Cellular and molecular overview of gestational diabetes mellitus: Is it predictable and preventable?

Table 1 A summary of preventive strategies for gestational diabetes mellitus

Ref.	Study design	Patients	Intervention	Result
Song et al[44], 2016	Meta-analysis of 29 RCTs	11487 pregnant women	Diet or physical activity during pregnancy	(1) Intervention groups resulted in 18% (95%CI: 5%-30%) reduction in the risk of GDM (P = 0.0091); and (2) Intervention was effective especially before the 15th gestational week (RR: 0.80, 95%CI: 0.66-0.97)
Guo et al[45], 2019	Meta-analysis of 47 RCTs	15745 participants	Diet and exercise during pregnancy	(1) Combination intervention were preventive of GDM (RR 0.77, 95%CI: 0.69-0.87); and (2) Exercise of moderate intensity for 50-60 min twice a week could lead to an approximately 24% reduction in GDM
Bennett et al[46], 2018	Systematic review and meta-analysis of 45 studies	15293 participants	Diet and exercise during pregnancy	(1) Diet intervention reduced GDM risk by 44% (RR: 0.56, 95%CI: 0.36-0.87); (2) PA intervention reduced GDM risk by 38% (RR: 0.62, 95%CI: 0.50-0.78); (3) PA interventions in southern European group reduced GDM risk by 37% (RR: 0.63, 95%CI: 0.50-0.80); and (4) Diet and PA interventions in Asian group reduced GDM risk by 62% (RR: 0.38, 95%CI: 0.24-0.59) and 32% (RR: 0.68, 95%CI: 0.54-0.86), respectively
Sanabria-Martínez et al[48], 2015	Meta-analysis of 13 RCTs	2873 pregnant women	Physical exercise during pregnancy	(1) Physical exercise decreased the risk of GDM by 31% (RR = 0.69; P = 0.009); and (2) Decreases were also observed in maternal weight (WMD = -1.14 kg; 95%CI: -1.50 to -0.78; P < 0.001)
Davenport et al[49], 2018	A systematic review and meta-analysis including 106 studies	273182 participants	Exercise, alone or in combination (dietary + exercise)	(1) Exercise-only interventions, but not exercise + cointerventions, reduced odds of GDM (n = 6934; OR: 0.62, 95%CI: 0.52 to 0.75); and (2) Also reduced odds of gestational hypertension (n = 5316; OR: 0.61, 95%CI: 0.43 to 0.85) and pre-eclampsia (n = 3322; OR: 0.59, 95%CI: 0.37 to 0.9) compared with no exercise
Martínez-Vizcaíno et al[50], 2022	An umbrella review: 23 systematic reviews and meta-analyses and 63 RCTs were included		Single exercise interventions	(1) Single exercise interventions reduced GDM incidence in most systematic reviews and meta-analyses around 39%; (2) Single exercise interventions also reduced gestational hypertension incidence in most systematic reviews and meta-analyses around 47%; and (3) Particularly when supervised, with low-to-moderate intensity level, and initiated early during the first trimester of pregnancy
Griffith et al[55], 2020	An overview of Cochrane Reviews (11 Cochrane Reviews with 71 trials)	23154 women	Diet, exercise, and combination; dietary supplements such as vitamin D and probiotics, pharmaceuticals such as metformin	(1) A combination of exercise and diet of possible benefit in reducing the risk of GDM; (2) Unknown benefit or harm of a low glycemic index diet vs a moderate-high glycemic index diet on the risk of GDM; (3) Supplementation with vitamin D and metformin were of possible benefit in reducing the risk of GDM; and (4) There was insufficient high-quality evidence to establish the effect on the risk of GDM of diet or exercise alone, probiotics, vitamin D with calcium or other vitamins and minerals
Melero et al[61], 2020	RCT	284 participants	MedDiet vs control	MedDiet intervention reduced GDM rate with adjusted RR 0.77 (95%CI: 0.61-0.97, P = 0.008)
Assaf-Balut et al[62], 2017	RCT	874 participants	MedDiet vs control	MedDiet intervention reduced GDM rate with adjusted RR 0.75 (95%CI: 0.57-0.98; P = 0.039)
Al Wattar et al[63], 2019	Multicenter RCT	1252 participants	MedDiet vs control	MedDiet intervention reduced GDM rate with adjusted RR 0.65 (95%CI: 0.47-0.91, P = 0.01)
Tobias et al[64], 2012	Retrospective cohort	15254 participants	MedDiet, DASH	(1) MedDiet was associated with a 24% lower risk (RR: 0.76; 95%CI: 0.60-0.95; P = 0.004); and (2) DASH with a 34% lower risk (RR: 0.66; 95%CI: 0.53-0.82; P = 0.0005)
Tobias et al[64], 2012	Retrospective cohort	4413 participants	MedDiet, DASH	(1) MedDiet was associated with a 40% lower risk (RR: 0.60; 95%CI: 0.44-0.82; P = 0.002); and (2) DASH with a 46% lower risk (RR: 0.54; 95%CI: 0.39-0.73; P < 0.001)
Luoto et al[67], 2016	RCT	256 participants	Probiotic with/without dietary counseling vs control	One probiotic intervention reduced the frequency of GDM; 13% (diet/probiotics), 36% (diet/placebo), and 34% (control); P = 0.003
Callaway et al[68], 2019	RCT	411 overweight and obese pregnant women	Probiotic vs placebo	(1) GDM occurred in 12.3% in the placebo arm and 18.4% in the probiotics arm (P = 0.10); and (2) Probiotics did not prevent GDM in overweight and obese pregnant women
Davidson et al[69], 2021	7 RCTs	1647 participants	Probiotic with either placebo or diet	(1) It was uncertain if probiotics had any effect on the risk of GDM compared to placebo (RR: 0.80, 95%CI: 0.54-1.20) due to low-certainty evidence; and (2) High-certainty evidence suggested an increased risk of pre-eclampsia with probiotic administration (RR: 1.85, 95%CI: 1.04- 3.29) and increased the risk of hypertensive disorders of pregnancy (RR: 1.39, 95%CI: 0.96-2.01)
Mijatovic-Vukas et al[70], 2018	A systematic review and meta-analysis of 40 trials	30871 pregnant women	A variety of dietary regimens, prepregnancy and early pregnancy PA	(1) MedDiet, DASH were associated with 15%-38% reduced RR of GDM; and (2) Compared to no PA, any prepregnancy and early pregnancy PA was associated with 30% and 21%, respectively, reduced odds of GDM
De-Regil et al[71], 2016	Cochrane database systematic. review with 15 RCTs	2833 females	Vitamin D alone or in combination with other micronutrients during pregnancy	(1) Similar risk of GDM among those taking vitamin D supplements or no intervention/placebo (RR: 0.43, 95%CI: 0.05-3.45) very low quality evidence; and (2) Vitamin D supplements may lower risk of pre-eclampsia risk (RR: 0.52, 95%CI: 0.25-1.05) low quality evidence
Pérez-López et al[72], 2015	A systematic review and meta-analysis of 13 RCTs	2299 females	Vitamin D supplementation during pregnancy	Incidence of pre-eclampsia, GDM, weight, preterm birth, and cesarean section were not influenced by vitamin D supplementation

CI: Confidence interval; DASH: Dietary Approaches to Stop Hypertension; GDM: Gestational diabetes mellitus; MedDiet: Mediterranean diet; OR: Odds ratio; PA: Physical activity; RCT: Randomized controlled trial; RR: Risk ratio; WMD: Weighted mean differences.