Screening for Turner Syndrome-Associated Hyperglycemia: Evaluating Hemoglobin A1c and Fasting Blood Glucose.

Introduction: Individuals with Turner syndrome (TS) are at increased risk of developing diabetes mellitus (DM). Currently, annual DM screening with hemoglobin A1c (HbA1c) with or without fasting blood glucose (FBG) is recommended starting at age 10. However, the optimal DM screening for individuals with TS is not known. The purpose of this study was to evaluate the correlation between HbA1c, FBG, and the 2-h oral glucose tolerance test (OGTT). A second goal was to query whether optimal HbA1c and FBG cut points for TS-associated DM and impaired glucose tolerance (IGT), as defined by the OGTT 2-h blood glucose (BG), might differ from those for the general population.

Methods: Individuals with TS ≥ age 10 from the TS: Genotype Phenotype study in the National Institute of Child Health and Human Development's Data and Specimen Hub (DASH) who had 2-h OGTT BG, HbA1c, and FBG were included. Correlations between HbA1c, FBG, and 2-h OGTT BG were evaluated. Areas under the receiver operative characteristic (ROC-AUC) curves were generated. Optimal cut points for predicting TS-associated IGT (2-h BG ≥7.77 mmol/L) and DM (2-h BG ≥11.10 mmol/L) were determined.

Results: 348 individuals had complete data (2-h OGTT BG <7.77 mmol/L, n = 239; TS-associated IGT, n = 79; DM, n = 30). ROC-AUC was poor for HbA1c to predict IGT (0.57, 0.49-0.65) but better for DM (0.81, 0.71-0.90). ROC-AUC was also poor for FBG to predict IGT (0.63, 0.56-0.70) but better for DM (0.85, 0.77-0.93). At a cut point of 38 mmol/mol (5.6%), HbA1c had 67% sensitivity (95% CI: 47-83%) and 86% specificity (95% CI: 82-90%) for identifying TS-associated DM defined by 2-h OGTT BG.

Conclusions: The correlation of HbA1c and 2-h OGTT BG is lower in TS than in other published studies regarding type 2 DM. HbA1c is fairly specific for DM in TS but lacks sensitivity, especially at currently utilized levels. Future research should focus on characterizing individuals with TS whose glycemic status is discordant, as this may provide additional insights into the pathophysiology of glucose metabolism in TS. Longitudinal assessment of glycemia as it relates to micro- and macrovascular complications in individuals with TS will further inform DM screening in this population.