Iraqi J Pharm Sci, Vol.23(2) 2014 Lipid profile , fasting blood sugar and colelithiasis 51 Lipid Profile and Fasting Blood Sugar Analysis in Patients with Cholelithiasis Rajaa N.Al-Atrakchey * , Mohammed A.Taher **,1 and Ibtehal N.Saeed ** * Imam Al – Hussein Medical City ,Karbala ,Iraq. ** Department of Clinical Laboratory Sciences, College of Pharmacy, University of Baghdad,Baghdad,Iraq. Abstract Cholelithiasis is one of the commonest surgical problems and one of the most common gastrointestinal diseases throughout the world but its pathogenesis remains unclear. Many theories have been proposed forward to explain the mechanism of stone formation. It is not fully clear if symptomatic gallstone disease is associated with a specific pattern of some biochemical abnormalities, as lipid profile and fasting blood sugar in serum of patients. This study was designed to estimate lipid profile and fasting blood sugar in the sera of patients with cholelithiasis in comparison with normal individuals (control). In this study, 104(male=16, female=88) were symptomatic gallstone patients (aged 42.79± 12.18 years), and 38(male=6 and female=32) were apparently healthy controls (aged 40.03± 7.47 years). Blood samples were collected from symptomatic gallstones patients before their cholecystectomy operation. Over night fasting, blood samples were collected from all subjects to evaluate serum lipid profile: Total cholesterol (TC), triglyceride (TG), high density lipoprotein-cholesterol (HDL-c), low density lipoprotein-cholesterol (LDL-c), very low density lipoprotein-cholesterol (VLDL-c) and fasting serum glucose (FSG). There was a significant increase (P<0.05) in serum: TC, TG, LDL-c, VLDL-c and FSG of patients with cholelithiasis compared to the apparently healthy controls. The study also showed that there was a significant decrease (P<0.05) in serum HDL-c in gallstone patients compared to control. In conclusion, cholelithiasis was associated with lipid profile and fasting serum glucose abnormality that be the cause or the effect of gallstone formation. These findings should be taken into consideration while treating gallstone patients. Key words: Gallstones, Cholesterol, Cholecystectomy. صيغت اندهىٌ ويستىي سكر اندو انصبئى عُد انًرضً وانًصببيٍ بحصً انًرارةتحهيم رجبء َعًت اييٍ االطرقجٍ * ، يحًد عببس طبهر **،1 و ابتهبل َىرٌ سعيد ** * .،مشبالء،اىؼشاقاىحسٍِ اىطبٍت االٍبً ٍذٌْت ** . فشع اىؼيً٘ اىَخخبشٌت اىسشٌشٌت ، ميٍت اىصٍذىت ، خبٍؼت بغذاد ،بغذاد ،اىؼشاق الخالصة ٌؼذ ٍشض حصى اىصفشاء أحذ اىَشبمو اىدشاحٍت اىشبئؼت ٗٗاحذا ٍِ اٍشاض اىدٖبص اىٖعًَ االمثش شٍ٘ػب ح٘ه اىؼبىٌ ىنِ بشنو ٗاظح أّ ٍِ غٍش اىَؼشٗف . ٗقذ ٗظؼج اىنثٍش ٍِ اىْظشٌبث ىخ٘ظٍح آىٍت حشنو اىحصبة. اٍشاظٍخٔ ٌنخْفٖب بؼط اىغَ٘ض فً ٗ سنش اىذً فً حبىت اىصٍبً ٍسخٌ٘بث شحً٘ اىذً ٍثو اىخغٍشاث اىنٍٍَبئٍت اىحٌٍ٘ت اسحببغ ٍشض حصى اىصفشاء بَْػ ٍؼٍِ ىبؼط فً ٍصو اىَشظى اىزٌِ ٌؼبُّ٘ ٗ سنش اىذً فً حبىت اىصٍبً ٍسخٌ٘بث اىشحًٕ٘زٓ اىذساست ىَؼشفت ٗقذ حٌ حصٌٍَ .ٍصو دً اىَشظى (. ٍدَ٘ػت اىسٍطشة)ٍغ االشخبص االصحبء ٍِ حصى اىصفشاء ٍقبسّت سْت ، 12.18± 42.79 اسٌٌَٕثيُ٘ ٍدَ٘ػت اىَشظى ٍؼذه اػٌ( رم٘س 16اّثى ٗ 88)ٍئت ٗاسبؼت اشخشك فً ٕزٓ اىذساست . سْت 7.47± 40.03 ٌَثيُ٘ ٍدَ٘ػت اىسٍطشة ٍؼذه اػَبسٌٕ( رم٘س 6اّثى ٗ 32)ٗثَبٍّت ٗثالثُ٘ . ػٍْبث اىذً حٌ خَؼٖب ٍِ ٍشظى حصى اىصفشاء قبو ػَيٍت اسخئصبه اىَشاسة ، اىذُٕ٘ ( TC)اىن٘ىٍسخشٗه اىنيً :شحً٘ اىَصو ش٘اموػٍْبث اىذً حٌ سحبٖب ٍِ اىَشظى ٗاالصحبء بؼذ اىصً٘ ىٍال ىقٍبس اىَشحبػ اىبشٗحٍِ اىشحًَ رٗ اىنثبفت اى٘اغئت, ( HDL-C)اىَشحبػ ببىن٘ىسخشٗه اىبشٗحٍِ اىشحًَ رٗ اىنثبفت اىؼبىٍت، ( TG)اىثالثٍت س اىذً فً حبىت ، ٗسل ( VLDL-C)خذا اىَشحبػ ببىن٘ىسخشٗه اىبشٗحٍِ اىشحًَ رٗ اىنثبفت اى٘اغئت , ( LDL-C)ببىن٘ىسخشٗه (. (FSG اىصٍبً ٗم٘ىسخشٗه اىبشٗحٍِ اىشحًَ رٗ اىنثبفت اى٘اغئت اىن٘ىٍسخشٗه اىنيً ٗاىذُٕ٘ اىثالثٍت: فً ٍصو اىذً (P <0.05)ٗخذث صٌبدة ٍؼٌْ٘ت اىَشاسة ٍقبسّت فً اىَشظى اىزٌِ ٌؼبُّ٘ ٍِ حصى ٗ سنش اىذً فً حبىت اىصٍبًخذا ٗم٘ىسخشٗه اىبشٗحٍِ اىشحًَ رٗ اىنثبفت اى٘اغئت اىذً ىن٘ىسخشٗه اىبشٗحٍِ اىشحًَ رٗ اىنثبفت اىؼبىٍت فً ٍصو (p<0.05)مَب اظٖشث اىذساست ٗخ٘د اّخفبض ٍؼْ٘ي .ببألصحبء حبىت اىصٍبً ٗ سنش اىذً فًحصى اىَشاسة ٍشحبػ بخغٍش ٍسخٌ٘بث شحً٘ اىذً ّسخْخح اُ ٍشض . ّفس اىَشظى ٍقبسّت ببألصحبء فً . ٌْبغً أُ حؤخز ٕزٓ اىْخبئح بؼٍِ االػخببس أثْبء ػالج ٍشظى حصى اىَشاسة ىزا. اىحصبةىخنٌِ٘ اىخً قذ حنُ٘ ّبحدت اٗ ٍسببت .استئصبل انًرارة, كىنسترول , حصً انًرارة : انكهًبث انًفتبحيت 1 Corresponding author E-mail:sad5554@yahoo.com Received:1 /3/2014 Accepted:28 /9/2014 Iraqi J Pharm Sci, Vol.23(2) 2014 Lipid profile , fasting blood sugar and colelithiasis 52 Introduction The presence of stones in the gallbladder is referred to as cholelithiasis (from the Greek: chol, "bile" + lith-, "stone" + iasis-, "process") (1) . Cholelithiasis or Gallstone disease (GD), is one of the most prevalent gastrointestinal diseases, with a substantial burden to health care systems (2) . Gallstones (GS) are abnormal masses of a solid mixture of cholesterol crystals, mucin, calcium bilirubinate, and proteins that have affected people for centuries (3) . Gallstone formation is multifactorial, and known risk factors are advancing age, female gender, genetics- ethnicity, obesity, rapid weight loss, diet, drugs, and activity (4) . The association of gallbladder (GB) stone disease with metabolic abnormalities such as diabetes, dyslipidemia, obesity, and hyperinsulinemia has supported the hypothesis that GB stone formation is a type of metabolic syndrome (5,6) . Gallstones are classified as cholesterol, pigmented or mixed stones based on their chemical composition (7,8) . The role of serum lipid in the etiology of cholelithiasis is very important and particularly in cholesterol gallstones in which serum lipid profile are altered which is suggestive of metabolic syndrome. Research suggests that metabolic syndrome is a risk factor for gallstones (9) . Low levels of high-density lipoprotein cholesterol (HDL-c) and high triglycerides are associated with gallstone disease (10) . Cholecystectomy is the standard and definitive treatment for symptomatic gallbladder stones and can be performed regardless of the type, number, and size of the stones (11,12) . It is effective and safe, with low rates of complications (14%) and mortality (0.17%). For cholesterol gallstones, current medical treatment includes: litholytic therapy (stone dissolution) by oral bile acid litholysis with chenodeoxycholic acid and/or ursodeoxycholic acid (UDCA) (13,14) , and lithotripsy (stone shattering) (15) . The aim of our study is to evaluate the biochemical changes in some serum parameters (lipid profile and fasting serum glucose) in gallstone patients compared to controls. Subjects and Methods The study was carried out on patients with clinical and imaging features confirming symptomatic cholelithiasis admitted to Imam AL-Hussein Medical City, Safeer AL-Hussein Surgical Center and Maitham AL-Tammar Surgical Hospital in Karbala City from February to October 2013. Patients with symptomatic gallstones had a history of (pain located in the epigastrium and/or right upper quadrant; recurrent symptoms occurring at different intervals; and episodes lasting 30 minutes or more. The pain may present with one or more of the following: associated nausea and vomiting; radiating to the back and/or right infrasubscapular region; and causing one to awaken from sleep in the middle of the night (16) , an abdominal ultrasonography is the standard diagnostic test for gallstone detection (17) ). A total number of 104 patients were included in this study, among which 88 females and 16 males in age group ranged between 18-75 years with a mean ±SD (42.79 ± 12.18). These were compared with 38 (age and sex matched) healthy controls (32 females, 6 males), with mean age ±SD (40.03 ± 7.47). The patients were selected not have liver cirrhosis, viral hepatitis, renal failure, thyroid disease, asthma and diabetes mellitus nor Pancreatitis and Gallbladder cancer nor those taking anti- hyperlipidemic drugs that may interfere with the data obtained. Samples cllection After an overnight fasting, 5 milliliters venous blood samples were collected from patients before laparoscopic cholecystectomy and from healthy volunteers in plain tubes. After allowing the blood to clot at room temperature for about 30 minutes, blood samples were centrifuged at 5000 rpm for about 5 minutes to obtain serum. The serum samples were stored at -20 0 C until analysis was performed. Biochemical assay methods Biochemical assay was done at Imam AL- Hussein Medical City, laboratory department using ARCHITECT plus, Abbott4000, Automated auto-analyzer. The assay was include: serum total cholesterol (18) , serum triglyceride (19) , serum high density lipoprotein-cholesterol (20) , serum low density lipoprotein-cholesterol and very low density lipoprotein-cholesterol were calculated using Friedewald formula (21) , and serum glucose level (22) . Statistical analysis The following statistical data analysis approaches were done through the Statistical Package for Social Sciences (SPSS 17) and Excel application were used in order to analyze and assess the results of the study (23) :  Statistical tables.  Mean value and standard deviation (SD).  Bivariate comparisons were examined for parameters using pearson rank correlation coefficients (r). Iraqi J Pharm Sci, Vol.23(2) 2014 Lipid profile , fasting blood sugar and colelithiasis 53  Graphical presentation.  Student's t-test was used to examine the degree of significance. P values less than 0.05 was considered significant. Results Table (1) and figures (1), (2) and (3) showed that the levels of total cholesterol, LDL, VLDL, TG, and fasting serum glucose were significantly higher (p<0.05), while the levels of HDL were significantly lower (p<0.05) in the sera of gallstone patients in comparison with healthy control group. Table (1): Serum lipid profile and Fasting serum glucose in gallstone patients and controls. Data are expressed as mean ±SD (standard deviation), N=number of patients or controls. TG: triglyceride, HDL: high density lipoprotein, LDL: low density lipoprotein, VLDL: very low density lipoprotein and FBS: fasting serum glucose. P <0.05 : significant. Figure 1: Mean serum total cholesterol (cholesterol), triglyceride (TG) and low density lipoprotein (LDL) in patients with cholelithiasis and healthy controls (milligram per deciliter). Figure 2: Mean serum high density lipoprotein (HDL) and very low density lipoprotein (VLDL) in patients with cholelithiasis and healthy controls (milligram per deciliter). Figure 3: Mean of serum fasting blood sugar (FBS) in patients with cholelithiasis and healthy controls (milligram per deciliter). Parameters/ (mg/dl) mean ± SD Patients N=104 Controls N=38 P- value Total cholesterol 197.64 ± 49.68 178.78 ± 37.60 <0.05 TG 180.006 ± 50.00 159.71 ± 25.12 HDL 46.78 ± 11.062 52.59 ± 8.53 LDL 115.76 ± 37.694 97.24 ± 21.015 VLDL 36.83 ± 17.82 30.20 ± 7.82 FSG 112.73 ± 25.53 101.88 ± 28.50 Iraqi J Pharm Sci, Vol.23(2) 2014 Lipid profile , fasting blood sugar and colelithiasis 54 Table (2): Pearson rank correlations between parameters. *Significant at P <0.05 and ** high significant at P <0.01 Table (2) showed that there were positive correlations between:  serum total cholesterol and TG (r= 0.323, P< 0.05), serum total cholesterol and LDL (r= 0.76, P< 0.05), and serum total cholesterol and VLDL (r= 0.42, P< 0.05).  serum TG and VLDL (r= 0.53, P< 0.05).  serum LDL and VLDL (r= 0.24, P< 0.05). Discussion The present study observe low serum HDL levels and high serum triglyceride, total cholesterol and LDL levels in patients with cholelithiasis which is in agreement with other studies (24,25) , Virupaksha HS et al (10) , Channa NA et al, found that lipids elevation in cholelithiasis, seems to play a major contributing role in the pathogenesis of gallstones in females of up to 45 years age (25) . The elevation of serum total cholesterol and TG levels in patients may be due to: Gallstone patients have abnormal secretory mechanism for bile acids and phospholipids, decrease bile acids and phospholipids (which solubilize cholesterol in the bile) will increase cholesterol precipitation (26) ,and some of gallstone patients may present with metabolic syndrome which is a cluster of symptoms such as glucose intolerance, high total cholesterol, hyperinsulinemia, increased VLDL and/or total cholesterol, decrease HDL and hypertension who indicate that the metabolic syndrome is one of the risk factors for gallstone disease (27) . Previous study described a decrease in HDL in gallstone patients, and there will be a return to the normal condition after gallstone removal (28) . The high LDL was seen in gallstone patients in this study either due to abnormal secretary function and/or prolonged high fatty diet and agree with Zhao et al (26) , and down regulation of LDL-ApoB receptors by inhibition of LDL-ApoB receptor gene expression (29) . Hyperlipidemia are strong risk factors in cholelithiasis as estimated previously (30) . Life style and dietary modification are effective measures for the prevention of cholelithiasis (31) . The previous observation indicate that medications used to treat dyslipidemia may be of value in the prevention and treatment of cholelithiasis (32) . There was significant positive correlation (r= 0.53, P<0.05) between serum VLDL and TG in patients with cholelithiasis in the present study. Cholelithiasis is associated with hypertriglyceridemia (10,33) . Hypertriglyceridemia is associated with decreased HDL-cholesterol (HDL-c) and increased small dense LDL (34) . LDL particles are formed as VLDL lipoproteins lose triglyceride through the action of lipoprotein lipase and they become smaller and denser (fewer fat molecules with same protein transport shell), containing a higher proportion of cholesterol esters (35,36) . A positive correlation (r = 0.32, P< 0.05) between serum Parameters (mg/dl) T . c h o le st e r o l T G H D L L D L V L D L F B S T. cholesterol 1 .323 ** .127 .760 ** .427 ** -.030- .000 .140 .000 .000 .725 TG .323 ** 1 .060 .123 .532 ** .123 .000 .489 .155 .000 .153 HDL .127 .060 1 -.012- -.006- -.044- .489 .894 .944 .610 LDL .760 ** .123 -.012- 1 .243 ** -.023- .000 .155 .894 .004 .786 VLDL .427 ** .532 ** -.006- .243 ** 1 .067 .000 .000 .944 .004 .440 FBS -.030- .123 -.044- -.023- .067 1 .725 .153 .610 .786 .440 http://en.wikipedia.org/wiki/VLDL http://en.wikipedia.org/wiki/Lipoprotein_lipase http://en.wikipedia.org/wiki/Lipoprotein_lipase http://www.rpi.edu/dept/bcbp/molbiochem/MBWeb/mb2/part1/lipoprot.htm Iraqi J Pharm Sci, Vol.23(2) 2014 Lipid profile , fasting blood sugar and colelithiasis 55 triglyceride and serum total cholesterol in patients with cholelithiasis was observed in the present study, which is in agreement with the other study demonstrated that there was a significant positive correlation between total cholesterol and TG levels (37) . In present study, fasting serum glucose (FSG) was significantly higher (p<0.05) in gallstone patients compared to healthy controls, in agreement with other studies performed by Simona Tîrziu, et al. (38) and Jindal N, et al. (39) "they reported that fasting glucose levels were significantly increased in gallstone patients as compared to controls". Gallstone disease appeared strongly associated with fasting glycemia (40) . There was a positive correlation between prevalence of gallstone with higher fasting glucose. The possible mechanisms for this association may be as follows: hyperglycemia inhibits bile secretion from the liver and disturbs gallbladder contraction (41) . Gallstone disease appears to be strongly associated with metabolic syndrome, and the more the components of metabolic syndrome, the higher the prevalence of gallstone disease, and elevated fasting blood glucose is one of component of metabolic syndrome that associated with gallstone disease (42) . 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