Page 128 - Human Bile Acid Metabolism: a Postprandial Perspective

Chapter 7
three equidistant identical meals, compared to healthy control subjects (28). We hypothesized that an altered diurnal rhythm of postprandial BA excursions in obese patients with type 2 diabetes contributes to the altered diurnal rhythm in glucose metabolism. In the present study we determined the diurnal rhythm of postprandial BA excursions after three equidistant, equicaloric meals in obese subjects with type 2 diabetes and lean healthy control subjects. We used tandem mass spectrometry to detect the primary BAs cholic acid (CA) and chenodeoxycholic acid (CDCA) and the secondary BAs deoxycholic acid (DCA) and ursodeoxycholic acid (UDCA) in their conjugated and unconjugated forms.
Materials and methods
Subjects
This study is an ancillary study of a previous study investigating the diurnal rhythms in glucose metabolism and adipose tissue gene expression of obese patients with type 2 diabetes (28). Briefly, we included 6 male obese patients with type 2 diabetes according to the 2010 American Diabetes Association (ADA) criteria (10), BMI 25-40 kg/m2, age 30-75 yr, and 6 healthy age-matched male control subjects with BMI ≤ 25 kg/m2. Exclusion criteria were any acute or chronic disease that impairs metabolism or food digestion or absorption, shift work in the month prior to study participation and crossing more than one time zone in the month prior to study participation. In addition, type 2 diabetes patients were excluded if they used any antidiabetic drug other than metformin. Subjects were recruited by announcements at public locations, in local newspapers and patient magazines.
Study protocol
The study was approved by the Institutional Review Board of the AMC, and performed according to the Declaration of Helsinki of October 2004. The study was registered as NTR3234. The study was performed between February 2012 and March 2013 at the department of Endocrinology and Metabolism of the AMC. During a three-day baseline assessment, participants completed food diaries and a sleep-wake log. Subsequently, on the morning of day 1, the average wake-up time and sleep time were determined for each participant from the sleep-wake log. Individual Zeitgeber Times (ZT) were determined with ZT 0 representing average wake-up time. From the lunch on day 1, participants consumed three
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