-c reduction increased. Low baseline LDL-c and endpoint LDL-c levels were risk factors involved in increasing HbA1c level during statin therapy. Conclusions: Statin therapy worsens the glycemic control of T2DM in target LDL-c level and LDL-c reduction dependent manners.

Plasma Clusterin and the CLU Gene rs11136000 Variant Are Associated with Mild Cognitive Impairment in Type 2 Diabetic Patients

Objective: Type 2 diabetes mellitus (T2DM) is related to an elevated risk of mild cognitive impairment (MCI). Plasma clusterin is reported associated with the early pathology of Alzheimers disease (AD) and longitudinal brain atrophy in subjects with MCI. The rs11136000 single nucleotide polymorphism within the clusterin (CLU) gene is also associated with the risk of AD. We aimed to investigate the associations among plasma clusterin, rs11136000 genotype and T2DM-associated MCI. Methods: A total of 231 T2DM patients, including 126 MCI and 105 cognitively healthy controls were enrolled in this study. Demographic parameters were collected and neuropsychological tests were conducted. Plasma clusterin and CLU rs11136000 genotype were examined. Results: Plasma clusterin was significantly higher in MCI patients than in control group (p = 0.007). In subjects with MCI, plasma clusterin level was negatively correlated with Montreal cognitive assessment and auditory verbal learning test_delayed recall scores (p = 0.027 and p = 0.020, respectively). After adjustment for age, educational attainment, and gender, carriers of rs11136000 TT genotype demonstrated reduced risk for MCI compared with the CC genotype carriers (OR = 0.158, χ2 = 4.113, p = 0.043). Multivariable regression model showed that educational attainment, duration of diabetes, high-density lipoprotein cholesterol (HDL-c), and plasma clusterin levels are associated with MCI in T2DM patients. Conclusions: Plasma clusterin was associated with MCI and may reflect a protective response in T2DM patients. TT genotype exhibited a reduced risk of MCI compared to CC genotype. Further investigations should be conducted to determine the role of clusterin in cognitive decline. Trial registration Advanced Glycation End Products Induced Cognitive Impairment in Diabetes: BDNF Signal Meditated Hippocampal Neurogenesis ChiCTR-OCC-15006060; http://www.chictr.org.cn/showproj.aspx?proj=10536

Serum Insulin Degrading Enzyme Level and Other Factors in Type 2 Diabetic Patients with Mild Cognitive Impairment

BACKGROUND AND AIMS Insulin degrading enzyme (IDE) contributes to the degradation processes of insulin and Aβ. We aimed to investigate the role of IDE in type 2 diabetes patients with mild cognitive impairment (MCI). METHODS A total of 146 individuals with type 2 diabetes were enrolled and divided into two groups according to the Montreal Cognitive Assessment (MoCA) score. Demographic characteristics, cognitive function and serum IDE level were examined. RESULTS There were 75 patients with MCI and 71 patients without MCI. Diabetic patients with MCI had a higher serum level of IDE compared with the control group (p > 0.001). Among patients with MCI, serum IDE level was positively correlated with the MoCA score (r = 0.839; p > 0.001). Correlation analysis demonstrated that IDE was positively correlated with MoCA score (r = 0.815; p > 0.001) but negatively correlated with the Trail Making Test-B (r = -0.413; p > 0.001), fasting blood-glucose (r = -0.372; p > 0.001), glycosylated hemoglobin (r = -0.214; p = 0.015), homeostasis model of assessment for insulin resistance (r = -0.560; p > 0.001) and the mean amplitude of glycemic excursions (r = -0.551; p > 0.001) in all subjects. In logistic regression analysis for MCI, IDE (p = 0.010) was an independent variable, after adjusting for age, sex, education, liver function, kidney function, and lipid levels. CONCLUSION This study demonstrated a greater likelihood of MCI with decreasing serum IDE in patients with type 2 diabetes.

Association between Plasma Levels of PAI-1, tPA/PAI-1 Molar Ratio, and Mild Cognitive Impairment in Chinese Patients with Type 2 Diabetes Mellitus

BACKGROUND Plasminogen activator inhibitor 1 (PAI-1) and tissue plasminogen activator (tPA) are involved in the complications of type 2 diabetes mellitus (T2DM) and early pathology of Alzheimers disease. OBJECTIVE This study aimed to investigate the association between plasma PAI-1, tPA/PAI-1 molar ratio, and mild cognitive impairment (MCI) in Chinese T2DM patients. METHODS A total of 162 Chinese T2DM patients were recruited and divided into two groups according to the Montreal Cognitive Assessment score. Demographic data were collected, plasma PAI-1 and tPA levels were measured through enzyme-linked immunosorbent assay, tPA/PAI-1 molar ratio was calculated, and neuropsychological test results were examined. The association between PAI-1, tPA/PAI-1 molar ratio, and cognition was analyzed. RESULTS There were 66 diabetic MCI patients and 96 healthy cognition participants (controls). T2DM patients with MCI displayed significantly increased plasma PAI-1 levels (p = 0.016) and decreased tPA/PAI-1 molar ratio (p = 0.021) compared with the controls. High PAI-1 levels and low tPA/PAI-1 molar ratio were associated with MCI in T2DM patients, e.g., plasma level of PAI-1 were negatively correlated (r = -0.343, p = 0.007) with logic memory in T2DM patients with MCI. Linear regression analysis further revealed that PAI-1 concentration was an independent factor of diabetic MCI (p = 0.001). CONCLUSIONS High PAI-1 levels and low tPA/PAI-1 molar ratio were significantly correlated with T2DM-associated cognitive impairment, especially memory function, in Chinese patients.

Lipoprotein-associated Phospholipase A2 Is Associated with Risk of Mild Cognitive Impairment in Chinese Patients with Type 2 Diabetes

Type 2 diabetes mellitus (T2DM) is a low-grade chronic inflammatory diseases, which have been implicated in the pathogenesis of cognitive decline. We aim to evaluate associations between inflammatory markers and the risk of mild cognitive impairment (MCI) in T2DM. This study of 140 diabetic patients involved 71 with MCI and 69 controls. Clinical parameters, neuropsychological tests, high sensitivity C reactive protein (hsCRP), interleukin-6 (IL-6), lipoprotein-associated Phospholipase A2 (Lp-PLA2) mass and activity were measured. The results showed significantly higher plasma hsCRP, IL-6, Lp-PLA2 mass and activity in MCI group compared to controls. In T2DM with MCI, the Montreal Cognitive Assessment (MoCA) score was positively correlated with education level and high-density lipoprotein cholesterol (HDL-c), but inversely correlated with age, glycosylated hemoglobin, intima-media thickness (IMT), hsCRP, IL-6, and Lp-PLA2 mass and activity. Correlation analysis showed that both plasma Lp-PLA2 mass and activity were positively correlated with total cholesterol, low-density lipoprotein cholesterol, and IMT but negatively associated with MoCA score. Multivariable logistic regression analysis indicated higher hsCRP, Lp-PLA2 mass, Lp-PLA2 activity, and lower HDL-c to be independent risk factors increasing the possibility of MCI in T2DM. In conclusion, plasma Lp-PLA2 and hsCRP were found to be associated with the risk of MCI among T2DM patients.

Increased Plasma Homocysteine Level is Associated with Executive Dysfunction in Type 2 Diabetic Patients with Mild Cognitive Impairment

BACKGROUND Homocysteine (Hcy) is involved in the pathogenesis of type 2 diabetes mellitus (T2DM) and Alzheimers disease. OBJECTIVE We aimed to investigate the role of Hcy in T2DM patients with mild cognitive impairment (MCI), and to determine whether methylene tetrahydrofolate reductase (MTHFR) C677T or cystathionine beta-synthase (CBS) 844ins68 polymorphism is related to T2DM-associated MCI. METHODS We recruited 285 T2DM patients and divided them into two groups, 140 patients with MCI, and 145 healthy-cognition controls, on the basis of Montreal Cognitive Assessment (MoCA) scores. Demographic characteristics, clinical parameters, and neuropsychological tests were assessed. MTHFR C677T and CBS 844ins68 polymorphisms were analyzed. RESULTS The MCI group exhibited significantly higher plasma total Hcy (tHcy) levels than control group (p < 0.001). Plasma tHcy level was negatively correlated with MoCA scores (p = 0.002), but positively associated with Trail Making Test A and B scores (p = 0.044; p = 0.005, respectively). Multivariable logistic regression model showed that high tHcy level was an independent factor for MCI in T2DM patients. No significant difference was observed in the genotype or allele distributions of MTHFR and CBS between MCI and control groups. We did not find significant MCI risks in MTHFR T allele compared with C allele, and in CBS I allele compared with D allele (OR = 1.361, p = 0.067; OR = 1.048, p = 0.909, respectively). CONCLUSION Increased plasma tHcy level was significantly related to T2DM-associated MCI, especially executive dysfunction. Further investigation with a large population size should be conducted to confirm these findings.

Diabetes as a risk factor for acute coronary syndrome in women compared with men: a meta-analysis, including 10,856,279 individuals and 106,703 acute coronary syndrome events.

Diabetes mellitus is a significant cause of death and disability worldwide and is a strong risk factor for acute coronary syndrome (ACS). Whether diabetes confers the same excess risk of ACS in both sexes is unknown. Therefore, we undertook a meta‐analysis to estimate the relative risk (RR) for ACS associated with diabetes in men and women.

Association of Increased Serum ACE Activity with Logical Memory Ability in Type 2 Diabetic Patients with Mild Cognitive Impairment

Background: Angiotensin-converting enzyme (ACE) is involved in the chronic complications of type 2 diabetes mellitus (T2DM) and Alzheimers disease. This study aimed to assess the pathogenetic roles of ACE and the genetic predisposition of its insertion/deletion (I/D) polymorphism in mild cognitive impairment (MCI) among T2DM patients. Methods: A total of 210 T2DM patients were enrolled. Among these patients, 116 satisfied the MCI diagnostic criteria and 94 exhibited healthy cognition. The cognitive functions of the patients were extensively assessed. The serum level and activity of ACE were measured via enzyme-linked immunosorbent assay and ultraviolet spectrophotography. The single-nucleotide polymorphisms of I/D gene of ACE were analyzed. Results: The serum level and activity of ACE in diabetic MCI patients (p = 0.022 and p = 0.008, respectively) were both significantly higher than those in the healthy controls. A significant negative correlation was found between their ACE activity and logical memory test score (LMT) (p = 0.002). Multiple stepwise regression iterated the negative correlation between ACE activity and LMT score (p = 0.035). Although no significant difference was found in the genotype or allele distribution of ACE I/D polymorphism between the groups, the serum levels and activity of ACE were higher in the DD group than in the ID and II groups (p < 0.05). Conclusions: Serum ACE activity could better predict logical memory in T2DM patients than ACE level. Further investigations on a large population size are necessary to test whether the D-allele of the ACE gene polymorphism is susceptible to memory deterioration.