Gallstones can be divided into the following types: cholesterol stones, pigment stones, and mixed stones. Cholesterol stones must be at least 80% cholesterol by weight. Other common constituents are primarily of bilirubin (insoluble bilirubin pigment polymer) and calcium (calcium phosphate) salts that are found in bile.Between 35% and 90% of stones are cholesterol stones. During the formation of cholesterol stones, impaired motility of gallbladder smooth muscle (GBSM), increased residual volume of fasting gallbladder and decreased contractility play an important role[23–25]. Long bile retention time in gallbladder may lead to high concentration in gallbladder bile and promote cholesterol precipitation in epithelial cells. Occasionally chronic bacterial infections, although asymptomatic, can also be a cause of GSD[27, 28].
Metabolic syndrome was first proposed by Reaven in 1993, which was then called X syndrome. The main clinical manifestations were insulin resistance (IR), hyperinsulinemia, impaired glucose tolerance (IGT), hypertension and abnormal atherogenic lipid metabolism. Different definitions of MetS have been proposed, reviewed, recommended, and even questioned over the decades., the World Health Organization (WHO) first proposed a working definition centering on IR or hyperglycemia. The National Cholesterol Education Program's Adult Treatment Panel III (NCEP ATP III) of the United States proposed diagnostic criteria for MS in 2001.
In the past 20 years, the national choreol education program's Adult Treatment Panel III (NCEP ATP III) of the United States and IDF have proposed new definitions successively, but they have these core components including central observatory, dyslipidemia, hypertention, and insulin resistance. In fact, it also proved to be reliable and universally accepted diagnostic tool.[33–35].
This study aimed to evaluate the association of MS with characteristics of gallstone. The results showed that The incidence of gallstones in MetS patients is increased compared with patients without MetS. A subgroup analysis by sex analysis showed that both men and women had an increased incidence. Analysis of various factors including MS components, the incidence of cholelithiasis increased in older patients, obesity-related factors, high blood lipids TC, WC, BMI were positively correlated with the incidence of cholelithiasis, fasting blood glucose Diabetes and hypertension are also positively correlated with the incidence of cholelithiasis. In male subjects, metabolic syndrome was associated with presence of gallstones, and the size of gallstones.
In recent years, insulin resistance is another hot topic among metabolic abnormalities associated with GSD. Not only obese people, insulin resistance can be also occur in people with normal weight. A study in a Hispanic population found that GS was associated with insulin resistance, fatty liver and metabolic syndrome. Insulin resistance is a risk factor for GS. Insulin resistance may play an important role in the pathogenesis of GS favoring the production of cholesterol supersaturated bile and altering gallbladder function. Nakeeb et al.  demonstrated that insulin resistance alone may be responsible for gallbladder dysmotility, which may result in acalculous cholecystitis or gallstone formation.
Even have evidence supports the contention that insulin resistance not only directly induce gallbladder inflammation increase mucus production and alter gallbladder function, but could also favors the secretion by the liver of cholesterol supersaturated bile. The latter seems more accepted pathogenic link. GS increase of cholesterol saturation in gallbladder bile, a phenomenon related to increase of body cholesterol synthesis and hypersecretion of biliary cholesterol as observed in obesity.Park et al. stated that adiponectin acted as a critical element in the development of insulin resistance, the lower the rate of obesity, weight, and BMI, the higher the concentration of adiponectin and that this information would be helpful for the treatment of diabetes.
The definition presented by the IDF that emphasizes abdominal obesity as a sine qua non diagnostic factor . In fact, it has been confirmed that some indicators such as larger waist circumference, higher BMI and hyperlipidemia are obese manifestations. Recent data from animal and human studies have shown that the gallbladder of obese people is enlarged and their response to neurotransmitters is usually reduced. A high-fat diet can lead to abnormal emptying of the gallbladder. Drugs that inhibit the absorption of lipids, normalize gallladder function, and prevent cholesteric crystal and gallstone formation. In addition, obese and high carbohydrate diet had increased gallbladder tissue levels of tumor necrosis factor-alpha, interleukin-6 and interleukin-1 beta. These changes lead to decreased smooth muscle function and diminished gallbladder absorption .
The function of bile components secretory also increased in GS patients. In a study from Chile, increased bile synthesis was found in GS patients . In terms of direct bilirubin, also normal mean values for total bilirubin (15.96 ± 5.23 µmol/L), but pathological ones for direct bilirubin (7.78 ± 5.41 µmol/L), as well as the modification of the normal subunit direct to indirect bilirubin ratio, in the sense of the equalization, only in the group with metabolic syndrome and gallstones.
Although there is no parallel relationship with blood lipids level, increased lipid components excretion through bile directly promote the formation of cholesterol stones. Total cholesterol, direct bilirubin and especially lean body weight might provide simple stratification tools for obese women, outlining a high risk profile for developing gallstones.