Page 136 - Human Bile Acid Metabolism: a Postprandial Perspective

Chapter 7
of the individual BA subtypes or conjugates showed a diurnal rhythm in plasma excursions.
Postprandial BA peaks occurred significantly earlier after all meals in obese patients with type 2 diabetes. Previous publications comparing postprandial BA concentrations between healthy and pathological states have not addressed this (9-11). The earlier peaks may be explained by increased intestinal uptake and/ or decreased liver sinusoidal uptake of BAs (25). Specifically, increased intestinal absorption can be facilitated by hypertrophic changes of the gut mucosa in patients with type 2 diabetes (35; 36). In addition, the expression of hepatic BA transporters is negatively correlated with BMI (37) and reduced hepatic BA uptake may contribute to the earlier peak levels in patients with type 2 diabetes. The difference in peak time did not extend to differences in BA peak concentrations or AUCs, which are mostly determined by meal size and composition (10).
This study was specifically designed to detect diurnal rhythms in postprandial glucose and BA excursions, but not to detect small differences in fasting plasma BA levels or postprandial BA excursions between obese patients with type 2 diabetes and healthy control subjects. Consequently, we cannot confirm previously published studies showing that obese patients with type 2 diabetes have elevated plasma BA levels compared to healthy subjects (9-12). Although we stopped metformin prior to the study, we cannot exclude the possibility that chronic metformin use influenced our results since it increases the bile acid pool within the intestine and modulates the intestinal microbiome (38).
In conclusion, in the present study with equidistant equicaloric meals we did not detect a diurnal rhythm in the postprandial BA responses in either healthy subjects or obese patients with type 2 diabetes. Therefore, the altered diurnal rhythm of glucose tolerance in patients with type 2 diabetes is unlikely to be caused by an altered diurnal rhythm in plasma BA responses.
134