Increased serum levels of betatrophin in pancreatic cancer-associated diabetes.
Long-standing diabetes or glucose intolerance is recognized as a crucial event in the process of pancreatic cancer. Betatrophin, a novel liver-derived hormone, promotes β-cell proliferation and improves glucose intolerance. However, the relationship between betatrophin and PDAC-associated diabetes is not fully understood. To evaluate the serum betatrophin levels in PDAC-associated diabetes, a total 105 Taiwanese subjects including 15 healthy subjects, and 12 patients having PDAC with normal glucose tolerance (PDAC-NGT), 12 patients having PC with impaired glucose tolerance (PDAC-IGT), and 66 patients having PC with diabetes mellitus (PDAC-DM) were enrolled for this study. Serum betatrophin and carbohydrate antigen 19-9 (CA19-9) levels were analyzed by enzyme-linked immunosorbent assay (ELISA). Compared to healthy subjects, PDAC patients had higher levels of betatrophin and CA19-9. Consistently, betatrophin protein was significantly expressed in pancreatic ductal of PDAC-associated DM patients using immunohistochemistry (IHC) method. Furthermore, multivariate regression analysis showed the betatrophin was significantly and positively independent with T category (β= 0.605, P=0.010), serum albumin (β= 0. 423, P=0.021), lipase (β= 0.292, P=0.039), and blood urea nitrogen (BUN) (β= 0.303, P=0.040). Further, the betatrophin was three folds of having PDAC-associated diabetes with the highest odds ratio [OR=3.39; 95% CI (1.20-9.57); P=0.021) and receiver operating characteristic (ROC) curve analysis showed that AUC value of betarophin was 0.853 which is slightly larger than AUC value of CA19-9 (0.792) in PDAC-DM patients. Interestingly, AUC value of betarophin plus CA19-9 was 0.988 in PDAC-DM patients. Therefore, betatrophin combined CA19-9 may serve as a potential biomarker for PDAC-associated diabetes.
Department of Biological Science and Technology, National Chiao Tung University, Hsinchu 300, Taiwan.
Hendra
H
Susanto
Department of Biological Science and Technology, National Chiao Tung University, Hsinchu 300, Taiwan.
Ta-Yu
TY
Liu
Department of Biological Science and Technology, National Chiao Tung University, Hsinchu 300, Taiwan.|Department of Internal Medicine, National Taiwan University Hospital Hsin-Chu Branch, Hsinchu 300, Taiwan.
Chang-Chiang
CC
Chen
Institute of Statistics, National Chiao Tung University, Hsinchu 300, Taiwan.
Jerry D T
JD
Purnomo
Department of Biological Science and Technology, National Chiao Tung University, Hsinchu 300, Taiwan.
Shu-Fan
SF
Chen
Department of Biological Science and Technology, National Chiao Tung University, Hsinchu 300, Taiwan.
Chih-Hong
CH
Wang
D000368:Aged; D000091306:Angiopoietin-Like Protein 8; D000075802:Angiopoietin-like Proteins / Q000097:blood*; D014408:Biomarkers, Tumor / Q000097:blood; D018395:CA-19-9 Antigen / Q000097:blood; D016022:Case-Control Studies; D049109:Cell Proliferation; D048909:Diabetes Complications / Q000097:blood*; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000097:blood*; D036361:Peptide Hormones / Q000097:blood*; D012372:ROC Curve; D013624:Taiwan
C576683:ANGPTL8 protein, human; D000091306:Angiopoietin-Like Protein 8; D000075802:Angiopoietin-like Proteins; D014408:Biomarkers, Tumor; D018395:CA-19-9 Antigen; D036361:Peptide Hormones
betatrophin; diabetes; glucose intolerance; insulin resistance; pancreatic cancer