Why do men get gallstones? Roles of abdominal fat and hyperinsulinaemia

The factors predisposing to gallstones in men are unknown except for advancing age. We have investigated them in a random stratified sample of 838 men aged 40-69 years, including 58 with gallstone disease. There was no association between gallstones and body mass index or gain in weight since the age of 20. However, there was a significant and step-wise relationship with waist-hip circumference ratio. Men in the highest quartile of waist-hip ratio had a relative risk of gallstones of 2.1[95% confidence limits (CL) 1.0-4.6] compared with those in the lowest quartile. Men with gallstone disease had increased plasma insulin levels both in the fasting state and after a snack meal, but normal plasma glucose. Men in the highest of three bands of fasting plasma insulin had a relative risk of gallstones of 2.0 (95% CL 1.1-3.6) compared with those in the lowest band. Men in the highest band of both plasma insulin and waist-hip ratio had a three-fold increase in risk of gallstones. There was no association between gallstones and plasma cholesterol, triglycerides, high density lipoprotein (HDL) cholesterol or HDL subfractions. The data suggest that loss of physical fitness with deposition of abdominal fat predisposes men to gallstones or, at least, that change in shape matters more than change in size. A possible mechanism is insulin resistance leading to hyperinsulinaemia.