Elevated levels of betatrophin in patients with newly diagnosed diabetes
Abstract
Introduction. Betatrophin is primarily produced in the liver and regulates the metabolism of triglycerides. Its elevated concentration might be associated with an increased risk of type 2 diabetes. The aim of the study was to evaluate the impact of betatrophin on beta cell function and to compare the concentration of betatrophin in patients newly diagnosed with type 1 diabetes mellitus (T1DM including LADA), type 2 diabetes mellitus (T2DM) and a control group (CG) of healthy volunteers.
Patients and methods. The study included 210 patients with newly diagnosed diabetes (70 with T1DM, 140 with T2DM) and 70 CG. To evaluate the relationship between betatrophin and insulin secretion, a glucagon stimulation test was conducted.
Results. Serum betatrophin concentrations were significantly elevated in T1DM and T2DM in comparison to the control group (3.47 [Q1 = 2.28, Q3 = 4.54] in T1DM vs. 1.81 [Q1 = 1.04, Q3 = 2.67] ng/ml in CG, p < 0.001; 3.12 [Q1 = 1.89, Q3 = 4.48] in T2DM vs. 1.81 [Q1 = 1.04, Q3 = 2.67] ng/ml in CG, p < 0.001). No statistically significant differences in betatrophin concentration were observed between the T1DM and T2DM groups. Significant correlations were established between betatrophin, triglyceride (TG) and high-density lipoprotein (HDL) levels in all study participants, and C-peptide in the T1DM group.
Conclusions. Betatrophin concentration was significantly elevated in patients with newly diagnosed T1DM and T2DM, compared to the control group and could be a biomarker of diabetes. Our study provided evidence which supports the impact of betatrophin on lipid metabolism. The positive correlation between betatrophin and C-peptide in the T1DM group suggests that betatrophin is associated with insulin secretion in T1DM.
Keywords: betatrophinC-peptideglucagon stimulation testnewly diagnosed diabetes
References
- Gray KA, Yates B, Seal RL, et al. Genenames.org: the HGNC resources in 2015. Nucleic Acids Res. 2015; 43: D1079–D1085.
- Dong XY, Pang XW, Yu ST, et al. Identification of genes differentially expressed in human hepatocellular carcinoma by a modified suppression subtractive hybridization method. Int J Cancer. 2004; 112(2): 239–248.
- Quagliarini F, Wang Y, Kozlitina J, et al. Atypical angiopoietin-like protein that regulates ANGPTL3. Proc Natl Acad Sci U S A. 2012; 109(48): 19751–19756.
- Ren G, Kim JiY, Smas CM. Identification of RIFL, a novel adipocyte-enriched insulin target gene with a role in lipid metabolism. Am J Physiol Endocrinol Metab. 2012; 303(3): E334–E351.
- Zhang R. Lipasin, a novel nutritionally-regulated liver-enriched factor that regulates serum triglyceride levels. Biochem Biophys Res Commun. 2012; 424(4): 786–792.
- Abu-Farha M, Al-Khairi I, Cherian P, et al. Increased ANGPTL3, 4 and ANGPTL8/betatrophin expression levels in obesity and T2D. Lipids Health Dis. 2016; 15(1): 181.
- Abu-Farha M, Abubaker J, Noronha F, et al. Higher plasma betatrophin/ANGPTL8 level in type 2 diabetes subjects does not correlate with blood glucose or insulin resistance. Sci Rep. 2015; 5: 10949.
- Chen Xi, Lu P, He W, et al. Circulating betatrophin levels are increased in patients with type 2 diabetes and associated with insulin resistance. J Clin Endocrinol Metab. 2015; 100(1): E96–100.
- Abu-Farha M, Abubaker J, Noronha F, et al. Lack of associations between betatrophin/ANGPTL8 level and C-peptide in type 2 diabetic subjects. Cardiovasc Diabetol. 2015; 14: 112.
- Adamska A, Łebkowska A, Jacewicz M, et al. Serum concentrations of betatrophin and its association with indirect indices of insulin resistance and beta cell function in women with polycystic ovary syndrome. Int J Endocrinol. 2017; 2017: 2316986.
- Yi P, Park JS, Melton DA. Retraction Notice to: Betatrophin: A Hormone that Controls Pancreatic β Cell Proliferation. Cell. 2017; 168(1-2): 326.
- Gusarova V, Alexa CA, Na E, et al. ANGPTL8/betatrophin does not control pancreatic beta cell expansion. Cell. 2014; 159(3): 691–696.
- Cox AR, Lam CJ, Bonnyman CW, et al. Angiopoietin-like protein 8 (ANGPTL8)/betatrophin overexpression does not increase beta cell proliferation in mice. Diabetologia. 2015; 58(7): 1523–1531.
- Cox AR, Barrandon O, Cai EP, et al. Resolving Discrepant Findings on ANGPTL8 in β-Cell Proliferation: A Collaborative Approach to Resolving the Betatrophin Controversy. PLoS One. 2016; 11(7): e0159276.
- Yi P, Park JS, Melton DA. Perspectives on the activities of ANGPTL8/betatrophin. Cell. 2014; 159(3): 467–468.
- Alberti K, Zimmet PZ. Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus. Provisional report of a WHO Consultation. Diabetic Medicine. 1998; 15(7): 539–553, doi: 10.1002/(sici)1096-9136(199807)15:7<539::aid-dia668>3.0.co;2-s.
- Hu H, Sun W, Yu S, et al. Increased circulating levels of betatrophin in newly diagnosed type 2 diabetic patients. Diabetes Care. 2014; 37(10): 2718–2722.
- Al-Daghri NM, Rahman S, Sabico S, et al. Circulating betatrophin in healthy control and type 2 diabetic subjects and its association with metabolic parameters. J Diabetes Complications. 2016; 30(7): 1321–1325.
- Akour A, Kasabri V, Boulatova N, et al. Levels of metabolic markers in drug-naive prediabetic and type 2 diabetic patients. Acta Diabetol. 2017; 54(2): 163–170.
- Yue S, Wu J, Zhang J, et al. The relationship between betatrophin levels in blood and T2DM: a systematic review and meta-analysis. Dis Markers. 2016; 2016: 1–7.
- Gómez-Ambrosi J, Pascual E, Catalán V, et al. Circulating betatrophin concentrations are decreased in human obesity and type 2 diabetes. J Clin Endocrinol Metab. 2014; 99(10): E2004–E2009.
- Yamada H, Saito T, Aoki A, et al. Circulating betatrophin is elevated in patients with type 1 and type 2 diabetes. Endocr J. 2015; 62(5): 417–421.
- Tokumoto S, Hamamoto Y, Fujimoto K, et al. Correlation of circulating betatrophin concentrations with insulin secretion capacity, evaluated by glucagon stimulation tests. Diabet Med. 2015; 32(5): 653–656.
- Gómez-Ambrosi J, Pascual-Corrales E, Catalán V, et al. Altered concentrations in dyslipidemia evidence a role for ANGPTL8//betatrophin in lipid metabolism in humans. J Clin Endocrinol Metab. 2016; 101(10): 3803–3811.
- Zhang R. The ANGPTL3-4-8 model, a molecular mechanism for triglyceride trafficking. Open Biol. 2016; 6(4): 150272.
- Dang F, Wu R, Wang P, et al. Fasting and feeding signals control the oscillatory expression of Angptl8 to modulate lipid metabolism. Sci Rep. 2016; 6: 36926.
- Nidhina Haridas PA, Soronen J, Sädevirta S, et al. Regulation of angiopoietin-like proteins (ANGPTLs) 3 and 8 by insulin. J Clin Endocrinol Metab. 2015; 100(10): E1299–E1307.