Association of genetic and epigenetic changes of insulin like growth factor binding protein-1 in Egyptian patients with type 2 diabetes mellitus.

BACKGROUND: Diabetes is one of the global health threat. Type 2 Diabetes mellitus (T2DM) is associated with life-threatening complications. This work, aimed to study the association between T2DM and IGFBP-1 gene methylation, gene polymorphism and serum levels of IGFBP-1. METHOD: We included 100 subjects with T2DM and 100 control. DNA methylation of IGFBP-1 was analyzed using pyrosequencing, IGFBP-1 gene polymorphism was analyzed using real time polymerase chain reaction and serum level of IGFBP-1 was measured by ELISA. RESULTS: There was DNA hyper methylation levels of IGFBP1 gene at each of the six CpG sites in T2DM patients than control (P < 0.001). IGFBP-1 gene polymorphism (rs 2854843) CC pattern was significantly associated with DM, P = 0.002. Also, there was decrease in serum IGFBP-1 in patients with T2DM than control group (P < 0.001). CONCLUSION: We concluded that DNA hyper methylation of IGFBP-1 gene and CC polymorphism (rs 2854843) of IGFBP-1 gene are associated with T2DM in Egyptian patients, also, decrease serum level of IGFBP-1. Further cohort study is recommended with large sample size to detect which one, epigenetic changes or polymorphism of IGFBP-1 gene, is the cause of T2DM or even both.

Correction: Plasma microRNAs biomarkers in mild cognitive impairment among patients with type 2 diabetes mellitus.

[This corrects the article DOI: 10.1371/journal.pone.0236453.].

Plasma microRNAs biomarkers in mild cognitive impairment among patients with type 2 diabetes mellitus.

OBJECTIVES: To assess the potential value of some miRNAs as diagnostic biomarkers for mild cognitive impairment (MCI) among patients with type2 diabetes mellitus (T2DM) and to identify other risk factors for MCI among them. METHODS: This study enrolled 163 adults with T2DM using face to face interview. Cognitive function with its domains was assessed using Adenbrooke's Cognitive Examination III (ACE III). Lipid profile, glycated hemoglobin, and miR-128, miR-132, miR- 874, miR-134, miR-323, and miR-382 expressions, using quantitative real-time PCR, were assessed. RESULTS: MCI was detected among 59/163 (36.2%) patients with T2DM. Plasma expression of miR-132 was significantly higher in T2DM patients with MCI compared to those without MCI and to normal cognitive healthy individuals (median = 2, 1.1 and 1.2 respectively, P < 0.05. Logistic regression analysis showed that higher miR-132 expression with adjusted odds ratio (AOR): 1.2 (95% CI 1.0-1.3), female gender (AOR:2.1; 95%CI 1.0-4.3), education below postgraduate (secondary and university education with AOR: 9.5 & 19.4 respectively) were the significant predicting factors for MCI among T2DM patients. Using ROC curve, miR-132 was the only assayed miRNA that significantly differentiates T2DM patients with MCI from those with normal cognition with 72.3% sensitivity, 56.2% specificity, and 63.8% accuracy (P < 0.05). Other studied miRNAs showed lower sensitivity and specificity for detecting MCI among studied T2DM participants. CONCLUSION: MCI affects nearly one-third of adult patients with T2DM. A significantly over expression of miR-132 was detected among T2DM with MCI compared to those with normal cognition.

Risk Factors Associated with Mild Cognitive Impairment among Apparently Healthy People and the Role of MicroRNAs.

BACKGROUND: Mild cognitive impairment (MCI) is a stage between the expected cognitive decline of normal ageing and the serious decline of dementia. AIM: To identify risk factors and role of miRNAs associated with mild cognitive impairment (MCI) among employees. SUBJECTS AND METHOD: A cross-sectional study was carried out on 186 employees aged between 40 and 65 years. Cognitive function was evaluated using ACEIII, MoCA, and Quick cognitive tests. Medical history and lifestyle were assessed. Family 132 & 134 miRNA expressions were assessed by real-time PCR. RESULTS: MCI was detected among 14 / 186 (7.5%). miRNA 132 expression was the only significant miRNAs to detect MCI with low sensitivity and specificity (70%). The logistic analysis revealed that higher miRNA132 expressions, low monthly intake of; vegetables, unroasted nuts, low education and higher ALT levels were predicting factors for MCI with AOR 1.1 (1.01-3.3), 1.2 (1.04-1.43), 0.8 (0.8-0.98), 2.7 (1.9-7.4) and 1.6 (1.1-2.3) respectively. CONCLUSION: MiRNAs expression showed low sensitivity and specificity in detecting MCI; only miRNA 132 might be used. Several modifiable factors seem to reduce the risk of MCI.

Peroxisome proliferator-activated receptor-γ polymorphism (rs1801282) is associated with obesity in Egyptian patients with coronary artery disease and type 2 diabetes mellitus.

OBJECTIVE: Peroxisome Proliferator-Activated Receptor-γ (PPAR-γ) gene is one of the possible genes linking diabetes mellitus (DM) with coronary artery disease (CAD). The aim of this study is to clarify whether PPAR-γ Pro12Ala polymorphism is associated with the development of CAD in type 2 diabetic patients and to evaluate PPAR-γ Pro12Ala polymorphism genetic distribution in type 2 DM (T2DM) Egyptian subjects. METHODS: PPAR-γ Pro12Ala polymorphism was determined by Real-Time PCR in serum of 405 subjects classified into 4 groups; T2DM patients (n = 105), T2DM with CAD (n = 100), CAD patients (n = 100) and healthy controls (n = 100). RESULTS: The PPAR-γ Pro12Ala polymorphism was associated significantly with T2DM with CAD (group2) (OR = 3, 95% CI = (1.5-6); p = 0.001). In this study, T2DM with CAD complications carrying the PPAR-γ Pro12Ala polymorphism had higher BMI than those without the PPAR-γ Pro12Ala polymorphism (p < 0.0001). CAD patients carrying PPAR-γ Pro12Ala polymorphism had considerable insulin resistance features. Plasma paraoxanase 1(PON1) level was considerably reduced among our 3 studied groups in comparison to control group (p < 0.001). CONCLUSIONS: PPAR-γ Pro12Ala polymorphism might represent a novel risk factor for CAD in T2DM.