The physiological role of bile acid‐mediated glucagon‐like peptide‐1 release in humans: The Cerebrotendinous Xanthomatosis Mixed Meal Test study.

Bile acids (BAs) have traditionally been regarded as nutrient‐emulgators but may play an important role in energy metabolism. Primary bile acids are secreted in the bile and are dehydroxylated by the bacterial flora in the colon to form the secondary bile acids. BAs may stimulate the production of glucagon‐like peptide‐1 (GLP‐1) that stimulates insulin secretion and inhibits glucagon secretion in the pancreas in a glucose‐dependent fashion. Additionally, it reduces gastrointestinal motility and appetite. Cerebrotendinous xanthomatosis (CTX, OMIM #213700) is an autosomal recessive disorder characterized by a deficiency of sterol 27‐hydroxylase leading to a defective BA synthesis (decreased amount of the BA chenodeoxycholate (CDCA)). It is not known whether CTX patients exhibit physiological deficiencies with regard to
postprandial plasma GLP‐1 responses, glucose uptake, free fatty acid (FFA) suppression and plasma insulin levels. Studying postprandial glucose metabolism in these patients will provide insight in the metabolic role of BAs. We hypothesize that CTX patients, when untreated, have lower postprandial GLP‐1 and insulin levels with higher plasma glucose and FFA levels compared to matched healthy control subjects.

Thus, the primary aim of the present protocol is to determine the role of chenodeoxycholate for postprandial GLP‐1 responses (and the resulting metabolic consequences) in humans.

We hypothesize that CTX patients, when untreated for a short period, differ from matched healthy controls in the response to a test meal. CTX patients are expected to have lower postprandial GLP‐1 and insulin levels with higher plasma glucose and FFA levels.

One occoasion, 3hr meal test.

Mixed meal test: Liquid meal test (standard protocol) during which blood withdrawals are taken for 2-4 hours to measure glucose, insulin, bile acids and incretins.