ORIGINAL ARTICLE
Evaluation of the Circulating Betatrophin Concentration and its Possible Correlations Among Diabetic Patients with Dyslipidemia
Dislipidemili Diyabetik Hastalarda Dolaşımdaki Betatrofin Konsantrasyonunun ve Muhtemel Korelasyonlarının Değerlendirilmesi
Received Date : 27 Sep 2018
Accepted Date : 16 Dec 2018
Rasha M. HUSSEIN*, **
*Department of Biochemistry, Faculty of Pharmacy, Beni-Suef University, 62514 Beni-Suef, Egypt
**Department of Pharmaceutics and Pharmaceutical Technology, College of Pharmacy, Mutah University, Karak, Jordan
Doi: 10.25179/tjem.2018-63011 - Makale Dili: EN
Turk J Endocrinol Metab 2019;23:1-7
ABSTRACT
Objective: The circulating betatrophin levels in diabetic patients, treated with insulin or with oral hypoglycemic agents, were measured. The correlation between betatrophin levels and the glucose/lipid variables was also analyzed.
Material and Methods: Thirty-six diabetic patients (18 insulin- treated and 18 oral hypoglycemics-treated) and 16 age-and sex-matched non-diabetic controls were enrolled. The serum levels of betatrophin, glucose, and lipids were measured.
Results: The serum betatrophin levels were significantly lower in both the insulin-treated and oral hypoglycemicstreated diabetics compared to the controls (32.8±3.6 and 48.4±5.2 vs. 54.4±3.7, respectively, p<0.001). Pearson’s bivariate correlation analysis showed that betatrophin was positively correlated with total cholesterol (r=0.303, p=0.029), LDL-cholesterol (r=0.339, p=0.014) and triglyceride (r=0.562, p=0.015) levels.
Conclusion: The circulating betatrophin levels were reduced in diabetic patients compared to the non-diabetic controls, and positively correlated with lipid parameters but not with glucose levels.
Keywords: ANGPTL8; betatrophin; Diabetes mellitus; glucose; lipids
ÖZET
Amaç: İnsülin veya oral hipoglisemik ajanlarla tedavi edilen diyabetik hastalarda dolaşımdaki betatrofin seviyeleri ölçüldü. Ayrıca, betatrofin seviyeleri ile glukoz/lipit değişkenleri arasındaki korelasyon analiz edildi.
Gereç ve Yöntemler: Otuz altı diyabetik hasta (insülinle tedavi edilen 18 ve oral hipoglisemik ile tedavi edilen 18), yaş ve cinsiyeti eşleştirilmiş 16 diyabetik olmayan kontrol çalışmaya dâhil edildi. Serum betatrofin, glukoz ve lipit seviyeleri ölçüldü.
Bulgular: Serum betatrofin düzeyleri hem insülinle hem de oral hipoglisemikle tedavi edilen diyabetiklerde kontrollere kıyasla anlamlı derecede düşük bulundu (sırasıyla 32,8±3,6 ve 48,4±5,2’ye karşı 54,4±3,7, p<0,001). Pearson iki değişkenli korelasyon analizi, betatrofinin total kolesterol (r=0,303, p=0,029), LDL-kolesterol (r=0,339, p=0,014) ve trigliserid (r=0,562, p=0,015) düzeyleri ile pozitif korelasyon gösterdiğini ortaya koydu.
Sonuç: Dolaşımdaki betatrofin seviyeleri diyabetik hastalarda diyabetik olmayan kontrollere göre azaldı ve lipit parametreleriyle pozitif korelasyon gösterdi, ancak glukoz seviyeleri ile göstermedi.
Anahtar Kelimeler: ANGPTL8; betatrofin; Diabetes mellitus; glukoz; lipidler
KAYNAKLAR
- Gao T, Jin K, Chen P, Jin H, Yang L, Xie X, Yang M, Hu C, Yu X. Circulating betatrophin correlates with triglycerides and postprandial glucose among different glucose tolerance statuses--a case-control study. PLoS One. 2015;10:e0133640. [Crossref] [PubMed]
- Zaccardi F, Webb DR, Yates T, Davies MJ. Patho- physiology of type 1 and type 2 diabetes mellitus: a 90-year perspective. Postgrad Med J. 2015;92:63-69. [Crossref] [PubMed]
- Tuomi T, Santoro N, Caprio S, Cai M, Weng J, Groop L. The many faces of diabetes: a disease with in- creasing heterogeneity. Lancet. 2014;383:1084- 1094. [Crossref]
- Keenan HA, Sun JK, Levine J, Doria A, Aiello LP, Eisenbarth G, Bonner-Weir S, King GL. Residual in- sulin production and pancreatic β-cell turnover after 50 years of diabetes: Joslin Medalist Study. Dia- betes. 2010;59:2846-2853. [Crossref] [PubMed]
- Bagust A, Beale S. Deteriorating beta‐cell function in type 2 diabetes: a long ‐term model. QJM. 2003;96:281-288. [Crossref] [PubMed]
- Zhang R. Lipasin, a novel nutritionally-regulated liver-enriched factor that regulates serum triglyc- eride levels. Biochem Biophys Res Commun. 2012;424:786-792. [Crossref] [PubMed]
- Kugelberg E. Diabetes: betatrophin--inducing β -cell expansion to treat diabetes mellitus? Nat Rev En- docrinol. 2013;9:379. [Crossref] [PubMed]
- Lickert H. Betatrophin fuels β cell proliferation: first step toward regenerative therapy? Cell Metab. 2013;18:5-6. [Crossref] [PubMed]
- Quagliarini F, Wang Y, Kozlitina J, Grishin NV, Hyde R, Boerwinkle E, Valenzuela DM, Murphy AJ, Cohen JC, Hobbs HH. Atypical angiopoietin-like protein that regulates ANGPTL3. Proc Natl Acad Sci U S A. 2012;109:19751-19756. [Crossref] [PubMed] [PMC]
- Wang Y, Quagliarini F, Gusarova V, Gromada J, Valen- zuela DM, Cohen JC, Hobbs HH. Mice lacking ANGPTL8 (Betatrophin) manifest disrupted triglyc- eride metabolism without impaired glucose home- ostasis. Proc Natl Acad Sci U S A. 2013;110: 16109-16114. [Crossref] [PubMed] [PMC]
- Tang T, Li L, Tang J, Li Y, Lin WY, Martin F, Grant D, Solloway M, Parker L, Ye W, Forrest W, Ghilardi N, Oravecz T, Platt KA, Rice DS, Hansen GM, Abuin A, Eberhart DE, Godowski P, Holt KH, Peterson A, Zambrowicz BP, de Sauvage FJ. A mouse knockout library for secreted and transmembrane proteins. Nat Biotechnol. 2010;28:749-755. [Crossref] [PubMed]
- Espes D, Lau J, Carlsson PO. Increased circulating levels of betatrophin in individuals with long-stand- ing type 1 diabetes. Diabetologia. 2014;57:50-53. [Crossref] [PubMed] [PMC]
- Fu Z, Berhane F, Fite A, Seyoum B, Abou-Samra AB, Zhang R. Elevated circulating lipasin/betatrophin in human type 2 diabetes and obesity. Sci Rep. 2014;4:5013. [Crossref] [PubMed] [PMC]
- Espes D, Martinell M, Carlsson PO. Increased circu- lating betatrophin concentrations in patients with type 2 diabetes. Int J Endocrinol. 2014;2014: 323407. [Crossref] [PubMed] [PMC]
- Gómez-Ambrosi J, Pascual E, Catalán V, Rodríguez A, Ramírez B, Silva C, Gil MJ, Salvador J, Frühbeck G. Circulating betatrophin concentrations are de- creased in human obesity and type 2 diabetes. J Clin Endocrinol Metab. 2014;99:E2004-E2009. [Crossref] [PubMed]
- Fenzl A, Itariu BK, Kosi L, Fritzer-Szekeres M, Kautzky-Willer A, Stulnig TM, Kiefer FW. Circulating betatrophin correlates with atherogenic lipid profiles but not with glucose and insulin levels in insulin-re- sistant individuals. Diabetologia. 2014;57:1204- 1208. [Crossref] [PubMed]
- Yamada H, Saito T, Aoki A, Asano T, Yoshida M, Ikoma A, Kusaka I, Toyoshima H, Kakei M, Ishikawa SE. Circulating betatrophin is elevated in patients with type 1 and type 2 diabetes. Endocr J. 2015;62:417-421. [Crossref] [PubMed]
- Li S, Liu D, Li L, Li Y, Li Q, An Z, Sun X, Tian H. Cir- culating betatrophin in patients with type 2 dia- betes: a meta-analysis. J Diabetes Res. 2016;2016:6194750. [Crossref] [PubMed] [PMC]
- Hussein RM. Biochemical relationships between bone turnover markers and blood glucose in pa- tients with type 2 diabetes mellitus. Diabetes Metab Syndr. 2017;11:S369-372. [Crossref] [PubMed]
- Cox AR, Barrandon O, Cai EP, Rios JS, Chavez J, Bonnyman CW, Lam CJ, Yi P, Melton DA, Kushner JA. Resolving discrepant findings on ANGPTL8 in β- cell proliferation: a collaborative approach to re- solving the betatrophin controversy. PloS One. 2016;11:e0159276. [Crossref] [PubMed] [PMC]
- Hu H, Sun W, Yu S, Hong X, Qian W, Tang B, Wang D, Yang L, Wang J, Mao C, Zhou L, Yuan G. Increased circulating levels of betatrophin in newly di- agnosed type 2 diabetic patients. Diabetes Care. 2014;37:2718-2722. [Crossref] [PubMed]
- Chen X, Lu P, He W, Zhang J, Liu L, Yang Y, Liu Z, Xie J, Shao S, Du T, Su X, Zhou X, Hu S, Yuan G, Zhang M, Zhang H, Liu L, Wang D, Yu X. Circulating betatrophin levels are increased in patients with type 2 diabetes and associated with insulin resist- ance. J Clin Endocrinol Metab. 2014;100:E96-E100. [Crossref] [PubMed]
- Erol O, Ellidağ HY, Ayık H, Özel MK, Derbent AU, Yıl- maz N. Evaluation of circulating betatrophin levels l diabetes mellitus. Gynecol Endocrinol. 2015;31:652-656. [Crossref]
- Ebert T, Kralisch S, Wurst U, Lössner U, Kratzsch J, Blüher M, Stumvoll M, Tönjes A, Fasshauer M. Be- tatrophin levels are increased in women with ges- tational diabetes mellitus compared to healthy pregnant controls. Eur J Endocrinol. 2015;173:1-7. [Crossref] [PubMed]
- Guo K, Lu J, Yu H, Zhao F, Pan P, Zhang L, Chen H, Bao Y, Jia W. Serum betatrophin concentrations are significantly increased in overweight but not in obese or type 2 diabetic individuals. Obesity (Silver Spring). 2015;23:793-797. [Crossref] [Pub- Med]
- Jiao Y, Le Lay J, Yu M, Naji A, Kaestner KH. Elevated mouse hepatic betatrophin expression does not in- crease human β-cell replication in the transplant setting. Diabetes. 2014;63:1283-1288. [Crossref] [PubMed] [PMC]
- Hossain P, Kawar B, El Nahas M. Obesity and diabetes in the developing world--a growing challenge. N Engl J Med. 2007;356:213-215. [Crossref] [PubMed]