Mechanisms of action of duodenal mucosal resurfacing in insulin resistant women with polycystic ovary syndrome

V Kaur, GK Dimitriadis, B Perez-Pevida, DS Bansi, C Jayasena, D Bate, R Houghton, BA Fielding, D Balfoussia, L Webber, Y Miao, F Mears, N Jackson, L Coppin, J Perez, M Williams, B Johnson, AM Umpleby, HS Randeva, AD Miras

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Background
Duodenal mucosal resurfacing (DMR) is a novel day-case endoscopic intervention which results in weight loss-independent reductions in HbA1c in patient with type 2 diabetes mellitus (T2DM). We hypothesized that DMR works by increasing insulin sensitivity and we aimed to investigate the mechanism of action of DMR through longitudinal metabolic phenotyping in humans.

Methods
Thirty-two insulin-resistant women with polycystic ovary syndrome (PCOS) and obesity were randomised in a double-blinded manner to DMR or sham endoscopy. They underwent measurements of insulin sensitivity using euglycaemic hyperinsulinaemic clamps, insulin secretion using oral glucose tolerance tests and reproductive function using weekly reproductive hormone profiles and ovarian ultrasonography for 6 months post-intervention.

Results
A small increase in total body insulin sensitivity measured by the clamp was observed in both groups at week 12. An increase in insulin sensitivity, as measured by HOMA-IR, was observed in both groups at week 24. There was an increase in the number of menses (median 2 DMR, 0.5 sham). There were no significant differences between the two groups in these outcomes or insulin secretion.

Conclusions
These findings suggest that DMR does not work by increasing insulin sensitivity in euglycaemic, insulin resistant women with PCOS. The procedure may exert its effects only in the context of hyperglycaemia or pathologically hyperplastic, insulin-desensitised duodenal mucosa.
Original languageEnglish
Article number154908
Number of pages8
JournalMetabolism
Volume125
Early online date7 Oct 2021
DOIs
Publication statusPublished (in print/issue) - 31 Dec 2021

Keywords

  • Insulin
  • resistance
  • Polycystic ovarian syndrome
  • Endoscopoic
  • Ovulation
  • Small intestine

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