Abstract
Gene expression profiles offer a multidimensional view of metabolic diseases, typically characterized by a single parameter, and can provide a basis for choosing between therapies yielding a common clinical end point. We applied such an approach in gestational diabetes mellitus (GDM). Gene expression was examined in four maternal tissues and placentas from normal patients and euglycemic GDM patients, undergoing elective Cesarean sections at term, treated either by diet or diet plus insulin. Deviations from normal were 11-fold greater for the patients treated by diet, alone, than for patients treated by diet plus insulin. Assuming the achievement of a ‘normal’ gene expression profile, in addition to euglycemia, is a desirable outcome of treatment, insulin treatment appears to have a beneficial effect in the treatment of GDM. Subsequently, we utilized the expression data to identify serum biomarkers that provide ways to monitor the benefits of insulin treatment in GDM.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 6 print issues and online access
$259.00 per year
only $43.17 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
American Diabetes Association. Gestational diabetes mellitus. Diabetes Care 2003; 26 (Suppl 1): S103–S105.
Farrell M . Improving the care of women with gestational diabetes. MCN Am J Matern Child Nurs 2003; 28: 301–305.
Kjos SL, Buchanan TA . Gestational diabetes mellitus. N Engl J Med 1999; 341: 1749–1756.
Jovanovic L, Pettitt DJ . Gestational diabetes mellitus. JAMA 2001; 286: 2516–2518.
Buchanan TA, Xiang A, Kjos SL, Lee WP, Trigo E, Nader I et al. Gestational diabetes: antepartum characteristics that predict postpartum glucose intolerance and type 2 diabetes in Latino women. Diabetes 1998; 47: 1302–1310.
Dornhorst A, Rossi M . Risk and prevention of type 2 diabetes in women with gestational diabetes. Diabetes Care 1998; 21 (Suppl 2): B43–B49.
Kim C, Newton KM, Knopp RH . Gestational diabetes and the incidence of type 2 diabetes: a systematic review. Diabetes Care 2002; 25: 1862–1868.
Major CA, deVeciana M, Weeks J, Morgan MA . Recurrence of gestational diabetes: who is at risk? Am J Obstet Gynecol 1998; 179: 1038–1042.
Xiong X, Saunders LD, Wang FL, Demianczuk NN . Gestational diabetes mellitus: prevalence, risk factors, maternal and infant outcomes. Int J Gynaecol Obstet 2001; 75: 221–228.
Hadden DR . When and how to start insulin treatment in gestational diabetes: a UK perspective. Diabet Med 2001; 18: 960–964.
Damm P . Gestational diabetes mellitus and subsequent development of overt diabetes mellitus. Dan Med Bull 1998; 45: 495–509.
Holness MJ, Langdown ML, Sugden MC . Early-life programming of susceptibility to dysregulation of glucose metabolism and the development of Type 2 diabetes mellitus. Biochem J 2000; 349 (Part 3): 657–665.
Evans E, Patry R . Management of gestational diabetes mellitus and pharmacists’ role in patient education. Am J Health Syst Pharm 2004; 61: 1460–1465.
Albareda M, Caballero A, Badell G, Piquer S, Ortiz A, de Leiva A et al. Diabetes and abnormal glucose tolerance in women with previous gestational diabetes. Diabetes Care 2003; 26: 1199–1205.
Vidaeff AC, Yeomans ER, Ramin SM . Gestational diabetes: a field of controversy. Obstet Gynecol Surv 2003; 58: 759–769.
Adfggf D . Intensive diabetes management: implications of the DCCT and UKPDS. Diabetes Educ 28: 735–740.
Giuffrida FM, Castro AA, Atallah AN, Dib SA . Diet plus insulin compared to diet alone in the treatment of gestational diabetes mellitus: a systematic review. Braz J Med Biol Res 2003; 36: 1297–1300.
Sameshima H, Kamitomo M, Kajiya S, Kai M, Furukawa S, Ikenoue S . Early glycemic control reduces large-for-gestational-age infants in 250 Japanese gestational diabetes pregnancies. Am J Perinatol 2000; 17: 371–376.
Langer O . Oral hypoglycemic agents and the pregnant diabetic: ‘from bench to bedside’. Semin Perinatol 2002; 26: 215–224.
Langer O, Conway DL, Berkus MD, Xenakis EM, Gonzales O . A comparison of glyburide and insulin in women with gestational diabetes mellitus. N Engl J Med 2000; 343: 1134–1138.
Staudt LM . Molecular diagnosis of the hematologic cancers. N Engl J Med 2003; 348: 1777–1785.
Rosenwald A, Wright G, Chan WC, Connors JM, Campo E, Fisher RI et al. The use of molecular profiling to predict survival after chemotherapy for diffuse large-B-cell lymphoma. N Engl J Med 2002; 346: 1937–1947.
van de Vijver MJ, He YD, van’t Veer LJ, Dai H, Hart AA, Voskuil DW et al. A gene-expression signature as a predictor of survival in breast cancer. N Engl J Med 2002; 347: 1999–2009.
Nachum Z, Ben-Shlomo I, Weiner E, Shalev E . Twice daily versus four times daily insulin dose regimens for diabetes in pregnancy: randomised controlled trial. Br Med J 1999; 319: 1223–1227.
Turok DK, Ratcliffe SD, Baxley EG . Management of gestational diabetes mellitus. Am Fam Physician 2003; 68: 1767–1772.
Shimkets RA, Lowe DG, Tai JT, Sehl P, Jin H, Yang R et al. Gene expression analysis by transcript profiling coupled to a gene database query. Nat Biotechnol 1999; 17: 798–803.
Lindsey CC, Carter AW, Mangum S, Greene D, Richardson A, Brown SJ et al. A prospective, randomized, multicentered controlled trial to compare the annual outcomes of patients with diabetes mellitus monitored with weekly fructosamine testing versus usual care: a 3-month interim analysis. Diabetes Technol Ther 2002; 4: 637–642.
Chen HS, Chen RL, Chang ZY, Li HD . A comparison of fructosamine and HbA1c for home self-monitoring blood glucose levels in type 2 diabetes. Zhonghua Yi Xue Za Zhi (Taipei) 2002; 65: 151–155.
Pi-Sunyer FX . The epidemiology of central fat distribution in relation to disease. Nutr Rev 2004; 62 (Suppl 7 Part 2): S120–S126.
Karelis AD, St-Pierre DH, Conus F, Rabasa-Lhoret R, Poehlman ET . Metabolic and body composition factors in subgroups of obesity: what do we know? J Clin Endocrinol Metab 2004; 89: 2569–2575.
Sartipy P, Loskutoff DJ . Monocyte chemoattractant protein 1 in obesity and insulin resistance. Proc Natl Acad Sci USA 2003; 100: 7265–7270.
Shanmugam N, Reddy MA, Guha M, Natarajan R . High glucose-induced expression of proinflammatory cytokine and chemokine genes in monocytic cells. Diabetes 2003; 52: 1256–1264.
Takaishi H, Taniguchi T, Takahashi A, Ishikawa Y, Yokoyama M . High glucose accelerates MCP-1 production via p38 MAPK in vascular endothelial cells. Biochem Biophys Res Commun 2003; 305: 122–128.
Christiansen T, Richelsen B, Bruun JM . Monocyte chemoattractant protein-1 is produced in isolated adipocytes, associated with adiposity and reduced after weight loss in morbidly obese subjects. Int J Obes Relat Metab Disord 2005; 29: 146–150.
Langer O, Yogev Y, Xenakis EM, Brustman L . Overweight and obese in gestational diabetes: the impact on pregnancy outcome. Am J Obstet Gynecol 2005; 192: 1768–1776.
Boney CM, Verma A, Tucker R, Vohr BR . Metabolic syndrome in childhood: association with birth weight, maternal obesity, and gestational diabetes mellitus. Pediatrics 2005; 115: e290–e296.
Ehrenberg HM, Mercer BM, Catalano PM . The influence of obesity and diabetes on the prevalence of macrosomia. Am J Obstet Gynecol 2004; 191: 964–968.
Gillman MW, Rifas-Shiman S, Berkey CS, Field AE, Colditz GA . Maternal gestational diabetes, birth weight, and adolescent obesity. Pediatrics 2003; 111: e221–e226.
Vohr BR, McGarvey ST, Tucker R . Effects of maternal gestational diabetes on offspring adiposity at 4–7 years of age. Diabetes Care 1999; 22: 1284–1291.
Acknowledgements
We thank R Patricelli, Esq., (WHUSA), Dr J M Rothberg (CuraGen) and Dr RA Shimkets (CuraGen) for encouragement and support of this study. We also thank the other physicians and practice managers/coordinators who recruited, tracked and provided clinical information about patients: Mario Cohen, MD, Deborah Hoffman, MD, Helen Trymbulak, MD, Vinay Ranade, MD, Gary Nobert, MD, Neville Graham, MD, Patricia Fagan, MD, Thomas Allan, MD.
Author information
Authors and Affiliations
Corresponding author
Additional information
DUALITY OF INTEREST
All work reported in this study was sponsored by CuraGen Corporation and performed in collaboration with Women Health Care USA.
Rights and permissions
About this article
Cite this article
Ort, T., Voss, M., Lichtmacher, A. et al. Pharmacogenomic assessment of treatment options in gestational diabetes. Pharmacogenomics J 5, 338–345 (2005). https://doi.org/10.1038/sj.tpj.6500333
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.tpj.6500333