Increased Prevalence of Beta-Cell Dysfunction despite Normal HbA1c in Youth and Young Adults with Turner Syndrome

Abstract

<b><i>Introduction:</i></b> Adult women with Turner syndrome (TS) have a high prevalence of diabetes and β-cell dysfunction that increases morbidity and mortality, but it is unknown if there is β-cell dysfunction present in youth with TS. This study aimed to determine the prevalence of β-cell dysfunction in youth with TS and the impact of traditional therapies on insulin sensitivity (SI) and insulin secretion. <b><i>Methods:</i></b> Cross-sectional, observational study recruited 60 girls with TS and 60 healthy controls (HC) matched on pubertal status. Each subject had a history, physical exam, and oral glucose tolerance test (OGTT). Oral glucose and c-peptide minimal modeling was used to determine β-cell function. <b><i>Results:</i></b> Twenty-one TS girls (35%) met criteria for prediabetes. Impaired fasting glucose was present in 18% of girls with TS and 3% HC (<i>p</i> value = 0.02). Impaired glucose tolerance was present in 23% of TS girls and 0% HC (<i>p</i> value &#x3c;0.001). The hemoglobin A1c was not different between TS and HC (median 5%, <i>p</i> = 0.42). Youth with TS had significant reductions in SI, β-cell responsivity (Φ), and disposition index (DI) compared to HC. These differences remained significant when controlling for body mass index <i>z</i>-score (<i>p</i> values: 0.0006, 0.002, &#x3c;0.0001 for SI, Φ total, DI, respectively). <b><i>Conclusions:</i></b> β-Cell dysfunction is present in youth with TS compared to controls. The presence of both reduced insulin secretion and SI suggest a unique TS-related glycemic phenotype. Based on the data from this study, we strongly suggest that providers employ serial OGTT to screen for glucose abnormalities in TS youth.