Myo-inositol nutritional supplement for prevention of gestational diabetes (EMmY): a randomised, placebo-controlled, double-blind pilot trial with nested qualitative study

Amaefule CE; Drymoussi Z; Gonzalez Carreras FJ; Pardo Llorente MDC; Lanz D; Dodds J; Sweeney L; Pizzo E; Thomas A; Heighway J; Daru J; Sobhy S; Poston L; Khalil A; Myers J; Harden A; Hitman G; Khan KS; Zamora J; Pérez T; Huda MSB; Thangaratinam S

doi:10.1136/bmjopen-2021-050110

Myo-inositol nutritional supplement for prevention of gestational diabetes (EMmY): a randomised, placebo-controlled, double-blind pilot trial with nested qualitative study

Amaefule CE, Drymoussi Z, Gonzalez Carreras FJ, Pardo Llorente MDC, Lanz D, Dodds J, Sweeney L, Pizzo E, Thomas A, Heighway J, Daru J, Sobhy S, Poston L, Khalil A, Myers J, Harden A, Hitman G, Khan KS, Zamora J, Pérez T, Huda MSB, Thangaratinam S

Published March 11, 2022 BMJ open

DOI 10.1136/bmjopen-2021-050110 PMID 35277398 PMC PMC8919454

RRM Academy Synopsis

Trial of myo-inositol to prevent gestational diabetes is feasible

A pilot randomized trial of 198 high-risk pregnant women at five UK hospitals found that a full trial of myo-inositol to prevent gestational diabetes can be run. Women on myo-inositol had lower insulin levels and a lower insulin resistance score than women on placebo. Adherence was low, and the powder form and nausea were key barriers.

Key Findings

Of 1326 women screened, 773 were potentially eligible and 205 were recruited. Researchers randomized 198 women, 99 to each arm, and had outcomes for 178 women by delivery.
Women reported taking 52% (SD 44) of doses on average by 28 weeks of pregnancy, and 34% (SD 41) by 36 weeks.
At 28 weeks, HOMA-IR, a measure of insulin resistance, and serum insulin were both lower with myo-inositol than with placebo. The authors found no differences between the groups in other glucose measures.
Gestational diabetes by 28 weeks affected 14 of 99 women on myo-inositol and 13 of 99 on placebo. By delivery, by any criteria, it affected 24 of 99 and 20 of 99.
Preterm birth occurred in 6 of 99 women on myo-inositol and 10 of 99 on placebo. Large-for-gestational-age babies numbered 6 of 99 and 11 of 99.

Interpretation

The EMmY trial was a pilot randomized trial with interviews, built to test whether a larger trial can run. The authors judge recruitment, randomization and follow-up feasible in this multiethnic, high-risk population. Women linked low adherence to the sweet, sandy powder and to nausea in pregnancy, and asked for a tablet. The authors note that the small sample means no statistical significance can be attributed to the large-baby estimate.

RRM Context

RRM looks for the cause of a condition, and insulin resistance, which this trial measured, is a known driver of PCOS, now also called PMOS. The authors say earlier myo-inositol pregnancy trials came from one country and enrolled only Caucasian women.

Our editorial summary of this paper, not the article's abstract.

Abstract

Objectives

To determine the feasibility and acceptability of conducting a randomised trial on the effects of myo-inositol in preventing gestational diabetes in high-risk pregnant women.

Design

A multicentre, double-blind, placebo-controlled, pilot randomised trial with nested qualitative evaluation.

Setting

Five inner city UK National Health Service hospitals

Participants

Multiethnic pregnant women at 12+0 and 15+6 weeks' gestation with risk factors for gestational diabetes.

Interventions

2 g of myo-inositol or placebo, both included 200 µg folic acid, twice daily until delivery.

Primary outcome measures: Rates of recruitment, randomisation, adherence and follow-up.

Secondary outcome measures: Glycaemic indices (including homoeostatic model assessment-insulin resistance HOMA-IR), gestational diabetes (diagnosed using oral glucose tolerance test at 28 weeks and by delivery), maternal, perinatal outcomes, acceptability of intervention and costs.

Results

Of the 1326 women screened, 58% (773/1326) were potentially eligible, and 27% (205/773) were recruited. We randomised 97% (198/205) of all recruited women (99 each in intervention and placebo arms) and ascertained outcomes in 90% of women (178/198) by delivery. The mean adherence was 52% (SD 44) at 28 weeks' and 34% (SD 41) at 36 weeks' gestation. HOMA-IR and serum insulin levels were lower in the myo-inositol vs placebo arm (mean difference -0.6, 95% CI -1.2 to 0.0 and -2.69, 95% CI -5.26 to -0.18, respectively). The study procedures were acceptable to women and healthcare professionals. Women who perceived themselves at high risk of gestational diabetes were more likely to participate and adhere to the intervention. The powder form of myo-inositol and placebo, along with nausea in pregnancy were key barriers to adherence.

Conclusions

A future trial on myo-inositol versus placebo to prevent gestational diabetes is feasible. The intervention will need to be delivered in a non-powder form to improve adherence. There is a signal for efficacy in reducing insulin resistance in pregnancy with myo-inositol.

Trial Registration

ISRCTN48872100.

Chiamaka Esther Amaefule, Zoe Drymoussi, Francisco Jose Gonzalez Carreras, Maria Del Carmen Pardo Llorente, Doris Lanz, Julie Dodds, Lorna Sweeney, Elena Pizzo, Amy Thomas, James Heighway, Jahnavi Daru, Soha Sobhy, Lucilla Poston, Asma Khalil, Jenny Myers, Angela Harden, Graham Hitman, Javier Zamora, Teresa Pérez, Mohammed S B Huda

C Amaefule, Z Drymoussi, F Carreras, M Llorente, D Lanz, J Dodds, L Sweeney, E Pizzo, A Thomas, Jim Heighway, Jimmy Heighway, J Heighway, J Daru, S Sobhy, L Poston, A Khalil, Jennifer Myers, J Myers, A Harden, G Hitman, J Zamora, T Pérez, M Huda

PMID 35277398 35277398 DOI 10.1136/bmjopen-2021-050110 10.1136/bmjopen-2021-050110 Amaefule et al. 2022, Amaefule 2022

Myo-inositol nutritional supplement for prevention of gestational diabetes (EMmY): a randomised, placebo-controlled, double-blind pilot trial with nested qualitative study

Trial of myo-inositol to prevent gestational diabetes is feasible

Key Findings

Interpretation

RRM Context

Abstract

By this author

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