Primary prevention of gestational diabetes mellitus through nutritional factors: a systematic review

Our initial research in the aforementioned electronic databases produced 1992 citations. Eighty-five articles were identified as potential articles for further full text review. After the next exclusion process, 28 articles were included and another seven were added from reference lists. The most important reason for exclusion was that diet or supplements were evaluated as a treatment for GDM, not as a primary prevention. We identified a total of 35 relevant articles (Fig. 1. Legend; Flow-chart of prospective cohort studies and clinical trials included in the systematic review. The search used the following combinations of terms: “diet” or “nutrition” and “gestational diabetes mellitus”. A second search was done with the terms “supplement” and “gestational diabetes mellitus”. Filters; Human; languages: English, French and Spanish; date: up to June 30, 2016). Twenty-eight were related to diet and primary prevention of GDM, eight were clinical trials (Additional file 1: Table S1) and 20 were prospective cohort studies (Additional file 2: Table S2). There were eight articles related to supplements and primary prevention of GDM, six clinical trials (Additional file 3: Table S3) and two prospective cohort studies (Additional file 4: Table S4). Lastly, there was one article [8] that studied whether dietary and supplemental iron were related to the occurrence of GDM (Additional file 2: Tables S2 and Additional file 4: Table S4).

Of the 14 clinical trials included, only one was not randomized [9]. All women were pregnant when intervention had begun in the clinical trials. The diagnosis of GDM was based on the Oral Glucose Tolerance Test (OGTT), although the measurements of the OGTT was not the same in all articles, some considered the fasting glucose level abnormal when ≥ 5.3 mmol/l [9‐11], but others consider it to be abnormal when ≥ 4.8 mmol/l [12], ≥5.1 mmol/l [13, 14] or ≥5.5 mmol/l [15]. Furthermore, the glucose level readings at 1 h and at 2 h were also different. One article studied GDM incidence as a secondary outcome [16] and another one does not give a definition of GDM, although they studied glucose blood levels during the pregnancy of the participants [17].

The observational studies were adjusted for the most important variables (such as age, parity, tobacco products, BMI, physical activity, family history of diabetes, alcohol, ethnicity, total calories consumed). Twelve of these articles [8, 18‐28] were based on the Nurses’ Health Study II cohort, which includes more than 13,000 women who reported a singleton pregnancy. In this cohort, GDM cases were identified through self-reported information. The principal measures estimated in these studies were Risk Ratios (RR) and differences in means of GDM incidence.

On one hand, no diet intervention was found to significantly reduce the incidence of GDM except for the intervention of the non-randomized controlled pragmatic trial [11] and the intervention on lifestyle (including diet) of Koivusalo et al. [10], (see Additional file 1: Table S1). Wolff et al. [17] found that an intensive intervention reduces the deterioration of glucose metabolism in obese pregnant women, though they did not report any incidence of GDM. Only two supplement interventions with probiotics and myo-inositol during pregnancy showed a decrease in the rates of GDM compared with a placebo. Luoto et al. [12] intervention showed that probiotics (Lactobacillus Rhamnosus GG and Bifidobacterium Lactis Bb12) reduced the incidence of GDM; 13% (diet/probiotics) versus 36% (diet/placebo) and 34% (control), p = 0.003. Luoto et al. [12] explain in their article that probiotic consumption may protect against GDM because these microorganisms can modify intestinal microbiota, altering the fermentation of dietary polysaccharides and improving intestinal barrier function. They also mentioned the importance of the capability of probiotics to regulate the inflammatory pathways. It is understandable that the protection against GDM provided by probiotics, could be mediated through immunomodulatory pathways and polysaccharide fermentation. Moreover, myo-inositol supplements were found to reduce the incidence of GDM in pregnant women (Matarrelli et al. [14]: RR = 0.127; 95% CI, 0.032–0.502; p = 0.001 and D’Anna et al. [13]: OR = 0.34; 95% CI, 0.17–0.68; p = 0.001) and appear to be an insulin sensitizer. It was reported to reduce plasma glucose levels in insulin resistant conditions such as polycystic ovary syndrome and during the third trimester of GDM pregnancies [29]. The subjacent mechanism of myo-inositol on metabolic benefits is not defined at the moment. It may produce an intracellular effect directly on the activation of acetil CoA carboxylase stimulating lipogenesis. Another theory says that it is a precursor of D-chiro-inositol, which contains inositol phosphoglycan in the extracellular matrix of the cells. 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 [30]. This explains how myo-inositol interacts in the insulin-signaling cascade [31].

On the other hand, the observational studies collected in Table S2 (Additional file 2) showed that achieving a healthier dietary pattern [25], such a Mediterranean dietary pattern, and lowering the intake of foods with high heme iron content, sugar sweetened cola, potatoes, fatty foods and sweets, can reduce the incidence of GDM, especially among the high-risk population and before getting pregnant [8, 21‐23, 32‐34].

Known evidence indicates that women who develop GDM have altered functions of β-cells and insulin resistance, limiting their capacity to cope with the metabolic challenges of pregnancy [35]. Similarly, it is known that iron is a redox-active transitional metal, a strong pro-oxidant which promotes the creation of hydroxyl radicals, increasing oxidative stress. The pancreatic β-cell is particularly sensitive to this type of stress due to weak antioxidant protection [36]. Nevertheless, adherence to healthy diets, such as the Mediterranean one, may reduce GDM risk by minimizing such susceptibilities before pregnancy. Common components of these dietary patterns include fruits and vegetables, relatively small amounts of red and processed meats, and high quality carbohydrates. Fruits and vegetables in particular have many antioxidant properties, in addition to providing fiber and micronutrients such as magnesium and vitamin C. The combination of all these factors may protect against metabolic deterioration counteracting free radicals and improving systemic oxidative stress [37].

It is possible that a publication bias may have occurred as there is a limited amount of publications related to the study of primary intervention of GDM through diet, and absorption of supplements, probiotics and other minerals. In addition, the researchers are not discounting the existence of other articles in databases that were not used for this study.

In this systematic review we found that the majority of the interventions done during pregnancy are not effective in preventing GDM, and although there were cases where supplements proved to be beneficial, the evidence is very scarce. However, dietary patterns prior to pregnancy seem to reduce the risk of GDM. Programs encouraging young women to achieve a healthy dietary pattern before getting pregnant seem to be the best way to prevent GDM. Measures adopted during pregnancy seem to be ineffective because they require more time to properly curb the development of GDM, especially among the high-risk population.

There is a strong need for additional research on this topic. Although some prospective cohort studies have found an association between some nutrients or dietary patterns and the incidence of GDM, the existence of consistency of the results in other populations should be very desirable to prove causal associations between nutritional factors and the risk of GDM. We did not find any controlled trial that evaluated the intervention in dietary pattern before patients get pregnant and the incidence of GDM. Nevertheless, there is an ongoing European multicenter randomized controlled trial in overweight and obese pregnant women on lifestyle intervention and/or vitamin D supplementation [38]. Researchers have recently published the results of the pilot study finding that a healthy eating has a preventive impact on the risk of GDM [39]. Final results of the trial will be published in the near future.