Gallstones and Plasma Lipids in a Danish Population

A cross-sectional study of gallstone disease, ascertained by ultrasonography, comprised 4581 men and women of Danish origin, aged 30, 40,50, and 60 years, of whom 3608 (79%) attended the investigation. The prevalence was assessed in relation to plasma concentrations of total cholesterol, high-density-lipoprotein cholesterol, low-density-lipoprotein cholesterol, and triglyceride. In the univariate analysis gallstone disease was significantly associated with high triglyceride and low high-density-lipoprotein cholesterol. No significant association among gallstones and total cholesterol and low-density-lipoprotein cholesterol was seen. In multivariate analyses triglyceride lost its significant association with gallstone disease, whereas total cholesterol became negatively associated with gallstones. This was seen for both the high-density-lipoprotein and the low-density-lipoprotein fraction of cholesterol. The difficulties in analysing present plasma lipid status with gallstone prevalence must be stressed. Looking only at small gallstones, which could represent newly formed stones, a change from a negative to a positive association between gallstone and both low-density-lipoprotein cholesterol and total cholesterol was seen.     

Serum lipids and gallstones: a case-control study

The role of serum lipids in the etiology of cholesterol gallstones and pigment gallstones was assessed in a case-control study. The study included 250 cases with surgically or ultrasonographically confirmed cholecystolithiasis and 526 hospital control patients. The highest gallstone risk was found at low high-density cholesterol levels and high triglyceride levels. An additional weakly negative association was found between total cholesterol level and gallstone risk. These findings were similar for cholesterol gallstones and pigment gallstones. The association between body mass index and gallstone risk disappeared after adjustment for serum lipids in a multivariate analysis. This study confirms previous reports on the association between gallstone risk and serum lipids. The similarity between cholesterol and pigment gallstones with regard to their association with serum lipids indicates that these types of gallstones share more causal factors than previously suggested. The absence of an effect of body mass index independent from serum lipids (as shown by the multivariate analysis) suggests that serum lipids are more closely linked to the pathogenesis of gallstones than obesity.     

Bile acid synthesis is increased in Chilean Hispanics with gallstones and in gallstone high-risk Mapuche Indians

BACKGROUND & AIMS: Gallstone disease is an important, costly health-care problem in Western societies. It is still unclear whether hepatic lipid regulatory enzymes play primary or secondary roles in gallstone formation. In this study, the aim was to investigate whether the synthesis of bile acids and cholesterol is increased in gallstone disease and to test whether such a metabolic change, if present, might occur before gallstone formation. METHODS: A total of 125 Chilean Hispanic women (80 without gallstones and 45 with gallstones) matched for age and body mass index were investigated, along with 40 Chilean Mapuche Indian women (20 without gallstones and 20 with gallstones), a population group in which the prevalence for gallstone disease is very high. Fasting blood plasma samples were assayed for 7 alpha-hydroxy-4-cholesten-3-one and lathosterol, 2 strong indicators for hepatic bile acid and body cholesterol synthesis, respectively. RESULTS: Plasma 7 alpha-hydroxy-4-cholesten-3-one levels, corrected for plasma cholesterol, were significantly increased by 50% in Hispanic women with gallstones as compared with gallstone-free Hispanics (P < 0.006). As compared with Hispanic women without gallstones, plasma 7 alpha-hydroxy-4-cholesten-3-one levels were increased by > or =100% (P < 0.002) in Mapuche Indian women, independently of whether gallstones were present. Plasma lathosterol, corrected for plasma cholesterol, was significantly increased by 22% in Hispanic women with gallstones and in Mapuche Indian women compared with Hispanic women. CONCLUSIONS: The results indicate that the synthesis of bile acids and cholesterol is induced in gallstone disease and precedes gallstone development. These inductions presumably occur as a response to an increased intestinal loss of bile acids.     

Prevalence of cholesterol gallstones positively correlates with per capita daily calorie intake

BACKGROUND/AIMS: Gallstone composition has changed over the past decades in East Asian countries with a prominent increase in the prevalence of cholesterol gallstones. This trend is possibly due to the westernization of dietary habits. This study was undertaken to delineate the changing trends in gallstone composition in Japan since the 1920s and to assess dietary influences on gallstone composition. METHODOLOGY: Between 1971 and 1999, 1264 Japanese patients underwent cholecystectomy for gallstone disease in Niigata University Medical Hospital. Gallbladder stones retrieved from each patient were classified into four types by gross inspection of the cut surface and infrared spectroscopy: cholesterol stone, black pigment stone, brown pigment stone, and other stones. The literature was reviewed to find both changing trends in gallstone composition before 1971 and dietary changes since 1950 in Japan. RESULTS: The prevalence of cholesterol gallstones among Japanese patients undergoing cholecystectomy increased steadily until the 1970s and declined thereafter (P<0.001). Among dietary factors, only per capita daily total calorie intake strongly correlated with cholesterol gallstone prevalence (r=0.93, P=0.02). CONCLUSIONS: During the 20th century, the prevalence of cholesterol gallstones in the Japanese population increased steadily until the 1970s declining thereafter. Per capita daily total calorie intake appears to be the predominant dietary factor affecting cholesterol gallstone prevalence.     

Bile and plasma lipid composition in non-obese normo-lipidemic subjects with and without cholesterol gallstones

ABSTRACT— A two-stage study was carried out to characterize the bile and plasma lipid composition in normolipidemic non-obese patients with and without cholesterol gallstones. The first stage involved 11 patients with cholesterol gallstones admitted for elective cholecystectomy and a control group of 16 patients without cholesterol gallstones undergoing elective laparotomy. Bile samples were obtained intraoperatively by aspiration from the gallbladder. The bile of all the gallstone patients was supersaturated with cholesterol and its nucleation time was much shorter than that of bile in the control group (2.5 days vs 22.5 days, respectively, P<0.001). The biliary fatty acid profile of phosphatidylcholine (PC) and free fatty acids (FFA) of gallstone patients was similar to that of the control group. C-22 fatty acids were found in a higher concentration in the FFA than in the PC fatty acids (P<0.05) in both groups of patients. Plasma triglyceride levels in the gallstone patients were significantly higher than those in the control group and the biliary cholesterol level correlated with that of plasma triglycerides. In the second stage of the study, plasma lipid profiles were obtained in two additional groups of patients, 20 patients with and 24 patients without cholesterol gallstones, for an in-depth characterization of the differences in plasma lipid profiles. The gallstone patients were found to have not only significantly higher concentrations of plasma triglycerides but increased cholesterol and phospholipid level as well. These differences were essentially due to a higher lipid content of the plasma VLDL fraction, similar to the pattern of patients with type IV hyperlipoproteinemia.     

Lipids and lipoprotein changes after heart and liver transplantation in a patient with homozygous familial hypercholesterolemia

Changes in lipids and lipoprotein fractions were studied 6 months after a combined heart and liver transplantation in a patient with terminal ischemic heart disease due to homozygous familial hypercholesterolemia. The double transplant was followed by striking decreases in total and low-density-lipoprotein cholesterol levels (-71% and -79%) and content of apolipoprotein B in the low-density-lipoprotein fraction (-74%). There was also an increase in high-density-lipoprotein cholesterol (+7.8%). These changes are greater than those reported with portacaval shunt or plasma exchange. Liver transplantation may be considered in selected patients with homozygous familial hypercholesterolemia.     

Metabolic syndrome and gallstone disease

AIM: To investigate the association between metabolic syndrome (MetS) and the development of gallstone disease (GSD).METHODS: A cross-sectional study was conducted in 7570 subjects (4978 men aged 45.0 ± 8.8 years, and 2592 women aged 45.3 ± 9.5 years) enrolled from the physical check-up center of the hospital. The subjects included 918 patients with gallstones (653 men and 265 women) and 6652 healthy controls (4325 men and 2327 women) without gallstones. Body mass index (BMI), waist circumference, blood pressure, fasting plasma glucose (FPG) and serum lipids and lipoproteins levels were measured. Colorimetric method was used to measure cholesterol, high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C). Dextrose oxidizing enzyme method was used to measure FPG. Subjects were asked to complete a questionnaire that enquired about the information on demographic data, age, gender, histories of diabetes mellitus, hypertension, and chronic liver disease and so on. Metabolic syndrome was diagnosed according to the Adult Treatment Panel III (ATP III) criteria. Gallstones were defined by the presence of strong intraluminal echoes that were gravity-dependent or attenuated ultrasound transmission.RESULTS: Among the 7570 subjects, the prevalence of the gallstone disease was 12.1% (13.1% in men and 10.2% in women). BMI, waist circumference, systolic blood pressure, diastolic blood pressure, fasting blood glucose and serum triglyceride (TG) in cases group were higher than in controls, while serum high-density lipid was lower than in controls. There were significant differences in the waist circumference, blood pressure, FPG and TG between cases and controls. In an age-adjusted logistic regression model, metabolic syndrome was associated with gallstone disease. The age-adjusted odds ratio of MetS for GSD in men was 1.29 [95% confidence interval (CI), 1.09-1.52; P = 0.0030], and 1.68 (95% CI, 1.26-2.25; P = 0.0004) in women; the overall age-adjusted odds ratio of MetS for GSD was 1.42 (95% CI, 1.23-1.64; P < 0.0001). The men with more metabolic disorders had a higher prevalence of gallstone disease, the trend had statistical significance (P < 0.0001). The presence of 5 components of the MetS increased the risk of gallstone disease by 3.4 times (P < 0.0001). The prevalence of GSD in women who had 5 components of MetS was 5 times higher than in those without MetS component. The more the components of MetS, the higher the prevalence of GSD (P < 0.0001). The presence of 5 components of the MetS increased the risk of gallstone disease by 4.0 times.CONCLUSION: GSD appears to be strongly associated with MetS, and the more the components of MetS, the higher the prevalence of GSD.     

Macronutrients and insulin resistance in cholesterol gallstone disease

Cholelithiasis is a major source of digestive morbidity worldwide. Cholesterol stones account for the majority of gallstones in the United States and other Western countries. The pathogenesis of cholesterol gallstone disease is multifactorial with key factors including cholesterol supersaturation of bile, altered biliary motility, and nucleation and growth of cholesterol crystals. Increasing evidence suggests that many, but not all, causative factors of cholesterol gallstones are related to insulin resistance which, in association with obesity, has reached an epidemic level worldwide. Experimental studies show that hyperinsulinemia, a key feature of insulin resistance, may cause increased hepatic cholesterol secretion and cholesterol supersaturation of bile and gallbladder dysmotility, and thereby may enhance gallstone formation. Insulin resistance syndrome can be modified by environmental factors, including dietary factors. The impact of diet on insulin sensitivity is mediated by both dietary composition and its energy content. The contribution of specific dietary elements to the prevalence and incidence of cholesterol gallstone disease has been explored in animal and human studies. There is considerable evidence to suggest that different types of fatty acids, independent of the total amount of fat consumption, affect insulin sensitivity and cholesterol gallstone disease differently. The effects of salt intake, consumption of protein and carbohydrates, and alcohol drinking on insulin resistance are controversial. Additional intervention trials and controlled experimental feeding studies are needed to further clarify these relationships and to provide useful prophylactic and therapeutic strategies.     

Cigarette smoking,alcohol use,and gallstone risk in Japanese men

BACKGROUND/AIM: Results of epidemiological studies concerning the association between smoking and alcohol use and gallstone risk are inconsistent. We examined the relation of smoking and alcohol use to gallstone disease in Japanese men. METHODS: We investigated 174 cases having gallstones as determined by ultrasonography, 104 cases of postcholecystectomy state, and 6,906 controls having a normal gallbladder in the consecutive series of 7,637 men aged 48-59 years receiving a retirement health examination at four hospitals of the Self-Defense Forces from 1986 to 1994. Fifty men had been aware of having gallstones. Known gallstones and postcholecystectomy state were combined as known gallstone disease. Smoking and drinking habits were ascertained by a self-administered questionnaire. Statistical adjustment was made for body mass index, glucose tolerance status, Self-Defense Forces rank, hospital, and either cigarette smoking or alcohol use. RESULTS: Cigarette smoking was not measurably associated with either prevalent gallstones or postcholecystectomy state, nor with either newly diagnosed gallstones or known gallstone disease. Alcohol use was related to a significant decrease in the prevalence odds of both gallstones and postcholecystectomy state, and the decrease was slightly more profound for known gallstone disease. CONCLUSIONS: Cigarette smoking is probably unrelated to the gallstone risk, and alcohol consumption seems to confer protection against gallstone formation.     

Policosanol,an Aliphatic Alcohol Sugarcane Derivative: Use in Patients Intolerant of or Inadequately Responsive to Statin Therapy

Policosanol is a compound derived from sugarcane wax with low-density-lipoprotein (LDL) cholesterol-lowering properties. The aim of this study is to evaluate the effect of Policosanol on LDL cholesterol reduction in patients intolerant of statin therapy or on concomitant statin therapy but not at target LDL cholesterol levels. Twenty-one patients treated with policosanol 10 mg twice a day for 156 ± 63 days were analyzed retrospectively. Pre- and posttreatment fasting lipid profiles were collected and statistical analysis was performed as paired t-tests. Data were further analyzed into subgroups based on the presence or absence of statin therapy. In the 21 patients, LDL cholesterol decreased by 17% (p < 0.001) and total cholesterol decreased by 9.4% (p < 0.001). No significant changes were seen in high-density-lipoprotein (HDL) cholesterol or triglyceride levels. In the 6 patients treated with a statin and Policosanol, there was also a 17% LDL cholesterol reduction (p = 0.005). In the 15 patients treated only with Policosanol, LDL cholesterol was also decreased by 17% (p = 0.003). Policosanol use was observed to be associated with a mild-to-moderate (17%) decrease in LDL cholesterol. This association was observed in patients intolerant of statin therapy and in those receiving adjunctive Policosanol with statin therapy.     

Serum and bile lipid levels in patients with and without gallstones

The aim of the present study was to investigate predisposing factors that lead to the formation of gallstones. In a group of 70 patients (51 with gallstones and 19 without, 20 possible risk factors were studied: percent of ideal body weight, the presence of superoxide dismutase in erythrocytes and in serum, lipid peroxide in serum, total serum cholesterol (Ch), high density lipoprotein (HDL)-cholesterol (Ch), low-density lipoprotein (LDL)-Ch, very low-density lipoprotein (VLDL)-Ch, serum triglyceride (TG), HDL-TG, LDL-TG, VLDL-TG, serum bile acids (lithocholic acid, deoxycholic acid, chenodeoxy cholic acid, ursodeoxycholic acid, and cholic acid) and serum apolipoproteins (apo A-1, apo B-100, and apo A-1/apo B-100). Levels of apo B-100 and serum insulin in patients with gallstone were strikingly higher, and superoxide dismutase in erythrocytes was significantly lower than in individuals with no gallstones. Apo A-1 and HDL-Ch were also higher and LDL-Ch was lower in the gallstone group, albeit non-significantly so (P>0.05) byt-test. However, Apo A-1, HDL-Ch, and LDL-Ch showed remarkably good discriminatory power in stepwise discriminant analysis of the 20 factors. Bile lipid composition was also measured and the cholesterol saturation index was calculated, but no significant differences were seen between the two groups. The results demonstrate that serum lipid patterns differ to some extent in patients with and without gallstones. Lipid derangement may contribute to the development of gallstone disease.     

Increase in serum total cholesterol and low-density lipoprotein cholesterol by high-dose chenodeoxycholic acid in patients with radiolucent gallstones significantly reversed during preventive low dose after gallstone dissolution

This study examines the effects of high-dose chenodeoxycholic acid (CDCA) on serum lipids and lipoproteins in 25 patients who underwent a 12-month therapy with CDCA for the dissolution of cholesterol gallstones. All patients received a daily dose of CDCA of 15 mg/kg body weight. Complete dissolution of gallstones was achieved in 16 cases. After 6 months of therapy the mean total cholesterol levels and low-density lipoprotein cholesterol (C-LDL) significantly increased (p less than 0.001). The decrease of mean triglyceride levels was significant too (p less than 0.01), although it was greater among patients with effective gallstone dissolution than in patients with persistent gallstones. The effects of high-dose CDCA after 12 months of therapy were similar to those observed at 6 months. 12 patients of the gallstone dissolution group were treated with a continuous low dose of CDCA (250 mg/day) for preventing gallstone recurrence. 6 months after dissolution, the mean total cholesterol levels and C-LDL significantly decreased (p less than 0.01 and less than 0.05, respectively). High-dose administration of CDCA produced an increase in total cholesterol and C-LDL, but did not alter high-density lipoprotein cholesterol levels. These effects were significantly reversed when a preventive low dose of CDCA was given after gallstone dissolution.     

The prevalence of gallstone disease in a defined cohort of patients with Crohn's disease

OBJECTIVE: Crohn's disease (CD) is associated with a high prevalence of gallstone disease but the relative risk has not been completely established. Ileal disease or resection have been considered as contributing factors to the increased risk. The aim of this study was to evaluate the prevalence of gallstone disease in a defined cohort of CD patients, to evaluate possible risk factors, and to evaluate the relative risk compared with the general population. METHODS: All inhabitants in Stockholm County born in 1933-1935 or 1953-1955, with CD diagnosed between 1955-1989 and not having had a previous cholecystectomy, were invited for an ultrasonography of the gallbladder. The prevalence of gallstone disease was related to disease extent, previous intestinal resections, age, and gender. The relative risk of developing gallstones was calculated using a recent study of gallstone disease in general, with similar age groups as controls. RESULTS: We found that 26.4% had gallstone disease (relative risk [RR] = 1.8; 95% confidence interval [CI], 1.2-2.7). The number of previous intestinal resections was the only significant risk factor. There was no significant difference in gallstone disease between gender (28.2% vs 24.1%) or age (34% vs 21.8%). CONCLUSIONS: Patients with Crohn's disease, regardless of gender and age, have almost a doubled risk of developing gallstone disease compared with the general population. Circumstances related to laparotomy may contribute to the increased risk. The lack of association between the disease extent and the site of previous intestinal resection, together with a previous finding of normal cholesterol saturation of the bile in patients with CD, indicate that these patients may develop pigment stones rather than cholesterol stones.     

Gallstone disease in an elderly population: the Silea study

BACKGROUND: Little is known on gallbladder emptying and gallstone composition in the elderly. AIMS AND SUBJECTS: Cross-sectional survey on the prevalence of gallstone disease and associated factors, gallstone characteristics and gallbladder emptying in a population aged > or = 60 years. METHODS: Gallstone number and size as well as gallbladder motor function were assessed by ultrasound. Gallstone composition and pattern were evaluated by conventional radiology and computed tomography (CT) based on Hounsfield units (HU). RESULTS: Gallstones were found in 148/1,065 subjects (13.9%), while 136 subjects (12.8%) were cholecystectomized with an overall prevalence of gallstone disease of 26.7% (sex ratio: F > M). Multiple gallstones (62.7%) and small gallstones (52%, diameter < or = 15 mm) were seen; silent gallstones accounted for 93.9% of the total. Only diabetes mellitus in women was significantly associated with cholelithiasis. Gallbladder fasting volumes were larger in gallstone carriers than in controls (P < 0.01); residual and ejection volumes were also significantly greater in gallstone carriers, whereas ejection fractions were similar in the two groups (50.3% +/- 2.4 versus 54.9% +/- 3.0; not significant). Gallstone calcifications were detected in 29/91 gallstone carriers by X-ray and in another 20 by CT (HU > 90). Moreover, 35 gallstone carriers had a score < or = 50 HU and six had attenuation values between 50 and 90 HU. Six gallstone patterns were identified: hypo-isodense, homogeneously dense, rimmed, laminated, core-hyperdense, gas-containing. CONCLUSIONS: In the elderly, the prevalence of gallstone disease is very high, especially in women, but gallstone size, number and pattern and gallbladder emptying do not differ from those reported in the middle-aged gallstone population. Advanced age is associated with a high rate of calcified, probably pigment stones.     

Secretion of biliary lipids in young Chilean women with cholesterol gallstones.

The early appearance of cholesterol gallstones is very common in Chile. To elucidate the mechanisms involved in this phenomenon, the size of the bile acid pool and the secretion of biliary lipids were studied in two groups of young women with normal weights and radiologically functioning gallbladders: nine with cholesterol gallstones and 14 healthy volunteers. The bile acid pool was similar in control and gallstone patients. The secretory rates of bile acids and phospholipids were comparable and significantly correlated in both groups. On the other hand, cholesterol output was higher in gallstone patients. In controls there was a significant correlation between the output of bile acids and cholesterol, but no correlation was found in the gallstone group. This study suggests that cholesterol hypersecretion into the bile is a major factor in the pathogenesis of cholesterol gallstone disease in young Chilean women with normal weights.     

Gallstones and diet in a Danish population

A cross-sectional study of gallstone disease, ascertained by ultrasonography, comprised 4581 men and women of Danish origin, aged 30, 40, 50, and 60 years, of whom 3608 (79%) took part in the investigation. The prevalence was assessed in relation to alcohol intake and number of daily meals. A randomly chosen subgroup of 593 persons was interviewed about their dietary habits. Both in the univariate and the multivariate analysis, gallstone disease was significantly related to abstinence from alcohol but not to number of meals. There was a trend towards positive association between gallstones and intake of refined sugars and total fat, whereas a negative trend was found between gallstones and intake of fibres and polyunsaturated to saturated fat ratio. None of the associations were significant. The same relations were observed when gallstones less than 10 mm were used in the analysis. The problem of assessing diet in relation to gallstone prevalence is stressed.     

血浆过氧化脂质和载脂蛋白A1,B水平与NIDDM大血管病 变的关系

测定了41例NIDDM病人(25例有大血管病变,16例无血管并发症)及33例正常人的血浆Lpo、ApoA_1、ApoB和脂蛋白。NIDDM各组与正常对照组、NIDDM合并大血管病变组与无血管病变组之间比较,前者Lpo、ApoB水平升高,ApoA_1水平下降,且差异极显著。提示上述变化与NIDDM大血管病变的发生关系密切。NIDDM病人血浆Lpo水平与ApoB、LDL-C、TC、TG的水平呈极显著正相关,提示NIDDM病人Lpo代谢异常与其他血脂代谢异常有伴同关系。     

Gallstone prevalence and biliary lipid composition in inflammatory bowel disease

Biliary cholesterol saturation has been correlated with disease variables that might effect bile acid loss in ileitis patients with (N=9) or without (N=8) intestinal resection having a defined prevalence of gallstones. In addition, cholesterol saturation was determined in ulcerative colitis patients (N=7) and gallstone patients (N=18) as well as in 5 normal controls. Biliary cholestrol saturation in ileitis patients both with and without resection was similar to that in gallstone patients yet the prevalence of gallstones was only 12%. Cholesterol saturation did not correlate with ileal resection nor the extent, duration, or activity of ileitis. Biliary cholesterol saturation was not different in ulcerative colitis patients from that in normal subjects. It is concluded that cholesterol saturation of bile alone does not account for the high prevalence of cholesterol gallstones that has been reported in ileitis patients.Supported in part by the National Foundation for Ileitis and Colitis, Inc. and NIH grant AM 15631.     

Prevalence of gallstone disease in patients with end-stage renal disease treated with hemodialysis in Korea

BACKGROUND/AIMS: Gallstone disease is one of the major causes of morbidity in adults. Hemodialysis has been found to increase the risk of gallstone formation secondary to increased biliary cholesterol and biliary saturation index. However, there is very little data on the prevalence of gallstones in hemodialysis patients. METHODOLOGY: We compared the prevalence of gallstone disease in patients with end-stage renal disease treated with hemodialysis with that of 208 age- and sex-matched controls (non-uremic group). Patients who had chronic liver disease, renal disease, and diabetes were excluded from the control group. RESULTS: In our study, we found a prevalence for gallstone of 18.2% in patients with end-stage renal disease treated with hemodialysis, which was significantly higher than 5.3% in the non-uremic control. Most of our hemodialysis patients had asymptomatic cholecystolithiasis. Hemodialysis patients with cholecystolithiasis were significantly older than patients without gallstones. We did not find a difference in sex and duration of hemodialysis treatment between patients with and without gallstones. CONCLUSIONS: Our results suggest that the prevalence of gallstone disease is higher in patients with end-stage renal disease treated with hemodialysis than in the non-uremic population in Korea.     

Association between insulin, insulin resistance, and gallstone disease in Korean general population]

BACKGROUND/AIMS: Diabetes is one of the risk factors of gallstone diseases. Many studies found a positive association between insulin and gallstones in individuals with diabetes. However, this association is unclear in non-diabetes. So we conducted a case-control study for the evaluation of the association between gallstone diseases and fasting serum insulin level, insulin resistance in non-diabetic Korean general population. METHODS: This study was a prospective case-control study on 118 Korean subjects which included clinical examination, abdominal ultrasound, and blood chemistries. Serum fasting insulin level were determined by radioimmunoassay and concentrations of cholesterol, glucose, and triglycerides by standard enzymatic colorimetric methods. Insulin resistance was determined by the homeostasis model assessment (HOMA-IR). Body mass index (BMI), percentage of body fat, and waist hip ratio were also measured. RESULTS: We studied 118 subjects with no clinical evidence of diabetes mellitus and serum glucose <126 mg/dL. Compared with controls (n=89), cases (n=29) had higher levels of serum insulin, glucose, triglyceride levels, and BMI. In t-test and chi-square test for variables, the association between gallstone disease and serum insulin, HOMA-IR index, and BMI were statistically significant (p<0.05). In multiple logistic regression analysis, gallstone disease risk increased with the level of serum insulin (p=0.024, odds ratio=1.376) and HOMA-IR index (p=0.013, odds ratio=2.006). CONCLUSIONS: We suggest that hyperinsulinemia and insulin resistance could be associated with gallstone formation in individuals without clinical diagnosis of diabetes mellitus and with normal serum glucose level.