1,5-Anhydroglucitol, a discriminatory gas chromatography-mass spectrometry (GC-MS) metabolomic marker in adolescents with type 1 diabetes-quantified using the plasma Glycomark® assay

Abstract

Objective: Assess plasma 1,5-Anhydroglucitol (1,5-AG) by the quantitative GlycoMark® assay in adolescents with type 1 diabetes (T1D) and controls after identifying this discriminative metabolomic marker using semi-quantitative GC-MS profiling. Methods: We reported a case control study in a tertiary paediatric hospital: 27 (14F) adolescents with T1D (age (median, interquartile range) 15.5, 14.7-16.4 years; duration 7.7; 6.0-11.8 years; HbA1c 9.1, 8.1-10.1%); glucose 13.35 (7.60-17.85) and 27 (14F) controls (age 15.1, 14.4-16.8 years). BMI was <95th percentile. Fasting plasma and urine metabolomes were profiled by GC-MS and compared between cohorts (1). The molecule most influential in separating the groups was 1,5-AG (identified by an open profiling approach, without any bias or specific targeting). 1,5-AG is a short-term marker of glycaemic control (7-14 days) that competes with glucose for renal reabsorption. Otherwise stable levels of 1,5-AG are depleted as blood glucose exceeds the renal threshold. Plasma 1,5-AG was subsequently quantified using a two-step enzymatic assay (GlycoMark®). Statistics Univariate: Mann-Whitney U-test, Spearman correlation. Multivariate: PCA, OPLS-DA, OPLS. Results: Plasma 1,5-AG measured by GlycoMark® (μg/ml) was 0.48, 0.10-1.66 and 24.50, 21.60-31.15 (median, interquartile range) for T1D (n = 26) and control (n = 27) participants respectively. Levels were significantly lower in the T1D group (p < 0.0001). T1D group values are overestimated (8 values below the assay limit of 0.1 μg/ml). Plasma 1,5-AG measured by GlycoMark® was also more influential on group classification than fasting glucose or HbA1c. Conclusion: Plasma 1,5-AG measured by the quantitative GlycoMark ® assay, like the semi-quantitative GC-MS result, was more influential on group classification than fasting glucose or HbA1c. The metabolic profile of adolescents with diabetes appears to be influenced by short term (7-14 days) hyperglycaemia.L720732022015-11-20 <br />