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

doi:10.1016/j.metabol.2021.154908

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 journal › Article › peer-review

8 Citations (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 language	English
Article number	154908
Number of pages	8
Journal	Metabolism
Volume	125
Early online date	7 Oct 2021
DOIs	https://doi.org/10.1016/j.metabol.2021.154908
Publication status	Published (in print/issue) - 31 Dec 2021

Keywords

Insulin
resistance
Polycystic ovarian syndrome
Endoscopoic
Ovulation
Small intestine

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.metabol.2021.154908

Cite this

Kaur, V., Dimitriadis, GK., Perez-Pevida, B., Bansi, DS., Jayasena, C., Bate, D., Houghton, R., Fielding, BA., Balfoussia, D., Webber, L., Miao, Y., Mears, F., Jackson, N., Coppin, L., Perez, J., Williams, M., Johnson, B., Umpleby, AM., Randeva, HS., & Miras, AD. (2021). Mechanisms of action of duodenal mucosal resurfacing in insulin resistant women with polycystic ovary syndrome. Metabolism, 125, Article 154908. https://doi.org/10.1016/j.metabol.2021.154908

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title = "Mechanisms of action of duodenal mucosal resurfacing in insulin resistant women with polycystic ovary syndrome",

abstract = "BackgroundDuodenal 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.MethodsThirty-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.ResultsA 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.ConclusionsThese 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.",

keywords = "Insulin, resistance, Polycystic ovarian syndrome, Endoscopoic, Ovulation, Small intestine",

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

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doi = "10.1016/j.metabol.2021.154908",

language = "English",

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journal = "Metabolism",

issn = "0026-0495",

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Kaur, V, Dimitriadis, GK, Perez-Pevida, B, Bansi, DS, Jayasena, C, Bate, D, Houghton, R, Fielding, BA, Balfoussia, D, Webber, L, Miao, Y, Mears, F, Jackson, N, Coppin, L, Perez, J, Williams, M, Johnson, B, Umpleby, AM, Randeva, HS & Miras, AD 2021, 'Mechanisms of action of duodenal mucosal resurfacing in insulin resistant women with polycystic ovary syndrome', Metabolism, vol. 125, 154908. https://doi.org/10.1016/j.metabol.2021.154908

TY - JOUR

T1 - Mechanisms of action of duodenal mucosal resurfacing in insulin resistant women with polycystic ovary syndrome

AU - Kaur, V

AU - Dimitriadis, GK

AU - Perez-Pevida, B

AU - Bansi, DS

AU - Jayasena, C

AU - Bate, D

AU - Houghton, R

AU - Fielding, BA

AU - Balfoussia, D

AU - Webber, L

AU - Miao, Y

AU - Mears, F

AU - Jackson, N

AU - Coppin, L

AU - Perez, J

AU - Williams, M

AU - Johnson, B

AU - Umpleby, AM

AU - Randeva, HS

AU - Miras, AD

PY - 2021/12/31

Y1 - 2021/12/31

N2 - BackgroundDuodenal 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.MethodsThirty-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.ResultsA 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.ConclusionsThese 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.

AB - BackgroundDuodenal 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.MethodsThirty-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.ResultsA 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.ConclusionsThese 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.

KW - Insulin

KW - resistance

KW - Polycystic ovarian syndrome

KW - Endoscopoic

KW - Ovulation

KW - Small intestine

UR - https://spiral.imperial.ac.uk/handle/10044/1/92602

U2 - 10.1016/j.metabol.2021.154908

DO - 10.1016/j.metabol.2021.154908

M3 - Article

C2 - 34627875

SN - 0026-0495

VL - 125

JO - Metabolism

JF - Metabolism

M1 - 154908

ER -

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

Abstract

Keywords

UN SDGs

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