Association between Gallstones and diabetics type II Iraqi patients Iraqi J Pharm Sci, Vol.20(2) 2011 Gallstones and DM. Type 2 38 Association between Gallstones and Diabetics Type 2 Iraqi Patients Anmar H. Altaie* ,1 *Department of Pharmacotherapeutics, College of Pharmacy,University of Al-Mustansyria, Baghdad,Iraq Abstract Gallstone disease is one of the most common complications among diabetic patients especially type 2 DM. Till now, there is no specific and certain factor that explain the incidence of gallstones among type 2 diabetic patients and many risk factors are taken collectively to estimate its intensity and severity compared to non diabetic counter parts. This clinical study was designed to evaluate and report the incidence and severity of gallstones among type 2 diabetics and non diabetics regarding certain factors. 20 diabetic females and 20 diabetic males were collected as patients′ group and have had gallstones while 20 females and 20 males who have had gallstones without diabetes mellitus type 2 were collected as controls′ group. The age, weight, and both of the size and number of gallstones of diabetic patients and controls were correlated to demonstrate the prevalence of gallstones among the patients′ and controls′ groups. The study showed that the mean ages of female patients is slightly higher (p<0.05) than the female controls. On the other hand there was a significant difference (p<0.05) between female and male control subjects. The body mass index (BMI) of male patients was significantly higher (p<0.05) than the male controls, while there was a significant difference (p<0.05) between female and male control subjects. The results of the study presented that the stone size of female patients was significantly higher (p<0.05) than the female and male controls, while the stone diameter of male patients was significantly higher (p<0.05) than the male and female controls. The stone number of female patients was significantly higher (p<0.05) than the female and male controls, while the stone number of male patients was significantly higher (p<0.05) than the male and female controls. These findings suggest that the incidence of gallstones was higher in type 2 diabetics both in males and females than the non diabetics and more in females than males who were non diabetics. Key words: Diabetes mellitus, gallstones, gender, ultrasound الخالصة الًٌْع الثّاًٖ. دخٔ اٙى، ل٘س ٌُاك عاهل هعّ٘ي ابذاء السنشٕ خصْص الوشاسة أدذ أمثش الخعق٘ذاِث ب٘ي الوشضٔهشض دصٔ العْاهَل َهأُْخْرة بشنل جواعٖ ّاى الًٌْع الثّاًٖ ابذاء السنشٕ خصْص ُّهخَأَمِّذ الزٕ ُّْٗضُخ دادثتَ دصٔ الوشاسة ب٘ي الوشضٔ . ُزٍ الذساسِت السشٗشِٗت ُصّووْج ّغ٘ش الوصاب٘ي بذاء السنشٕ الًٌْع الثّاًٖ ابذاء السنشٕ خصْص الوشضٔلخَخو٘ي مثافخَِ ّشذَّحَِ ب٘ي هي االًاد 0ٓ. ّغ٘ش الوصاب٘ي بذاء السنشٕ الًٌْع الثّاًٖ اشذَِّة دصٔ الوشاسة ب٘ي الوشضىبذاء السنشٕ خصْصحق٘٘ن لخَق٘٘ن ّل بذاء السنشٕ هي الٌْع الثاًٖ اٗضا , جوعْا معٌ٘ت هشضٔ ّماًْا هشضٔ هي الزمْس 0ّٓبذاء السنشٕ هي الٌْع الثاًٖ هشٗضاث ّحن فذصِن هخخبشٗا للخأمذ هي عذم اصابخِن بالسنشٕ هي الزمْس جوعْا معٌ٘ت 0ّٓ هي االًاد 0ٓذصٔ الوشاسة بٌ٘وا هصاب٘ي ب الوصاب٘ي بذاء السنشٕ هي الٌْع وشاسة للوشضٔدجِن ّعذِد دصٔ ال ّ الوشضٔ ّصىّ دصٔ الوشاسة فقط. ُعوش ّماى عٌذُن للًاد ( p<0.05) هي هخْسط االعواس أعلٔ قل٘لً االًادِ للوشضٔ هخْسط االعواسالذساستَ بأّى الثاًٖ ّغ٘ش الوصاب٘ي بَ اظِشث . إّى هخْسط االعواس للزمْس ّاالًاد الزٗي اخزّا معٌ٘ت ( ب٘ي p<0.05هي الٌاد٘ت األخشٓ ماى ٌُاك إخخلف ُاّم ) الزٗي اخزّا معٌ٘ت ، بٌ٘وا ماى ٌُاك إخخلف (معٌ٘تأخزّا الزٗي )الزمْس ( ِهيْ p<0.05ِهْي الوشضٔ الزمِْس أعلٔ جذاً ) بٖ .ام .إ ( دلَ٘ل مخلتَ الجسن ) دصٔ الوشاسة دجنًَخائُِج الذساسِت ّضذج. معٌ٘ت للزمْس ّاالًاد الزٗي اخزّا بٖ .ام .إ ()دل٘ل مخلت الجسن ( ب٘ي p<0.05ُاّم ) الوشضٔ الزمِْس أعلٔ دصٔ الوشاسة لذٓ بٌ٘وا قطش لذٓ االًاد ّالزمْس الزٗي اخزّا معٌ٘ت ,( p<0.05أعلٔ جذاً ) االًاد للوشضٔ هي ( p< 0.05) أعلٔ جذاً ًاداالالوشضٔ دصٔ الوشاسة لذٓ إّى عذَد الزمْس ّاالًاد الزٗي ارّا معٌ٘ت . ( ِهْي p<0.05جذاً ) الزمْس ّاالًاد الزٗي ِهْي ( p< 0.05)أعلٔ جذاً الزمْسالوشضى دصٔ الوشاسة لذٓ إّى عذَد ، بٌ٘وا الزمْس ّاالًاد الزٗي اخزّا معٌ٘ت مل فٖ الزمِْس ّاإلًاد لذٓ الوصاب٘ي بذاء السنشٕ هي الٌْع الثاًٖ فٖ أعلٔ دصٔ الوشاسةحَقخشُح ُزٍ الٌخائجِ بأّى دادثتَ ارّا معٌ٘ت. ّمزلل اعلٔ فٖ االًاد هي الزمْس هي الوصاب٘ي بذصٔ الوشاسة ّ غ٘ش هصاب٘ي بذاء السنشٕ . Introduction Diabetes is a chronic condition caused by a relative or an absolute lack of insulin (1) . It is associated with abnormalities in carbohydrate, fat, and protein metabolism and results in chronic complications including microvascular, macrovascular, and neuropathic disorders (2) . Several distinct types of DM exist and are caused by a complex interaction of genetics, environmental factors, and life-style choices. The two broad categories of DM are designated type 1 and type2 (3) . Gallstones (chole = “bile”,lithia = “stone”, and -sis = “process”) are the most common digestive disease causing huge hospitalizations annually worldwide (4) . Gallstones can occur anywhere within the biliary tree, including the gallbladder and the common bile duct (5) . 1Corresponding author E- mail : altaii1978@yahoo.com Received : 12/5/2011 Accepted :8/10/2011 Iraqi J Pharm Sci, Vol.20(2) 2011 Gallstones and DM. Type 2 39 Gallstones are formed by concretion or accretion of normal or abnormal bile constituents. They are divided into two major types: cholesterol stones account for 80% of the total, with pigment stones comprising the remaining 20% (3) .Gallstones can occur at any age, although they are rare under the age of 10 years and most common at 50–60 years in both sexes. Women are more prone to develop gallstones than men (6) ..There are several factors which directly affect the formation of gallstones as; sex, age, obesity, diet with high calories, diabetes mellitus, hemolytic anemia, estrogen and clofibrate therapy etc (7,8,9) .Diabetic subjects are reported to have a two to three fold increase in the prevalence of cholesterol gallstone. Inadequate emptying of gallbladder and increased fasting gallbladder volume has been reported in various studies (10) .In the present study , the incidence of gallstones in type 2 diabetics is made in correlation with age, sex and weight, the size and number of stones were taken in consideration. Materials and Methods This study was carried out on (80) patients. Of those 40 subjects (20 males, 20 females) have gallstones without diabetes mellitus type 2 served as a control group and 40 patients(20 males, 20 females) have diabetes mellitus type 2 with gallstones. Certain exclusion criteria were followed to avoid interference of any other factors like drugs or pathological conditions with this research, which include: patients with history of gallstones and received previous therapy or undergoing treatment, patients with history of clinical disorders like hyperlipidemia, hepatic disorders and those taking medications other than prescribed for DM type 2. Those patients were diagnosed and treated in Al-yarmook Teaching Hospital under supervision of specialist physicians. Type 2 diabetic patients were diagnosed and selected based on American Diabetes Association criteria of DM (2004): fasting plasma glucose concentration ≥ 126mg/dl, 2hr postprandial glucose concentration ≥ 200mg/dl and whose age at the onset of type 2 DM was equal or greater than 40 years. Gallstones identification, size and number were determined by ultrasonography which is thought to be the most appropriate technique in the diagnosis of the gallstones. Statistical ِ Analysis The results were expressed as mean± SD, student t-test and ANOVA test were used to examine the degree of significance which is considered significant as P value <0.05. Results Both of table 1 and figure 1, show the age distribution of patients depending on their gender. The mean ages of female patients having gallstones and DM type 2 was (56.2±9.24) years, is slightly higher (p<0.05) than the female controls having gallstones without diabetes (49.5±10.62) years while the mean ages of male patients having gallstones and DM type 2 was (58±10.5) years is significantly indifferent (p<0.05) from the male controls having gallstones without diabetes (58.2±10.88) years . On the other hand there was a significant difference (p<0.05) in the mean age between female and male control subjects (49.5±10.62), (59.58±10.5) years old respectively. Table 1: Characteristics of study parameters for both control subjects (having gallstones without type 2 DM) and patient subjects(having gallstones and type 2 DM) Type and no. of patients Age (year) mean± SD BMI kg/m 2 mean± SD Gallstones′ size (mm) mean± SD Gallstones′ number mean± SD Non diabetic females(20) 49.5±10.62 27.217±2.96# 3.37±1.31 3.0±1.0 Diabetic females(20) 56.2±9.24* 27.218±2.6# 7.49±4.35*# 5.0±3.0*# Non diabetic males(20) 58.2±10.88# 25.05±2.78 3.36±1.63 2.0±1.0 Diabetic males(20) 58.2±10.88# 28.48±2.57* 6.4±3.48*# 5.0±3.0*# *Significantly different from control (p< 0.05). # Significantly different between groups (p<0.05) Iraqi J Pharm Sci, Vol.20(2) 2011 Gallstones and DM. Type 2 40 Figure 1: The mean age of both control subjects (having gallstones without type 2 DM) and patient subjects(having gallstones and type 2 DM) As presented in table 1 and figure 2, the body mass index (BMI) of female patients having gallstones and type 2 DM (27.218±2.6) kg/ m 2 was significantly indifferent (p<0.05) than the female controls (27.217±2.96) kg/ m 2 , while the BMI of male patients having gallstones and DM type 2 (28.48±2.57) kg/ m 2 was significantly higher (p<0.05) than the male controls (25.05±2.78) kg/ m 2 . On the other hand there was a significant difference (p<0.05) between female and male controls (27.218±2.6), (25.05±2.78) kg/ m 2 respectively ,and between female patients (27.217±2.96) kg/ m 2 and male control (25.05±2.78) kg/ m 2 .The stone diameter of female patients having gallstones and DM type 2 was (7.49±4.35)mm is significantly higher (p<0.05) than the female and male controls having gallstones without diabetes (3.37±1.31), (3.36±1.63) mm respectively, while the stone diameter of male patients having gallstones and DM type 2 was (6.4±3.48) mm, is significantly higher (p<0.05) than the male and female controls having gallstones without diabetes was (3.36±1.63), (3.37±1.31) mm ,respectively as shown in both of table 1 and figure 3.Table 1 and figure 4, also present that the stone number of female patients having gallstones and DM type 2 was (5.0±3.0), is significantly higher (p<0.05) than the female and male controls having gallstones without diabetes (3.0±1.0) (2.0±1.0) respectively, while the stone number of male patients having gallstones and DM type 2 was (5.0±3.0), is significantly higher (p<0.05) than the male and female controls having gallstones without diabetes (2.0±1.0), (3.0±1.0) respectively. Figure 2: The BMI(kg/ m 2 ) of both control subjects (having gallstones without type 2 DM) and patient subjects(having gallstones and type 2 DM) Iraqi J Pharm Sci, Vol.20(2) 2011 Gallstones and DM. Type 2 41 Figure 3: The gallstone diameter(mm) of both control subjects (having gallstones without type 2 DM) and patient subjects(having gallstones and type 2 DM) Figure 4: The gallstone number of both control subjects (having gallstones without type 2 DM) and patient subjects(having gallstones and type 2 DM) Discussion Gallstone disease is one of the most common digestive diseases (4) . Many studies investigate and demonstrate the relationship between gallstones and type 2 DM. Ali Ekecik et al (11) reported a statically significant difference (p<0.01) in the frequency of gallstones between 200 non diabetic control group and 200 diabetic patients, the incidence was 10.5%(21/200) in the control group versus 27%(54/200) in type 2 diabetic patients. One of the risk factors for cholesterol gallstones includes increasing age and female gender. In the present study as showed in table 1, the age of the patients regarding the gender plays a great role in the incidence of gallstones in that the incidence was significantly higher between female and male control subjects. On the other hand there was a significant difference (p<0.05) among females having type 2 diabetes than the controls, while age plays non-significant role in the incidence of gallstones among type 2 diabetic males than the controls. The incidence was insignificantly higher between female and male patients having type 2 DM suggesting the role of factors other than the relationship between age and gender.The mean age of onset of gallstones among both the control and patient females was totally lower than the mean age of both the control and patient males. This finding may be attributed to the fact that females are reported to have prevalence of gallstones till the age of 50 probably due to hormonal influence on bile composition and gallbladder motility (12) . The results of this study is in harmony with that done by Rupali Saxena et al (12) , who found that 67.5% of the diabetic patients with gallbladder disorder Iraqi J Pharm Sci, Vol.20(2) 2011 Gallstones and DM. Type 2 42 were females, as well as by Sun H. et al (13) who stated that the incidence of gallstone was higher in females than in males and with increasing age 40-64 or ≥65years, while Champan et al (14) stated that subjects of both sexes with type 2 DM, had higher prevalence of gallstones than controls. Another risk factor for the increased incidence of gallstones in type 2 diabetics is obesity. Table 1 shows the effect of body weight regarding gender on the incidence of gallstones where the incidence was significantly higher between female and male control subjects, while insignificant between female and male diabetic patients but again significantly different between male patients having gallstones and type 2 DM and control males. The results of this study agree with a study done by A. B. Olokoba et al (15) who founded that the diabetic patients had a significantly higher mean BMI than the controls (P < 0.01) in 100 type 2 diabetic patients and 100 age- and sex-matched controls. But again obesity alone is independent risk factor among obese type 2 diabetic patients and a number of factors are collectively responsible for the increasing incidence of gallstones and type 2 DM. In diabetics, lipid concentration of plasma and bile increase. The obesity observed in diabetic patients has diverse effects on increased cholesterol synthesis and bile saturation (16,17) Additionally, in the obese, gallbladders may not empty normally or completely (18) . As BMI increases, the risk for developing gallstones also rises. For women, obesity is an even stronger risk factor for developing gallstones and women with a BMI greater than 32 may be as much as three times as likely to develop gallstones as those with a BMI of 24 or 25. The risk may be seven times higher in women with a BMI above 45 than in those with a BMI under 24 (19) , and this may explain why there was insignificant difference between the control and the diabetic females. The last two parameters are the gallbladder stones′ sizes and numbers and their associated incidence among controls and type 2 diabetic patients. Both of the size and number of gallstones were significantly higher in female and male patients than in the both sexes of the controls. The supersaturation of bile with cholesterol, nucleation of monohydrate crystals and dysfunction of gall bladder are the three important factors that cause gallstone formation (20,21) .Hypomotility of gallbladder cause gallstone formation in diabetes mellitus and other chronic disorder like obesity (22) .The gallbladder of diabetic patients are generally large and its motility is disturbed (23) . These events are probably due to the dysfunction of the gall bladder wall . The combined effects of poor emptying and possibly decreased ejection fraction rate and increased fasting volume could lead to bile stasis within the gallbladder and the formation of stones (24) . 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Diabetic cholecystomegaly.JAMA.1985;408:357-9. 24. Takahashi T, Yamamura T, Yokoyama E, et al. Impaired contractile motility of the gallbladder after gastrectomy. Am J Gastroenterol. 1986; 81: 672-77 file:///C:/bio/Jennifer-R-Scott-6038.htm