Advertisement

Metabolic Brain Disease

, Volume 32, Issue 3, pp 773–778 | Cite as

Sitagliptin down-regulates retinol-binding protein 4 and reduces insulin resistance in gestational diabetes mellitus: a randomized and double-blind trial

  • Xia Sun
  • Zhendong Zhang
  • Hui Ning
  • Hong SunEmail author
  • Xianghong JiEmail author
Original Article

Abstract

Gestational diabetes mellitus (GDM) is a condition that affects increasing number of pregnant women worldwide. Sitagliptin was reported to alleviate symptoms of type 2 diabetes mellitus by reducing serum levels of retinol-binding protein 4 (RBP-4). We investigated the effectiveness of sitagliptin on insulin sensitivity parameters in GDM patients. Pregnant GDM women in the 2nd trimester were recruited for this study. Participants were then assigned randomly to sitagliptin treatment group or placebo treatment group, and administered sitagliptin or placebo daily for 16 weeks. Glucose and insulin profiles, as well as serum RBP-4 level, were measured at both baseline and end of the study. After 16 weeks of treatment, participants in the STL group exhibited significantly improved levels of fasting plasma glucose and serum insulin, homeostasis model of assessment of β cell function (HOMA-β) and insulin resistance (HOMA-IR), compared with those in the placebo group. Serum levels of RBP-4 were also markedly decreased in the sitagliptin treatment group, and more importantly it was positively correlated with improved insulin resistance parameters. Our study supports a potentially promising role of sitagliptin in improving insulin resistance by decreasing RBP-4 in GDM-affected women.

Keywords

Sitagliptin Gestational diabetes mellitus Insulin resistance Dipeptidyl peptidase-4 Retinol-binding protein 4 

Notes

Compliance with ethical standards

Funding

None.

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

References

  1. American Diabetes A (2014) Diagnosis and classification of diabetes mellitus. Diabetes Care 37(Suppl 1):S81–S90. doi: 10.2337/dc14-S081 CrossRefGoogle Scholar
  2. Casey BM, Duryea EL, Abbassi-Ghanavati M, Tudela CM, Shivvers SA, McIntire DD, Leveno KJ (2015) Glyburide in women with mild gestational diabetes: a randomized controlled trial. Obstet Gynecol 126:303–309. doi: 10.1097/AOG.0000000000000967 CrossRefPubMedGoogle Scholar
  3. Catalano PM, Kirwan JP, Haugel-de Mouzon S, King J (2003) Gestational diabetes and insulin resistance: role in short- and long-term implications for mother and fetus. J Nutr 133:1674S–1683SPubMedGoogle Scholar
  4. Chan TF et al (2007) Increased serum retinol-binding protein 4 concentrations in women with gestational diabetes mellitus. Reprod Sci 14:169–174. doi: 10.1177/1933719106298407 CrossRefPubMedGoogle Scholar
  5. Choi SH et al (2008) High plasma retinol binding protein-4 and low plasma adiponectin concentrations are associated with severity of glucose intolerance in women with previous gestational diabetes mellitus. J Clin Endocrinol Metab 93:3142–3148. doi: 10.1210/jc.2007-1755 CrossRefPubMedGoogle Scholar
  6. Derosa G, Carbone A, D'Angelo A, Querci F, Fogari E, Cicero AF, Maffioli P (2012) A randomized, double-blind, placebo-controlled trial evaluating sitagliptin action on insulin resistance parameters and beta-cell function. Expert Opin Pharmacother 13:2433–2442. doi: 10.1517/14656566.2012.730519 CrossRefPubMedGoogle Scholar
  7. Du M, Wang B, Liang Z, Dong M, Chen D (2015) The relationship between retinol-binding protein 4 concentrations and gestational diabetes mellitus in Chinese women. Gynecol Obstet Investig. doi: 10.1159/000398794 Google Scholar
  8. Gardosi J, Francis A (2009) A customized standard to assess fetal growth in a US population. Am J Obstet Gynecol 201(25):e21–e27. doi: 10.1016/j.ajog.2009.04.035 Google Scholar
  9. Hadden DR, McLaughlin C (2009) Normal and abnormal maternal metabolism during pregnancy. Semin Fetal Neonatal Med 14:66–71. doi: 10.1016/j.siny.2008.09.004 CrossRefPubMedGoogle Scholar
  10. Hamza N, Berke B, Cheze C, Agli AN, Robinson P, Gin H, Moore N (2010) Prevention of type 2 diabetes induced by high fat diet in the C57BL/6 J mouse by two medicinal plants used in traditional treatment of diabetes in the east of Algeria. J Ethnopharmacol 128:513–518. doi: 10.1016/j.jep.2010.01.004 CrossRefPubMedGoogle Scholar
  11. Hu H et al (2015) Sitagliptin downregulates retinol-binding protein 4 and upregulates glucose transporter type 4 expression in a type 2 diabetes mellitus rat model. Int J Clin Exp Med 8:17902–17911PubMedPubMedCentralGoogle Scholar
  12. Huang QT, Huang Q, Luo W, Li F, Hang LL, Yu YH, Zhong M (2015) Circulating retinol-binding protein 4 levels in gestational diabetes mellitus: a meta-analysis of observational studies. Gynecol Endocrinol 31:337–344. doi: 10.3109/09513590.2015.1005594 CrossRefPubMedGoogle Scholar
  13. Kayal A et al (2016) Women in India with gestational diabetes mellitus strategy (WINGS): methodology and development of model of care for gestational diabetes mellitus (WINGS 4). Indian J Endocrinol Metab 20:707–715. doi: 10.4103/2230-8210.189230 CrossRefPubMedPubMedCentralGoogle Scholar
  14. Khovidhunkit W, Pruksakorn P, Plengpanich W, Tharavanij T (2012) Retinol-binding protein 4 is not associated with insulin resistance in pregnancy. Metabolism 61:65–69. doi: 10.1016/j.metabol.2011.05.019 CrossRefPubMedGoogle Scholar
  15. Klein K et al (2010) Retinol-binding protein 4 in patients with gestational diabetes mellitus. J Women's Health (Larchmt) 19:517–521. doi: 10.1089/jwh.2009.1615 CrossRefGoogle Scholar
  16. Kondo Y et al (2016) Sitagliptin monotherapy has better effect on insulinogenic index than glimepiride monotherapy in Japanese patients with type 2 diabetes mellitus: a 52-week, multicenter, parallel-group randomized controlled trial. Diabetol Metab Syndr 8:15. doi: 10.1186/s13098-016-0131-y CrossRefPubMedPubMedCentralGoogle Scholar
  17. Lain KY, Catalano PM (2007) Metabolic changes in pregnancy. Clin Obstet Gynecol 50:938–948. doi: 10.1097/GRF.0b013e31815a5494 CrossRefPubMedGoogle Scholar
  18. Lamers D et al (2011) Dipeptidyl peptidase 4 is a novel adipokine potentially linking obesity to the metabolic syndrome. Diabetes 60:1917–1925. doi: 10.2337/db10-1707 CrossRefPubMedPubMedCentralGoogle Scholar
  19. Legardeur H, Girard G, Journy N, Ressencourt V, Durand-Zaleski I, Mandelbrot L (2014) Factors predictive of macrosomia in pregnancies with a positive oral glucose challenge test: importance of fasting plasma glucose. Diabetes Metab 40:43–48. doi: 10.1016/j.diabet.2013.01.008 CrossRefPubMedGoogle Scholar
  20. Lewandowski KC et al (2008) Elevated concentrations of retinol-binding protein-4 (RBP-4) in gestational diabetes mellitus: negative correlation with soluble vascular cell adhesion molecule-1 (sVCAM-1). Gynecol Endocrinol 24:300–305. doi: 10.1080/09513590802141052 CrossRefPubMedGoogle Scholar
  21. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC (1985) Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28:412–419CrossRefPubMedGoogle Scholar
  22. Muscelli E et al (2012) Mechanisms for the antihyperglycemic effect of sitagliptin in patients with type 2 diabetes. J Clin Endocrinol Metab 97:2818–2826. doi: 10.1210/jc.2012-1205 CrossRefPubMedGoogle Scholar
  23. Noy N (2000) Retinoid-binding proteins: mediators of retinoid action. Biochem J 348(Pt 3):481–495CrossRefPubMedPubMedCentralGoogle Scholar
  24. Rohrborn D, Bruckner J, Sell H, Eckel J (2016) Reduced DPP4 activity improves insulin signaling in primary human adipocytes. Biochem Biophys Res Commun 471:348–354. doi: 10.1016/j.bbrc.2016.02.019 CrossRefPubMedGoogle Scholar
  25. Saucedo R, Zarate A, Basurto L, Hernandez M, Puello E, Mendoza-Lorenzo P, Ostrosky-Wegman P (2014) RBP4 gene variants are associated with insulin resistance in women with previous gestational diabetes. Dis Markers 2014:269208. doi: 10.1155/2014/269208 CrossRefPubMedPubMedCentralGoogle Scholar
  26. Sell H et al (2013) Adipose dipeptidyl peptidase-4 and obesity: correlation with insulin resistance and depot-specific release from adipose tissue in vivo and in vitro. Diabetes Care 36:4083–4090. doi: 10.2337/dc13-0496 CrossRefPubMedPubMedCentralGoogle Scholar
  27. Suresh PS, Nuggehally SR, Mullangi R (2016) A concise review of the bioanalytical methods for the quantitation of sitagliptin, an important dipeptidyl peptidase-4 (DPP4) inhibitor, utilized for the pharmacokinetic characterization of the drug. Biomed Chromatogr. doi: 10.1002/bmc.3705 Google Scholar
  28. Wiwanitkit V (2012) Retinol-binding protein 4, insulin resistance and pregnancy. Metabolism 61:e9. doi: 10.1016/j.metabol.2012.03.008 CrossRefPubMedGoogle Scholar
  29. Zhaoxia L, Mengkai D, Qin F, Danqing C (2014) Significance of RBP4 in patients with gestational diabetes mellitus: a case-control study of Han Chinese women. Gynecol Endocrinol 30:161–164. doi: 10.3109/09513590.2013.871515 CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  1. 1.Qingdao Municipal HospitalQingdaoChina

Personalised recommendations