Clinical application of 1,5-anhydroglucitol measurements in patients with hepatocyte nuclear factor-1alpha maturity-onset diabetes of the young

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 a lowered plasma concentration. As a low renal threshold for glucose has been described in hepatocyte nuclear factor-1alpha (HNF-1alpha) maturity-onset diabetes of the young (MODY), the 1,5-AG level may be altered in these patients. The purpose of this study was to assess the 1,5-AG levels in patients with HNF-1alpha MODY and in type 2 diabetic subjects with a similar degree of metabolic control. In addition, we aimed to evaluate this particle as a biomarker for HNF-1alpha MODY.

Research design and methods: We included 33 diabetic patients from the Polish Nationwide Registry of MODY. In addition, we examined 43 type 2 diabetic patients and 47 nondiabetic control subjects. The 1,5-AG concentration was measured with an enzymatic assay (GlycoMark). Receiver operating characteristic (ROC) curve analysis was used to evaluate 1,5-AG as a screening marker for HNF-1alpha MODY.

Results: The mean 1,5-AG plasma concentration in diabetic HNF-1alpha mutation carriers was 5.9 microg/ml, and it was lower than that in type 2 diabetic patients (11.0 microg/ml, P = 0.003) and in nondiabetic control subjects (23.9 microg/ml, P < 0.00005). The ROC curve analysis revealed 85.7% sensitivity and 80.0% specificity of 1,5-AG in screening for HNF-1alpha MODY at the criterion of <6.5 microg/ml in patients with an A1C level between 6.5 and 9.0%.

Conclusions: 1,5-AG may be a useful biomarker for differential diagnosis of patients with HNF-1alpha MODY with a specific range of A1C, although this requires further investigation. However, the clinical use of this particle in diabetic HNF-1alpha mutation carriers for metabolic control has substantial limitations.

Figure 1

Individual value plot of 1,5-AG concentrations against A1C levels in HNF-1α MODY and type 2 diabetic groups. □, adult MODY patients; ▪, type 2 diabetic patients; ○, nondiabetic HNF-1α mutation carriers.

Figure 2

ROC curve analysis for the diabetic patients with normal serum creatinine concentrations and A1C levels ≥6.5 and ≤9.0%. A: ROC curve. Marker represents optimal value. B: Sensitivity and specificity plotted against a cutoff value of plasma 1,5-AG concentration. Additional vertical gridlines represent the optimal cutoff value of 6.5 μg/ml.