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401 DUODENAL MUCOSAL RESURFACING ELICITS IMPROVEMENT IN GLYCEMIC AND HEPATIC PARAMETERS IN TYPE 2 DIABETES: COMPLETE 1 YEAR RESULTS FROM THE FIRST MULTICENTER STUDY

      Introduction

      Abnormalities in duodenal mucosa, nutrient absorption and enteroendocrine cell population are thought to play a pathophysiological role in the development of insulin resistance in patients with type 2 diabetes (T2D). Duodenal exclusion via bariatric surgery confers an insulin sensitizing metabolic benefit that is, in part, weight-independent. Duodenal Mucosal Resurfacing (DMR) is an endoscopic procedure that resurfaces the duodenal mucosa through hydrothermal ablation and may confer similar metabolic benefits using a less invasive procedure. Here we report the 12 month efficacy data of all subjects included in the first multicentre study involving DMR.

      Methods

      We conducted a single arm, open label, multicenter study in which T2D patients (HbA1c 7.5-10.0%; age 25-75y; BMI 24-40kg/m2; oral glucose lowering medication) received a single DMR procedure. DMR consists of balloon catheter based circumferential mucosal lifting followed by hydrothermal ablation. Glucose lowering medication was kept stable for ≥6mo post DMR but could be adjusted according to care guidelines thereafter. Efficacy was assessed by analyzing HbA1c, fasting plasma glucose (FPG), Homeostasis Model Assessment index (HOMA-IR), hepatic transaminases and weight up to 12mo post DMR compared to baseline (Δ) in the complete study population, while also assessing a subgroup with adequate β-cell reserve (fasting plasma insulin [FPI] >15uU/ml) using repeated measures ANOVA with Bonferroni correction and correction for initial (3mo) weight loss.

      Results

      Baseline characteristics (n=46) are shown in Table 1. ΔHbA1c (mean±SE) was -1.3±0.2 (p=0.007) and -1.0±0.2% (p=0.008) at 9 and 12mo FU. ΔFPG was -40±11 (p=0.016) and -41±10 mg/dL (p=0.007) at 9 and 12mo FU. 12mo ΔHOMA-IR was -4.0±1.1 (p=0.018). Δ weight was -3.4±0.7 and -3.1±0.8kg (p=0.012) at 3 and 6mo with some rebound at 12mo: -2.1±1.0kg (p=0.43). ΔALT was -10±3 (p=0.024) and -8±3 (p=0.137) at 3 and 12mo. ΔAST was -5±2 (p=0.053) and -5±2 U/L (p=0.058) at 9 and 12mo. Fig 1 includes post DMR changes in HbA1c, FPG, HOMA-IR, weight, ALT and AST with additional changes in the adequate β-cell reserve subgroup (n=19, 12mo ΔHbA1c -1.4±0.4%, ΔFPG -48±9 mg/dL, ΔHOMA-IR -6.2±1.0) and ALT and AST divided into subgroups based on baseline level tertiles (low, middle, high).

      Conclusion

      A single DMR procedure produced sustained reductions in HbA1c, FPG, and HOMA-IR and observed reductions in transaminase levels up to 12 months, with more evident glycaemic effects in patients with preserved β-cell function and more evident hepatic effects in patients with high baseline ALT and AST. Larger, randomized controlled studies are planned to further establish efficacy, safety and durability of the metabolic DMR effects and mechanistic studies are being conducted to elucidate the mechanism of action of DMR.
      Tabled 1Table 1. Clinical characteristics at baseline (full cohort)
      Patient characteristicsValue (n=46)
      Age, years (range)55 (31–69)
      Sex, n (%) male, female29 (63), 17 (37)
      Duration of type 2 diabetes, years (range)6 (1–11)
      Weight (kg)91 ± 13
      BMI (kg/m2)32 ± 4
      HbA1c (%)8.6 ± 0.8
      FPG (mg/dL)196 ± 48
      HOMA-IR7.7 ± 5.6
      AST (U/L)26 ± 10
      ALT (U/L)38 ± 22
      Data are mean ± SD or n (%), unless otherwise stated
      Figure thumbnail fx1
      Figure 1 – Post DMR change (mean ± SE) in (A) HbA1c, (B) FPG, (C) HOMA-IR, (D) weight, (E) ALT and (F) AST. A-D Dotted lines represent an adequate β-cell reserve subgroup (n=19). E-F ALT and AST levels divided into tertiles based on baseline levels. ALT tertiles (E): high >39U/L (red), middle 28-39U/L (orange), low (F): high >28U/L (red), middle 21-28U/L (orange), low