Abnormal secretion or action of insulin has been considered the main cause of changes in carbohydrate, lipid and protein metabolism during diabetes mellitus.This study presents serum amino acid (measured by reversed HPLC) & lipid profiles (by enzymatic methods) in 99 diabetic patients (age range 14 - 74 y) as modulated by the type of disease and degree of metabolic control (reflected by HbA1c level). These patients are grouped into optimally controlled (11 with HbA1c <= 7.9%); acceptably controlled 23 with HbA1c< = 10.1) and poorly controlled (65 with HbA1c > 10.1). Forty two of the diabetics belong to Type I & 57 to Type II diabetes mellitus. The results obtained from the diabetics are compared with those obtained from 40 non-diabetic subjects (age range 18 - 40 y). Both groups of diabetics & non-diabetics are subdivided into normo- & hypertensives. Other clinical parameters like proteinuria and body mass index (BMI) are considered in the study. Increase in serum branched chain amino acids (BCAAs) [ valine, leucine and isoieucine] and decrease in serum asparate, giutamine, alanine, arginine and methionine are noticed in ail diabetics, with the presence of a significant correlations between serum serine and HbA1c (r = 0.29, p = 0.003) and serine and sugar (r = 0.25, p=0.001). Combination of changes in insulin activity and amino acid utilization by liver and peripheral tissue might be the main causative agent. Sex and age are two factors which might affect the changes. The reduction in gluconeogenic amino acids (giutamine and alanine) with the increase in the rate of giuconeogenesis in DM (about 2 fold the normal) could be attributed to increased splanchnic extraction of such amino acids for glucose synthesis. Serum arginine reduction could be due to increased arginase activity with the resultant increase in the hydrolysis of arginine to ornithine and urea, and increase in urinary excretion of nitric oxide metabolites. Generally, variation in the degree of metabolic control shows trivial effect on serum branched chain amino acids, while aianine is lower significantly in the optimally controlled than the poorly controlled groups as compared to their normal controls. This could be explained by the low effect of effective insulin on the amino acid. The degree of reduction in serum glutamine is increased with the deterioration in the metabolic control due to increased rate of gluconeogenesis and low rates of its oxidation and forearm release. On the other hand the reduction in serum aspartate (specially In the poorly controlled diabetics) could be due to its use in urea synthesis which is increased with the reduction in insulin activity. The poorly controlled diabetics show a significant increase in serum serine, lysine and phenylalanine in addition to BCAAs . This could be referred to ineffective insulin that results in Increased rate of proteolysls. Serum histidine shows variable pictures in the different metabolically controlled groups due to different number of hypertensives Included in each group. An association between serum histidine & hypertension appears to exist from the present resutts.something which has not been reported before & needs further study. A significant correlation is also found between serum phenylalanine and the 24 hour urine protein (r = 0.28 , P = 0.02) in the poorly controlled group which shows the highest degree of proteinuria .Poor metabolic control also causes a marked reduction in serum methionine where its liver metabolism is affected by insulin availability.The diabetic patients of the present study have normal serum creatlnine despite variable degree of proteinuria which is correlated with the degrees of metabolic control , being the highest in the poorly controlled patients, & with the duration of the disease. The two types of DM show different changes in serum amino acid concentrations including an increase in phenylalanine in Type I ; serine in Type II, reduction in aianine and glutamine in Type II with a higher HbA1c , fasting serum glucose and 24 hour urinary protein in Type I. Hypertension, also, has an effect on serum amino acid picture showing a general increase in glutamic acid, histidine, phenylalanine, tryptophan and tyrosine in both diabetic and non-diabetic subjects ; while aspartate is high in the hypertensive diabetics only. Phenylalanine, tyrosine and methionine are amino acids related to the synthesis of adrenaline and are increased by hypertension as evident from both diabetic and non-diabetic hypertensives ,when compared to their normotensive equivalents. Dyslipidemia of diabetes mellitus Involves an increase in all serum lipids except the HDLc which shows a significant reduction. Dyslipidemia of DM could be attributed to poor glycemic control that reflects insulin insufficiency or resistance with consequent increase in lipid mobilization and tissue protein breakdown.Hypertriglyceridemla (high VLDL) is the predominant feature of DM (specially Type 10 and is greathy affected by the metabolic control being significantly higher In the poorly controlled than the optimally and acceptably controlled groups. The effects of hypertension on serum lipids included an increase In total cholesterol, triglycerides, low density lipoprotein cholesterol & low density to the high density lipoproteln cholesterol ratio with a reduction in the high density lipoprotein cholesterol in the hypertensives of both diabetics and non-diabetic subjects; when compared with their normotensive groups. A number of significant correlations, exist between different serum amino acids and various serum lipids as: tryptophan and low density lipoprotein cholesterol (r = 0.72, P = 0.009); phenylalanine and low density iipoprotein cholestrol (r=0.82 , P=0.001) ; histldine and total cholesterol (r=0.62, P=0.03) phenylalanine and total cholesterol ( r = 0.75 , P = 0.005 ) and lysine and total cholesterol ( r = 0.61; P = 0.035) in the hypertensive normoproteinuric non-diabetic subjects. The correlations in the hypertensive diabetics (with high 24 hour urinary protein) include tryptophan and triglyceride (r = 0.46, P =0.02); tryptophan and HDLc (r=0.41, P=0.04) and histidine and HDLC/HDLC ratio (r = -0.4 , P = 0.05). Expiainations of many of the metabolic changes appeared during the study have been fully mentioned and discussed. Aim of the study . To present changes in serum amino acids and lipids by diabetes mellitus as modulated by type of diabetes, metabolic control and hypertension