<b>OBJECTIVE</b>
<div><p>To
investigate the roles of insulin clearance and insulin secretion in the
development of hyperinsulinemia in obese subjects and to reveal the association
between insulin clearance and bile acids (BAs).</p>
<p><b> </b></p>
<p><b>RESEARCH DESIGN AND METHODS</b></p>
<p>In cohort 1, insulin secretion, sensitivity and endogenous
insulin clearance were evaluated with an oral glucose tolerance test (OGTT) in
460 recruited participants. In cohort 2, 81 participants underwent an <a>intravenous glucose tolerance test</a> (IVGTT) and a
hyperinsulinemic-euglycemic clamp to assess insulin secretion, endogenous and
exogenous insulin clearance, and insulin sensitivity. Based on insulin
resistance levels ranging from mild to severe, nondiabetic obese participants were
further divided into 10 quantiles in cohort 1 and into tertiles in cohort 2. Forty
serum BAs were measured in cohort 2 to examine the association between BAs
and insulin clearance.</p>
<p><b> </b></p>
<p><b>RESULTS</b></p>
<p>All obese participants had impaired insulin clearance,
and it worsened with additional insulin resistance in nondiabetic obese
subjects. However, insulin secretion was unchanged from quantile 1 to 3 in
cohort 1, and no difference was found in cohort 2. After adjustments for all confounding
factors, serum conjugated BAs, especially glycodeoxycholic acid (GDCA, β=-0.335,
P=0.004) and taurodeoxycholic acid (TDCA, β=-0.333, P=0.003), were negatively correlated
with insulin clearance<a>. The ratio of </a><a></a><a>unconjugated to conjugated BAs (UnconBA/ConBA</a>, β=0.335, P=0.002) was positively correlated
with insulin clearance.</p>
<p><b> </b></p>
<p><b>CONCLUSIONS</b></p>
<p>Hyperinsulinemia in obese subjects might be primarily induced by decreased
insulin clearance rather than increased insulin secretion. Changes in
circulating conjugated BAs, especially GDCA and TDCA, might play an important role in regulating insulin
clearance.</p></div>