Abstract
Pancreatogenic diabetes mellitus (T3cDM) is a highly frequent complication of pancreatic disease, especially chronic pancreatitis, and it is often misdiagnosed as type 2 diabetes mellitus (T2DM). A correct diagnosis allows the appropriate treatment of these patients, improving their quality of life, and various technologies have been employed over recent years to search for specific biomarkers of each disease. The main aim of this metabolomic project was to find differential metabolites between T3cDM and T2DM. Reverse-phase liquid chromatography coupled to high-resolution mass spectrometry was performed in serum samples from patients with T3cDM and T2DM. Multivariate Principal Component and Partial Least Squares-Discriminant analyses were employed to evaluate between-group variations. Univariate and multivariate analyses were used to identify potential candidates and the area under the receiver-operating characteristic (ROC) curve was calculated to evaluate their diagnostic value. A panel of five differential metabolites obtained an area under the ROC curve of 0.946. In this study, we demonstrate the usefulness of untargeted metabolomics for the differential diagnosis between T3cDM and T2DM and propose a panel of five metabolites that appear altered in the comparison between patients with these diseases.
Highlights
Diabetes mellitus (DM) is characterized by the destruction or dysfunction of pancreatic β-cells, producing progressive hyperglycemia [1]
It has been reported that around 30% of patients with Chronic pancreatitis (CP) develop type 3c DM (T3cDM) [5], which is often wrongly diagnosed as type 1 DM (T1DM) or especially type 2 DM (T2DM) [6]
350 features were excluded for unacceptable variability (RSD > 30%); 279 features were differentially expressed between study samples (T3cDM and T2DM) and organic solvent (OS) samples and were rejected as contaminants
Summary
Diabetes mellitus (DM) is characterized by the destruction or dysfunction of pancreatic β-cells, producing progressive hyperglycemia [1]. It has been reported that around 30% of patients with CP develop T3cDM [5], which is often wrongly diagnosed as type 1 DM (T1DM) or especially type 2 DM (T2DM) [6]. In 2017, a study in the UK found that 559 of 31,789 adults newly diagnosed with DM had a history of pancreatic disease and that most of them (87.8%) were classified as T2DM [7]. The correct diagnosis of T3cDM and T2DM is important because they are both risk factors for pancreatic cancer (PC) [8,9] and because higher concentrations of hemoglobin A1c are observed in patients with T3cDM, who require insulin earlier in comparison to those with T2DM [10]
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