Background
Insulin resistant conditions such as T2DM, obesity and PCOS are significant contributors of morbidity and mortality worldwide. At present, the principal treatment modalities are lifestyle measures, pharmacotherapy and metabolic surgery.
Although metabolic surgery is a highly-effective option, there remains no ideal remedy. This has resulted in the development of endoluminal procedures such as duodenal mucosal resurfacing (DMR) to fill the treatment gap. Initial DMR results suggests efficacy in patients with T2DM.
The DOMINO trial aimed to investigate the insulin-sensitising effect of DMR in women with PCOS, as a model of insulin resistance, as it additionally allowed assessment of reproductive function.
Methods
This was a mechanistic study conducted using a multi-centre prospective double-blinded sham-controlled RCT design. Thirty women of reproductive potential with PCOS, insulin resistance and oligomenorrhoea were randomised to receive either DMR or a sham endoscopic procedure with 6 months follow-up.
All participants were investigated with OGTTs and hyperinsulinaemic-euglycaemic clamps pre- and post-procedure. Participants were also investigated with weekly reproductive blood tests and pelvic ultrasound scans from 3-months post-procedure to completion of the trial.
Results
Thirty women (mean age 31.1years, mean BMI 42.5kg/m2, mean HOMA-IR 6.2) were recruited. The rate of glucose appearance (Ra) and disappearance (Rd)– to quantify insulin sensitivity– were not significantly different between the DMR and sham groups. Ovulatory events from pelvic ultrasound scans and reproductive blood tests did not demonstrate a difference between the two groups.
Conclusion
DMR use did not result in significant improvement in insulin sensitivity or reproductive function in women with PCOS, insulin resistance and oligomenorrhoea.
This suggests that the improvement in glycaemia and insulin resistance seen in patients with Type 2 diabetes melitus post-DMR is likely secondary to a pathophysiological difference that is not evident in a cohort of patients without T2DM.
However, further evidence is needed to substantiate this hypothesis.