Screening for MODY Mutations, GAD Antibodies, and Type 1 Diabetes– Associated HLA Genotypes in Women With Gestational Diabetes Mellitus

• Published in: Diabetes care Vol. 25; no. 1; pp. 68 - 71
• Main Authors: Weng, Jianping, Ekelund, Magnus, Lehto, Markku, Li, Haiyan, Ekberg, Göran, Frid, Anders, Åberg, Anders, Groop, Leif C., Berntorp, Kerstin
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.01.2002
• Subjects: Adult; Biological and medical sciences; Clinical Medicine; Diabetes; Diabetes in pregnancy; Diabetes Mellitus, Type 1 - genetics; Diabetes Mellitus, Type 1 - immunology; Diabetes Mellitus, Type 2 - genetics; Diabetes, Gestational - genetics; Diabetes, Gestational - immunology; Diabetes. Impaired glucose tolerance; Diseases of mother, fetus and pregnancy; Endocrine pancreas. Apud cells (diseases); Endocrinology and Diabetes; Endocrinopathies; Endokrinologi och diabetes; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Female; Genetic aspects; Genotype; Glucose Intolerance - genetics; Glucose Intolerance - immunology; Gynecology. Andrology. Obstetrics; HLA Antigens - genetics; HLA-DQ Antigens - genetics; HLA-DQ beta-Chains; Humans; Klinisk medicin; Medical and Health Sciences; Medical sciences; Medical screening; Medicin och hälsovetenskap; Middle Aged; Mutation; Patient Selection; Pregnancy; Pregnancy. Fetus. Placenta; Risk Assessment; Risk factors; Sweden; Type 1 diabetes; Women; Sweden; Endocrinopathy; Human; Immunopathology; Maturity onset diabetes young; HLA-System; Typing; Autoimmune disease; Genotype; Glucose tolerance test; Medical screening; Non insulin dependent diabetes; Pregnancy; Glutamic acide decarboxylase antibody; Gene; Risk factor; Insulin dependent diabetes; Female; Genetics; Mutation; Impaired glucose tolerance
• ISSN: 0149-5992; 1935-5548; 1935-5548
• DOI: 10.2337/diacare.25.1.68

Screening for MODY Mutations, GAD Antibodies, and Type 1 Diabetes– Associated HLA Genotypes in Women With Gestational Diabetes Mellitus Jianping Weng , MD, PHD 1 , Magnus Ekelund , MD 1 , Markku Lehto , PHD 1 , Haiyan Li , BM 1 , Göran Ekberg , MD 1 , Anders Frid , MD, PHD 2 , Anders Åberg , MD, PHD 3 , Leif C. Groop , MD, PHD 1 and Kerstin Berntorp , MD, PHD 1 1 Department of Endocrinology, Malmö University Hospital, Lund University, Malmö, Sweden 2 Department of Internal Medicine, Lund University Hospital, Lund University, Lund, Sweden 3 Department of Obstetrics and Gynecology, Lund University Hospital, Lund University, Lund, Sweden Abstract OBJECTIVE —To investigate whether genetic susceptibility to type 1 diabetes or maturity-onset diabetes of the young (MODY) increases susceptibility to gestational diabetes mellitus (GDM). RESEARCH DESIGN AND METHODS —We studied mutations in MODY1–4 genes, the presence of GAD antibodies, and HLA DQB1 risk genotypes in 66 Swedish women with GDM and a family history of diabetes. An oral glucose tolerance test was repeated in 46 women at 1 year postpartum. RESULTS —There was no increase in type 1 diabetes–associated HLA-DQB1 alleles or GAD antibodies when compared with a group of type 2 diabetic patients ( n = 82) or healthy control subjects ( n = 86). Mutations in known MODY genes were identified in 3 of the 66 subjects (1 MODY2, 1 MODY3, and 1 MODY4). Of the 46 GDM subjects, 2 had diabetes (4%) and 17 had impaired glucose tolerance (IGT) (37%) at 1 year postpartum. Of the two subjects who developed manifest diabetes, one carried a MODY3 mutation (A203H in the hepatocyte nuclear factor-1α gene). There was no increase in high-risk HLA alleles or GAD antibodies in the women who had manifest diabetes or IGT at 1 year postpartum. CONCLUSIONS —MODY mutations but not autoimmunity contribute to GDM in Swedish women with a family history of diabetes and increase the risk of subsequent diabetes. GCK, glucokinase GDM, gestational diabetes mellitus HNF, hepatocyte nuclear factor IGT, impaired glucose tolerance IPF1, insulin promoter factor-1 MODY, maturity-onset diabetes of the young NGT, normal glucose tolerance OGTT, oral glucose tolerance test PCR, polymerase chain reaction SSCP, single-strand conformation polymorphism Footnotes Address correspondence and reprint requests to Dr. Magnus Ekelund, Department of Endocrinology, Malmö University Hospital, S-205 02, Malmö, Sweden. E-mail address: magnus.ekelund{at}skane.se . Received for publication 9 May 2001 and accepted in revised form 9 October 2001. J.W. is currently affiliated with the Department of Endocrinology, the First Affiliated Hospital of SUMS, Guangzhou, China. M.L. is currently affiliated with the Department of Molecular Medicine, Intracellular Transport Unit, National Public Health Institute, Helsinki, Finland. J.W. and M.E. contributed equally to this work. A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.