|Year : 2013 | Volume
| Issue : 2 | Page : 97-101
Effect of cholelithiasis and cholecystectomy on serum lipids and blood glucose parameters
Neha Jindal, Gurjit Singh, Iqbal Ali, Gaurav Sali, Raghuveer Reddy
Department of General Surgery, Padm. Dr. D.Y. Patil Hospital and Research Centre, Pimpri, Pune, Maharashtra, India
|Date of Web Publication||13-Dec-2013|
Department of General Surgery, Padm. Dr. D.Y. Patil Hospital and Research Centre, Pimpri, Pune - 411 018, Maharashtra
Source of Support: None, Conflict of Interest: None
Background: Association between gallstone disease (GSD) and dyslipidemia has been shown in many studies. The aim of this study was to compare the serum lipid and serum glucose levels in patients with and without gallstone and also to determine changes in same parameters in gallstone patients before and after cholecystectomy.
Materials and Methods: A total of 71 patients with gallstone (Group A) and 96 without gallstone (Group B) were studied prospectively. Patients in both groups were investigated for GSD. Total cholesterol (TC), triglycerides (TG), high density lipoprotein cholesterol (HDL-c), low density lipoprotein cholesterol (LDL-c), atherogenic index (AI) and fasting glucose (FG) levels were estimated in both groups pre-operatively. Further, same parameters were studied in Group A post-operatively at 1 week and 1 month intervals.
Results: The serum levels of TC, TGs, LDL-c, AI and FG were found to be higher and levels of serum HDL-c were lower in gallstone patients than that of the control group, though not statistically significant. In patients with gallstone, significant decrease in TC, LDL-c, TG, AI and increase in HDL-c levels were observed post-cholecystectomy at both intervals. Post-operatively, rise in serum glucose levels at 1 week interval and decrease at 1 month interval were noticed in patients with GSD.
Conclusion: GSD is associated with abnormal lipid profile and serum glucose. Cholecystectomy leads to a significant decrease in these parameters except HDL-c in patients with GSD. The presence of gall stones should be perceived in the context of metabolic disorder, which may be investigated and treated. Asymptomatic gallstone patients may also be treated surgically resulting in improvement of above mentioned biochemical parameters.
Keywords: Cholecystectomy atherogenic index, cholesterol, dyslipidemia, gall stone disease, metabolic syndrome, triglycerides
|How to cite this article:|
Jindal N, Singh G, Ali I, Sali G, Reddy R. Effect of cholelithiasis and cholecystectomy on serum lipids and blood glucose parameters. Arch Int Surg 2013;3:97-101
|How to cite this URL:|
Jindal N, Singh G, Ali I, Sali G, Reddy R. Effect of cholelithiasis and cholecystectomy on serum lipids and blood glucose parameters. Arch Int Surg [serial online] 2013 [cited 2019 Nov 22];3:97-101. Available from: http://www.archintsurg.org/text.asp?2013/3/2/97/122926
| Introduction|| |
Gallstones are major public health problem today as most of them are detected incidentally  and only few patients present with acute complication of gallstones.  The types of gallstone include cholesterol gallstones, pigment gallstones and mixed gallstones. Major constituent of gallstones are cholesterol and bilirubin (conjugated and unconjugated bilirubin). ,,
The constitutional risk factors for cholesterol gallstones include female gender, , increasing age  and interaction between genetic and environmental factors.  Gall stones are associated with metabolic syndrome, which is defined as a cluster of multiple cardiovascular risk factors including central obesity, elevated fasting plasma glucose, high blood pressure, lower high density lipoprotein-cholesterol (HDL-c) and higher serum triglyceride (TG) levels.  Supersaturation of bile in cholesterol, enhanced nucleation of cholesterol crystals, impaired gallbladder emptying with stasis and intestinal hypomotility are the pathogenetic mechanisms responsible for cholesterol gallstone formation. 
There is a paucity of information on association of abnormal lipid profile parameters and serum glucose levels with gallstone disease (GSD) in Western India as earlier studies were carried out in other parts of the country.  Therefore, this study was undertaken to compare some serum lipid parameters including total cholesterol (TC), HDL-c, low density lipoprotein cholesterol (LDL-c), TG, atherogenic index (AI) and serum glucose levels in patients with and without GSD and effect of cholecystectomy on same.
| Materials and Methods|| |
This prospective study was conducted in the department of general surgery in our hospital from 2011 to 2012. It included 71 patients with GSD (Group A) and 96 controls without GSD (Group B) comprising of patients reporting for elective surgical procedures such as hernia, hydrocele, breast lesions, fissure-in-ano, fistula-in-ano, hemorrhoids, varicose veins and investigation for abdominal pain. Patients on lipid lowering agents and patients with renal failure, nephrotic syndrome, pancreatitis, cardiac failure, morbid obesity, hypothyroidism, sickle cell disease, hemoglobinopathies and pregnancy were excluded from both groups. Ethical approval was obtained from Institutional Ethical Committee before the commencement of the study. Patients consent was also obtained. All patients were examined and investigated for GSD based on the clinical grounds. Findings suggestive of cholelithiasis were confirmed on abdominal and pelvic ultrasound scan.
Serum fasting glucose (FG) levels and some lipid profile parameters were estimated in both groups pre-operatively by the under mentioned methods. Group A patients were additionally followed-up at 1 week and 1 month intervals post-operatively for estimation of serum FG, serum TC, TG, LDL-c, HDL-c and AI.
Fasting venous blood samples (3 ml) were collected under strict aseptic precautions and allowed to clot in plain tube. Serum was separated by centrifugation at 3000 rpm for 3 min and divided into two portions:
- A portion of 0.5 ml of serum taken in a plain tube for glucose estimation.
- Remaining serum used for estimation of lipid profile parameters.
Serum TC, TG, HDL-c and LDL-c levels were estimated by enzymatic end point method and serum FG was estimated by glucose-oxidase colorimetric method, using a kit supplied by Aspen Laboratories, which is in collaboration with Teco Diagnostics, USA and kit supplied by ERBA Mannheim German Company, manufactured by Transasia Bio-Medicals Limited in India, respectively. Transasia spectrophotometer was used to measure absorbance at 505 nm for TC, TG and FG and 600 nm for LDL-c.
AI was calculated using the equation:
AI = TC/HDL-c.
Results were tabulated, analyzed and subjected to statistical analysis. Chi-square test was used to ascertain any significant difference in the age group between study group and controls. Two-sample t-test was used to determine any significant difference in lipid profile between the study group and controls. Paired t-test was used to compare changes in lipid profile in the study group from pre-operative levels to 1 week post-operative and 1 month post-operative levels. A P < 0.05 was considered as statistically significant. Repeated measures of analysis of variance were used to see significant changes in varying parameters post-operatively in GSD group.
| Results|| |
Group A with 71 cases comprised of 42 females and 29 males, with male to female ratio of 1:1.4 while Group B with 96 controls consisted of 54 females and 42 males with male to female ratio of 1:1.2. Age ranged from 5 to 90 years in both groups [Table 1]. Average body mass index (BMI) of Group A and Group B was 26.45 kg/m 2 and 24.33 kg/m 2 , respectively.
On comparing lipid profile parameters and serum FG levels of individuals with (Group A) and without GSD (Group B), higher levels of serum TC, serum LDL-c, serum TG, AI and Lower levels of serum HDL-c were noticed in individuals with GSD though not statistically significant (P > 0.05). Furthermore, higher level of FG was noticed in individuals with GSD, though not statistically significant [Table 2].
In this study, out of 71 patients in Group A, 43 (60.56%) had one or other abnormal parameters in their lipid profile before cholecystectomy. Cholesterol was raised in 8.45% of patients. TG was raised in 25.35% of patients. Increased level of LDL-c was seen in 15.49% of patients and HDL-c was low in 11.26% of patients [Table 3]. However, among 60.56% of patients with abnormal parameters, rise in both TC and TG was seen in 2.81%, increase in TG with a decrease in HDL-c was seen in 4.22% and rise in both TG and LDL-c was seen in 5.63% of patients.
|Table 2: Lipid profi le parameters and fasting blood glucose in groups A and B|
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On comparing the changes in lipid profile parameters and serum FG levels in gallstone patients before and after cholecystectomy, significant decrease in serum TC, LDL-c and AI at 1 week interval was seen. However, decrease in TG with increase in HDL-c was noticed at 1 week interval post-operatively, though not significant. Significant decrease in serum TC, serum LDL-c, serum TG, AI and significant increase in serum HDL-c levels (P < 0.001) were noticed at 1 month interval post-operatively. There was a rise in serum FG levels at 1 week interval post-operatively. However, there was a significant decrease (P < 0.001) at 1 month interval post-operatively [Table 4].
|Table 4: Lipid profi le parameters and fasting blood glucose in the study group A pre-operatively, 1-week post-operatively and 1 month post-operatively|
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| Discussion|| |
In our study, the prevalence of GSD was higher in females than in males. This is in agreement with other studies , in which number of pregnancies and estrogen are attributed as causes for the gender difference. Estrogen increases biliary cholesterol secretion causing cholesterol supersaturation of bile.  However, one of the studies showed higher prevalence in men than in women.  Majority of studies conducted in the West concluded that women are more prone to develop cholelithiasis  as compared with men while studies in Asian patients have failed to identify gender related difference.  Liu et al.  found a higher incidence of cholelithiasis in men than in women below 50 years of age, but a higher incidence in women than in men in age groups above 50 years. In our study, high incidence of GSD was seen in middle age group (41-50 years). In certain studies, an older age has been found as a significant risk factor for GSD. , Long-term exposure to risk factors and sedentary activity, which is greater in elderly than younger population  are the causes for the same. According to Kaechele et al.  GSD is virtually absent in children and adolescents aged 8-19 years. However, in our study 4.22% of subjects belonging to study group were found to have GSD. Idiopathic cholelithiasis could be the reason for same. However, no hemolytic disorder or obesity was detected. Obesity is an important risk factor for GSD, more so for women than for men, especially considering that women with a BMI of 30 kg/m 2 or more have at least twice the risk of GSD as women with a BMI of less than 25 kg/m 2 .  However, in our study, BMI was less than 30 kg/m 2 . BMI and waist circumference have a significant association with higher risk of cholesterol gallstone. 
In the present study, mean concentrations of TC, LDL-c, TG and AI are found to be higher and that of HDL-c are found to be lower in patients with GSD as compared with the controls, though statistically not significant. Similar findings have been quoted in other studies. ,, The serum levels of HDL-c and lipoprotein in gallstone patients were found to be lower than that of the control group, whereas TC, TG and LDL-c concentrations were observed to be higher in gallstone patients than controls.  In this study, raised serum concentrations of TC seen in gallstone patients before cholecystectomy is in accordance with results of other studies. ,, This may be due to abnormal secretory mechanisms for bile acids and phospholipids.  Apart from this, some gallstone patients may present with metabolic syndrome, which is one of the risks factors for GSD. 
Serum concentrations of TC were significantly reduced in patients after cholecystectomy at 1 week interval and 1 month thereafter. Similar findings have been noticed in other studies. , This can be explained as TC is the precursor for bile acids, following cholecystectomy there is a significant increase in bile acids and phospholipids secretion rate leading to improvement in bile composition and a significant reduction in bile acids pool occurring due to rapid cycling around the enterohepatic circulation/hour, leading to reduction in serum TC.  Apart from this, up-regulation of Apo B/E receptors increases the entrance of cholesterol and other types of fat from blood into hepatocytes leading to formation of more bile acids. 
The significant rise in serum HDL-c in both time intervals following cholecystectomy when compared to pre-operative levels, which were decreased in gall stone patients in our study is in agreement with other studies , describing it as a decrease in HDL receptors activity in hepatocytes pre-operatively. This has been explained by the fact of abnormal secretory mechanisms for bile acids and phospholipids in gallstone patients before surgery.  The significant reduction in LDL-c following cholecystectomy at 1 week and 1 month intervals as compared to that before surgery is in accordance with findings of other studies. , The higher levels seen before cholecystectomy may be due to abnormal secretory function  or down-regulation of LDL-ApoB receptors by inhibition of LDL-ApoB receptor gene expression  or prolonged high fatty diet.  Furthermore, the gradual increase in lipoprotein lipase activity and hepatic lipase activity in gall stone patients may be considered. 
The significant reduction in LDL-c that was seen in gall stone patients in both time intervals after the operation can be attributed to the increase in bile acids and phospholipids secretion rate after cholecystectomy and up-regulation of LDL-ApoB receptors that leads to the increase entrance of LDL particles into the hepatocytes.  Inside the hepatocytes LDL-c particles bind to Lysosomes leading to delivery of more cholesterol into the intracellular cholesterol pool that synthesize bile using serum cholesterol as a precursor, in this condition, LDL-c will be reduced steadily after cholecystectomy. 
The significant decrease in TG at 1 week and 1 month intervals following cholecystectomy in our study is also found in another study.  The higher concentrations of TG seen before cholecystectomy may be due to abnormal secretory mechanisms  or signs of metabolic syndrome.  The significant decrease after cholecytectomy may be due to an increase in the bile acids and phospholipids secretion rate  or an increase in hepatic lipase activity that hydrolyses chylomicron and very low density lipoprotein (VLDL) to glycerol and free fatty acids, thus, leading to a decrease in TG that occurs after 1 month.  However, certain studies show a significant increase in TG after 1 week of surgery, which may be due to catabolic phase of trauma using TG as a source of energy due to the limited amount of carbohydrates or increased lipolysis due to surgical trauma and significant reduction after 1 month of surgery, may be due to increase in bile acids and phospholipids secretion rate or increase in hepatic lipase activity that hydrolyses chylomicrone and VLDL to glycerol and free fatty acids, when compared with that before cholecystectomy ,,
The significant reduction in the AI after cholecystectomy in both intervals when compared with that before the operation is in consonance with the results obtained by others.  Higher value of AI before cholecystectomy may be due to an abnormal increase in TC. 
The low FG levels seen before cholecystectomy occurs due to the fact that these patients present for medical intervention due to one of the complications of gall stone like acute cholecystitis that leads to loss of appetite and vomiting.  After 1 week, FG was significantly increased, may be due to the effect of the catabolic phase of surgical trauma leading to increase in serum concentration of adrenaline and noradrenalin, which are insulin antagonists. In addition, the increased serum insulin in the blood can lead to increase glycolysis and glucogenolysis, therefore increasing blood glucose concentration. After 1 month of cholecystectomy, the FG levels decreased, this is supported by the study of Mayne,  who described the return of serum glucose to the normal value after the end of catabolic phase. However, this disagrees with another study where the levels of FG were high at 1 month interval following cholecystectomy. 
It is emphasized that gallstones should now be regarded as a marker of an underlying metabolic disorder and investigated and treated accordingly and should not merely be considered as a surgical condition needing cholecystectomy as abnormal fasting lipid profile leads to increased risk of cardiovascular disease. 
| Conclusion|| |
GSD is associated with abnormal lipid profile and blood glucose parameters. Cholecystectomy leads to a significant decrease in TC, TG, LDL-c, AI, blood glucose and significant increase in HDL-c in patients with GSD. Therefore, beneficial effects of cholecystectomy in GSD on lipid and blood glucose parameters should warrant that even asymptomatic and incidentally detected patients with cholelithiasis are advised to undergo complete metabolic work-up and cholecystectomy.
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[Table 1], [Table 2], [Table 3], [Table 4]