Changes in Circulating Bile Acid Subtypes in Response to Weight-loss Diets Are Associated with Improvements in Glycemic Status and Insulin Resistance: The POUNDS Lost Trial

Objective: Various primary and secondary bile acids (BAs) may play pivotal roles in glucose/insulin metabolism. We investigated whether changes in specific BA subtypes were associated with long-term changes in glucose and insulin sensitivity.

Methods: This study included 515 adults with overweight or obesity who participated in a 2-year intervention study of weight-loss diets with different macronutrient intakes. Circulating primary and secondary unconjugated BAs and their taurine-/glycine-conjugates were measured at baseline and 6 months after the interventions. We analyzed associations of changes in BA subtypes with two-year changes in fasting glucose, insulin, and insulin resistance (HOMA-IR).

Results: Greater decreases in primary and secondary BA subtypes induced by the interventions were significantly associated with greater reductions of fasting insulin and HOMA-IR at 6 months, showing various effects across the BA subtypes. The reductions of specific BA subtypes (chenodeoxycholate [CDCA], taurocholate [TCA], taurochenodeoxycholate [TCDCA], and taurodeoxycholate [TDCA]) were significantly related to improved glucose levels at 6 months. The initial (6-month) decreases in primary and secondary BA subtypes (glycochenodeoxycholate [GCDCA], TCDCA, and glycoursodeoxycholate [GUDCA]) were also significantly associated with long-term improvements in glucose and insulin metabolism over 2 years. We found significant interactions between dietary fat intake and changes in the BA subtypes for changes in glucose metabolism (P < 0.05).

Conclusions: Weight-loss diet-induced changes in distinct subtypes of circulating BAs were associated with improved glucose metabolism and insulin sensitivity in adults with overweight or obesity. Dietary fat intake may modify the associations of changes in BA metabolism with glucose metabolism.