Elsevier

Annals of Epidemiology

Volume 12, Issue 2, February 2002, Pages 131-140
Annals of Epidemiology

Original article
Hyperinsulinemia, Dyslipidemia, and Obesity as Risk Factors for Hospitalized Gallbladder Disease: A Prospective Study

https://doi.org/10.1016/S1047-2797(01)00260-5Get rights and content

Abstract

PURPOSE: Prospective studies of gallbladder disease have investigated a limited number of risk factors and have been conducted predominantly in women. Determinants of hospitalized gallbladder disease were examined in a large, population-based cohort of men and women.

METHODS: Subjects, aged 45–64 years, were participants in the Atherosclerosis Risk in Communities (ARIC) Study who reported no history of gallbladder disease at baseline (n = 12,773). Incident cases of gallbladder disease were identified through surveillance of hospital discharges between the baseline visit (1987–1989) and 1996.

RESULTS: The crude incidence rate of hospitalized gallbladder disease was 3.8 per 1000 person-years. In women, increasing risk was observed for increasing levels of body-mass index and waist-to-hip ratio, whereas in men, increased risk was observed only in the morbidly obese (BMI ≥ 35). Fasting serum insulin, low HDL cholesterol, elevated triglycerides, and hormone replacement therapy were all positively associated with gallbladder disease risk. The relative risks associated with having one, two, or three or more components of the “multiple metabolic syndrome” in men were 1.45 (95% CI = 0.9–2.3), 2.17 (1.3–3.6), and 2.34 (1.3–4.3), respectively.

CONCLUSIONS: In men, hyperinsulinemia and dyslipidemia may have some role in the etiology of gallbladder disease beyond their association with obesity, whereas in women, increased body size, central adiposity, and hormone replacement therapy may be more important determinants of gallbladder disease.

Introduction

Gallbladder disease constitutes a considerable proportion of all hospitalizations related to digestive diseases in the United States. In 1996, there were an estimated 386,000 hospitalizations for cholelithiasis (1), nearly half a million cholecystectomies (1), and 2800 deaths related to gallbladder diseases other than cancer (2). Health expenditures related to gallstones alone have been estimated at $5 billion annually (3). Although it is well known that females are more likely than males to develop gallbladder disease, and that certain ethnic groups, such as Mexican 4, 5 and Native Americans 6, 7, are at increased risk, preventive efforts aimed at reducing the morbidity and economic burden associated with gallbladder disease will be dependent upon the identification of modifiable risk factors.

Although the role of obesity in gallbladder disease has been demonstrated widely, hypotheses regarding other risk factors have not been tested extensively using prospective methods. Prospective data in men and African Americans are particularly scarce. The comprehensive baseline data and thorough verification of cohort member hospitalizations make the Atherosclerosis Risk in Communities (ARIC) Study a convenient resource for examining a wide range of risk factors for incident, clinically recognized gallbladder disease. A number of potential risk factors are examined in this report, but particular attention is given to anthropometric variables, lipids, insulin, the combined effect of these factors as reflected by the “multiple metabolic syndrome” (8), and the sex-specific difference in roles these factors may play in the pathogenesis of gallbladder disease.

Section snippets

Subjects

The ARIC Study is a population-based, prospective cohort study of the natural history of cardiovascular disease in four U.S. communities: Forsyth County, NC; Jackson, MS (African Americans only); suburban Minneapolis, MN; and Washington County, MD. Complete details have been published elsewhere (9). Between 1987 and 1989, men and women, ages 45–64 years were recruited from each community and invited to attend a baseline clinic examination (Visit 1). After providing written informed consent,

Results

A total of 397 individuals were identified as having incident hospitalized gallbladder disease events during 104,872 person-years of follow-up (Table 1). Of the 397 incident cases, 343 (86%) had ICD-9 codes for cholecystectomy (51.22 or 51.23), and 347 (87%) had codes indicative of gallbladder calculus with or without cholecystitis (574.0, 574.1, or 574.2). The crude incidence rate of gallbladder disease hospitalization in this cohort was 3.8 per 1000 PY (Table 1). The crude incidence rate was

Discussion

Only one other prospective study of hospitalized gallbladder disease has included both whites and African Americans. Based on hospital discharge diagnoses of gallbladder disease, Sichieri and coworkers (16) observed comparable incidence rates per 1000 PY of 4.1 in white women, 2.6 in white men, 2.4 in African American women, and 1.5 in African American men. The younger age of the cohort in that study likely resulted in slightly lower incidence rates since increasing age has been associated with

Selected Abbreviations and Acronyms

ARIC = Atherosclerosis Risk in Communities

BMI = body mass index

HDL = high-density lipoprotein

ICD = International Classification of Diseases

LDL = low-density lipoprotein

PY = person-years

WHR = waist-to-hip ratio

Acknowledgements

This research was supported by contracts N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, and N01-HC-55022 from the U.S. National Heart, Lung, and Blood Institute. The authors thank the staff and participants in the ARIC Study for their important contributions.

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