Cholestasis and Autoimmune Liver DiseaseGallbladder disease is associated with insulin resistance in a high risk Hispanic population
Introduction
Cholesterol gallstone disease (GS) is highly prevalent in Western countries [1], [2], [3], [4]. Common risk factors of GS worldwide besides sex, age, obesity, parity and diabetes [1], [2], [3], [4], are Amerindian race [4], [5], [6], [7] and familial clustering [1], [8]. The association of GS to common metabolic abnormalities including obesity, diabetes, dyslipidemia and hyperinsulinemia [1], [2], [11], [12], [13], [14], [15], [16] has supported the hypothesis that GD is another member of the metabolic syndrome (MS) [17], [18], [19], as defined by the National Cholesterol Education Program's Adult Treatment Panel III report (NCEP ATP III) [20]. The current more accepted pathogenic link between insulin resistance and GS is the 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 [1], [2], [3], [4].
Insulin resistance and MS, besides the abnormalities of glucose and lipid metabolism, it includes a prothrombotic and a proinflammatory state, which are considered to play an important role in the pathogenesis of atherosclerosis and cardiovascular diseases [21], [22], [23], [24], [25]. Furthermore, some epidemiological studies have shown that cardiovascular disease is more frequent in gallstone patients suggesting a pathogenic link between these chronic diseases [26], [27], [28], [29]. Silent GS usually evolves with chronic inflammation of the gallbladder [9], [10]. It is generally accepted that chronic inflammation of the gallbladder in GS is induced by intermittent obstruction of the cystic duct, physical trauma by the presence of cholesterol crystals and stones, and occasional chronic bacterial infection, conditions that can be asymptomatic [9], [10]. However, chronic inflammation of the gallbladder could also be present in the absence of gallstones [30]. These observations allowed us to speculate that elevations of proinflammatory cytokines associated to obesity and insulin resistance [31], [32] could also participate in the pathogenesis of GD by promoting inflammation of the gallbladder mucosa.
Several biomarkers of low-grade systemic inflammation, particularly serum C- reactive protein (CRP) concentration, have been found associated to active low-grade chronic inflammation and to atherosclerosis. Serum CRP concentration has shown the strongest association with symptomatic atherosclerotic diseases (reviewed in [33], [34], [35], [36]). Serum CRP has also been found elevated in a number of chronic inflammatory diseases including chronic obstructive pulmonary disease [37], periodontitis [38], and rheumatoid arthritis [39], all of which could promote atherosclerosis and cardiovascular diseases through the increase of circulating proinflammatory cytokines (reviewed in [35], [36], [40], [41]). One of this chronic conditions could also be silent GS and chronic cholecystitis.
We compared here insulin resistance, metabolic parameters of the MS and serum CRP concentrations between a cohort of asymptomatic GS patients and a control group in a well characterized population. Results show that insulin resistance is an important risk factor for GS and suggests that GS is a constituent of the MS in this very high risk Chilean Hispanic population. No association was found between serum CRP concentrations and GS.
Section snippets
Population sample
This is a nested case–control study that included individuals from an initial sample of 1581 Hispanic subjects. Participants were 20–85 years old randomly selected middle low socio-economic subjects from a sample of households from the south-eastern urban area of Santiago and that participated in 1993 in a genetic epidemiology study of GS [7]. A computer program was used to select blocks at random to assure proportional representation. From the initial sample of subjects, by the year 2000, 58
Results
The general characteristics of control subjects and individuals with silent GS, cholecystectomy and total GS studied are shown in Table 1. There were 582 control individuals with 59% of women. Patients with GS were older than controls. From the total population with GS, 83% were women. The overall prevalence rate of total GS was 34% with a total of 299 patients, 42% with silent GS and 58% with a previous cholecystectomy. BMI and waist circumference were significantly higher among subjects with
Discussion
The present study demonstrates that insulin resistance, MS and fatty liver are associated to total GS in a Hispanic population that is prone to cholesterol gallstone formation [7]. It is important to emphasize that all subjects were studied under normal living conditions in only one point in time, therefore the relationships found in the analysis of the data should only be considered as potential associated risk factors for GS. Secondly, because of the relatively small number of individuals
Acknowledgements
This study was supported by the Fondo Nacional Científico y Tecnológico (FONDECYT), grants no. 1030744 to FN and no. 1040820 to JFM.
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