Evaluation of some risk factors affecting insulin resistance in diabetic patients

Abstract

Diabetes mellitus is a group of metabolic diseases characterized by high blood glucose levels that result from defects in insulin secretion, or action, or both. Insufficient production of insulin (either absolutely or relative to the body's needs), production of defective insulin (which is uncommon), or the inability of cells to use insulin properly and efficiently leads to hyperglycemia and diabetes. This latter condition affects mostly the cells of muscle and fat tissues, and results in a physiological condition known as "insulin resistance" . This is the principal problem in type 2 diabetes. Insulin is a hormone that is produced by the beta cells, which are cells that are scattered throughout the pancreas. The insulin produced is released into the blood stream and travels throughout the body. Insulin is an important hormone that has many actions within the body. Most of the actions of insulin are directed at metabolism (control) of carbohydrates (sugars and starches), lipids (fats), and proteins. Insulin also is important in regulating the cells of the body including their growth. Insulin resistance (IR) is a condition in which the cells of the body become resistant to the effects of insulin , that is the normal response to a given amount of insulin is reduced . As a result , higher levels of insulin are needed in order for insulin to have its effects . The resistance is seen with both the body's own insulin (endogenous) and if insulin is given through injection (exogenous). Certain cell types such as fat and muscle cells require insulin to absorb glucose . When these cells fail to respond adequately to circulating insulin , blood glucose levels rise . The liver helps regulate glucose levels by reducing the secretion of glucose in the presence of insulin. This normal reduction in the liver’s glucose production may not occur in people with insulin resistance. Hypertension , high triglyceride level (Hypertriglyceride-mia) ; low level of "good cholesterol" are the risk factors of DM and increased level of IR . Glutathione is an antioxidant protein preventing damage to important cellular components caused by reactive oxygen species such as free radicals andperoxides . Glutathione reduces disulfide bonds formed within cytoplasmic proteins to cysteines by serving as an electron donor . In the process , glutathione is converted to its oxidized form glutathione disulfide (GSSG) , also called L-glutathione . Once oxidized , glutathione can be reduced back by glutathione reductase , using NADPH as an electron donor . The ratio of reduced glutathione activity to oxidized glutathione activity within cells is often used as a measure of cellular toxicity . Tumor necrosis factor-alpha (TNF-α): is a 157-amino acid pro-inflammatory cytokine predominantly produced by monocytesmacrophages, and T-cells.TNF is a cytokine involved in systemic inflammation and is a member of a group of cytokines that stimulate the acute phase reaction. The primary role of TNF is in the regulation of immune cells. On the liver : stimulating the acute phase response, leading to an increase in C-reactive protein and a number of other mediators. It also induces insulin resistance by promoting serine-phosphorylation of insulin receptor substrate-1 (IRS-1), which impairs insulin signaling. Hepatitis C: is an infectious disease affecting primarily the liver, caused by the hepatitis C virus (HCV) . The infection is often asymptomatic, but chronic infection can lead to scarring of the liver and ultimately to cirrhosis , which is generally apparent after many years . In some cases , those with cirrhosis will go on to develop liver failure , liver cancer or life-threatening esophageal and gastric varies . The Cytochrome P450 enzyme family of heme-containing proteins represents one of the largest and most functionally diverse superfamilies found in nature. The main function of P450 is to facilitate the biotransformation of compounds by addition of functional groups suitable for conjugation and ultimate elimination from the organism. Chronic liver disease is another factor that has been reported to impair P450 drug metabolism in hepatic patients. Studies on altered hepatic P450 function have been reported in patients with cholestasis, hepatitis B and C, alcoholic liver disease, and cirrhosis. Subject : Fifty subject were included in the study and classified into 5 groups each group containing ten patients: Group 1:control group includediabetic patients with normalinsulin resistance level. Group 2:includediabetic patients with high level of insulinresistance. Group 3:include diabetic patientswith high levels of insulinresistance &positive hepatitis c virus. Group 4:include diabetic patients with high levels of bothinsulin resistance and TNF-α. Group 5:include diabetic patients with high level of insulinresistance and have coronary heart diseases.