Publications

Abstract

CONTEXT: The etiological mechanism of bile acid (BA) effects on insulin resistance and obesity is unknown. OBJECTIVE: To determine if plasma BA are elevated in human obesity and/or insulin resistance. DESIGN: Observational study. SETTING: Academic research center. PARTICIPANTS: 71 adult volunteers formed four groups: lean insulin-sensitive (BMI</=25kg/m 2, HOMA-IR<2.0, n=19), overweight/obese non-diabetic who were either insulin-sensitive (Obsensitive, BMI>25kg/m 2, HOMA-IR<1.5, n=11), or insulin-resistant (Obresistant, BMI>25kg/m 2, HOMA-IR>3.0, n=20), and type 2 diabetes (T2D, n=21). MAIN OUTCOME MEASURES: Insulin sensitivity by hyperinsulinemic-euglycemic clamp, body composition by dual energy x-ray absorptiometry, abdominal fat distribution and liver density by CT and plasma BA. RESULTS: In the Obresistant group, glucose infusion rate/fat free mass (GIR/FFM, an inverse measure of insulin resistance) was significantly lower, and visceral and liver fat higher, compared to lean and Obsensitive subjects, despite similar total adiposity in Obresistant and Obsensitive. Total BA concentrations were higher in Obresistant (2.62+/-1.5mmol/L, p=0.03) and T2D (3.36+/-2.26mmol/L, p=0.0004) versus Obsensitive (1.16+/-0.47mmol/L), but were similar between Obsensitive and lean (2.31+/-1.43mmol/L). Total BA were positively associated with waist circumference (R=0.245, p=0.041), visceral fat (R=0.360, p=0.002) and fibroblast growth factor 21 (R=0.341, p=0.004) and negatively associated with insulin sensitivity (R=-0.395, p=0.001), abdominal subcutaneous fat (R=-0.352, p=0.003), adiponectin (R=-0.375, P=0.001) and liver fat (Hounsfield units, an inverse marker of liver fat, R=-0.245, p=0.04). Conjugated BA were additionally elevated in T2D individuals (p<0.001). CONCLUSIONS: BA concentrations correlated with abdominal, visceral and liver fat in humans, though an etiological role in insulin resistance remains to be verified.