GALLSTONES AMONG PATIENTS WITH TYPE 2 DIABETES MELLITUS

The link between gallstones formation and diabetes mellitus remains controversial. The study aims to find the prevalence of gallstones in diabetic patients and its relation with status of control, and duration of diabetes mellitus. A case-control study was conducted in Al-Basrah General Hospital; Basrah city, southern Iraq from January 2015 to September 2015. The study enrolled 100 type 2 diabetic patients with no abdominal pain (60% females, 40% males) as a test group and 100 asymptomatic subjects with no diabetes mellitus (60% females, 40% males) as a control group. Both groups were comparable for gender, age, and body mass index and examined by ultrasound to find gallstones. Blood samples were taken for fasting blood glucose and body mass index was measured. Age, gender, family history of gallstones, and parity for females were recorded in both groups. The tested group was further divided into two subgroups with and without gallstones. The association between duration of diabetes mellitus and hemoglobin A1c level with gallstones was assessed. Gallstones were detected in (28%) of diabetic group and (12%) of controls, which was highly statistically significant (p value=0.005). The prevalence of gallstones was found to be significantly higher among those with more than 10 years of diabetes and poor glycemic control compared with those with less than 5 years and good glycemic control. The study suggested that diabetic patients are at higher risk for gallstones in comparison to non-diabetic patients. Gallstones are found to be higher in those patients with long duration of diabetes mellitus and poor glycemic control. Introduction allstones are solid substances in the gall-bladder because of changes in the composition of bile; increase cholesterol, increased amount of pigment material, decrease bile acid, and/or impaired gallbladder contraction, which would lead to inadequate gallbladder emptying after a fatty meal. They are divided into two main types: cholesterol gallstones which account of more than 90% of the total, and pigment gallstones which are categorized into black and brown types. The prevalence of cholesterol gallstone disease is rising in industrialized countries of Europe and North America. The lowest prevalence is seen in Africans and very low in south-east Asia. Many studies from around the world reported an increased prevalence of gallstones in patients with type2 diabetes. Although the association between diabetes mellitus type2 and gallstones is controversial, many studies revealed that diabetic patients are two to three times more risky for gallstones than nondiabetics. How diabetes predisposes to gallstones is not well understood. However, hypertriglyceridemia, inadequate emptying of gallbladder and increased volume, autonomic neuropathy (leading to gallbladder hypomotility and biliary stasis) and hyperinsulinemia have been suggested as contributing factors to the increased risk of gallstone development in diabetics. Ultrasonography is a rapid, noninvasive method for imaging the gallbladder, which has contributed greatly to our G


Introduction
allstones are solid substances in the gall-bladder because of changes in the composition of bile; increase cholesterol, increased amount of pigment material, decrease bile acid 1 , and/or impaired gallbladder contraction, which would lead to inadequate gallbladder emptying after a fatty meal 2 .They are divided into two main types: cholesterol gallstones which account of more than 90% of the total, and pigment gallstones which are categorized into black and brown types 3 .The prevalence of cholesterol gallstone disease is rising in industrialized countries of Europe and North America 4 .The lowest prevalence is seen in Africans 5 and very low in south-east Asia 6 .Many studies from around the world reported an increased prevalence of gallstones in patients with type2 diabetes.Although the association between diabetes mellitus type2 and gallstones is controversial, many studies revealed that diabetic patients are two to three times more risky for gallstones than nondiabetics 7 .How diabetes predisposes to gallstones is not well understood.However, hypertriglyceridemia 8 , inadequate emptying of gallbladder and increased volume 9 , autonomic neuropathy (leading to gallbladder hypo-motility and biliary stasis) 10 and hyperinsulinemia have been suggested as contributing factors to the increased risk of gallstone development in diabetics 11 .Ultrasonography is a rapid, noninvasive method for imaging the gallbladder, which has contributed greatly to our

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Bas J Surg, December, 22, 2016 understanding of the epidemiology of and risk factors for gallstones 12 .
The study aim was to find the prevalence of gallstones in diabetic patients, and its relation with status of control and duration of diabetes mellitus, and also with age, gender, BMI and family history of gallstones.surgery.Data obtained were analyzed using the statistical package for social sciences (SPSS) software version 20.0.Descriptive analysis was done using mean±standard deviation, frequency and percentage of each value.P value less than 0.05 was considered significant.

Results
Forty (20%) subjects out of 200 of studied population had gallstones, 28(28%) of them were in test group, and 12(12%) in control group, the difference was statistically significant (p=0.005),Table (I).Demographic distribution of the study; showed that the majority of subjects who participated in the study were females 60(60%) and minority were males 40(40%) in both groups.Their ages ranged between 30-79 years with a mean of (51.6±9.5) and (50.62±12.9)years in test and control groups respectively.Body mass index ranged between (<18.5->30) with a mean of (31±6.The prevalence of gallstones was found to be significantly higher among those with long duration of diabetes of more than 10 years as compared with those with short duration of diabetes of less than 5 years (P=0.006).This was statically significant,

Discussion
Gallstone disease is one of the most common digestive diseases 5 , and can occur anywhere within the biliary tree, including the gallbladder and the common bile duct 14 .Several studies from across the world reported an increased prevalence of gallstones in patients with diabetes mellitus 10 .This study has shown; that the frequency of gallstones is more in diabetic patients (28%) as compared with those nondiabetics (12%).These results were similar to previous study that was done by AL-Bayati et al 15 who showed that there was a higher prevalence of gallstone in diabetics (33%) as compared to controls (17%).Also Elmehdawi R et al 16 , showed that(39.75%) of Type 2 diabetes mellitus patients have ultrasonographic evidence of gallstones as compared to (17.5%) of healthy subjects.
Although age and family history of gallstones are well-recognized risk factors for the gallstones in both diabetics and non-diabetics but this study showed no statistically significant differences between the age, family history of gallstones and diabetes mellitus.This was similar to previous results of studies [17][18][19][20][21] .This can be explained by that increasing age causes increased biliary secretion of cholesterol, decreased size of bile acid pool, decreased secretion of bile salts 3 .Obesity and overweight are well-known risk factors for the development of gallstones, this study has shown that the gallstones were more prevalent in overweight diabetics than in non-diabetics (30.1%, 19% respectively).These results agree with a study done by A. B. Olokoba et al 22 , who found that diabetic patients had a significantly higher body mass index than the controls (P <0.01) in 100 type 2 diabetic patients and 100 age-and sex-matched controls.However, obesity alone is independent risk factor among obese type 2 diabetic patients and a number of other factors are responsible for the increasing incidence of gallstones in type 2 diabetes mellitus.In diabetics, lipid concentration of plasma and bile are increased, and obesity observed in diabetic patients has diverse effects on increased cholesterol synthesis, secretion, and bile saturation 23 .Diabetic women were more affected than non-diabetics women (35%, 8.3% respectively).The results of the study are in harmony with the results of Sodhi JS et al 24 .The higher rate in women is probably due to the effects of sex hormones and pregnancy.Estrogen causes an increase in cholesterol secretion while progesterone causes reduction in bile acid secretion 25 .These changes eventually lead to super saturation of bile with cholesterol, which facilitates gallstones formation.Oral contraceptive pills which contain more than 50 microgram of estrogen dose, are also contributing factor 26 .The number of parity in diabetic women with gallstones was significantly higher than those of non-diabetics with gallstone (36%, 4.6% respectively).These results were similar to study done by Chapman BA et al 19 .This association could be due to qualitative changes in bile and slowing of gallbladder emptying, which promotes bile stasis during multiple pregnancies 17,19 .The duration of diabetes was positively related to the prevalence of gallstone.These results agree with a study done by AL-Bayati et al 15 .However, another previous studies didn't show such an association 27,28 .This association could be the result of increased insulin resistance and increased risk of autonomic neuropathy with longer duration of diabetes mellitus 29 .There was a significant relationship between gallstones and increased hemoglobin A1C level which indicate a poor glycemic control 3 .This result was in agreement with a previously published study done by MacGregor IL et al 28 , which showed that gallstone formation was significantly greater in diabetics with high HbA1c level.Since the level of blood glucose concentration affect gallbladder motility in a way that an acute hyperglycemia reduces the gallbladder responsiveness to cholecystokinin-33 (CCK-33) in a dose dependent manner and that hyperglycemia reduces basal and CCK-33 stimulated plasma pancreatic polypeptide (PP) concentration, suggesting impaired cholinergic activity during hyperglycemia 28 .This study has concluded that the prevalence of gallstones was more in patients with diabetes mellitus especially in those with long duration of diabetes mellitus and those with poor glycemic control as compared to non-diabetic patients.