Download PDF
Horm Metab Res 2016; 48(03): 169-173
DOI: 10.1055/s-0035-1550009
Endocrine Care
© Georg Thieme Verlag KG Stuttgart · New York

Positive Association Between Betatrophin and Diabetic Retinopathy Risk in Type 2 Diabetes Patients

Y.-Y. Wang   *
1   Department of Endocrinology and Metabolism, Affiliated Hospital of Qingdao University, Qingdao, China
,
D. Zhang   *
2   Department of Special Medicine, School of Medicine, Qingdao University, Qingdao, China
,
Z.-Y. Jiang
3   Department of Physiology, School of Medicine, Qingdao University, Qingdao, China
,
X.-Q. Lu
4   School of Public Health, Qingdao University, Qingdao, China
,
X. Zheng
5   Clinical Laboratory, Qingdao Municipal Hospital, Qingdao, China
,
Y.-J. Yu
2   Department of Special Medicine, School of Medicine, Qingdao University, Qingdao, China
,
Y.-G. Wang
1   Department of Endocrinology and Metabolism, Affiliated Hospital of Qingdao University, Qingdao, China
,
J. Dong
2   Department of Special Medicine, School of Medicine, Qingdao University, Qingdao, China
3   Department of Physiology, School of Medicine, Qingdao University, Qingdao, China
› Author Affiliations
Further Information

Publication History

received 10 November 2014

accepted 28 April 2015

Publication Date:
10 February 2016 (online)

Also available at
    Permissions and Reprints

Abstract

Betatrophin is a recently identified protein that has been shown to be associated with lipid metabolism and insulin resistance. This study aimed to measure serum betatrophin concentrations in patients with type 2 diabetes (T2DM) and evaluate the association of betatrophin with diabetic retinopthy (DR). Serum betatrophin concentrations were compared between (1) gender-, age- and body mass index-matched T2DM patients with (n=17) or without (n=33) DR; (2) gender-, age-, and body mass index-matched healthy subjects (n=31), newly-diagnosed T2DM patients before treatment (n=24), and T2DM patients under antidiabetic treatment (n=35). Serum betatrophin concentrations were determined by the enzyme-linked immunosorbent assay. Multivariate logistic regression was performed to assess the association between betatrophin concentration and DR. Serum betatrophin concentration was significantly associated with DR in T2DM patients under treatment (Odds Ratio 2.01; 95% Confidence Interval 1.12–3.60; p=0.019). Betatrophin concentrations were significantly increased in treated T2DM patients compared to the healthy subjects (4.17±0.60 vs. 0.54±0.07 ng/ml; p<0.001). Serum betatrophin concentrations are increased in T2DM patients under antidiabetic treatment and positively associated with diabetic retinopathy.

Key words

betatrophin - type 2 diabetes - diabetic retinopathy

*  These authors contributed equally to this work.


 

  • References

  • 1 Antonetti DA, Klein R, Gardner TW. Diabetic retinopathy. N Engl J Med 2012; 366: 1227-1239
    CrossrefPubMedGoogle Scholar
  • 2 Lachin JM, Genuth S, Nathan DM, Zinman B, Rutledge BN. Effect of glycemic exposure on the risk of microvascular complications in the diabetes control and complications trial–revisited. Diabetes 2008; 57: 995-1001
    CrossrefPubMedGoogle Scholar
  • 3 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 USA 2012; 109: 19751-19756
    CrossrefPubMedGoogle Scholar
  • 4 Zhang R. Lipasin, a novel nutritionally-regulated liver-enriched factor that regulates serum triglyceride levels. Biochem Biophys Res Commun 2012; 424: 786-792
    CrossrefPubMedGoogle Scholar
  • 5 Ren G, Kim JY, 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: E334-E351
    CrossrefPubMedGoogle Scholar
  • 6 Dong XY, Pang XW, Yu ST, Su YR, Wang HC, Yin YH, Wang YD, Chen WF. Identification of genes differentially expressed in human hepatocellular carcinoma by a modified suppression subtractive hybridization method. Int J Cancer 2004; 112: 239-248
    CrossrefPubMedGoogle Scholar
  • 7 Yi P, Park JS, Melton DA. Betatrophin: a hormone that controls pancreatic beta cell proliferation. Cell 2013; 153: 747-758
    CrossrefPubMedGoogle Scholar
  • 8 Wang Y, Quagliarini F, Gusarova V, Gromada J, Valenzuela DM, Cohen JC, Hobbs HH. Mice lacking ANGPTL8 (Betatrophin) manifest disrupted triglyceride metabolism without impaired glucose homeostasis. Proc Natl Acad Sci USA 2013; 110: 16109-16114
    CrossrefPubMedGoogle Scholar
  • 9 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
    CrossrefPubMedGoogle Scholar
  • 10 Espes D, Lau J, Carlsson PO. Increased circulating levels of betatrophin in individuals with long-standing type 1 diabetes. Diabetologia 2014; 57: 50-53
    CrossrefPubMedGoogle Scholar
  • 11 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. Int J Endocrinol 2014; 57: 1204-1208
    PubMedGoogle Scholar
  • 12 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
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 14 Gomez-Ambrosi J, Pascual E, Catalan V, Rodriguez A, Ramirez B, Silva C, Gil MJ, Salvador J, Fruhbeck G. Circulating betatrophin concentrations are decreased in human obesity and type 2 diabetes. J Clin Endocrinol Metab 2014; 99: E2004-E2009
    CrossrefPubMedGoogle Scholar
  • 15 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
    CrossrefPubMedGoogle Scholar
  • 16 Espes D, Martinell M, Carlsson PO. Increased circulating betatrophin concentrations in patients with type 2 diabetes. Int J Endocrinol 2014; 2014: 323-407
    PubMedGoogle Scholar
  • 17 Hato T, Tabata M, Oike Y. The role of angiopoietin-like proteins in angiogenesis and metabolism. Trends Cardiovasc Med 2008; 18: 6-14
    CrossrefPubMedGoogle Scholar
  • 18 Parri M, Pietrovito L, Grandi A, Campagnoli S, De Camilli E, Bianchini F, Marchio S, Bussolino F, Jin B, Sarmientos P, Grandi G, Viale G, Pileri P, Chiarugi P, Grifantini R. Angiopoietin-like 7, a novel pro-angiogenetic factor over-expressed in cancer. Angiogenesis 2014; 17: 881-896
    CrossrefPubMedGoogle Scholar
  • 19 American Diabetes Association . Diagnosis and classification of diabetes mellitus. Diabetes Care 2013; 36 (Suppl. 01) S67-S74
    CrossrefPubMedGoogle Scholar
  • 20 Aldington SJ, Kohner EM, Meuer S, Klein R, Sjolie AK. Methodology for retinal photography and assessment of diabetic retinopathy: the EURODIAB IDDM complications study. Diabetologia 1995; 38: 437-444
    CrossrefPubMedGoogle Scholar
  • 21 Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985; 28: 412-419
    Google Scholar
  • 22 Fu Z, Abou-Samra AB, Zhang R. An explanation for recent discrepancies in levels of human circulating betatrophin. Diabetologia 2014; 57: 2232-2234
    CrossrefPubMedGoogle Scholar
  • 23 Espes D, Martinell M. Increased circulating betatrophin concentrations in patients with type 2 diabetes 2014; 323-407
    PubMed
  • 24 Warram JH, Martin BC, Krolewski AS, Soeldner JS, Kahn CR. Slow glucose removal rate and hyperinsulinemia precede the development of type II diabetes in the offspring of diabetic parents. Ann Intern Med 1990; 113: 909-915
    Google Scholar
  • 25 Camenisch G, Pisabarro MT, Sherman D, Kowalski J, Nagel M, Hass P, Xie MH, Gurney A, Bodary S, Liang XH, Clark K, Beresini M, Ferrara N, Gerber HP. ANGPTL3 stimulates endothelial cell adhesion and migration via integrin alpha vbeta 3 and induces blood vessel formation in vivo. J Biol Chem 2002; 277: 17281-17290
    CrossrefPubMedGoogle Scholar
  • 26 Shimizugawa T, Ono M, Shimamura M, Yoshida K, Ando Y, Koishi R, Ueda K, Inaba T, Minekura H, Kohama T, Furukawa H. ANGPTL3 decreases very low density lipoprotein triglyceride clearance by inhibition of lipoprotein lipase. J Biol Chem 2002; 277: 33742-33748
    CrossrefPubMedGoogle Scholar
  • 27 Sacks FM, Hermans MP, Fioretto P, Valensi P, Davis T, Horton E, Wanner C, Al-Rubeaan K, Aronson R, Barzon I, Bishop L, Bonora E, Bunnag P, Chuang LM, Deerochanawong C, Goldenberg R, Harshfield B, Hernandez C, Herzlinger-Botein S, Itoh H, Jia W, Jiang YD, Kadowaki T, Laranjo N, Leiter L, Miwa T, Odawara M, Ohashi K, Ohno A, Pan C, Pan J, Pedro-Botet J, Reiner Z, Rotella CM, Simo R, Tanaka M, Tedeschi-Reiner E, Twum-Barima D, Zoppini G, Carey VJ. Association between plasma triglycerides and high-density lipoprotein cholesterol and microvascular kidney disease and retinopathy in type 2 diabetes mellitus: a global case-control study in 13 countries. Circulation 2014; 129: 999-1008
    CrossrefPubMedGoogle Scholar