1262-P: Circulating Lysophosphatidic Acid Levels Suggest a Metabolic Pathway in T3cDM and Distinguish It from T2DM

• Published in: Diabetes (New York, N.Y.) Vol. 72; no. Supplement_1; p. 1
• Main Authors: KETAVARAPU, VIJAYASARATHY, ASLAM, MOHSIN, TALUKDAR, RUPJYOTI, AMANCHY, RAMARS, SRIPADI, PRABHAKAR, POWERS, ALVIN C., VENKAT NARAYAN, K.M., COATE, KATIE C., STAIMEZ, LISA R., JAGANNATHAN, RAM, REDDY D, NAGESHWAR, SASIKALA, MITNALA
• Format: Journal Article
• Language: English
• Published: New York American Diabetes Association 20-06-2023
• Subjects: Age; Diabetes; Diabetes mellitus; Fatty acids; Liquid chromatography; Lysophosphatidic acid; Mass spectrometry; Mass spectroscopy; Metabolic pathways; Metabolites; Metabolomics; Pancreatitis; Patients; Prediction models; Scientific imaging
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/db23-1262-P

Introduction: Diabetes associated with chronic pancreatitis (T3cDM) has distinct clinical features. We investigated metabolomics signature to distinguish T3cDM from T2DM.
Methods: Study participants (n=200); treatment naïve nonalcoholic calcific chronic pancreatitis [CP] patients (n=106, age 34.4±11.1 years, BMI 20.9±2.8), T2DM patients (n=68, age 46±10.7 years BMI 27.0±5.8), healthy controls (n=26, age 31.0±5.3 years, BMI 25.0±2.8) were recruited prospectively. OGTT was performed to define diabetes (ADA criteria) with 60% CP patients being normoglycemic, 19% having prediabetes and 21% with diabetes. Metabolomics was done on fasting plasma samples using liquid chromatography/mass spectrometry and quantifications were measured on tandem mass spectrometry. Student’s t-test, PLS-DA, ROCs were used to compare and compute to assess the performance of identified metabolites in distinguishing diabetes subtypes (T3cDM and T2DM). Regression analysis was employed to develop a prediction model.
Results: A total of 5493 and 4104 metabolites were detected in T3cDM and T2DM respectively. Untargeted metabolome profiling identified significant differences in fatty acid conjugates in CP. Fatty acid conjugates were 28% in normoglycemic CP, 60% in prediabetic CP, 13% in T3cDM as compared to 42% in controls. Among them, 57 fatty acid conjugates showed increased peak intensities. Comparison of absolute quantifications identified higher lysophosphatidic acid (LPA) in T3cDM 40.50±6.55, T2DM 21.65 ± 1.75; p=0.01 in comparison to controls 16.20±3.4 ng/ml. Sensitivity and specificity for LPA were 81.8%, 78.6% with AUC 80% (p<0.0001), 95% CI (70.6-87.8). Prediction model (null and full model p<0.0001) and its performance (Hosmer-Lemeshow test p=0.9) indicated high accuracy (AUC 87%; 95% CI, 77.8-92.7).
Conclusion: Increased Lysophosphatidic acid levels implicate glycerolipid pathway in the pathogenesis of T3cDM and can be used to distinguish T3cDM from T2DM.