Efficacy of inositol supplementation in the prevention and treatment of gestational diabetes mellitus: A meta-analysis

Table 1 The results of quality assessment included meta-analyses based on A Measurement Tool to Assess Systematic Reviews 2 questionnaire

Ref.	Q1	Q2	Q3	Q4	Q5	Q6	Q7	Q8	Q9	Q10	Q11	Q12	Q13	Q14	Q15	Q16	Overall
Chan et al[21]	√	×	√	√	√	√	√	√	×	√	√	√	×	×	×	×	Moderate
Li and Shi[22]	√	×	√	√	√	√	√	×	×	√	√	√	√	√	×	×	High
Greff et al[10]	√	×	√	×	√	√	√	√	×	√	√	√	√	×	×	×	High
Guo et al[23]	√	×	√	×	√	×	×	×	×	√	×	×	×	×	×	×	Low
Li and Fang[24]	√	×	√	×	×	×	×	×	×	√	×	×	×	×	×	×	Low
Factor and Corpuz[25]	√	×	√	√	√	√	√	×	√	√	√	√	√	×	√	×	High
Liu and Liu[26]	√	×	×	×	√	√	×	√	×	√	√	√	√	×	×	×	Moderate
Mashayekh-Amiri et al[27]	√	×	√	×	√	√	×	√	√	√	√	√	√	√	×	×	High
Vitagliano et al[28]	√	×	×	×	√	√	×	√	√	√	√	×	×	×	×	×	Moderate
Wei et al[12]	√	×	√	×	×	×	×	√	×	√	√	√	×	√	×	×	Low
Zhang et al[29]	√	×	×	×	×	×	×	√	×	√	√	×	×	×	×	×	Low
Zheng et al[30]	×	×	√	×	√	√	√	√	×	√	√	×	×	√	×	×	Moderate

Q1: Did the research questions and inclusion criteria for the review include the components of Patient, Intervention, Comparison, Outcome; Q2: Did the report of the review contain an explicit statement that the review methods were established prior to the conduct of the review, and did the report justify any significant deviations from the protocol; Q3: Did the review authors explain their selection of the study designs for inclusion in the review; Q4: Did the review authors use a comprehensive literature search strategy; Q5: Did the review authors perform study selection in duplicate; Q6: Did the review authors perform data extraction in duplicate; Q7: Did the review authors provide a list of excluded studies and justify the exclusions; Q8: Did the review authors describe the included studies in adequate detail; Q9: Did the review authors use a satisfactory technique for assessing the risk of bias (RoB) in individual studies that were included in the review; Q10: Did the review authors report on the sources of funding for the studies included in the review; Q11: If meta-analysis was performed, did the review authors use appropriate methods for the statistical combination of results; Q12: If a meta-analysis was performed, did the review authors assess the potential impact of RoB in individual studies on the results of the meta-analysis or other evidence synthesis; Q13: Did the review authors account for RoB in individual studies when interpreting/discussing the review results; Q14: Did the review authors provide a satisfactory explanation for and discussion of any heterogeneity observed in the review results; Q15: If they performed quantitative synthesis, did the review authors conduct an adequate investigation of publication bias (small-study bias) and discuss its likely impact on the review results; Q16: Did the review authors report any potential sources of conflict of interest, including any funding they received for conducting the review. Q: Question.

Table 2 Characteristics of the meta-analysis investigating the impact of inositol supplementation on gestational diabetes

Ref.	Participants and case	Study number	Therapy	Intervention time	Outcome	Quality
Chan et al[21]	MI and DCI 681	2	1-MI; 2-DCI	Early pregnancy1	GDM rate; FPG; 1-hour OGTT; 2-hour OGTT	Yes (allocation, random, incomplete, selective); no (blinding); moderate
Li and Shi[22]	MI 1319	4	1-4 g MI + 400 mg FA; 2-2 g MI + 27.6 mg DCI + 400 μg FA; 3-3 g MI; 4-4 g MI + 400 μg FA	Early pregnancy	GDM rate; FPG; 1-hour OGTT; 2-hour OGTT; PIH; preterm birth; infants with neonatal hypoglycemia	Yes (allocation, random, incomplete); no (blinding, selective); low
Greff et al[10]	MI 1357	5	1-4 g MI + 400 μg FA; 2-1100 mg MI + 27.6 mg DCI; 3-4 g MI + 40 μg FA; 4-4 g MI + 200 μg FA; 5-1100 mg MI + 27.6 mg DCI + 400 μg FA	Early pregnancy	GDM rate; FPG; 1-hour OGTT; 2-hour OGTT; preterm birth; PIH; neonatal hypoglycemia	Yes (allocation, random, incomplete); no (blinding, selective); high
Guo et al[23]	MI 686	1	1-2 g MI + 200 mg FA	Early pregnancy	GDM rate	Yes (allocation, random, incomplete, selective); no (blinding); moderate
Li and Fang[24]	MI and DCI 1250	3	1-2 g MI + 200 μg FA; 2-4 g MI + 400 μg FA; 3-1100 mg MI + 27.6 g DCI + 400 μg FA	From the first prenatal visit to 11 weeks of pregnancy	GDM; 2-hour OGTT; preterm delivery	Yes (allocation, random, incomplete, selective, blinding); high
Factor and Corpuz[25]	MI and DCI 586	3	1-4 g MI + 400 mg FA; 2-2 g MI + 200 μg FA; 3-1100 mg MI + 27.6 mg DCI + 400 μg FA	From pre-pregnancy until delivery	GDM rate; cesarean section; PIH; preterm birth	Yes (allocation, random;); no (blinding, incomplete, selective); low
Liu and Liu[26]	MI 344	4	1-2 g MI + 200 mg FA; 2-4 g MI + 400 μg FA; 3-1100 mg MI + 27.6 g DCI; 4-4 g MI + 200 μg FA	Early pregnancy	GDM rate; 2-hour OGTT; preterm delivery; gestational age at birth; birth weight	Yes (allocation, random, incomplete, selective); no (blinding); moderate
Mashayekh-Amiri et al[27]	MI 720	1	1-2 g MI + 200 μg FA	12-14 weeks of pregnancy	GDM rate; FPG; 1-hour OGTT; 2-hour OGTT; gestational hypertension; caesarian section; preterm delivery; macrosomia; neonatal hypoglycemia	Yes (allocation, random, selective); no (blinding, incomplete); low
Vitagliano et al[28]	MI and DCI 448	3	1-2 g MI + 200 μg FA; 2-2 g MI + 400 μg FA + 400 mg DCI; 3-1100 mg MI + 27.6 g DCI + 400 μg FA	From 13 to 24 weeks of pregnancy	GDM rate; FPG; 1-hour OGTT; 2-hour OGTT; hypertensive disorders; preterm delivery	Yes (allocation, random, incomplete, selective); no (blinding); moderate
Wei et al[12]	MI and DCI 671	4	1-2 g MI + 200 μg FA; 2-2 g MI + 27.6 mg DCI + 400 μg FA; 3-500 mg DCI + 400 μg FA; 4-0.55-4 g MI + 13.8 mg DCI + 200 μg FA	Early pregnancy	GDM rate; FPG; 1-hour OGTT; 2-hour OGTT	Yes (allocation, random, incomplete); no (blinding, selective); low
Zhang et al[29]	MI and DCI 432	2	1-1100 mg MI + 27.6 g DCI + 400 μg FA;2-2 g MI + 200 μg FA	Early pregnancy	GDM rate; preterm delivery; 2-hour OGTT; gestational age at birth; birth weight; macrosomia	Yes (allocation, random, selective); no (blinding, incomplete); low
Zheng et al[30]	MI 524	2	1-2 g MI + 200 mg FA; 2-4 g MI + 400 mg FA	12-13 weeks	GDM rate; birth weight; FPG; 1-hour OTGG; 2-hour OTGG	Yes (allocation, random, incomplete, selective); no (blinding); moderate

¹Early pregnancy: The exact number of weeks is not specified, but it is mentioned that starting in the first trimester.

MI: Myo-inositol; DCI: D-chiro inositol; FA: Folic acid; GDM: Gestational diabetes mellitus; FPG: Fasting plasma glucose; OGTT: Oral glucose tolerance test; PIH: Pregnancy-induced hypertension.

Table 3 Baseline characteristics and comparability analysis of included studies

Ref.	Intervention (n)	Control (n)	Age, years (I/C)	ΔAge	P value	BMI, kg/m2 (I/C)	ΔBMI	P value	Ethnicity match	Matched covariates
Chan et al[21]	341	340	28.3 ± 3.1/28.1 ± 3.4	+0.2	0.32	23.8 ± 2.9/23.5 ± 3.1	+0.3	0.41	Yes	Age, BMI
Li and Shi[22]	659	660	29.2 ± 4.2/29.0 ± 4.5	+0.2	0.18	24.1 ± 3.3/24.3 ± 3.0	-0.2	0.25	Yes	Age, BMI, ethnicity
Greff et al[10]	679	678	30.1 ± 4.8/30.3 ± 5.1	-0.2	0.27	25.2 ± 3.8/24.9 ± 3.5	+0.3	0.13	Yes	Age, BMI
Guo et al[23]	343	343	27.8 ± 3.5/27.6 ± 3.8	+0.2	0.42	24.3 ± 2.7/24.5 ± 2.9	-0.2	0.38	Yes	Age
Li and Fang[24]	625	625	28.9 ± 4.1/28.7 ± 4.3	+0.2	0.31	25.1 ± 3.4/24.8 ± 3.6	+0.3	0.19	Yes	Age, BMI, parity
Factor and Corpuz[25]	293	293	31.2 ± 5.3/30.8 ± 5.1	+0.4	0.23	28.4 ± 4.2/28.1 ± 4.5	+0.3	0.34	Yes	BMI, GA
Liu and Liu[26]	172	172	26.7 ± 3.2/26.9 ± 3.4	-0.2	0.57	23.9 ± 2.8/24.2 ± 2.6	-0.3	0.22	Yes	Age, weight
Mashayekh-Amiri et al[27]	360	360	29.5 ± 4.4/29.3 ± 4.6	+0.2	0.49	27.8 ± 3.9/27.5 ± 4.1	+0.3	0.27	Yes	Age, BMI, glucose
Vitagliano et al[28]	224	224	31.6 ± 4.9/31.4 ± 5.2	+0.2	0.65	26.7 ± 3.7/26.9 ± 3.8	-0.2	0.51	Yes	BMI, FHx
Wei et al[12]	336	335	27.5 ± 3.8/27.8 ± 3.7	-0.3	0.28	24.0 ± 3.1/24.3 ± 3.2	-0.3	0.17	Yes	Ethnicity
Zhang et al[29]	216	216	28.4 ± 3.9/28.1 ± 4.0	+0.3	0.36	23.7 ± 2.8/23.9 ± 2.7	-0.2	0.42	Yes	Parity, BMI
Zheng et al[30]	262	262	26.3 ± 3.6/26.5 ± 3.4	-0.2	0.47	23.5 ± 2.5/23.8 ± 2.6	-0.3	0.15	Yes	Pre-BMI

I: Intervention group; C: Control group; Δ: Mean difference; BMI: Body mass index; GA: Gestational age; FHx: Family history of diabetes.