Can Gestational Diabetes Mellitus be Prevented?

According to the American Diabetes Association, gestational diabetes mellitus (GDM) is defined as a metabolic disorder, characterized by hyperglycemia, usually detected during the late second or early third trimester.[1] There is a dramatic increase in the reported rates of GDM worldwide. Globally, the prevalence of GDM varies widely, largely because of different diagnostic criteria. Saeedi et al. reported that the global prevalence of GDM was 14.7% based on the International Association of Diabetes and Pregnancy Study Groups criteria.[2] In 2019, a meta-analysis using the same criteria reported that the highest pooled prevalence (11.4%) of GDM was in South Asia (Bangladesh, India, and Sri Lanka) compared to the rest of the world (3.6%–6.0%).[3] Findings from the demographic health survey showed that the overall prevalence of GDM in Bangladesh was 35%, with increased odds of GDM observed among women living in the urban areas and those aged ≥25 years.[4] GDM is a heterogeneous disorder that results from interactions between multiple risk factors, both genetic and environmental.[5] Previously, lifestyle intervention studies focusing on the prevention of type 2 diabetes showed a risk reduction of 58%.[6,7] No similar findings among high-risk women for GDM have been published. Adherence to a healthy lifestyle before pregnancy is, however, associated with reduced GDM risk.[8] A systematic review and meta-analysis showed that dietary, physical activity, diet plus physical activity, metformin, and myo-inositol interventions reduce the incidence of GDM compared with control interventions.[9] However, currently, there is no systematized strategy for GDM prevention. It is believed that due to the parallels in the pathogenesis and risk factors of GDM and type 2 diabetes mellitus (T2DM), it is likely that interventions that are effective in preventing T2DM may also be effective in preventing GDM. These factors include eating patterns, physical activity, a decline in obesity rates, and weight gain during pregnancy.[10] Evidence shows that weight loss is not recommended during pregnancy (even in obese women), rather it is suggested to achieve adequate weight and nutritional control before conception and between pregnancies. In some groups of patients with diagnosed insulin resistance, such as polycystic ovary syndrome or metabolic syndrome patients, for the prevention of GDM, it is suggested to introduce metformin therapy. Glueck et al. observed a 10-fold decrease in the incidence of GDM in this group of patients.[11] However, daily administration of 3 g of metformin in nondiabetic obese pregnant patients from early pregnancy to delivery did not reduce the incidence of GDM.[12] In recent years, a beneficial effect on insulin sensitivity of other factors, such as fiber, myo-inositol, and probiotics, has also been observed. A beneficial effect of micronutrients such as Vitamin D, iron, and selenium on glucose metabolism has been noted.[13] INDIVIDUALIZED DIET Several diets have been analyzed to reduce the risk of GDM and prevent maternal and fetal complications. A low-glycemic index diet, diets with energy restrictions (1/3 reduction of calories), low carbohydrate content, and high-fiber diets were discussed. According to some recommendations, the currently available evidence on the prevention of GDM revealed that most interventions performed during pregnancy have a nonsignificant effect on the prevention of GDM.[14] A diet with a low glycemic index reduces the increase in insulin resistance observed in pregnancy. However, in an overview of Cochrane Reviews, the benefit or harm of a low glycemic index diet versus a moderate–high-glycemic index diet on the risk of GDM is unknown.[15] There are controversies regarding carbohydrate-restricted diets for the prevention of GDM because replacing dietary carbohydrates with fat may have a detrimental effect on the mother's insulin resistance and may lead to excessive fat accumulation in the fetus.[16] Although several studies suggested that restricted-energy diets and carbohydrate diets can minimize weight gain during pregnancy without increasing the risk of ketonuria and/or intrauterine growth restriction, one should be very careful in prescribing such diets to pregnant women. The Institute of Medicine recommends 46–65 energy percent from carbohydrates and a minimum of 175 g of carbohydrates daily to ensure appropriate fetal growth and cerebral development and function.[17] The Mediterranean diet (MedDiet) is defined by plant-rich meals with olive oil as the main source of additional fat, with low consumption of processed meat (1 or fewer servings per week) and red meat (<2 servings per week); moderate consumption of white meat (2 servings per week), eggs (2–4 servings per week), and fish or seafood (2 or more servings per week); and high consumption of low-fat dairy products (2 servings per day). It has been published that MedDiet with additional pistachios and virgin olive oil can be used to prevent GDM.[18] In summary, in a meta-analysis published by Rogozińska et al., interventions that were mainly based on diet decreased the rates of GDM by 33%. However, the authors concluded that GDM cannot be prevented by dietary or mixed approach interventions, and they suggested a trend toward a beneficial effect in patients of mainly diet-based interventions, with the potential to significantly reduce the risk of GDM only in obese and overweight women.[19] PHYSICAL ACTIVITY The American Dietetic Association and the American Nutrition Society stated that women who exercised during pregnancy gained significantly less fat and that moderate exercise may reduce the risk of GDM.[20] A meta-analysis provides evidence that in-facility physical activity programs started before the 20th week of gestation can significantly decrease the incidence of GDM among women at high risk.[21] Another meta-analysis showed that diet was effective in gestational diabetes prevention, while exercise was not. However, a sub-analysis showed that exercise was effective only when introduced in the first trimester; physical activity started in the second trimester was not effective. In addition, mild–moderate exercise was effective in contrast to vigorous physical activity.[22] PROBIOTICS In a meta-analysis performed by Rogozińska et al., the risk of GDM was reduced by 60% for probiotics (with diet) compared to standard care.[19] Callaway et al. performed a double-blind, randomized controlled trial to analyze whether probiotics (Lactobacillus rhamnosus and Bifidobacterium animalis ssp. lactis) given from the second trimester of pregnancy in overweight and obese patients may decrease the risk of GDM. This study did not confirm the effectiveness of such a strategy.[23] MYO-INOSITOL Myo-inositol, an isomer of inositol, is one of the intracellular mediators of the insulin signal and is associated with insulin sensitivity in type 2 diabetes.[24] The best sources of inositol are grains, meat, fresh fruits and vegetables, corn, and legumes. The average dietary intake contains 1 g of inositol/day. In a meta-analysis performed by Rogozińska et al., the risk of GDM was reduced by 60% for myo-inositol in comparison to standard care.[19] In another overview of Cochrane Reviews, it was noticed that myo-inositol supplementation during pregnancy versus control possibly reduced the risk of GDM: risk ratio [RR] = 0.43 and 95% confidence interval [CI] 0.29–0.64.[15] The mechanism of the beneficial effect of myo-inositol is not fully understood. It may exert an intracellular effect directly on the activation of acetyl-CoA carboxylase and induce lipogenesis stimulation. It has been proposed that the binding of insulin to specific receptors stimulates D-chiro-inositol, facilitating the transport to the inside of the cell.[25] Another hypothesis suggests that myo-inositol is a precursor to D-chiro-inositol, which contains inositol phosphoglycate in the extracellular matrix of cells. It has been postulated that insulin binding to specific receptors can stimulate D-chiro-inositol, improving transport to the inside of the cell. It clarifies the role of myo-inositol in the insulin-signaling cascade.[26] VITAMIN D There is some evidence that an insufficient supply of Vitamin D in early pregnancy may be correlated with an increased risk of GDM.[27] In the prospective cohort study performed by Bao et al., the authors analyzed Vitamin D intake in supplementation and diet and its influence on GDM risk. The study resulted with the conclusion that supplementation of Vitamin D 1–399 IU/day and ≥400 IU/day reduced the risk of GDM by 20% (RR = 0.8; 95% CI 0.67–0.96) and 29% (RR = 0.71; 95% CI 0.56–0.9), respectively (P = 0.002).[28] CONCLUSION It is postulated that most interventions performed during pregnancy are not entirely successful in GDM prevention. Although there is evidence that some supplements can be beneficial, these trials demonstrate only limited evidence. However, prepregnancy dietary patterns appear to reduce the risk of GDM. Programs that introduce appropriate dietary patterns for women before pregnancy appear to be the first line of GDM prevention. However, some interventions, such as adherence to a diet as healthy as the MedDiet, optimal physical activity, supplementing Vitamin D, fiber, myo-inositol, and probiotics containing L. rhamnosus and Bifidobacterium lactis could become standard practice. However, further studies are needed to evaluate the effects of supplements in large, multicenter, randomized trials involving a wider group of patients, with different ethnicities.