Abstract

Objective: 1, 5-anhydroglucitol (1,5-AG) is a short-term marker of metabolic control in diabetes. Its renal loss is stimulated in hyperglycemic conditions by glycosuria, which results in lowered plasma concentration. As low renal threshold for glucose has been described in HNF-1α MODY, 1,5-AG level may be altered in these patients. The purpose of this study was to assess the 1,5-AG levels in HNF-1α MODY patients and in type 2 diabetes (T2DM) subjects with a similar degree of metabolic control. In addition, we aimed to evaluate this particle as a biomarker for HNF-1α MODY.

Research Design and Methods: We included 33 diabetic patients from the Polish Nationwide Registry of MODY. In addition, we examined 43 T2DM patients and 47 non-diabetic controls. 1,5-AG concentration was measured with an enzymatic assay (GlycoMark). The ROC (receiver operation characteristic) analysis was utilized to evaluate 1,5-AG as a screening marker for HNF-1α MODY.

Results: The mean 1, 5-AG plasma concentration in diabetic HNF-1α mutation carriers was 5.9 μg/ml and it was lower than in T2DM patients (11.0 μg/ml, p=0.003), and in non-diabetic controls (23.9 μg/ml, p<0.00005). The ROC analysis revealed 85.7% sensitivity and 80.0% specificity of 1,5-AG in screening for HNF-1α MODY at the criterion of <6.5 μg/ml in patients with HbA_1c level between 6.5% and 9.0%.

Conclusions: 1, 5-AG may be a useful biomarker for differential diagnosis of HNF-1α MODY patients with a specific range of HbA_1c, although it requires further investigation. However, the clinical use of this particle in diabetic HNF-1α mutation carriers for metabolic control has substantial limitations.