Endocrine Abstracts

Mutations in the (glucokinase) GCK gene are, along with the HNF1A gene mutations, the most frequent cause of (maturity onset diabetes of the young) MODY. Heterozygous loss-of-function GCK mutations result in a moderate fasting hyperglycemia. The GCK-MODY patients are usually free from microvascular complications; however, little is known about atherosclerosis and intermediate related phenotypes. We aimed to examine intima-media thickness (IMT) and endothelial function in GCK-MODY and HNF1A-MODY.

62 GCK-MODY, 40 HNF1A-MODY patients and 44 non-diabetic controls were examined. Carotic artery IMT and brachial artery FMD and (nitroglycerin mediated dilatation) NMD were assessed by ultrasonography. These parameters were compared with test for difference between two groups (t-test or Mann–Whitney U-test) or three groups (one-way-ANOVA or the Kruskal–Wallis test with post hoc test).

BMI was similar in all three groups – 23.8±4.4, 24.1±3.7 and 24.0±3.8 in GCK-MODY, HNF1A-MODY and controls respectively (P=0.6930). Patients were diagnosed with diabetes at similar age (GCK-MODY: 25.6±13.7 years vs HNF1A-MODY: 27.2±12, P=0.6334). Glycemic control was similar in diabetic groups as in the GCK-MODY group the mean HbA1c was 6.4%±0.7, while in HNF1A-MODY patients it reached 6.7±1.4 (P=0.9274). The average maximum IMT was not different – 0.71±0.17 mm in GCK-MODY, 0.75±0.14 in HNF1A-MODY, and 0.7±0.15 in the controls (P=0.1251). Mean IMT were as follow – 0.62±0.15 mm in GCK-MODY, 0.67±0.12 in HNF1A-MODY and 0.62±0.12 in controls (P=0.0267). Post hoc analysis showed a difference between GCK-MODY and HNF1A-MODY (P=0.0427). The mean FMD was 11.1±4.7% in GCK-MODY, 10.0±5.0 in HNF1A-MODY and 14.2±4.9 in the controls (P=0.0031). The differences between GCK-MODY and HNF1A-MODY vs controls were significant (P=0.0043, P=0.0002 respectively).

Both examined MODY groups showed evidence of early atherosclerosis or endothelial dysfunction. Mild hyperglycemia in the GCK-MODY seems to have impact on the occurrence of intermediate atherosclerotic phenotypes.