الفهرس 
Introduction and aim of workOnly 14 pages are availabe for public view
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Abstract
This study is mainly concerned with diabetes control in case of hepatic insufficiency in both experimental rats and in volunteer patients. In attempt to achieve this work, cirrhosis was induced in rats using CCl4 and diabetes was induced by STZ. Both cirrhosis and diabetes were induced in the same animal by induction of cirrhosis first using CCl4 followed by induction of diabetes using STZ. These three models were used for both prophylactic and subacute treatment. In the clinical trials, the study was carried out on three main groups of patients (the first one was cirrhotic, the second one was diabetic and third one was cirrhotic diabetic patients). The group comprised five patients, no obese male subjects, aged 35 to 52 years, moderate income and below 90kg body weight. All had no cirrhotic or diabetic complications, follow restricted diet, no other drugs were used with our regimen.
Several parameters (ALT, AST, ALP, MDA, LDH and albumin) were measured to evaluate the hepatic status in both prophylactic and chronic treatment. Moreover other parmeters were measured to evaluate the improvement in the diabetic statues e.g., blood glucose level, OGTT, insulin, insulin resistance, glycohaemoglobin, serum cholesterol level, high density lipoprotein and low density lipoprotiens. These parameters were measured in both rats and human.
Three agents; Silymarin (has hepatoprotective properties), aloe (has antidiabetic activity) and gliclazide (has antidiabetic activity) were used in this study alone and combined interchangeable administration in the recommended doses in both rats (prophylactic and subacute) and patients volunteers.
from these results, it could be concluded that:
• Cirrhosis may lead to hyperglycemia, glucose intolerance, hyperinsulinemia, insulin resistance, and elevations in ALT, AST, ALP, MDA, LDH and reduction of albumin levels.
• Cirrhosis may participate to a large extent in the incidence of diabetes mellitus due in part to glucose intolerance, hyperinsulinemia and insulin resistance.
• Protection of liver from agents like acetaminophen, carbon tetrachloride, ethanol, hydrocarbons, oral contraceptive, Troglitazone, valproic acid, diclofenac and many other compounds that may cause liver insufficiency may participate in delaying the incidence and controlling of diabetes mellitus.
• Silymarin delayed the incidence of diabetes mellitus in normal and cirrhotic rats; this may by due to its ability to protect both the liver and pancreas against free radicals that produced from CCl4 and STZ. This effect may result from increased levels of endogenous antioxidant substances e.g., glutathione, super oxide dismutase, vitamin E and C.
• Gliclazide and its combination with silymarin delayed the incidence of diabetes in normal and cirrhotic rats. This effect may be due to their ability to improve status of liver and pancreas by increasing the concentration of the endogenous antioxidants.
• Silymarin, aloe, gliclazide and their combination were able to improve hyperglycemia, hyperinsulinemia and insulin resistance this may be due to the improvement in liver status.
• Improvement of liver status by drugs that increase the endogenous antioxidant substances may lead to improvement in the diabetic state in both human and animals.
• Aloe has antidiabetic and antihyperlipidemic activity in both experimental animals and patients. This effect may due to its ability to; inhibition of the glycogenolysis and gluconeogenesis processes, increasing glucose utilization by tissues and decreasing advanced glycation end products.
• Silymarin has antidiabetic effect in experimental rats. This may attribute to the improvement of the liver status, through its antioxidant activity. This may lead to increased protein synthesis, increased regeneration of the hepatocyte membrane, which in turn increased the glucose transporters and insulin receptors in liver tissues.
• The control of diabetes becomes so difficult as the liver functions are impaired.
• The use of hepatoprotective drugs like silymarin in families’ history diabetes may delay the incidence of diabetes.
• The antidiabetic effect of gliclazide was more pronounced when given concurrently with either silymarin (in diabetic and cirrhotic-diabetic) or aloe (in diabetic) in both experimental and clinical trial.
• Drugs combinations are preferable in the treatment of diabetes in case of hepatic insufficiency. This combination preferred to posses antioxidant properties and not exert load on the liver.