title: Metabolic, hormonal characteristics and genetic variants of TCF7L2 associated with development of gestational diabetes mellitus in Mexican women.
abstract: BACKGROUND
  Variation in TCF7L2 gene is associated with type 2 diabetes and with gestational diabetes mellitus in several populations, but there are no data in Mexican women with gestational diabetes mellitus. In this study, we examined metabolic and hormonal measurements as well as TCF7L2 genetic variants.
  
  
  METHODS
  We selected 108 pregnant women with normal glucose tolerance and 90 with gestational diabetes mellitus according to 2010 American Diabetes Association criteria matched for gestational week. We collected data on blood pressure, body mass index (BMI) and concentrations of blood glucose, HbA1c , lipids profile, insulin and glucagon-like peptide-1 (GLP-1). The genotyping of rs7903146 and rs12255372 polymorphisms were made with polymerase chain reaction-restriction fragment length polymorphism.
  
  
  RESULTS
  Actual and pre-gestational BMI, fasting glucose and HbA1c were higher (p < 0.001), and high-density lipoprotein cholesterol was lower (p < 0.02) in gestational diabetes mellitus women than euglycemic women. No significant differences were found for lipids, insulin and homeostasis model assessment-insulin resistance. Gestational diabetes mellitus women had high GLP-1 levels (32 vs 24, p < 0.004) and decreased β-cell function (266 vs 438, p < 0.001). The frequency of rs12255372 risk allele in gestational diabetes women was significantly higher than that in euglycemic women (χ²  = 8.96; p < 0.003) and confers a risk for gestational diabetes mellitus (OR = 9.1, 95% CI 2.8-29, p < 0.0002; and OR = 4.3, 95% CI 1.6-11.4, p < 0.003 based on dominant and co-dominant model, respectively). The generalized linear model showed that low beta function, high pre-gestational BMI and rs12255372 risk allele are independently associated with gestational diabetes.
  
  
  CONCLUSIONS
  The elevated GLP-1 levels in gestational diabetes women suggested some abnormality in insulin secretion. The low β-cell function, high pre-gestational BMI and rs12255372 risk allele are risk factors independently associated with the development of gestational diabetes.
authors.affiliation: Departamento de Ciencias Médicas, División Ciencias de la Salud, Universidad de Guanajuato, 20 de Enero 929, Colonia Obregón, León, Guanajuato, 37320, Mexico.
authors.forename: Ruth
authors.initials: R
authors.lastname: Reyes-López
authors.forename: Elva
authors.initials: E
authors.lastname: Pérez-Luque
authors.forename: Juan Manuel
authors.initials: JM
authors.lastname: Malacara
mesh_terms: D000328:Adult; D000483:Alleles; D015992:Body Mass Index; D008076:Cholesterol, HDL / Q000032:analysis; D003430:Cross-Sectional Studies; D016640:Diabetes, Gestational / Q000097:blood / Q000209:etiology / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D052216:Glucagon-Like Peptide 1 / Q000097:blood; D006801:Humans; D007328:Insulin / Q000097:blood / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism; D039382:Maternal Nutritional Physiological Phenomena; D008800:Mexico; D050177:Overweight / Q000503:physiopathology; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D058118:Transcription Factor 7-Like 2 Protein / Q000235:genetics*; D055815:Young Adult
chemical_list: D008076:Cholesterol, HDL; D007328:Insulin; C544894:TCF7L2 protein, human; D058118:Transcription Factor 7-Like 2 Protein; D052216:Glucagon-Like Peptide 1
keywords: GDM hormonal characteristics; TCF7L2 gene polymorphisms; gestational diabetes