Endocrine Abstracts

Introduction: Diabetes mellitus (DM) develops early in Turner syndrome (TS) and appears not related to common risk factors. The precise mechanism of its development is still a matter of debate: a defective insulin response seems to be involved, but the role of incretins is still undefined.

Objective: To evaluate the implication of incretin release in the early stages of DM development in TS.

Materials and Methods: 153 Turner patients with normal glucose tolerance (NGT) state at baseline were prospectively evaluated for DM development until 2020 (75 gr OGTT every two years). Samples were collected at 0, 30, 60, 90 and 120 min: glucose and insulin dosage was immediately performed, while incretins were dosed at study end on samples stored at -80°. 10 TS with newly diagnosed DM (120 min glucose ≥ 200 mg/dl) and 10 NGT TS (0 min glucose <100 mg/dl and 120 min glucose <140 mg/dl) were finally evaluated. 19 females comparable for age, BMI and waist circumference were used as controls, 6 with a new diagnosis of type 2 DM and 13 with NGT. An autoimmune cause of DM was excluded by dosing specific autoantibodies. EMD Millipore Corporation© kits were used to measure incretins, through enzyme linked immunosorbent assay (ELISA).

Results: Within controls, insulin to glucose ratio (INS/GLUC) was significantly higher in DM compared to NGT at OGTT 0 (P=0.003), 90 (P=0.052) and 120 min (P<0,001). Differently, within TS, INS/GLUC ratio was comparable between DM and NGT, except a borderline significant decrease at times 60 (P=0.062) and 90 min (P=0.064) in DM; INS/GLUC total area under the curve was also tendentially decreased (P=0.081) in DM vs NGT. GLP-1 levels were similar in TS NGT and DM patients at any time during OGTT, while baseline GLP-1 was significantly higher in DM vs NGT controls (57.5pmol/l±19.0 vs 34.2 ± 7.80; P=0.05) and higher with a borderline significance at 30 and 60 min (P=0.072; P=0.058). Regarding GIP, DM controls had higher levels than NGT controls only at 30 min (100.9pmol/l±35.0 vs 68.8±30.9, P= 0.046), but there was no such distinction in TS.

Conclusions: In TS, DM has a specific pathogenesis, with insulin secretion deficiency present since the earliest stages. This study suggests that incretins are one of the mechanisms potentially involved in the pathogenetic process, probably through an insufficient release. Further studies on larger cohorts will be needed to provide stronger results and guide clinical practice.