الفهرس 
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Abstract
Type 2 diabetes mellitus (T2DM) is a chronic disease characterized by hyperglycemia due to various degrees of insulin resistance and impaired insulin secretion secondary to genetic and environmental factors which adversely affect β - cell function and tissue insulin sensitivity.
The chronic hyperglycemia and altered cellular homeostasis associated with DM lead to diffuse vascular damage and multi-organ dysfunction. In the long term, patients with DM have the risk of developing both micro- and macrovascular complications.
Microvascular complications (due to damage to small blood vessels) include diabetic kidney disease (DKD), diabetic retinopathy and diabetic neuropathy which are the major causes of renal insufficiency, blindness and non-traumatic lower limb amputation, respectively, while macrovascular complications (due to damage to larger blood vessels) are mainly represented by atherosclerotic disease and its manifestations, such as peripheral arterial disease (PAD), stroke, and coronary artery disease (CAD).
DKD develops in a large number of patients with T2DM and it is a leading cause of end-stage renal disease (ESRD) worldwide. It may be present at diagnosis of T2DM and the presence of DKD markedly increases cardiovascular risk in patients with T2DM.
DKD usually manifests a clinical syndrome including persistent albuminuria, increased blood pressure, sustained reduction in estimated glomerular filtration rate (eGFR), increased cardiovascular events and cardiovascular event-associated mortality.
Deaths due to cardiovascular events and infections are highly prevalent and increase with progression to ESRD and patients on dialysis more likely to die than their counterparts in the general population.
The Notch 2 gene carries the instructions for making a protein called Notch 2 which is synthesized in the endoplasmic reticulum and expressed in multiple cells and tissues including the brain, thyroid gland, adrenal gland, the pancreas, the liver, the kidney, the gastrointestinal tract and the skin. Notch 2 has an important role in cell development in addition to regulation of various immune and metabolic functions.
ABCC8 gene provides instructions for making the sulfonylurea receptor 1 (SUR1) protein. The SUR1 protein is one subunit of the ATP-sensitive potassium (KATP) channel that is found across cell membranes in the beta cells of the pancreas. The KATP channel controls the secretion of insulin out of beta cells into the bloodstream.
The present study was carried to evaluate the expression of ABCC8 and Notch 2 genes in patients with T2DM and to study the relation of their expression with DKD. This study was conducted on 80 patients with T2DM, including 40 patients with DKD and another 40 patients without DKD in addition to 40 healthy subjects of matched age and sex as a control group.
The results showed that the expression of Notch 2 gene was higher in patients with T2DM compared to controls and patients with DKD showed upregulated expression of Notch 2 gene compared to those without DKD. Also, The results showed that the expression of ABCC8 gene was higher in patients with T2DM compared to controls but there was no significant difference in ABCC8 gene expression between patients with DKD and patients without DKD. However, despite that both genes showed higher expression in patients with T2DM compared to controls, the study showed that both genes acted independently of each other and there was no co-expression in their action.
In patients with T2DM, ABCC8 gene expression showed a significant positive correlation with HbA1c while there was no statistically significant correlation with other studied parameters. Also, Notch 2 gene expression showed a significant positive correlation with HbA1C, FPG and uACR and a significant negative correlation with eGFR while there was no statistically significant correlation with other studied parameters. Both genes expression showed no significant correlation with total cholesterol, LDL-C, HDL-C, triglycerides, ESR and CRP.
The results also showed that the mean HbA1C percentage and the mean value of FPG in patients with DKD was statistically significantly higher compared to those without DKD indicating an important role of poor glycemic control in the development of DKD. Also, there was no statistically significant difference between the mean values of the total serum cholesterol, HDL-C and LDL-C in patients with DKD and patients without DKD but on the other hand, the mean serum triglyceride level in patients with DKD was statistically significantly higher than mean level of serum triglycerides in the group of patients without DKD. Moreover, regarding the markers of inflammation, patients with DKD showed higher levels of ESR and CRP compared to patients without DKD.
The results showed that patients with T2DM had higher mean values of BMI and waist circumference compared to controls. Also, patients with T2DM had higher levels of total cholesterol, LDL-C, triglycerides, ESR, CRP and uACR in addition to lower mean values of HDL-C compared to control group.