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.
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.
Eur J Endocrinol. 2015 Mar;172(3):277-83. doi: 10.1530/EJE-14-0713. Epub 2014 Dec 10.
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.
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.
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.
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.
Both examined MODY groups demonstrated evidence of endothelial dysfunction. In addition, HNF1-MODY patients seem to be more prone to an early atherosclerotic phenotype.
葡萄糖激酶（GCK）基因突变以及肝细胞核因子 1A（HNF1A）基因突变是导致青年发病型糖尿病（MODY）的最常见原因。GCK-MODY 患者通常表现为中等程度的空腹高血糖，但关于这些患者的动脉粥样硬化和中间相关表型知之甚少。
检查 GCK 基因突变携带者和 HNF1A-MODY 患者的颈动脉内膜中层厚度（IMT）和肱动脉血流介导的扩张（FMD）评估的内皮功能。
共检查了 64 名 GCK 基因突变携带者、52 名 HNF1A 基因突变携带者和 53 名非糖尿病对照者。通过超声检查评估 IMT 和 FMD。采用适当的统计检验比较各组间的差异，并进行多元线性回归分析与 IMT 和 FMD 的相关性。
所有组的临床特征相似，检查时的平均年龄分别为 GCK、HNF1A 和对照组的 35.1、41.1 和 39.5 岁。HNF1A-MODY 组的平均 IMT 值最高：7.0±1.4mm，而 GCK 基因突变携带者为 6.3±1.4mm，对照组为 6.3±1.3mm（P=0.008）。调整可能的临床和生化混杂因素后，HNF1A-MODY 患者的 IMT 仍高于 GCK-MODY 患者（P=0.02）和对照组（P=0.0003）。与对照组（13.9±4.7%；P=0.0001）相比，HNF1A（9.9±4.6%）和 GCK-MODY（11.1±4.6%）患者的 FMD 明显较低。调整后，HNF1A-MODY（P=0.0005）和 GCK-MODY 患者（P=0.01）的 FMD 仍低于对照组。
两种检查的 MODY 组均表现出内皮功能障碍的证据。此外，HNF1-MODY 患者似乎更容易出现早期动脉粥样硬化表型。
