Horm Metab Res 2017; 49(06): 434-439
DOI: 10.1055/s-0043-104383
Endocrine Care
© Georg Thieme Verlag KG Stuttgart · New York

Plasma Betatrophin Levels of Subjects Classified with Normal, Impaired, and Diabetic Glucose Tolerance, and Subjects with Impaired Fasting Glucose

Sibel Ozyazgan
1   Department of Medical Pharmacology, Cerrahpaşa Faculty of Medicine, Istanbul University, İstanbul, Turkey
,
Burak Onal
1   Department of Medical Pharmacology, Cerrahpaşa Faculty of Medicine, Istanbul University, İstanbul, Turkey
,
Eda Merve Kurtulus
2   Department of Medical Biochemistry, Cerrahpaşa Faculty of Medicine, Istanbul University, İstanbul, Turkey
,
Hafize Uzun
2   Department of Medical Biochemistry, Cerrahpaşa Faculty of Medicine, Istanbul University, İstanbul, Turkey
,
Gokhan Akkan
1   Department of Medical Pharmacology, Cerrahpaşa Faculty of Medicine, Istanbul University, İstanbul, Turkey
,
Dildar Konukoglu
2   Department of Medical Biochemistry, Cerrahpaşa Faculty of Medicine, Istanbul University, İstanbul, Turkey
› Author Affiliations
Further Information

Publication History

received 06 October 2016

accepted 09 February 2017

Publication Date:
28 March 2017 (online)

Abstract

This study was aimed to investigate whether betatrophin shows glucose intolerance or not. To access the plasma betatrophin levels after basal and glucose load, groups were classified as normal glucose tolerance (NGT), impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and diabetic glucose tolerance (DGT) according to WHO 2012 criteria. An oral glucose tolerance test was performed on age-matched subjects (n=220) with a body mass index (BMI)<27 kg/m2. Subjects were categorized as normoglycemic (n=55), IFG (n=50), IGT (n=60), and DM (n=55) according to the WHO criteria. Baseline betatrophin levels in DGT are significantly higher than in NGT (p<0.005), IFG (p<0.004), and IGT (p<0.001). Male subjects have significantly higher betatrophin levels than female subjects (p<0.01). In DGT, betatrophin of male subjects was found to be significantly higher than the betatrophin of male subjects in NGT (p<0.04), IFG (p<0.01), and IGT (p<0.01). Significant relationship between betatrophin and both ages and HbA1c in all groups were observed. When ages were accepted as an independent factor, significant correlation between betatrophin and ages were found. Betatrophin is increased and associated with age and HbA1c in DGT. Males had higher betatrophin levels compared with females in DGT group. As no obvious betatrophin deficiency to substitute in IFG and IGT individuals were observed, betatrophin levels appeared to be related to the pathogenesis of the diabetic stages rather than prediabetic stages.

 
  • References

  • 1 American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care 2008; 1 Suppl S55-S60
  • 2 Penn L, White M, Lindström J, den Boer AT, Blaak E, Eriksson JG, Feskens E, Ilanne-Parikka P, Keinänen-Kiukaanniemi SM, Walker M, Mathers JC, Uusitupa M, Tuomilehto J. Importance of weight loss maintenance and risk prediction in the prevention of type 2 diabetes: analysis of European Diabetes Prevention Study RCT. PLoS One 2013; 8: e57143
  • 3 Vaz JA, Patnaik A. Diabetes mellitus: exploring the challenges in the drug development process. Perspect Clin Res 2012; 3: 109-112
  • 4 World Health Organization (WHO). Definition and diagnosis of diabetes mellitus and intermediate hyperglycemia: report of a WHO/IDF consultation. Geneva: WHO; 2006
  • 5 Tseng YH, Yeh YH, Chen WJ, Lin KH. Emerging regulation and function of betatrophin. Int J Mol Sci 2014; 15: 23640-23657
  • 6 Espes D, Martinell M, Liljebäck H, Carlsson PO. Betatrophin in Diabetes Mellitus: the Epidemiological Evidence in Humans. Curr Diab Rep 2015; 15: 104
  • 7 Baschetti R. E volutionary legacy: form of ingestion, not quantity, is the key factor in producing the effects of sugar on human health. Med Hypotheses 2004; 63: 933-938
  • 8 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-resistant individuals. Diabetologia 2014; 57: 1204-1208
  • 9 Espes D, Lau J, Carlsson PO. Increased circulating levels of betatrophin in individuals with long-standing Type 1 Diabetes. Diabetologia 2014; 57: 50-53
  • 10 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
  • 11 Espes D, Martinell M, Carlsson PO. Increased circulating betatrophin concentrations in patients with type 2 diabetes. Int J Endocrinol 2014 323407
  • 12 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
  • 13 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 diagnosed type 2 diabetic patients. Diabetes Care 2014; 37: 2718-2722
  • 14 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 resistance. J Clin Endocrinol Metab 2015; 100: E96-E100
  • 15 Kushner JA. The role of aging upon b cell turnover. J Clin Invest 2013; 123: 990-995
  • 16 Saisho Y, Butler AE, Manesso E, Elashoff D, Rizza RA, Butler PC. β-cell mass and turnover in humans: effects of obesity and aging. Diabetes Care 2013; 36: 111-117
  • 17 Gómez-Ambrosi J, Pascual E, Catalán V, Rodríguez A, Ramírez B, Silva C, Gil MJ, Salvador J, Frühbeck G. Circulating betatrophin concentrations are decreased in human obesity and type 2 diabetes. J Clin Endocrinol Metab 2014; 99: E2004-E2009
  • 18 Xie X, Gao T, Yang M, Chen P, Jin H, Yang L, Yu X. Associations of betatrophin levels with irisin in Chinese women with normal glucose tolerance. Diabetol Metab Syndr 2015; 7: 26
  • 19 Trebotic LK, Klimek P, Thomas A, Fenzl A, Leitner K, Springer S, Kiefer FW, Kautzky-Willer A. Circulating betatrophin is strongly increased in pregnancy and gestational diabetes mellitus. PLoS One 2015; 10: e0136701
  • 20 Faerch K, Borch-Johnsen K, Holst JJ, Vaag A. Pathophysiology and aetiology of impaired fasting glycaemia and impaired glucose tolerance: does it matter for prevention and treatment of type 2 diabetes?. Diabetologia 2009; 52: 1714-1723
  • 21 Ghasemi H, Tavilani H, Khodadadi I, Saidijam M, Karimi J. Circulating betatrophin levels are associated with the lipid profile in type 2 diabetes. Chonnam Med J. 2015; 51: 115-119
  • 22 Zhang R, Abou-Samra AB. A dual role of lipasin (betatrophin) in lipid metabolism and glucose homeostasis: consensus and controversy. Cardiovasc Diabetol 2014; 13: 133
  • 23 Gusarova V, Alexa CA, Na E, Stevis PE, Xin Y, Bonner-Weir S, Cohen JC, Hobbs HH, Murphy AJ, Yancopoulos GD, Gromada J. ANGPTL8/ betatrophin does not control pancreatic beta cell expansion. Cell 2014; 159: 691-696
  • 24 Jiao Y, Le Lay J, Yu M, Naji A, Kaestner KH. Elevated mouse hepatic betatrophin expression does not increase human b-cell replication in the transplant setting. Diabetes 2015; 63: 1283-1288
  • 25 Li S, Liu D, Li L, Li Y, Li Q, An Z, Sun X, Tian H. Circulating betatrophin in patients with type 2 diabetes: a meta-analysis. J Diabetes Res 2016 6194750
  • 26 Abu-Farha M, Abubaker J, Al-Khairi I, Cherian P, Noronha F, Hu FB, Behbehani K, Elkum N. Higher plasma betatrophin/ANGPTL8 level in Type 2 Diabetes subjects does not correlate with blood glucose or insulin resistance. Sci Rep 2015; 5: 10949
  • 27 Yi P, Park JS, Melton DA. Betatrophin: a hormone that controls pancreatic beta cell proliferation. Cell 2013; 153: 747-758