Metabolomic characteristics of fatty pancreas

Objective:

Increased pancreatic fat content (PFC) is associated with impaired beta cell function in patients with prediabetes. Recent data suggest that pancreatic fat together with factors such as hepatokines and high levels of free fatty acids affects insulin secretion. We investigated possible circulating markers of pancreatic fat by applying a broad metabolomic approach.

Methods:

361 participants of the Tübingen Family Study (TUEF) who are at increased risk of type 2 diabetes were included. All participants underwent a 75 g OGTT to assess glucose tolerance. Insulin secretion was estimated with AUC_{C-Peptide 0 – 120}/AUC_{Glucose 0 – 120}. Magnetic resonance imaging was performed to quantify PFC. From the subgroup of 152 subjects with prediabetes (IFG and/or IGT), individuals with extremes of high and low PFC (20 each) were selected. Groups were matched for anthropometric parameters, visceral fat content, liver fat content and insulin sensitivity. Plasma metabolites were analyzed using the AbsoluteIDQ® p400 HR Kit by Biocrates®.

Results:

PFC of all 152 subjects with prediabetes correlated negatively with insulin secretion, adjusted for insulin sensitivity (beta -0.16, p < 0.05). Applying an ANOVA with false discovery rate approach levels of aminoacids, biogenic amines and monosaccharides were similar between the groups with high/low PFC (p > 0.90). Levels of polar lipids such as lysophosphatidylcholines, phosphatidylcholines, sphingomyelins and ceramides as well as levels of neutral lipids such as aclycarnitines, diglycerides, triglycerides, cholesteryl esters did not differ between the groups (p > 0.90).

Discussion:

PFC is negatively associated with insulin secretion, but is not associated with a specific metabolic fingerprint in plasma of individuals with prediabetes.