An inconsistent association has been found between gallbladder disease and
diabetes mellitus. We hypothesized that insulin resistance rather than diab
etes status may be a primary factor involved in gallstone formation. A tota
l of 5,653 adult participants in the third United States National Health an
d Nutrition Examination Survey without known diabetes underwent gallbladder
ultrasonography and phlebotomy after an overnight fast for measurement of
serum insulin, C-peptide, and glucose. Gallbladder disease was defined as u
ltrasound-documented gallstones or evidence of cholecystectomy. Subjects we
re characterized as having normal fasting glucose (<110 mg/dL), impaired fa
sting glucose (110 to < 126 mg/dL), or undiagnosed diabetes (greater than o
r equal to 126 mg/dL). After controlling for other known gallbladder diseas
e risk factors, among women, undiagnosed diabetes was associated with incre
ased risk of gallbladder disease (prevalence ratio [PR] = 1.91, 95% confide
nce interval [CI] = 1.29-2.83); whereas impaired fasting glucose was unasso
ciated, Gallbladder disease risk in women increased with levels of fasting
insulin (PR = 1.63, 95% CI = 1.11-2.40) and C-peptide (PR = 2.07, 95% CI =
1.32-3.25) comparing highest to lowest quintiles. However, the association
of gallbladder disease with undiagnosed diabetes was not diminished when th
e model included fasting insulin (PR = 1.85, 95% CI = 1.24-2.77), In men, t
here was a statistically nonsignificant association with undiagnosed diabet
es (PR = 2.11, 95% CI = 0.76-5.85), but no association of gallbladder disea
se with insulin or C-peptide, Among women higher fasting serum insulin leve
ls increased the risk of gallbladder disease, bur did not account for the i
ncreased risk in persons with diabetes.