Characterization of Turner Syndrome-associated Diabetes Mellitus

Diabetes mellitus (DM) risk factors in Turner syndrome (TS) may include autoimmunity, obesity, β-cell dysfunction, genetic predisposition, and insulin resistance (IR).

This work aimed to evaluate glucose tolerance and DM risk factors in adults with TS.

A single-center study with 2 phases was conducted to determine the prevalence of DM and to assess DM risk markers comparing women with TS with and without impaired glucose tolerance (IGT). The study took place at a tertiary referral center, University College Hospitals. A total of 106 women with TS (age range, 18-70 years) undergoing annual health surveillance underwent oral glucose tolerance tests (OGTTs), with additional samples for autoimmunity and genetic analysis. Main outcome measures included glucose tolerance, insulin, autoimmune, and single-nucleotide variation (SNV) profile.

OGTT screening showed that among those without a previous DM diagnosis, 72.7% had normal glucose tolerance, 19.5% had IGT, and 7.6% were newly diagnosed with DM. OGTT identified more cases of DM than glycated hemoglobin A1c sampling alone. Women with IGT or DM were older, with higher body mass index and IR. No association was found between autoimmune markers glutamic acid decarboxylase (GAD), islet antigen-2, and zinc transporter 8, risk karyotypes, or selected SNVs and DM. In DM cases, GAD positivity was associated with requirement for insulin therapy. The median age of onset of the diagnosis of DM was 36 years (range, 11-56 years).

In the spectrum of DM subtypes, TS-associated DM lies between type 1 and type 2 DM with features of both. Key factors include weight and IR. Assessing C-peptide or GAD antibodies may aid future insulin requirement.