Study of MultI-eLectrode EndovaScular DenervaTiOn in PatieNts with Type 2 Diabetes MEllitus (MILESTONE): 6-month Analysis from the First-in-human Proof-of-concept Study

Purpose: To assess safety and glycemic indices at 6 months in the study of endovascular denervation (EDN) procedure, in patients with type 2 diabetes mellitus (T2DM).

Materials and Methods: Using a novel six-electrode catheter system, EDN was conducted on the celiac artery (CA), and aorta between CA and the superior mesenteric artery (SMA). The primary outcomes were evaluated by the safety, HbA1c, homeostasis-model assessment of insulin resistance (HOMA-IR), and fasting plasma glucose (FPG). The antidiabetic medication, lifestyle, physical condition, blood pressure (BP), and plasma biochemistry were also recorded.

Results: A total of 11 T2DM patients were included for analysis. The technical success was 100% and no severe treatment-related adverse events or major complications were observed. Both HbA1c and HOMA-IR significantly reduced at 6 months, from 9.9±1.6 to 8.0±2.4% (P = 0.005), and from 13.3 (IQR 5.9-46.1) to 6.0 (IQR 3.1-11.9) (P = 0.016), respectively. At 1, 3, and 6 months of follow-ups, FPG levels were 10.2±0.8, 10.1±1.2, and 9.6±1.7 mmol/L, respectively, compared to 15.4±1.6 mmol/L at baseline (P = 0.001, < 0.001, and < 0.001, respectively), and 2hPG levels were 11.8±3.0, 11.4±4.0, and 11.0±5.9 mmol/L, respectively, compared to 17.9±6.0 mmol/L at baseline (P = 0.001, 0.001, and 0.002, respectively). OGTT based 3-hour C-peptide release test showed improved beta-cell function (AUC 0.23 (IQR 0.18-0.32) vs. 0.28 (IQR 0.21-0.38) pmol/mL, P = 0.046). A reduction of daily insulin injection was also observed (24 (IQR 15.5-47) vs. 19 (IQR 9-27.5) IU, P = 0.018) without changes in lifestyle. Improvements of liver function were observed although physical conditions, BP, plasma norepinephrine, angiotensin II, and blood lipids were not changed during follow-ups.

Conclusion: The 6-month analysis from this trial shows that EDN using the novel six-electrode catheter system at the new sites of CA and aorta between CA and SMA elicits a clinically significant improvement in hyperglycemia in patients with T2DM, with good tolerability.