This study, a randomized, double-blind, controlled trial attempt, strove to investigate the impact of myo-inositol supplementation on the prevention of gestational diabetes in overweight, pregnant women. The estimated sample size was established based on 50% reduction in the occurrence of gestational diabetes (primary outcome) with the alpha value of 80% (2- tailed alpha of 0.05) and the beta value of 20%. The target sample size comprised approximately 30 subjects in each group, assuming an adverse reaction of 15% and an expected loss of 20% in the follow-up.
The myo-inositol group received the daily intake of 2000 mg myo-inositol plus 200 micrograms folic acid from 14–24 gestational weeks . The control group also received the daily intake of 400 µg of folic acid from 14–24 gestational weeks. The diagnosis of gestational diabetes was done through 75-g 2-hour oral glucose tolerance test (OGTT) at 24–28 gestation weeks. If a value was ≥ 92mg/dl at 0 hours, ≥ 180 mg/dl at 1-hour, and ≥ 153 mg/dl at 2-hour, then it was regarded as diagnostic gestational diabetes .
Seventy six singleton, overweight, pregnant women (pre pregnancy BMI ≥ 25 and < 30 kg/ m2) , aged 18–40, were enrolled at their first visits (the first trimester pregnancy). They were chosen from two clinics of gynecology and obstetrics in Babol. The study was carried out over the period between April 2018 and February 2020. Having elucidated the procedure and the possible side effects of myo-inositol supplement, the researchers gave the written informed consents to the participants to fill out. The women with diabetes, a history of hypertension, cardiovascular diseases, current smoking or drinking habits were excluded from the study. Those who had experienced the death of family members or received corticosteroids during pregnancy were also excluded from the study. Moreover, the eligible participants’ attributes, including their age, parity, family history of diabetes, neck circumference, the self-reported pre-pregnancy BMI, and the pre-pregnancy waist circumference were meticulously recorded. Blood samples were also collected after an overnight fasting of 10–12 hours in order to measure fasting glucose, fasting insulin, total cholesterol, and triglyceride. The serum glucose and lipids were defined based on commercially available kits (Pars Azmoon, Tehran, IR Iran). Serum insulin concentration was done through Elisa kit (DRG Diagnostics, Marburg, Germany). The homeostasis model assessment-estimated insulin resistance (HOMA-IR) value was calculated through the bellowing formula: fasting insulin in µU/mL multiply fasting glucose in mg/dL divided by 405. Finally, sixty eligible women were randomly assigned to either a control or a myo-inositol group based on the blocked randomization with a block size of 4, which was done through a computer-generated random numbers. The randomization was conducted at both clinics of gynecology and obstetrics. Random number listing and concealment allocation were conducted through no clinical investigations in order to guarantee that each subject had an equal chance of being selected for the intervention group or the control group. The sachets containing 2000 mg of a myo-inositol supplementation powder (LO.LI. Pharma ,Rome, Italy, Inofulic) and 200 µg of folic acid for the intervention group and the sachets containing 400 µg of folic acid for the control group were prepared by a pharmacist. It should be mentioned that the sachets for the control group were identical in color, flavor and texture. The Pharmacist sealed all the envelopes and assigned a number to each envelope. Each participant was provided with seventy sachets for a total of 10 weeks. Telephone call reminders were made every week to those receiving the sachets. All pregnant women were requested to bring the remaining sachets during their prenatal visits to monitor their compliance with the procedure of the study. The final compliance was assessed at the time of OGTT through counting sachets. If 90% of sachets had been actually taken, the individual’s compliance was acceptable. All women were advised not to take other vitamins or supplements except for the daily intake of 60 mg iron supplement. The participants, the researcher collecting data, and the person analyzing the data were all blinded to treatment allocation. The break of the blinding codes was done by the pharmacist after data analysis.
The incidence of gestational diabetes (abnormal oral glucose tolerance test) at 24–28 gestational weeks was the primary outcome of this study. In addition, the secondary outcomes were: the evaluation of insulin resistance and lipid profile, insulin therapy, inappropriate gestational weight gain, caesarean section, pregnancy-induced hypertension / pre-eclampsia, preterm delivery (< 37 gestational weeks), fetal macrosomia (> 4 kg), shoulder dystocia, neonatal respiratory distress syndrome (RDS), and neonatal intensive care unit (NICU) admissions. The occurrence of adverse drug effects caused by intervention such as the presence of uterine contractions, headache, nausea / vomiting, diarrhea, tiredness, and flatulence were all assessed during follow-up visits.
Two participants, one in each group, were excluded from the study during the follow up due to their mid-trimester abortions. Also, there were two losses in the follow-up phase in myo-inositol group due to lack of desire to continue the study (one woman) and severe side effect (on women with headache). Finally, 27 women in myo-inositol and 29 women in the control group completed the study (Fig. 1).
The data analysis was performed using SPSS statistics version 20 (IBM, Chicago, IL). All continuous variables were normally distributed. T-test was used to compare the means of the two groups. The primary and secondary outcomes were assessed through a multiple regression approach for the analysis of covariance (ANCOVA) for parametric parameters and relative risk (RR) with 95% confidence intervals (CI) for non-parametric using MedCalc® (https://www.medcalc.org/calc/relative_risk.php). A value of P < 0.05 was regarded as statistically significant.