The role of amino acids in diabetes mellitus and its metabolic traits have been suggested previously; however, studied to a very limited scale in the Saudi patient population. Patients diagnosed with diabetes mellitus were included in the current clinical study. Sample was representative and in accordance with the national population distribution. Blood samples were drawn and assayed for glucose, total cholesterol, triglyceride, high density lipoprotein and low density lipoprotein. General biochemical markers, such as alkaline phosphatase (ALP), creatinine kinase (CK), aspartate transaminase (AST), alanine transaminase (ALT) and blood urea nitrogen (BUN) were assessed. Serum amino acids of different categories (essential, semi-essential and metabolic indicator amino acids) were assessed. Correlation co-efficient between each amino acid and serum glucose level was calculated. The current study showed positive correlation between amino acid level and glucose serum concentration in male while it showed negative correlation in female Saudi diabetic patients. Male patients had significantly higher methionine concentration parallel to their glycemic status. Metabolic indicator amino acids significantly changed in concordance with the glycemic status of female patients more than in male patients. In conclusion, serum amino acid is positively correlated with glycemic status in Saudi male diabetic patients while negatively correlated in female patients. Yet, further study would be recommended to utilize serum amino acid profile as surrogate parameter for the metabolic complications of diabetes mellitus.
Journal of Advanced Research (2012) 3, 305–313 Cairo University Journal of Advanced Research www.ksu.edu.sa ORIGINAL ARTICLE Trend analysis of the correlation of amino acid plasma profile with glycemic status in Saudi diabetic patients Fahad A Al-Abbasi * Department of Biochemistry, Faculty of Science, King Abdulaziz University, P.O Box 50077, Jeddah 21523, Saudi Arabia Received 21 April 2011; revised October 2011; accepted October 2011 Available online 16 November 2011 KEYWORDS Amino acid; Diabetes mellitus; Saudi Arabia; Trend analysis Abstract The role of amino acids in diabetes mellitus and its metabolic traits have been suggested previously; however, studied to a very limited scale in the Saudi patient population Patients diagnosed with diabetes mellitus were included in the current clinical study Sample was representative and in accordance with the national population distribution Blood samples were drawn and assayed for glucose, total cholesterol, triglyceride, high density lipoprotein and low density lipoprotein General biochemical markers, such as alkaline phosphatase (ALP), creatinine kinase (CK), aspartate transaminase (AST), alanine transaminase (ALT) and blood urea nitrogen (BUN) were assessed Serum amino acids of different categories (essential, semi-essential and metabolic indicator amino acids) were assessed Correlation co-efficient between each amino acid and serum glucose level was calculated The current study showed positive correlation between amino acid level and glucose serum concentration in male while it showed negative correlation in female Saudi diabetic patients Male patients had significantly higher methionine concentration parallel to their glycemic status Metabolic indicator amino acids significantly changed in concordance with the glycemic status of female patients more than in male patients In conclusion, serum amino acid is positively correlated with glycemic status in Saudi male diabetic patients while negatively correlated in female patients Yet, further study would be recommended to utilize serum amino acid profile as surrogate parameter for the metabolic complications of diabetes mellitus ª 2011 Cairo University Production and hosting by Elsevier B.V All rights reserved * Corresponding author Tel.: +966 559399935; fax: +966 26952288 E-mail address: alabassif@gmail.com 2090-1232 ª 2011 Cairo University Production and hosting by Elsevier B.V All rights reserved Peer review under responsibility of Cairo University doi:10.1016/j.jare.2011.10.001 Production and hosting by Elsevier Introduction Diabetes mellitus (DM) is a very common metabolic disease with expected worldwide burden of 300 million population in the year 2020 Kingdom of Saudi Arabia is classified level-4 DM disease burden with 717,000 patients in the year 2009 [1] There have been changes over the last 20 years in the geographical distribution of the incidence of diabetes with significant decline in the industrialized countries and rise in the developing countries [2] Kingdom of Saudi Arabia, a Middle 306 Eastern country, experienced significant economical improvement over the last 20 years This has resulted in adopting the ‘‘Western’’ life style with respect to nutritional habits and physical exercise Such changes might be coupled with improvement in health services; while on the other hand it could be associated with decline in the healthy eating habits and increase in the consumption of junk food [3] DM is an insulin/glucose metabolic-endocrinal disease primarily characterized by elevated blood glucose and inability of glucose utilization in the peripheral tissues such as adipose and muscle tissues [4] DM with both its major subtypes, insulin dependent diabetes mellitus and insulin independent diabetes mellitus, is accompanied by several vascular, neurological, immunological, and biochemical pathological changes [5] Estimating early signs of these target organs pathological effect using non-invasive techniques represents an important issue for clinicians in order to avoid late organ debilitations Serum glucose and c-peptide encountered the major classic parameters to assess the glycemic and insulin efficiency statuses clinically [6] In addition, several other biomarkers have been suggested for detailed or specific assessment of the diabetic status such as glucosenated hemoglobin for long term glycemic assessment [7] Amino acids comprise the building blocks of proteins found in structural tissues of the body Amino acids are essential to life in free or polymeric form as peptides Amino acids play important roles in activities, such as neurotransmission, pH regulation, cholesterol metabolism, pain control, detoxification, and control of inflammatory response [8] Many amino acids can be synthesized by the body Others, the essential amino acids, cannot be endogenously synthesized in adequate amounts, so that they must be obtained from the diet [9] The eight essential amino acids in humans are: isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, and valine [10] Semi-essential amino acids are those for which there is some endogenous synthesis, however, not enough for physiological needs These include arginine, histidine, cysteine, and taurine (for infants) [11] Other amino acids are considered metabolic indicators for several impairments in metabolism such as, beta-alanine, citrulline, homocysteine, cystathionine, ornithine, and alphaaminoadipic acid These amino acids provide information on conversion capability in the body or dietary adequacy of the essential amino acids [12] Several references donated an important role of amino acids are a variety of many disorders, nonetheless DM Some metabolic steps of amino acids related to vascular complications (methionine and arginine) exhibit a defective response to insulin in type-2 DM with nephropathy However, gross alterations in the response of whole-body protein turnover are not evident in type-2 DM, specific investigations reveal subtle abnormalities in metabolic steps of selected amino acids [13] Also it was reported that, circulating amino acid concentrations not worsen the already attenuated glucose disposal in hyperglycemic type diabetic men [14] Also, specific amino acid or amino acid balance could be used as a predictive plasma marker for Type-2 DM [15] Herein, in the current study on diabetic Saudi patients, we are assessing the correlation between the glycemic status of Saudi DM patients and their serum amino acid profile This study might provide new insights into further metabolic interference of DM in Saudi population F.A Al-Abbasi Patients and methods Subjects A total of 63 adult DM patients (27 males and 38 females) entered the study at a time after reading and accepting the institutional consensus All participants were clinically diagnosed type-I DM according to the standard procedures within Saudi health care institutes (inclusion criteria) Any patient with combined sever illness or sever diabetic complications was excluded from the study (exclusion criteria) The study design was approved by the clinical ethics committee in Ministry of Health Clinical examination Body mass index (BMI) was calculated as body weight (in kg) divided by squared height (in meters) The procedure for the measurements of weight, height, waist circumference and hip circumference, systolic and diastolic blood pressures was according to the standard procedures within Saudi health care institutes Collection of blood samples Venous blood samples (two samples) were withdrawn from peripheral vein while the patient is sitting Blood samples were allowed to clot, centrifuge and the sera were kept frozen at À20 °C for biochemical assessment Another blood sample was collected in heparinized tube for amino acid analysis Serum glucose determination Serum samples were used for glucose analysis on a glucose analyzer (Beckman Paragon, Fullerton, CA, USA) The method depends on the rate of oxygen consumption by the enzyme glucose oxidase in order to convert glucose into gluconic acid and hydrogen peroxide Oxygen rate consumption was determined by sensitive oxygen electrode The instrument was calibrated prior to glucose determination using quality control samples provided with the solutions The mean values obtained on the controls were within the values quoted by the manufacturer The results were expressed by SI units (mmol/l) The intra and inter assay coefficients of variation were 1.7% and 2.6%, respectively Biochemical assessments Biochemical assessments were assessed in isolated sera using specific kits purchased from Dade Behring, Marburg, Germany Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were assessed as previously described [18] Creatinine was determined via picric acid chromophore interaction assay [19] Creatinine kinase (CK), alkaline phosphatase (ALP) and blood urea nitrogen (BUN) were determined in sera using the manufacturer standard operating protocol of the kit Serum lipid analysis Analysis was done using the Cobas Mira S Clinical Analyzer, Roche Diagnostics Unimate cholesterol and Unimate triglyceride were used for measuring total cholesterol and triglycerides, respectively Trend of amino acids profile in Saudi diabetic patients Table 307 Glycemic, lipid profile and biochemical parameters in normoglycemic and hyperglycemic Saudi diabetic patients Normoglycemic group Male (n = 13) Glucose Cholesterol HDL-c LDL-c TG ALP CK ALT AST BUN 108.7 ± 14.7 170 ± 55.5 49.3 ± 8.6 99.6 ± 55.7 137.1 ± 49.6 92.5 ± 29.6 0.98 ± 0.4 23.7 ± 12.7 16.2 ± 8.2 19.8 ± 16.2 Hyperglycemic group Female (n = 14) 110.6 ± 22.6 169.0 ± 39.7 60.5 ± 14.7 83.3 ± 23.7 138.1 ± 48.1 97.7 ± 16.5 0.8 ± 0.3 17.7 ± 7.2 16.3 ± 3.6 14.2 ± 4.6 Male (n = 14) * 198.3 ± 71.4 165.3 ± 33.1 55.3 ± 11.8 81.4 ± 38.3 226.2* ± 166.6 103.1 ± 30.5 1.07 ± 0.8 22.9 ± 9.6 16.0 ± 7.1 16.7 ± 7.3 p-Value Female (n = 22) * 228.5 ± 61.6 164.7 ± 29.3 57.5 ± 7.7 79.6 ± 23.6 111.5 ± 67.2 99.1 ± 19.6 0.6 ± 0.2 18.1 ± 8.2 16.3 ± 6.3 12.3 ± 4.3 Male Female 0.0005 0.4 0.112 0.252 0.0449 0.2235 0.372 0.441 0.474 0.2722 0.00000035 0.365 0.256 0.417 0.1206 0.437 0.022 0.455 0.499 0.123 Table Plasma concentration of essential, semi-essential and metabolic indicator amino acids in normoglycemic and hyperglycemic Saudi diabetic patients Normoglycemic group Male Hyperglycemic group p-Value Female Male Female Male Female Essential amino acids THR 3.0 ± 6.7 VAL 2.1 ± 2.1 MET 1.3 ± 2.0 ILE 2.3 ± 3.3 TYR 2.8 ± 2.4 PHE 1.5 ± 2.1 LEU 2.1 ± 2.4 LYS 3.6 ± 6.9 Total 18.7 ± 24.4 3.4 ± 4.6 3.6 ± 6.1 1.1 ± 2.0 2.6 ± 3.3 4.6 ± 8.2 3.4 ± 4.6 5.0 ± 8.5 7.9 ± 10.4 31.7 ± 39.5 3.5 ± 4.2 3.0 ± 3.3 3.6* ± 4.4 3.1 ± 3.8 2.7 ± 3.6 3.4 ± 5.9 2.8 ± 3.2 10.2 ± 13.6 32.4 ± 34.8 1.7 ± 3.1 1.5 ± 2.1 0.9 ± 2.0 1.4 ± 2.2 1.4 ± 3.5 1.2* ± 2.3 1.9 ± 3.0 5.1 ± 8.6 15.1 ± 23.5 0.4058 0.1974 0.0467 0.2741 0.4768 0.1322 0.2735 0.0660 0.1250 0.0894 0.0651 0.3901 0.1054 0.0578 0.0350 0.0610 0.1904 0.0611 Semi-essential amino acids TAU 2.5 ± 3.7 CYS2 1.3 ± 1.4 HIS 0.6 ± 0.8 ARG 2.8 ± 4.4 Total ± 9.1 2.5 ± 3.6 4.2 ± 5.1 1.6 ± 2.8 6.1 ± 11.3 14.4 ± 17.8 3.0 ± 3.3 2.3 ± 2.8 2.0* ± 3.0 4.8 ± 6.6 12.0 ± 13.8 2.3 ± 6.7 1.0* ± 2.4 0.4* ± 0.8 2.8 ± 4.9 6.5 ± 11.1 0.3642 0.1357 0.0475 0.1867 0.1452 0.4689 0.0081 0.0303 0.1173 0.0562 Metabolic indicator amino acids AAA 2.3 ± 2.4 ALA 1.9 ± 2.2 CIT 2.0 ± 2.5 HYC2 1.6 ± 2.3 ORN 3.0 ± 4.7 Total 10.7 ± 11.4 3.9 ± 4.9 2.4 ± 3.2 3.9 ± 5.1 2.0 ± 2.3 4.7 ± 6.7 16.9 ± 17.9 2.9 ± 4.3 2.3 ± 4.2 3.4 ± 5.1 2.2 ± 2.9 4.1 ± 4.6 15.0 ± 16.7 1.2* ± 2.9 0.9 ± 2.6 1.5* ± 2.6 0.7* ± 1.3 1.3* ± 2.6 5.6* ± 10.5 0.3205 0.3676 0.1816 0.2758 0.2720 0.2258 0.0238 0.0753 0.0311 0.0242 0.0179 0.0117 The assay for total cholesterol was done using the enzymatic method, which is an enzymatic colorimetric test with cholesterol esterase and cholesterol oxidase Triglycerides were also assayed using an enzymatic colorimetric test with glycerol phosphate oxidase A high density lipoprotein (HDL) cholesterol precipitating reagent, magnesium sulfate at a concentration of 0.26 mol/l was used to remove low density lipoprotein (LDL) cholesterol, total cholesterol and very low density lipoprotein (VLDL) HDL cholesterol was, then, determined by an enzymatic colorimetric method LDL cholesterol was estimated by using the formula: LDL cholesterol = total cholesterol À (HDL cholesterol + 0.46 · triglyceride) The intra and inter-assay coefficients of variation were 2.2% and 2.6%, respectively, for total cholesterol and 2.2% and 2.2% respectively, for triglycerides [20,21] Amino acid analysis The plasma was separated from heparinized blood samples by centrifugation at °C, and one aliquot was deproteinized with sulfosalicylic acid (10% w/v) as described, and the supernatant was stored along with another aliquot of untreated plasma at À20 °C [13] Individual amino acids were determined on the SSA supernatants by standard procedures using lithium buffer systems on a Beckman 121M Amino Acid Analyzer (Beckman Instruments Inc., Palo Alto, Ca.) No specific measures were taken apart from minimizing the period between sampling and analysis, to assure the stability of glutamine, glutamate and aspartate The values reported reflect this approach to sample handling [16] Tryptophan was analyzed separately 308 F.A Al-Abbasi Aminoacid conc (µg/µl) 12 THR 30 20 r = 0.22 15 10 0 100 200 300 Aminoacid conc (µg/µl) 20 MET 15 r = 0.5 10 100 200 300 14 100 14 12 10 200 300 400 ILE r = 0.15 400 TYR 12 400 Aminoacid conc (µg/µl) r = 0.24 100 200 300 400 PHE 25 20 10 r = 0.11 15 r = 0.16 10 0 100 200 300 400 LEU 12 Aminoacid conc (µg/µl) VAL 10 25 10 100 200 300 400 LYS 50 40 30 20 r= 0.026 r = 0.19 10 0 200 400 Glucose conc (mg/dl) 100 200 300 400 Glucose conc (mg/dl) Fig Correlation analysis for the association between fasting blood sugar and essential amino acids concentrations in plasma of male Saudi diabetic patients and subsequently in trichloracetic acid precipitated plasma and dialysate by a fluorimetric method [17] Data are expressed as mean ± SD Analysis of variance (One-way ANOVA) with Tukey’s post hoc test was used for testing the significance of parametric data using SPSSÒ for windows, version 10.0.1 p < 0.05 was taken as the cut off value for significance Results Assessment of glycemic, lipid profile and biochemical parameters in Saudi diabetic patients In the current study, to evaluate the correlation between glycemic status and amino acid profile in Saudi diabetic patients; fasting serum glucose level was taken as the primary criterion of group segregation into hyperglycemic and normoglycemic patient Patient demographic criteria were assessed and there was no significant difference in mean body mass index (BMI) of different groups, whether among male or female subjects Serum glucose of 140 mg% was considered as cut-off value for hyperglycemia according to the institutional guidelines Obviously, mean blood glucose was found significantly higher in hyperglycemic male and female groups (198.3 ± 71.4 and 228.5 ± 61.6 mg%, respectively) compared to their corresponding normoglycemic groups (108.7 ± 14.7 and 110.6 ± 22.6 mg%, respectively) (Table 1) In general, there were no significant differences in lipid profile parameters between normoglycemic and hyperglycemic corresponding groups with the exception of serum TG Serum Trend of amino acids profile in Saudi diabetic patients 309 Aminoacid conc (µg/µl) 15 THR 10 15 10 Aminoacid conc (µg/µl) r= -0.37 r= -0.35 0 100 200 300 10 400 MET -5 100 200 300 12 400 ILE 10 8 6 r = -0.0014 r= -0.37 2 0 100 200 300 40 Aminoacid conc (µg/µl) VAL 20 -5 400 TYR 30 -2 100 200 20 400 PHE 10 r= -0.34 r= -0.37 10 0 100 200 300 400 100 200 300 400 -5 40 LEU 30 LYS 40 30 20 20 r= -0.36 r= -0.38 10 10 0 -10 300 15 20 -10 Aminoacid conc (µg/µl) 25 100 200 300 400 Plasma glucose conc (mg/dl) -10 100 200 300 400 Plasma glucose conc (mg/dl) Fig Correlation analysis for the association between fasting blood sugar and essential amino acids concentrations in plasma of female Saudi diabetic patients TG in male hyperglycemic patients was elevated to about two folds its concentration in normoglycemic male group at p < 0.05 (Table 1) Also, we assessed several muscle (CK), kidney (BUN), and liver (ALP, AST and ALT) biochemical markers in hyperglycemic and normoglycemic Saudi diabetic patients No significant change in all assessed biochemical parameters was detected with the universal level of significance (p < 0.05) (Table 1) Plasma level of amino acids in Saudi diabetic patients Concentration of several amino acids of different categories (essential, semi-essential and metabolic indicator amino acids) was assessed in plasma of hyperglycemic and normoglycemic diabetic Saudi patients (males and females) Among essential amino acids, MET showed significant increase in plasma concentration of male hyperglycemic patient (3.6 ± 4.4 lg/ml) compared to corresponding normoglycemic group (1.3 ± 2.0 lg/ml) PHE showed significant decrease in plasma concentration of female hyperglycemic patient (1.2 ± 2.3 lg/ml) compared to corresponding normoglycemic group (3.4 ± 4.6 lg/ ml) at p < 0.05 No significant differences in other essential amino acids between hyperglycemic and normoglycemic diabetic Saudi patients at P < 0.05 (males and females) (Table 2) With respect to semi-essential amino acids, plasma concentrations of both CYS2 and HIS were significantly F.A Al-Abbasi Aminoacid conc (µg/µl) 310 TAU 14 12 10 r= 0.02 4 r= 0.16 2 0 Aminoacid conc (µg/µl) CYS 10 100 200 300 HIS 12 r= 0.16 0 100 200 300 100 400 200 300 400 ARG 30 25 20 15 10 10 400 r= 0.12 100 Plasma glucose conc (mg/dl) 200 300 400 Plasma glucose conc (mg/dl) Aminoacid conc (µg/µl) Fig Correlation analysis for the association between fasting blood sugar and semi-essential amino acids concentrations in plasma of male Saudi diabetic patients TAU 35 30 25 20 15 10 CYS2 20 15 10 r= -0.17 r= -0.45 0 100 200 300 400 100 200 300 400 Aminoacid conc (µg/µl) -5 12 50 HIS 10 ARG 40 30 10 -2 r= -0.316 20 r= -0.38 100 200 300 400 Plasma glucose conc (mg/dl) -10 100 200 300 400 Plasma glucose conc (mg/dl) Fig Correlation analysis for the association between fasting blood sugar and semi-essential amino acids concentrations in plasma of female Saudi diabetic patients decreased in female hyperglycemic Saudi patients (1.0 ± 2.4 and 0.4 ± 0.8 lg/ml, respectively) compared to normoglycemic group (4.2 ± 5.1 and 1.6 ± 2.8 lg/ml, respectively) at p < 0.05 On the other hand, plasma concentration of HIS was significantly increased in male hyperglycemic Saudi patients (2.0 ± 3.0 lg/ml) compared to corresponding normoglycemic (0.6 ± 0.8 lg/ml) group at p < 0.05 (Table 2) Interestingly, all metabolic indicator amino acids were significantly decreased in hyperglycemic female patients to about 25– 40% of its level in the corresponding normoglycemic group (p < 0.05) On the contrary, the plasma levels of all metabolic indicator amino acids in male hyperglycemic patients were higher than the corresponding normoglycemic group, however it did not reach the standard level of significance (p < 0.05) (Table 2) Aminoacid conc (µg/µl) Trend of amino acids profile in Saudi diabetic patients AAA 20 20 15 15 10 10 ALA r= 0.303 r= 0.073 0 Aminoacid conc (µg/µl) 311 100 200 300 400 100 200 300 400 20 CIT HCY2 10 15 10 r= 0.02 r= 0.19 0 100 200 300 400 100 200 300 400 Aminoacid conc (µg/µl) Plasma glucose conc (mg/dl) 14 12 10 ORN r= 0.1 100 200 300 400 Plasma glucose conc (mg/dl) Fig Correlation analysis for the association between fasting blood sugar and metabolic indicator amino acids concentrations in plasma of male Saudi diabetic patients Correlation between glucose and amino acids concentration in plasma of Saudi diabetic patients The correlation between plasma level of several amino acids and the glycemic status of diabetic Saudi patients (males and females) was assessed using trend analysis and by calculating the correlation co-efficient (r) Herein, the absolute value of r > 0.5 was considered as strong correlation; r < 0.25 will be described as weak correlation and r ranging from 0.25 to 0.5 will be considered as moderate correlation The sign before r (positive or negative) indicates direct or inverse correlation, respectively In general, there was clear gender difference in the correlation between plasma concentrations of sugar and all categories of amino acids in Saudi diabetic patients; the plasma level of all amino acids directly increased with the sugar concentration in male Saudi diabetic patients while inversely decreased with the increase in sugar concentration in female Saudi diabetic patients There was a positive correlation between all essential amino acids and blood glucose level in male Saudi diabetic patients The correlation of MET in male diabetic patients with blood glucose was strong (r = 0.5), while all other essential amino acids showed weak correlation (r ranging from 0.08 to 0.24) (Fig 1) On the other hand, MET showed almost no correlation with blood glucose level in female diabetic patients (r = À0.0014) All other amino acids were moderately associated with the plasma level of glucose in female diabetic patients (r ranging from À0.33 to À0.37) (Fig 2) In male patients, the correlation of all semi-essential amino acids with serum glucose level was positive but weak with r ranging from 0.02 to 0.17 (Fig 3) On the other hand, the correlation of semi-essential amino acids with serum glucose in female patients showed some diversity (Fig 4) High moderate negative correlation (r = À0.45) was observed between serum CYS2 and blood glucose in female diabetic patients HIS and ARG showed moderate negative correlation with serum glucose with r ranging from 0.32 to À0.37 in female diabetic Saudi patients Only TAU showed weak correlation (r = À0.17) with serum glucose in female Saudi diabetic patients Similar to semi-essential amino acid, all metabolic indicator amino acids showed positive weak to moderate correlation (r ranging from 0.017 to 0.303) with serum glucose in male Saudi diabetic patients (Fig 5) In contrast to male Saudi diabetic patients, all amino acids – except ALA – showed moderate to strong correlation co-efficient in female patients (Fig 6) HCY2 and ORN showed boarder line strong negative correlation with glucose level in female diabetic patients with r = 0.5, respectively AAA and CIT showed moderate negative 312 F.A Al-Abbasi Aminoacid conc (µg/µl) 20 AAA ALA 12 15 10 10 r= -0.2 r= -0.44 -5 0 100 200 300 20 Aminoacid conc (µg/µl) 14 400 CIT 15 100 200 300 400 HCY2 10 r= -0.417 r= -0.5 0 100 200 300 400 100 200 300 400 -2 -5 Aminoacid conc (µg/µl) Plasma glucose conc (mg/dl) ORN 25 20 15 10 r= -0.5 -5 100 200 300 400 Plasma glucose conc (mg/dl) Fig Correlation analysis for the association between fasting blood sugar and metabolic indicator amino acids concentrations in plasma of female Saudi diabetic patients correlation with glucose level in female patients with r = À0.44 and À0.42, respectively Discussion Diabetes mellitus is major metabolic disease that is associated with several disorders such as, microvascular disorders, hypercholesterolemia, obesity, and other nutritional disorders The role of amino acids in DM and its metabolic traits have been suggested previously; however, studied to a very limited scale in some populations such as Saudi patients In the current study, we have assessed the relation between several amino acids of different category and the glycemic status in Saudi diabetic patients Amino acids assessment can reflect and explain several structural, nutritional, physiological, and biochemical complications of DM; nonetheless in a population with such high prevalence of the disease [1] Only serum TG in male hyperglycemic patients was elevated in correspondence with the glycemic status That might be explained by the disturbance in glycolysis associated lipolysis in DM rather than direct relation with plasma glucose level Also, we cannot ignore nutritional implication that might affect serum TG in Saudi diabetic patients The elevated TG level in male rather than female diabetic patients might be attributed to hormonal influence [22] Triglycerides are affected during pregnancy and influenced by sex hormones [23] The elevated level of MET in male diabetic patient, herein, might be an early indicator for impaired MET metabolism and homocystinuria Strong correlation between MET and glycemic status in male diabetic patients rather than female might implicate higher susceptibility of male than female Saudi diabetic patients for homocystinuria In addition, this observation warrants further studies Microvascular complications of DM such as, coronary artery disease, myocardial infarction, peripheral and cerebral vascular occlusive diseases and stroke have been related to homocystinuria [24,25] The negative correlation between essential/semi essential amino acid and glycemic status would suggest trend for bad nutritional habits among female rather than in male Saudi patients In agreement, dietary balance has been an old problem for diabetic patients over decades that warrants careful attention [26,27] On the other hand, Saudi male diabetic patients would be more prone to diabetic microvascular complication secondary to early signs of homocystinuria [28] Trend of amino acids profile in Saudi diabetic patients In the current study, TAU did not show any correlation with the glycemic status in male or female patients of Saudi population Accordingly, no compensatory antioxidant protective machinery would help in the predicted microvascular complications, nonetheless, in male patient with hyperglycemia [29] Interestingly, the negative correlation between ARG and glucose in female Saudi patients would produce similar vascular occlusive complication due to nitric oxide synthesis impairment The extensive role of ARG in cardiovascular function, wound healing hormone release (especially insulin and glucagon) and neurotransmission exceeds the synthetic capacity of human body [30] All metabolic indicator amino acids showed much stronger correlation in female Saudi diabetic patients than in male patients Taking into consideration the metabolic nature of DM, we can explain such a phenomenon However, the stronger correlation in female than in male patients would be suggested to be attributed to sex hormone discrepancies [31] Conclusion We have shown some correlation between the serum level of several amino acids of different categories and glycemic status among Saudi type-1 diabetic patients in a gender dependent manner This study and further studies would be required to provide early vision for predicting some metabolic traits in diabetic patients in the Saudi population Acknowledgment The author would like to thank the Staff of the Institute of Diabetic center, Jeddah for their technical assistance References [1] World Health Organization The global burden of disease: 2004 update Geneva, WHO; 2008 [2] King H, Rewers M Diabetes in adults is now a third world problem The WHO ad hoc diabetes reporting group Bull World Health Organ 1991;69(6):643–8 [3] Alballa SR, Bamgboye EA, al-Sekeit M, Alballaa SR Causes of morbidity among a sample of elderly hospital patients in Riyadh, Saudi Arabia J Trop Med Hyg 1993;96(3):157–62 [4] Keen H, Ng Tang Fui S The definition and classification of diabetes mellitus Clin Endocrinol Metab 1982;11(2):279–305 [5] Wolffenbuttel BH Type diabetes mellitus Aspects of complications and treatment Neth J Med 1993;43(3–4):187–99 [6] Wahren J, Johansson BL, Wallberg-Henriksson H Does Cpeptide have a physiological role? Diabetologia 1994;37(Suppl 2):S99–S107 [7] Cameron FJ, Baghurst PA, Rodbard D Assessing glycemic variation: why, when and how? Pediatr Endocrinol Rev 2010;7(Suppl 3):432–44 [8] Thompson MR The role of amino acids in health and disease Westchester Med Bull 1946;14(5):9–14 [9] Chen H, Zhou X, Ou-Yang ZC Classification of amino acids based on statistical results of known structures and cooperativity of protein folding Phys Rev E Stat Nonlin Soft Matter Phys 2002;65(6 Pt 1):061907 [10] Litwack G, Fisher H Role of essential amino acids in the early formation of avian liver xanthine dehydrogenase activity Am J Physiol 1957;191(2):355–8 313 [11] Deschepper K, De Groote G Effect of dietary protein, essential and non-essential amino acids on the performance and carcase composition of male broiler chickens Br Poult Sci 1995;36(2): 229–45 [12] Weil-Malherbe H, Krebs HA Metabolism of amino-acids: the conversion of proline into glutamic acid in kidney Biochem J 1935;29(9):2077–81 [13] Tessari P, Cecchet D, Cosma A, Puricelli L, Millioni R, Vedovato M, et al Insulin resistance of amino acid and protein metabolism in type diabetes Clin Nutr 2011;30(3):267–72 [14] Bassil M, Burgos S, Marliss EB, Morais JA, Chevalier S, Gougeon R Hyperaminoacidaemia at postprandial levels does not modulate glucose metabolism in type diabetes mellitus Diabetologia 2011;54(7):1810–8 [15] Das UN, Repossi G, Dain A, Eynard AR L-arginine, NO and asymmetrical dimethylarginine in hypertension and type diabetes Front Biosci 2011;16:13–20 [16] Gerok W, Nieth H Quantitative amino acid determination in the blood serum and urine in kidney diseases Verh Dtsch Ges Inn Med 1959;65:639–43 [17] Gaitonde MK A fluorimetric method for the determination of tryptophan in animal tissues Biochem J 1974;139(3):625–31 [18] Bergmeyer HU, Scheibe P, Wahlefeld AW Optimization of methods for aspartate aminotransferase and alanine aminotransferase Clin Chem 1978;24(1):58–73 [19] Savdie E, Grosslight GM, Adena MA Relation of alcohol and cigarette consumption to blood pressure and serum creatinine levels J Chronic Dis 1984;37(8):617–23 [20] Friedewald WT, Levy RI, Fredrickson DS Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge Clin Chem 1972;18(6):499–502 [21] Rautela GS, Liedtke RJ Automated enzymic measurement of total cholesterol in serum Clin Chem 1978;24(1):108–14 [22] Dayspring TD, Pokrywka G Impact of triglycerides on lipid and lipoprotein biology in women Gend Med 2010;7(3):189–205 [23] Herrera E, Ortega-Senovilla H Disturbances in lipid metabolism in diabetic pregnancy – are these the cause of the problem? Best Pract Res Clin Endocrinol Metab 2010;24(4):515–25 [24] Selhub J, Jacques PF, Bostom AG, D’Agostino RB, Wilson PW, Belanger AJ, et al Association between plasma homocysteine concentrations and extracranial carotid-artery stenosis New Engl J Med 1995;332(5):286–91 [25] Brattstrom L, Lindgren A, Israelsson B, Malinow MR, Norrving B, Upson B, et al Hyperhomocysteinaemia in stroke: prevalence, cause, and relationships to type of stroke and stroke risk factors Eur J Clin Invest 1992;22(3):214–21 [26] Albarran NB, Ballesteros MN, Morales GG, Ortega MI Dietary behavior and type diabetes care Patient Educ Couns 2006;61(2):191–9 [27] Sorenson AW, Wyse BW, Wittwer AJ, Hansen RG An index of nutritional quality for a balanced diet New help for an old problem J Am Diet Assoc 1976;68(3):236–42 [28] van Guldener C, Stehouwer CD Hyperhomocysteinemia, vascular pathology, and endothelial dysfunction Semin Thromb Hemost 2000;26(3):281–9 [29] Gossai D, Lau-Cam CA The effects of taurine, taurine homologs and hypotaurine on cell and membrane antioxidative system alterations caused by type diabetes in rat erythrocytes Adv Exp Med Biol 2009;643:359–68 [30] Wu G, Meininger CJ, Knabe DA, Bazer FW, Rhoads JM Arginine nutrition in development, health and disease Curr Opin Clin Nutr Metab Care 2000;3(1):59–66 [31] Meyer MR, Clegg DJ, Prossnitz ER, Barton M Obesity, insulin resistance and diabetes: sex differences and role of oestrogen receptors Acta Physiol (Oxf) 2011;203(1):259–69 ... of amino acids in Saudi diabetic patients; the plasma level of all amino acids directly increased with the sugar concentration in male Saudi diabetic patients while inversely decreased with the. .. metabolic indicator amino acids concentrations in plasma of male Saudi diabetic patients Correlation between glucose and amino acids concentration in plasma of Saudi diabetic patients The correlation. .. normoglycemic and hyperglycemic corresponding groups with the exception of serum TG Serum Trend of amino acids profile in Saudi diabetic patients 309 Aminoacid conc (µg/µl) 15 THR 10 15 10 Aminoacid conc (µg/µl)