Gestational diabetes mellitus - risk factors and consequenses
Gestational diabetes mellitus (GDM) is defined as carbohydrate intolerance with onset or first recognition during pregnancy. It is characterized by impaired insulin secretion and action. Up to now there has been no international consensus regarding the definition of diagnostic criteria for GDM. In Sweden the diagnosis of GDM is based on a 75 g OGTT and in most areas defined as a 2-hour capillary plasma glucose concentration ≥10 mmol/L. According to these criteria approximately 2 % of pregnant women in Sweden develop GDM. In certain non-European ethnic groups the GDM prevalence is much higher; in Arab women up to 38% has been reported. The precise reason to this difference in susceptibility is not clear. Although most women with GDM revert to normal after delivery, diabetes develop in about 50% within 10 years postpartum, particularly type 2. However, in a worldwide perspective there is a great uncertainty in reported prevalence figures, both for GDM and future diabetes, due to differences in diagnostic criteria and follow up time.
It has long been clear that maternal hyperglycaemia is harmful to the foetus, but the maternal glucose level at which the risk of adverse pregnancy outcome increases is still controversial. The international Hyperglycaemia and Adverse Pregnancy Outcome (HAPO) study, initiated in 1999, addressed this question. The results showed strong continuous relations between maternal glucose levels, even below those diagnostic of diabetes, and increased risk of adverse perinatal outcome. Based on the HAPO study, new guidelines for the diagnosis of GDM have been suggested providing lower thresholds than those currently used all over the world. The predictive value of these guidelines for diabetes development after GDM remains to be elucidated.
Women with GDM often have a history of diabetes, suggesting a genetic component for the disease. Moreover the offspring of women with abnormal glucose tolerance during pregnancy are at higher risk of developing insulin resistance, obesity and diabetes at an early age. Genetic studies performed in order to identify susceptibility genes predisposing to GDM are inconsistent, which at least partially may be due to ethnic heterogeneity within the studied populations.
My projects concern different aspects of GDM and have generated doctoral work for five PhD-students. The research is translational and imply close co-operation between clinicians and experienced researchers within the lab.
Claes Ignell, MD, PhD, Rickard Claesson, MD, PhD-student, Magnus Ekelund, MD, PhD, Nael Shaat MD, PhD, Eva Anderberg, RNM (midwifery), PhD, Anastasia Papadopuolos, MD, PhD, Anders Frid, MD, PhD.
Research funds of Malmö University Hospital
Research funds of Skåne University Hospital
Skåne county council´s research and developmental foundation
Faculty of Medicine at Lund University
Anna Lisa and Sven-Eric Lundgren Foundation
Publications related to the projects
1. Ignell C, Claesson R, Anderberg E, Berntorp K. Trends in the prevalence of gestational diabetes mellitus in southern Sweden, 2003–2012. Acta Obstet Gynecol Scand 2014;93:420-4.
2. Claesson R, Ekelund M, Berntorp K. The potential impact of the new diagnostic criteria on the frequency of diabetes mellitus in Sweden. Acta Obstet Gynecol Scand 2013;92:1223-6.
3. Ignell C, Shaat N, Ekelund M, Berntorp K. The impact of ethnicity on glucose homeostasis after gestational diabetes mellitus. Acta Diabetol 2013;50:927-34.
4. Anderberg E, Steen-Carlsson K, Berntorp K. Use of health care resources after gestational diabetes mellitus - A longitudinel case-control anaysis. Scand J Public Health 2012, in press.
5. Ekelund M, Shaat N, Almgren P, Anderberg E, Landin-Olsson M, Lyssenko V, Groop L, Berntorp K. Genetic prediction of postpartum diabetes in women with gestational diabetes mellitus. Diabetes Res Clin Pract 2012 May 14. [Epub ahead of print]
6. Papadopoulou A, Lynch K, Anderberg E, Landin-Olsson M, Hansson I, Carl-David Agardh C-D, Lernmark Å, Berntorp K. HLA-DQB1 genotypes and islet cell autoantibodies against GAD65 and IA-2 in relation to development of diabetes post partum in women with gestational diabetes mellitus. Diabetes Res Clin Pract 2012;95:260-4.
7. Hjelm K, Berntorp K, Apelqvist J. Beliefs about health and illness in women with gestational diabetes mellitus born in Africa and Sweden. J Clin Nurs 2012:21:1374-86.
8. Ignell C, Berntorp K. Evaluation of the relationship between capillary and venous plasma glucose concentrations obtained by the HemoCue Glucose 201+ system during an oral glucose tolerance test. Scand J Clin Lab Invest 2011;71:670-5.
9. Anderberg E, Landin-Olsson M, Kalén J, Frid A, Ursing D, Berntorp K. Prevalence of impaired glucose tolerance and diabetes after gestational diabetes mellitus comparing different cut-off criteria for abnormal glucose tolerance during pregnancy. Acta Obstet Gynecol Scand 2011;90:1252-8.
10. Papadopoulou A, Lynch KF, Shaat N, Håkansson R, Ivarsson SA, Berntorp K, Agardh C-D, Lernmark Å on behalf of the DiPiS Study Group. Gestational diabetes mellitus is associated with TCF7L2 gene polymorphisms independent of HLA-DQB1*0602 genotypes and islet cell autoantibodies. Diabet Med 2011:28:1018-27.
11. Anderberg E, Källén K, Berntorp K. The impact of gestational diabetes mellitus on pregnancy outcome comparing different cut-off criteria for abnormal glucose tolerance. Acta Obstet Gynecol Scand 2010;89:1532-7.
12. Ekelund M, Shaat N, Almgren P, Groop L, Berntorp K. Prediction of postpartum diabetes in women with gestational diabetes mellitus. Diabetologia 2010;53:452-7.
13. Papadopoulou A, Lynch KF, Shaat N, Nilsson A, Lernmark B, Berntorp K, Ivarsson SA, Agardh CD, Lernmark A; DiPiS Study Group. The type 1 diabetes protective HLA DQB1*0602 allele is less frequent in gestational diabetes mellitus. Diabetologia 2009;52:1339-42.
14. Anderberg E, Berntorp K, Crang-Svalenius RN. Diabetes and Pregnancy. Women´s opinions about the care provided during the child-bearing year. Scand J Caring Sci 2009;23:161-70.
15. Hjelm K, Bard K, Berntorp K, Apelqvist J. Beliefs about health and illness postpartum in women born in Sweden and the Middle East. Midwifery 2009;25:564-75.
16. Anderberg E, Källén K, Berntorp K, Frid A, Aberg A. A simplified oral glucose tolerance test in pregnancy: compliance and results. Acta Obstet Gynecol Scand 2007;86:1432-6.
17. Shaat N, Lernmark A, Karlsson E, Ivarsson S, Parikh H, Almegren P, Berntorp K, Groop L. A variant in the transcription factor 7-like 2 (TCF7L2) gene is associated with an increased risk of gestational diabetes mellitus. Diabetologia 2007;50:972-9.
18. Shaat N, Karlsson E, Lernmark A, Ivarsson S, Lynch K, Patrikh H, Almgren P, Berntorp K, Groop L. Common variants in MODY genes increase the risk for gestational diabetes mellitus. Diabetologia 2006;49:1545-51.
19. Shaat N, Ekelund M, Lernmark Å, Ivarsson S, Almgren P, Berntorp K, Groop L. Association of the E23K polymorphism in the KCNJ11 gene with gestational diabetes mellitus. Diabetologia 2005;48:2544-51.
20. Shaat N, Ekelund M, Lernmark A, Ivarsson S, Nilsson A, Perfekt R, Berntorp K, Groop L. Genotypic and phenotypic differences between Arabian and Scandinavian women with gestational diabetes mellitus. Diabetologia 2004;47:878-84.
21. Weng J, Ekelund M, Leht M, Li H, Ekberg G, Frid A, Åberg A, Groop L, Berntorp K. Screening for MODY mutations, GAD antibodies and type 1 diabetes associated HLA genotypes in women with gestational diabetes. Diabetes Care 2002;25:68-71.
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