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.

Disclosure

V. Ketavarapu: None. M. Aslam: None. R. Talukdar: None. R. Amanchy: None. P. Sripadi: None. A.C. Powers: None. K. Narayan: None. K.C. Coate: None. L.R. Staimez: None. R. Jagannathan: None. N. D: None. M. Sasikala: None.

Funding

Science and Engineering Research Board, India Project (CRG/2019/005125)

© 2023 by the American Diabetes Association
2023
Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at http://www.diabetesjournals.org/content/license.