Associations of Plasma BACE1 Level and BACE1 C786G Gene Polymorphism with Cognitive Functions in Patients with Type 2 Diabetes: A Cross- Sectional Study

2020 ◽  
Vol 17 (4) ◽  
pp. 355-364 ◽  
Author(s):  
Sai Tian ◽  
Rong Huang ◽  
Dan Guo ◽  
Hongyan Lin ◽  
Jiaqi Wang ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Gene Polymorphism ◽  
Glycosylated Hemoglobin ◽  
Fasting Blood Glucose ◽  
Multivariable Logistic Regression Analysis ◽  
Model Assessment ◽  
Cross Sectional ◽  
Logical Memory ◽  
Bace1 Level

Background: β-Site APP-cleaving enzyme 1 (BACE1) is a key enzyme involved in the pathophysiology of Type 2 Diabetes Mellitus (T2DM) and Mild Cognitive Impairment (MCI). We aimed to investigate the potential associations of plasma BACE1 levels and BACE1 gene polymorphism with different cognitive performances in T2DM patients with MCI. Methods: The recruited 186 T2DM subjects were divided into 92 MCI group and 94 healthy-cognition controls, according to the Montreal Cognitive Assessment (MoCA) scores. Sociodemographic characteristics, clinical parameters and neuropsychological tests were assessed. BACE1 C786G gene polymorphism and plasma BACE1 level were determined. Results: Compared to controls, MCI patients exhibited higher plasma BACE1 levels. Plasma BACE1 levels were negatively associated with MoCA, Clock Drawing Test and Logical Memory Test scores, whereas positively associated with Trail Making Test-B time in the MCI group (all p<0.05), after adjusting fasting blood glucose, glycosylated hemoglobin, and homeostasis model assessment of insulin resistance by C-peptide. Multivariable logistic regression analysis showed a significant trend towards increased MCI risk with high plasma BACE1 level in T2DM patients (OR = 1.492, p = 0.027). The plasma BACE1 levels of GG and GC genotypes were obviously higher than that of CC genotype in T2DM-MCI patients (p = 0.035; p = 0.026, respectively). Conclusion: Increased plasma BACE1 levels were associated with poor overall cognition functions, especially visuospatial abilities, visual/logical memory and executive functions in T2DM-MCI patients. Additionally, elevated plasma BACE1 level was a risk factor for MCI in T2DM patients, and might be influenced by BACE1 C786G gene mutations.

scholarly journals G6PC2 rs560887 Gene Variant is Associated with Fasting Blood Glucose in the Admixed Mexican Population

2020 ◽  
Vol 10 (1) ◽  
pp. 26-29
Author(s):  
Rodrigo Fernández-Pons ◽  
Paula Costa-Urrutia ◽  
Jacqueline Solares-Tlapechco ◽  
Julio Granados ◽  
Martha E. Rodríguez-Arellano
Keyword(s):  
Type 2 Diabetes ◽  
Blood Glucose ◽  
Glycosylated Hemoglobin ◽  
Fasting Blood Glucose ◽  
Cross Sectional ◽  
Huge Impact ◽  
Mexican Mestizos ◽  
Control Study ◽  
Hba1c Levels

Background: In Mexico, type 2 diabetes prevalence is 13.7%, which has a huge impact on Mexican public health. There is an urgent need to focus on the prevention of pre-diabetes to decrease the likelihood of type 2 diabetes onset. Gene variants predisposed to increase Fasting Blood Glucose (FBG) and glycosylated hemoglobin (HbA1c) levels could be helpful for prevention purposes. This study aimed to analyze the association of the G6PC2 rs560887 variant with pre-diabetes in a Mexican-Mestizo population. Methods: A cross-sectional case-control study was performed in 960 Mexican Mestizos participants. The association of G6PC2 rs560887 with pre-diabetes was analyzed by logistic regression and with Fasting Blood Glucose (FBG) and glycosylated hemoglobin (HbA1c) by linear regression. Results: The G6PC2 rs560887 variant was significantly associated with FBG (β -1.80, p=0.03), but not with HbA1c or the presence of pre-diabetes. Conclusion: The G6PC2 rs560887 loci could be a potential early marker of type 2 diabetes.

Decreased circulating BMP-9 levels in patients with Type 2 diabetes is a signature of insulin resistance

2017 ◽  
Vol 131 (3) ◽  
pp. 239-246 ◽  
Author(s):  
Yong Luo ◽  
Ling Li ◽  
Xiaohui Xu ◽  
Tong Wu ◽  
Mengliu Yang ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Healthy Subjects ◽  
Fasting Blood Glucose ◽  
Oral Glucose ◽  
Model Assessment ◽  
Cross Sectional ◽  
Lipid Infusion ◽  
The Relationship

Bone morphogenetic protein 9 (BMP-9) has been demonstrated to improve glucose homoeostasis in diabetic mice. However, no report has demonstrated the relationship of circulating BMP-9 levels with insulin resistance (IR) or Type 2 diabetes mellitus (T2DM) in humans. The objective of the present study was to investigate the relationship between BMP-9 and IR in cross-sectional and interventional studies. Circulating BMP-9 levels were analysed by ELISA in 280 well-characterized individuals. Two-hour oral glucose tolerance test (OGTT) and euglycaemic–hyperinsulinaemic clamp (EHC) were performed in 20 healthy subjects. Acute IR was induced by lipid infusion for 4 h in 20 healthy volunteers. Real-time (RT)-PCR and Western blotting were used to assess mRNA and protein expression of BMP-9. The effect of a glucagon-like peptide-1 (GLP-1) receptor agonist (PEX168) on circulating BMP-9 was investigated in a 24-week treatment trial. Circulating BMP-9 levels were significantly higher in healthy subjects than in newly diagnosed patients with T2DM. Circulating BMP-9 negatively correlated with HbA1c, fasting blood glucose (FBG), OGTT, the area under the curve for glucose (AUCglucose) and homoeostasis model assessment of insulin resistance (HOMA-IR). Multivariate regression analyses showed that BMP-9 levels were independently associated with non-esterified fatty acid (NEFA) and AUCglucose. Both hyperinsulinaemia and lipid infusion decreased circulating BMP-9 levels. BMP-9 mRNA and protein expressions were significantly decreased in muscle and adipose tissues of T2DM patients. In the placebo treated group, BMP-9 levels continued to decline over time, whereas in the PEX 168 treated groups BMP-9 levels remained stable. Our data suggest that BMP-9 is likely to play an important role in IR in humans.

scholarly journals Oleuropein Ameliorates Advanced Stage of Type 2 Diabetes in db/db Mice by Regulating Gut Microbiota

Nutrients ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 2131
Author(s):  
Shujuan Zheng ◽  
Yanan Wang ◽  
Jingjing Fang ◽  
Ruixuan Geng ◽  
Mengjie Li ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Gut Microbiota ◽  
Relative Abundance ◽  
Fasting Blood Glucose ◽  
Therapeutic Effects ◽  
Model Assessment ◽  
Advanced Stage ◽  
Intestinal Microbes ◽  
Promising Therapeutic Approach

Previous studies have reported the therapeutic effects of oleuropein (OP) consumption on the early stage of type 2 diabetes. However, the efficacy of OP on the advanced stage of type 2 diabetes has not been investigated, and the relationship between OP and intestinal flora has not been studied. Therefore, in this study, to explore the relieving effects of OP intake on the advanced stage of type 2 diabetes and the regulatory effects of OP on intestinal microbes, diabetic db/db mice (17-week-old) were treated with OP at the dose of 200 mg/kg for 15 weeks. We found that OP has a significant effect in decreasing fasting blood glucose levels, improving glucose tolerance, lowering the homeostasis model assessment–insulin resistance index, restoring histopathological features of tissues, and promoting hepatic protein kinase B activation in db/db mice. Notably, OP modulates gut microbiota at phylum level, increases the relative abundance of Verrucomicrobia and Deferribacteres, and decreases the relative abundance of Bacteroidetes. OP treatment increases the relative abundance of Akkermansia, as well as decreases the relative abundance of Prevotella, Odoribacter, Ruminococcus, and Parabacteroides at genus level. In conclusion, OP may ameliorate the advanced stage of type 2 diabetes through modulating the composition and function of gut microbiota. Our findings provide a promising therapeutic approach for the treatment of advanced stage type 2 diabetes.

scholarly journals Potential Therapeutic Effects of Curcumin on Glycemic and Lipid Profile in Uncomplicated Type 2 Diabetes—A Meta-Analysis of Randomized Controlled Trial

Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 404
Author(s):  
Emma Altobelli ◽  
Paolo Matteo Angeletti ◽  
Ciro Marziliano ◽  
Marianna Mastrodomenico ◽  
Anna Rita Giuliani ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Lipid Profile ◽  
Effect Size ◽  
Meta Analysis ◽  
Statistical Significance ◽  
Glycosylated Hemoglobin ◽  
Cochrane Library ◽  
Therapeutic Effects ◽  
Model Assessment

Diabetes mellitus is an important issue for public health, and it is growing in the world. In recent years, there has been a growing research interest on efficacy evidence of the curcumin use in the regulation of glycemia and lipidaemia. The molecular structure of curcumins allows to intercept reactive oxygen species (ROI) that are particularly harmful in chronic inflammation and tumorigenesis models. The aim of our study performed a systematic review and meta-analysis to evaluate the effect of curcumin on glycemic and lipid profile in subjects with uncomplicated type 2 diabetes. The papers included in the meta-analysis were sought in the MEDLINE, EMBASE, Scopus, Clinicaltrials.gov, Web of Science, and Cochrane Library databases as of October 2020. The sizes were pooled across studies in order to obtain an overall effect size. A random effects model was used to account for different sources of variation among studies. Cohen’s d, with 95% confidence interval (CI) was used as a measure of the effect size. Heterogeneity was assessed while using Q statistics. The ANOVA-Q test was used to value the differences among groups. Publication bias was analyzed and represented by a funnel plot. Curcumin treatment does not show a statistically significant reduction between treated and untreated patients. On the other hand, glycosylated hemoglobin, homeostasis model assessment (HOMA), and low-density lipoprotein (LDL) showed a statistically significant reduction in subjects that were treated with curcumin, respectively (p = 0.008, p < 0.001, p = 0.021). When considering HBA1c, the meta-regressions only showed statistical significance for gender (p = 0.034). Our meta-analysis seems to confirm the benefits on glucose metabolism, with results that appear to be more solid than those of lipid metabolism. However, further studies are needed in order to test the efficacy and safety of curcumin in uncomplicated type 2 diabetes.

scholarly journals Are the metabolic benefits of resistance training in type 2 diabetes linked to improvements in adipose tissue microvascular blood flow?

2018 ◽  
Vol 315 (6) ◽  
pp. E1242-E1250 ◽  
Author(s):  
Donghua Hu ◽  
Ryan D. Russell ◽  
Devika Remash ◽  
Timothy Greenaway ◽  
Stephen Rattigan ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Blood Flow ◽  
Adipose Tissue ◽  
Resistance Training ◽  
Blood Volume ◽  
Fasting Blood Glucose ◽  
Microvascular Blood Flow ◽  
Oral Glucose ◽  
Model Assessment

The microcirculation in adipose tissue is markedly impaired in type 2 diabetes (T2D). Resistance training (RT) often increases muscle mass and promotes a favorable metabolic profile in people with T2D, even in the absence of fat loss. Whether the metabolic benefits of RT in T2D are linked to improvements in adipose tissue microvascular blood flow is unknown. Eighteen sedentary people with T2D (7 women/11 men, 52 ± 7 yr) completed 6 wk of RT. Before and after RT, overnight-fasted participants had blood sampled for clinical chemistries (glucose, insulin, lipids, HbA1c, and proinflammatory markers) and underwent an oral glucose challenge (OGC; 50 g glucose × 2 h) and a DEXA scan to assess body composition. Adipose tissue microvascular blood volume and flow were assessed at rest and 1 h post-OGC using contrast-enhanced ultrasound. RT significantly reduced fasting blood glucose ( P = 0.006), HbA1c ( P = 0.007), 2-h glucose area under the time curve post-OGC ( P = 0.014), and homeostatic model assessment of insulin resistance ( P = 0.005). This was accompanied by a small reduction in total body fat ( P = 0.002), trunk fat ( P = 0.023), and fasting triglyceride levels ( P = 0.029). Lean mass ( P = 0.003), circulating TNF-α ( P = 0.006), and soluble VCAM-1 ( P < 0.001) increased post-RT. There were no significant changes in adipose tissue microvascular blood volume or flow following RT; however those who did have a higher baseline microvascular blood flow post-RT also had lower fasting triglyceride levels ( r = −0.476, P = 0.045). The anthropometric, glycemic, and insulin-sensitizing benefits of 6 wk of RT in people with T2D are not associated with an improvement in adipose tissue microvascular responses; however, there may be an adipose tissue microvascular-linked benefit to fasting triglyceride levels.

scholarly journals Fenofibrate decreased microalbuminuria in the type 2 diabetes patients with hypertriglyceridemia

2020 ◽  
Author(s):  
Xiaomeng Sun ◽  
Jia Liu ◽  
Guang Wang
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Treatment Group ◽  
Glycosylated Hemoglobin ◽  
Fasting Blood Glucose ◽  
Control Group ◽  
Diabetic Patients ◽  
Fenofibrate Treatment

Abstract Background: This study was to research the efficacy of fenofibrate in the treatment of microalbuminuria in the patients with type 2 diabetes mellitus (T2DM) and hypertriglyceridemia. Methods: Type 2 diabetic patients (56) with microalbuminuria and hypertriglyceridemia aged 30 to 75 were randomly divided into the fenofibrate treatment group(n=28) and the control group (n=28) for 180 days. Urinary microalbumin /creatinine ratio (UACR) and other metabolic parameters were compared at baseline, during treatment and after treatment. Results: After 180 days, the reduction of levels of fasting blood glucose (FBG) and glycosylated hemoglobin (HbA1c) in two groups were no differences. In treatment group, uric acid (UA) (296.42 ± 56.41 vs 372.46 ± 72.78), triglyceride (TG) [1.51(1.17, 2.06) vs 3.04(2.21, 3.29)], and UACR [36.45 (15.78,102.41) vs 129.00 (53.00, 226.25)] were significantly decreased compared with the baseline. The high-density lipoprotein cholesterol (HDL-C) levels were significantly increased (1.22 ± 0.26 vs 1.09 ± 0.24) compared with the baseline. The decrease in UACR [-44.05(-179.47, -12.16) vs -8.15(-59.69, 41.94)]in treatment group was significantly higher compared with the control group. The decrease in UACR was positively associated with the decreases in TG ( r = 0.447, P = 0.042) and UA ( r = 0.478, P = 0.024) after fenofibrate treatment. Conclusion: In the patients with hypertriglyceridemia and type 2 diabetes mellitus, fenofibrate can improve microalbuminuria and do not increase the deterioration of glomerular filtration rate

scholarly journals Evaluation of the effect of MTNR1B rs10830963 gene polymorphism on the therapeutic efficacy of nateglinide in treating type 2 diabetes among Chinese Han patients

2019 ◽  
Author(s):  
Jinfang Song ◽  
Mingzhu Zhang ◽  
Jiang Ni ◽  
Tao Wang ◽  
Yi-Qing Zhao
Keyword(s):  
Type 2 Diabetes ◽  
Gene Polymorphism ◽  
Therapeutic Efficacy ◽  
Healthy Subjects ◽  
Venous Blood ◽  
Melting Curve ◽  
Allelic Frequency ◽  
Model Assessment ◽  
Chinese Han

Abstract Background: Several studies have shown the association of polymorphisms in the MTNR1B gene with type 2 diabetes mellitus (T2DM). However, there is no evidence about the impacts of its genetic polymorphism on the therapeutic efficacy of nateglinide. Therefore, this prospective case-control study was designed to investigate the effect of MTNR1B rs10830963 gene polymorphism on the therapeutic efficacy of nateglinide in treating T2DM. Methods: We genotyped 200 healthy subjects using the method of the high resolution of melting curve (HRM). A total of 60 T2DM patients were enrolled and given nateglinide (360 mg/d) for 8 weeks orally who had the same genotypes CYP2C9*1 and SLCO1B1 521TT respectively. The outcome was measured by collecting the venous blood samples before and at the 8th week of the treatment. Also, anthropometric measurements, glucose, and lipid metabolism were determined before and after the nateglinide treatment. Results: It was found that the risk G allelic frequency of MTNR1B rs10830963 was higher in T2DM patients when compared with the healthy subjects (P<0.05). 60 newly diagnosed patients with type 2 diabetes after completing the eight weeks treatment came for the follow-up visit and showed a reduction in fasting plasma glucose (FPG) levels with an increase in homeostasis model assessment for β cell HOMA-β in the carriers of genotype CG + GG at rs10830963, when compared with the wild-type CC (P <0.05). Conclusion: Thus, it was found that the MTNR1B rs10830963 polymorphism was associated with the therapeutic efficacy of nateglinide in T2DM patients. Also, the CC homozygotes had a better effect than G allele carriers. Trial registration: This study was registered in the Chinese Clinical Trial Register (No. ChiCTR-CCC13003536).

scholarly journals Association of ANGPTL8 and Resistin With Diabetic Nephropathy in Type 2 Diabetes Mellitus

2021 ◽  
Vol 12 ◽  
Author(s):  
Mengni Li ◽  
Rongping Fan ◽  
Xuemin Peng ◽  
Jiaojiao Huang ◽  
Huajie Zou ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Diabetic Nephropathy ◽  
Glycosylated Hemoglobin ◽  
Fasting Blood Glucose ◽  
Serum Levels ◽  
Hs Crp ◽  
The Relationship

BackgroundPrevious studies showed altered angiopoietin-like protein-8 (ANGPTL-8) and resistin circulating levels in type 2 diabetes mellitus (T2DM). Whether or not the alteration in ANGPTL-8 and resistin level can be a predictive maker for increased diabetic nephropathy risk remains unclear.AimTo Investigate the possible association of ANGPTL-8 and resistin with DN, and whether this association is affected by NAFLD status.MethodsA total of 278 T2DM patients were enrolled. Serum levels of ANGPTL8, resistin, BMI, blood pressure, duration of diabetes, glycosylated hemoglobin (HbA1c), fasting blood glucose (FPG), hypersensitive C-reactive protein (hs-CRP), lipid profile, liver, and kidney function tests were assessed. The relationship between DN with ANGPTL8 and resistin was analyzed in the unadjusted and multiple-adjusted regression models.ResultsSerum levels of ANGPTL8 and resistin were significantly higher in DN compared with T2DM subjects without DN (respectively; P &lt;0.001), especially in non-NAFLD populations. ANGPTL8 and resistin showed positive correlation with hs-CRP (respectively; P&lt;0.01), and negative correlation with estimated GFR (eGFR) (respectively; P=&lt;0.001) but no significant correlation to HOMA-IR(respectively; P&gt;0.05). Analysis showed ANGPTL8 levels were positively associated with resistin but only in T2DM patients with DN(r=0.1867; P&lt;0.05), and this significant correlation disappeared in T2DM patients without DN. After adjusting for confounding factors, both ANGPTL8(OR=2.095, 95%CI 1.253-3.502 P=0.005) and resistin (OR=2.499, 95%CI 1.484-4.208 P=0.001) were risk factors for DN. Data in non-NAFLD population increased the relationship between ANGPTL8 (OR=2.713, 95% CI 1.494-4.926 P=0.001), resistin (OR=4.248, 95% CI 2.260-7.987 P&lt;0.001)and DN. The area under the curve (AUC) on receiver operating characteristic (ROC) analysis of the combination of ANGPTL8 and resistin was 0.703, and the specificity was 70.4%. These data were also increased in non-NAFLD population, as the AUC (95%CI) was 0.756, and the specificity was 91.2%.ConclusionThis study highlights a close association between ANGPTL8, resistin and DN, especially in non-NAFLD populations. These results suggest that ANGPTL-8 and resistin may be risk predictors of DN.

scholarly journals Treatment with the Dipeptidyl Peptidase-4 Inhibitor Vildagliptin Improves Fasting Islet-Cell Function in Subjects with Type 2 Diabetes

2009 ◽  
Vol 94 (1) ◽  
pp. 81-88 ◽  
Author(s):  
David A. D'Alessio ◽  
Amanda M. Denney ◽  
Linda M. Hermiller ◽  
Ronald L. Prigeon ◽  
Julie M. Martin ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Blood Glucose ◽  
Cell Function ◽  
Glycosylated Hemoglobin ◽  
Fasting Blood Glucose ◽  
Dipeptidyl Peptidase ◽  
Islet Function ◽  
C Peptide ◽  
Dipeptidyl Peptidase 4

Abstract Context: Dipeptidyl peptidase 4 (DPP-4) inhibitors are proposed to lower blood glucose in type 2 diabetes mellitus (T2DM) by prolonging the activity of the circulating incretins, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1). Consistent with this mechanism of action, DPP-4 inhibitors improve glucose tolerance after meals by increasing insulin and reducing glucagon levels in the plasma. However, DPP-4 inhibitors also reduce fasting blood glucose, an unexpected effect because circulating levels of active GIP and GLP-1 are low in the postabsorptive state. Objective: The objective of the study was to examine the effects of DPP-4 inhibition on fasting islet function. Design: We conducted a randomized, double-blind, placebo-controlled trial. Setting: The study was performed in General Clinical Research Centers at two University Hospitals. Subjects: Forty-one subjects with T2DM were treated with metformin or diet, having good glycemic control with glycosylated hemoglobin values of 6.2–7.5%. Intervention: Subjects were treated with vildagliptin (50 mg twice daily) or placebo for 3 months, followed by a 2-wk washout. Major Outcome Measure: We measured insulin secretion in response to iv glucose and arginine before and after treatment and after drug washout. Results: There were small and comparable reductions in glycosylated hemoglobin in both groups over 3 months. Vildagliptin increased fasting GLP-1 levels in subjects taking metformin, but not those managed with diet, and raised active GIP levels slightly. DPP-4 inhibitor treatment improved the acute insulin and C-peptide responses to glucose (50 and 100% respectively; P &lt; 0.05) and increased the slope of the C-peptide response to glucose (33%; P = 0.023). Conclusion: Vildagliptin improves islet function in T2DM under fasting conditions. This suggests that DPP-4 inhibition has metabolic benefits in addition to enhancing meal-induced GLP-1 and GIP activity.

Sign in / Sign up

Export Citation Format

Share Document