title: Intima-media thickness and endothelial dysfunction in GCK and HNF1A-MODY patients.
abstract: OBJECTIVE
  Mutations in the glucokinase (GCK) gene, along with hepatocyte nuclear factor 1A (HNF1A) gene mutations, are the most frequent cause of maturity-onset diabetes of the young (MODY). GCK-MODY patients are typically characterized by a moderate fasting hyperglycemia; however, little is known about atherosclerosis and intermediate-related phenotypes in these subjects.
  
  
  METHODS
  To examine carotid artery intima-media thickness (IMT) and endothelial function assessed by brachial artery flow-mediated dilatation (FMD) in GCK gene mutations carriers and HNF1A-MODY.
  
  
  METHODS
  A total of 64 subjects with GCK gene mutations, and 52 HNF1A gene mutation carriers as well as 53 nondiabetic controls were examined. IMT and FMD were assessed by ultrasonography. Appropriate statistical tests were performed to assess differences between the groups, and multivariate linear regression was done for the association with IMT and FMD.
  
  
  RESULTS
  The clinical characteristics of all groups were similar with the mean age at examination of 35.1, 41.1, and 39.5 years for GCK, HNF1A and the control group respectively. The highest mean IMT value was in the HNF1A-MODY group: 7.0±1.4 mm, whereas it reached 6.3±1.4 mm in GCK mutation carriers and 6.3±1.3 mm in controls (P=0.008). After adjustment for possible clinical and biochemical cofounders, IMT remained higher in HNF1A-MODY patients as compared with GCK-MODY patients (P=0.02) and controls (P=0.0003). FMD was significantly lower in HNF1A (9.9±4.6%) and GCK-MODY (11.1±4.6%) patients in comparison with controls (13.9±4.7%; P=0.0001). After adjustment, FMD remained lower in HNF1A-MODY (P=0.0005) and GCK-MODY patients (P=0.01) as compared with controls.
  
  
  CONCLUSIONS
  Both examined MODY groups demonstrated evidence of endothelial dysfunction. In addition, HNF1-MODY patients seem to be more prone to an early atherosclerotic phenotype.
authors.affiliation: Department of Metabolic DiseasesJagiellonian University Medical College, 15 Kopernika Street, Krakow 31-501, PolandUniversity HospitalKrakow, PolandTranslational Medicine LaboratoryDepartment of Internal MedicineDepartment of Clinical BiochemistryJagiellonian University Medical College, Krakow, PolandDepartment of PediatricsOncology, Hematology and Diabetology, Medical University of Lodz, Lodz, Poland Department of Metabolic DiseasesJagiellonian University Medical College, 15 Kopernika Street, Krakow 31-501, PolandUniversity HospitalKrakow, PolandTranslational Medicine LaboratoryDepartment of Internal MedicineDepartment of Clinical BiochemistryJagiellonian University Medical College, Krakow, PolandDepartment of PediatricsOncology, Hematology and Diabetology, Medical University of Lodz, Lodz, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Szopa
authors.affiliation: Department of Metabolic DiseasesJagiellonian University Medical College, 15 Kopernika Street, Krakow 31-501, PolandUniversity HospitalKrakow, PolandTranslational Medicine LaboratoryDepartment of Internal MedicineDepartment of Clinical BiochemistryJagiellonian University Medical College, Krakow, PolandDepartment of PediatricsOncology, Hematology and Diabetology, Medical University of Lodz, Lodz, Poland.
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Osmenda
authors.affiliation: Department of Metabolic DiseasesJagiellonian University Medical College, 15 Kopernika Street, Krakow 31-501, PolandUniversity HospitalKrakow, PolandTranslational Medicine LaboratoryDepartment of Internal MedicineDepartment of Clinical BiochemistryJagiellonian University Medical College, Krakow, PolandDepartment of PediatricsOncology, Hematology and Diabetology, Medical University of Lodz, Lodz, Poland.
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Wilk
authors.affiliation: Department of Metabolic DiseasesJagiellonian University Medical College, 15 Kopernika Street, Krakow 31-501, PolandUniversity HospitalKrakow, PolandTranslational Medicine LaboratoryDepartment of Internal MedicineDepartment of Clinical BiochemistryJagiellonian University Medical College, Krakow, PolandDepartment of PediatricsOncology, Hematology and Diabetology, Medical University of Lodz, Lodz, Poland.
authors.forename: Bartłomiej
authors.initials: B
authors.lastname: Matejko
authors.affiliation: Department of Metabolic DiseasesJagiellonian University Medical College, 15 Kopernika Street, Krakow 31-501, PolandUniversity HospitalKrakow, PolandTranslational Medicine LaboratoryDepartment of Internal MedicineDepartment of Clinical BiochemistryJagiellonian University Medical College, Krakow, PolandDepartment of PediatricsOncology, Hematology and Diabetology, Medical University of Lodz, Lodz, Poland.
authors.forename: Jan
authors.initials: J
authors.lastname: Skupien
authors.affiliation: Department of Metabolic DiseasesJagiellonian University Medical College, 15 Kopernika Street, Krakow 31-501, PolandUniversity HospitalKrakow, PolandTranslational Medicine LaboratoryDepartment of Internal MedicineDepartment of Clinical BiochemistryJagiellonian University Medical College, Krakow, PolandDepartment of PediatricsOncology, Hematology and Diabetology, Medical University of Lodz, Lodz, Poland.
authors.forename: Barbara
authors.initials: B
authors.lastname: Zapala
authors.affiliation: Department of Metabolic DiseasesJagiellonian University Medical College, 15 Kopernika Street, Krakow 31-501, PolandUniversity HospitalKrakow, PolandTranslational Medicine LaboratoryDepartment of Internal MedicineDepartment of Clinical BiochemistryJagiellonian University Medical College, Krakow, PolandDepartment of PediatricsOncology, Hematology and Diabetology, Medical University of Lodz, Lodz, Poland.
authors.forename: Wojciech
authors.initials: W
authors.lastname: Młynarski
authors.affiliation: Department of Metabolic DiseasesJagiellonian University Medical College, 15 Kopernika Street, Krakow 31-501, PolandUniversity HospitalKrakow, PolandTranslational Medicine LaboratoryDepartment of Internal MedicineDepartment of Clinical BiochemistryJagiellonian University Medical College, Krakow, PolandDepartment of PediatricsOncology, Hematology and Diabetology, Medical University of Lodz, Lodz, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Guzik
authors.affiliation: Department of Metabolic DiseasesJagiellonian University Medical College, 15 Kopernika Street, Krakow 31-501, PolandUniversity HospitalKrakow, PolandTranslational Medicine LaboratoryDepartment of Internal MedicineDepartment of Clinical BiochemistryJagiellonian University Medical College, Krakow, PolandDepartment of PediatricsOncology, Hematology and Diabetology, Medical University of Lodz, Lodz, Poland Department of Metabolic DiseasesJagiellonian University Medical College, 15 Kopernika Street, Krakow 31-501, PolandUniversity HospitalKrakow, PolandTranslational Medicine LaboratoryDepartment of Internal MedicineDepartment of Clinical BiochemistryJagiellonian University Medical College, Krakow, PolandDepartment of PediatricsOncology, Hematology and Diabetology, Medical University of Lodz, Lodz, Poland malecki_malecki@yahoo.com maciej.malecki@uj.edu.pl.
authors.forename: Maciej T
authors.initials: MT
authors.lastname: Malecki
mesh_terms: D000328:Adult; D059168:Carotid Intima-Media Thickness; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005941:Glucokinase / Q000235:genetics / Q000378:metabolism*; D051538:Hepatocyte Nuclear Factor 1-alpha / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation / Q000235:genetics
chemical_list: D051538:Hepatocyte Nuclear Factor 1-alpha; D005941:Glucokinase