Introduction: Duodenal mucosal resurfacing (DMR) is a novel therapy for T2DM. It involves the hydrothermal ablation of up to 14 cm of the duodenal mucosa through a specially designed endoscopic catheter. The procedure is performed under general anaesthesia, patients are discharged the same day and it does not involve the implantation of a foreign body. Cohort studies have demonstrated that DMR induces meaningful hbA1c reductions of 0.9–1.4% by 3 months that are largely maintained at 12 months without significant weight loss. This weight loss-independent effect on glycaemia remains elusive. Herein, we sought to investigate the effect of DMR on insulin sensitivity and menstruation of euglycaemic patients with PCOS and insulin resistance.
Methods: In this first of its kind, double-blinded RCT with a 24 week follow-up, thirty insulin resistant PCOS women were randomised at 1:1 to either DMR or sham endoscopy. Diagnosis of PCOS was based on NIH criteria. Specialist lifestyle modification was delivered to all patients. All patients underwent OGTT to measure insulin secretion and the gold standard euglycaemic hyperinsulinaemic clamps with stable isotopes to measure insulin sensitivity, at baseline, 2 weeks and 3 months after intervention.
|DMR (n = 15)||Sham (n = 15)|
|Age (years)||30.60 ± 5.22||31.60 ± 6.94|
|Weight (kg)||107.76 ± 18.96||121.24 ± 12.58|
|BMI (kg/m2)||40.20 ± 6.63||44.71 ± 3.35|
|Body fat (%)||43.94 ± 3.47||46.08 ± 2.05|
|W/H ratio||0.87 ± 0.06||0.87 ± 0.09|
|HbA1c (mmol/mol)||39.67 ± 3.74||37.67 ± 5.33|
|Fasting glucose(mmol/l)||5.55 ± 0.67||5.05 ± 0.59|
|Fasting insulin (mIU/l)||21.99 ± 8.43||27.69 ± 13.86|
|HOMA-IR||6.20 ± 3.38||6.15 ± 2.93|
|DMR (n = 15)||Sham (n = 15)||P-value|
|Change in total insulin sensitivity at 12 weeks (mg/kg/min)||0.14 ± 0.97||0.24 ±1.74||0.367|
|Change in insulin sensitivity by HOMA-IR at 24 weeks||-0.39 ± 1.87||-1.19 ± 4.23||0.301|
|Number of menses in 24 weeks||3.00 [0.00, 5.00]||2.00 [1.00, 5.00]||0.434|
Conclusion: DMR didn’t increase insulin sensitivity in insulin resistant women with PCOS and obesity in this trial. Thus, selecting the duodenal mucosa as a therapeutic target may only be effective in T2DM but not in euglycaemic insulin resistant states. Future studies could examine the effect of DMR on insulin sensitivity in people with T2DM. Our results are likely limited by a relatively small sample size and short duration of follow-up compared to studies done in patients with T2DM.
05 Sep 2020 - 09 Sep 2020