الفهرس 
Diabetes Mellitus
Chronic complications of diabetes:Only 14 pages are availabe for public view
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Abstract
Diabetes mellitus is a group of metabolic diseases characterized by hyperglycemia with disturbance of carbohydrates, fat and protein metabolism resulting from defects in insulin secretion, insulin action or both. Diabetes mellitus can be classified into 4 main general categories: Type 1 diabetes (due to autoimmune β-cell destruction), Type 2 diabetes (due to a progressive loss of β-cell insulin secretion frequently on the background of insulin resistance), Gestational diabetes mellitus (GDM) and Specific types of diabetes due to other causes. Type 2 diabetes mellitus (T2-DM), previously referred to as “noninsulin-dependent diabetes” or ” adult-onset diabetes,” accounts for 90–95% of all diabetes. In 2013, 382 million adults aged 20–70 years worldwide had T2-DM. This number is expected to rise to 592 million by 2035. Over time, several complications occur such as cardiovascular disorders, retinopathy and nephropathy which can reduce the quality of life and life expectancy. Therefore, it is important to explore novel early biomarkers of diabetes able to predict, follow-up diabetes and to specifically subtype its different forms, to take appropriate therapeutic treatment. MicroRNAs (miRNAs) are small (19-25 nucleotides), singlestranded non-coding but functional RNAs. The microRNAs play a role in post-transcriptional regulation of gene expression in most eukaryotes by interacting with messenger RNAs (mRNAs) through complete or partial complementarities. MiRNAs have a key role in fine-tuning cellular functions such as proliferation, differentiation and apoptosis, and they are involved in carcinogenesis, glucose homeostasis, inflammation and other biological processes. The expression of miRNA can be changed in the blood because of cellular damage and tissue injury. Unlike intracellular miRNAs, circulating miRNAs release from cells based on their targeted functions. The expression profiles of these circulating miRNAs in serum, plasma, and other body fluids help for their use as novel minimally invasive biomarkers in diagnosing and monitoring human diseases because they are tightly correlated with various serious diseases including cancers, kidney disease, central nervous system diseases, cardiovascular diseases, diabetes, and viral infections. In genome-wide association studies (GWAS) have contributed to the identification of more than 80 susceptibility loci for type -2 diabetes. Several loci are reported to be targets of islet-expressed miRNAs, suggesting the involvement of miRNAs in the pathophysiology of diabetes mellitus. Micro RNA 146a is a family of microRNA precursors found in mammals, including humans. The human genome contains two miR-146 genes (miR-146a and miR-146b) on chromosome 5 and 10 respectively. MiR-146a has been identified as being expressed in 20 normal human tissues and organs, particularly the thymus and spleen, which are rich in lymphocytes and play an important roles in inflammation, immunity, autoimmune, viral infection and cancer. The miR-34 family members comprise three processed miRs that are encoded by two different genes: miR-34a is encoded by its own transcript on chromosome 1p36, whereas miR-34b and miR-34c share a common primary transcript encoded on chromosome 11q23. The miR- 34a plays an important role in cell cycle, cell differentiation, apoptosis and cancer. The aim of this work is to explore the value of serum micro RNAs (146-a and 34-a) in pre-diabetes and newly diagnosed type 2 diabetes (T2D) to evaluate its pathogenesis in type 2 diabetes patients. This study was carried out on 60 adult subjects, which were divided into three groups: group I (newly diagnosed Type 2diabetes mellitus “n-T2D”): Included 20 patients their age ranged from 35 -48 years. group II )pre-diabetes(: Included 20 cases their age ranged from 35-49 years.. group III (T2D-susceptible individuals with normal glucose tolerance): Included 20 cases their age ranged from 33 -47 years. All individuals included in this study were subjected, after definite written consent to the following assessment: I. Complete history taking including personal and family history . II. Clinical examination with particular attention to: Height, weight, with calculation of the body mass index. III. Laboratory investigations including: A) Routine investigation: 1. Fasting & postprandial blood glucose level. 2. Hemoglobin A1C . 3. Lipid profile (total cholesterol, triglycerides, HDL and LDL). 4. OGTT (oral glucose tolerance test) to confirm IFG and IGT B) Specific investigation: Detection of miRNAs (146a & 34a) by real time PCR (RT-PCR). The following results were obtained: • The mean value of both fasting and post-prandial blood glucose, HbA1c and triglycerides were significantly increased in newly diagnosed Type 2 diabetes mellitus (n-T2D) when compared to prediabetes and T2D-susceptible individuals with normal glucose tolerance. • There was significant difference in mean value of Micro RNA -146a and Micro RNA- 34a between the studied groups. • Expression levels of both Micro RNA -146a and Micro RNA- 34a were significantly elevated in newly diagnosed Type 2 diabetes mellitus (n-T2D) group in comparison by pre-diabetes and susceptible individuals with normal glucose tolerance. • There was positive significant correlation between both MicroRNA 146-a &MicroRNA 34-a expression, and fasting blood sugar, post – prandial blood sugar, glycated hemoglobin and triglycerides among newly diagnosed type-2 diabetic patients. • There was no significant correlation between either MicroRNA 146-a or MicroRNA 34-a expression and “age, sex, body mass index, cholesterol, high density lipoproteins or low density lipoproteins” in newly diagnosed type -2 diabetes patients. • There was significant positive correlation between MicroRNA 34-a expression (RQ) and MicroRNA 146-a expression (RQ) newly diagnosed type -2 diabetes mellitus, while there was no significant correlation observed as regard the 2 micro RNAs among pre-diabetic individuals.