Page 38 - Human Bile Acid Metabolism: a Postprandial Perspective

Chapter 2
homeostasis (1, 6, 16, 17). Such a concept could fit with the established notion that in T2D patients with a relatively low HbA1c (~7.5% [58 mmol/mol] or less), postprandial glycemia, as opposed to preprandial blood glucose, makes the predominant contribution to overall glycemic control (10). Indeed, postprandial hyperglycemia—an early defect seen in impaired glucose tolerance and T2D—is a major contributor to HbA1c and is even recognized as an independent risk factor for cardiovascular disease (18, 19)—alink that may also prove important considering the emerging evidence suggesting a role of bile acids in cardioprotection (20).
Substantial rearrangements of bile acid metabolism in T2D patients are well established, including changes in pool size, pool composition, synthesis rate, and postprandial plasma concentrations (21–27). We show that postprandial concentrations of secondary bile acids were higher in T2D patients vs NGT subjects. Indeed, on most study days, even fasting concentrations of total and secondary bile acids were higher in T2D patients vs NGT subjects. Moreover, we found increased postprandial CA concentrations (mainly glycine amidates), whereas CDCA concentrations (the predominant bile acid) were comparable among the groups. The design of the isovolemic and isocaloric meals allowed us to dissect in more detail how postprandial bile acid concentrations are affected by the fat content in the meal. Clearly, in both groups the high fat meal resulted in much higher plasma bile acid concentrations compared to the other meals—in fact, the CA and CDCA concentrations in T2D patients were equaled in the NGT group after the high fat meal (Figure 2). All four stimuli led to augmented DCA and UDCA concentrations in the T2D patients vs NGT subjects. Hence, postprandial concentrations of bile acids were clearly influenced acutely by meal composition. Most likely, this reflected increased gallbladder emptying after a larger fat stimulus (11) and increased enterohepatic circulation of all bile acid species, but it could also point toward the notion of acute effects of macronutrient composition constituting an important regulator of postprandial bile acid pool composition similar to changes seen after more extensive diet changes (28). Indeed, the meals also differed with regard to carbohydrate and protein content. Interestingly, even oral glucose resulted in increased TBA plasma concentrations in T2D patients, whereas concentrations in NGT subjects were almost unaffected. This could fit with our finding of increased gallbladder emptying in the T2D group (~30 vs ~20% in the NGT group) after the OGTT (11). Indeed, oral glucose is a minor stimulus for gallbladder contraction but—perhaps counterintuitively—a rather good stimulus for FGF19 secretion,
36