Page 135 - Human Bile Acid Metabolism: a Postprandial Perspective

Discussion
In the present study, we analyzed the diurnal rhythm in postprandial responses of all individual BA subtypes after equidistant equicaloric meals in type 2 diabetes patients and controls. Obese patients with type 2 diabetes show an attenuated diurnal rhythm of postprandial plasma glucose AUCs in response to equidistant identical meals, but no altered diurnal rhythm in postprandial BA AUCs. Therefore, it is unlikely that an altered rhythm in postprandial BA responses contributes to the disturbed diurnal rhythm in glucose metabolism in obese patients with type 2 diabetes.
Despite the demonstration in healthy human volunteers (17; 19) of a circadian
rhythm in BA synthesis, we did not observe a diurnal rhythm of postprandial
total BA excursions in either obese patients with type 2 diabetes or controls. It is
important to distinguish postprandial BA levels from BA biosynthesis. The former
can be measured with different mass spectrometry techniques whereas the latter
can be analyzed by different isotopic dilution methods or the measurement of
plasma 7α-hydroxy-4-cholesten-3-one (C4) levels (17; 19; 31). C4 strongly relates
to the hepatic enzymatic activity of CYP7A1 during diurnal changes. Possibly,
the rhythm in BA biosynthesis is buffered by the BA pool in the gallbladder and 7 the intestine, since the majority of postprandial plasma BAs originates from the
recirculating pool. Studies from the late 1970’s shows that the major determinant of serum BAs is their rate of intestinal absorption (25). Alternatively, the diurnal rhythm in BA biosynthesis may be counteracted by a rhythm in hepatic BA reuptake from the portal circulation, since in healthy humans hepatic cholesterol synthesis peaks during the night (32; 33), whereas BA biosynthesis peaks during the daytime (17).
Since individual BA subtypes have different receptor binding affinities (13-15), we analyzed the diurnal rhythms in the plasma excursions of cholic acid (CA) and chenodeoxycholic acid (CDCA) and the secondary BAs deoxycholic acid (DCA) and ursodeoxycholic acid (UDCA) in their conjugated and unconjugated forms. CDCA was the major constituent of postprandial BA excursions, and most BAs appeared in the glycine-conjugated form, both in control subjects and in obese patients with type 2 diabetes. This is consistent with previous studies on postprandial BA excursions in healthy subjects (12; 22; 26; 27; 34). However, none
Diurnal rythm of bile acids
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