Nuria García de la Torre

Gestational diabetes mellitus (GDM) is associated with several risks in the mother and the baby in the short and long term. With a growing incidence, it is paramount to reduce the development of GDM. Different nutritional interventions have been propose to reduce GDM risk. In different epidemiological studies and two RCTs, the Mediterranean diet (MedDiet) has proved a consistent reduction in GDM incidence. In addition, other benefits have been described, such as lower gestational weight gain; a decrease in insulin requirements when GDM was diagnosed; a reduction in episodes of urinary tract infections, emergency C-sections, and perineal trauma; lower rates of prematurity and large- and small-for-gestational-age newborns; and lower incidence of postpartum metabolic syndrome. Moreover, adherence to a MedDiet during pregnancy might provide benefits also in offspring health later in life. Mechanisms involved for this benefit include reduction in the plasma levels of inflammatory biomarkers, modulation of gene expression related to inflammation and oxidative stress, epigenomic changes in DNA methylation and circulating micro-RNAs (miRNAs), gene-diet interaction, and possibly changes in gut microbiota.

The San Carlos Gestational Diabetes Mellitus (GDM) prevention study, a nutritional intervention RCT based on a Mediterranean Diet (MedDiet), has been shown to reduce the incidence of GDM. The objective of this study is to investigate the relationship of leptin, adiponectin, interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-α), insulin and HOMA-IRand circulating miRNAs (miR-29a-3p, miR-103a-3p, miR-132-3p, miR-222-3p) with the appearance of GDM and with MedDiet-based nutritional intervention, at 24–28 gestational weeks (GW), and in glucose regulation 2–3 years post-delivery (PD). A total of 313 pregnant women, 77 with GDM vs. 236 with normal glucose tolerance (NGT), 141 from the control group (CG, MedDiet restricting the consumption of dietary fat including EVOO and nuts during pregnancy) vs. 172 from the intervention group (IG, MedDiet supplemented with extra virgin olive oil (EVOO) and pistachios during pregnancy) were compared at Visit 1 (8–12 GW), Visit 2 (24–28 GW) and Visit 3 (2–3 years PD). Expression of miRNAs was determined by the Exiqon miRCURY LNA RT-PCR system. Leptin, adiponectin, IL-6 and TNF-α, were measured by Milliplex^® immunoassays on Luminex 200 and insulin by RIA. Women with GDM vs. NTG had significantly higher leptin median (Q1–Q3) levels (14.6 (9.2–19.4) vs. 9.6 (6.0–15.1) ng/mL; p < 0.05) and insulin levels (11.4 (8.6–16.5) vs. 9.4 (7.0–12.8) µUI/mL; p < 0.001) and lower adiponectin (12.9 (9.8–17.2) vs. 17.0 (13.3–22.4) µg/mL; p < 0.001) at Visit 2. These findings persisted in Visit 3, with overexpression of miR-222-3p (1.45 (0.76–2.21) vs. 0.99 (0.21–1.70); p < 0.05)) and higher levels of Il-6 and TNF-α. When the IG is compared with the CG lower levels of insulin, HOMA-IR-IR, IL-6 levels at Visit 2 and 3 and leptin levels only at Visit 2 were observed. An overexpression of miR-222-3p and miR-103a-3p were also observed in IG at Visit 2 and 3. The miR-222-3p and miR103a-3p expression correlated with insulin levels, HOMA-IR, IL-6 and TNF-α at Visit 2 (all p < 0.05). These data support the association of leptin, adiponectin and insulin/HOMA-IR with GDM, as well as the association of insulin/HOMA-IR and IL-6 and miR-222-3p and miR-103a-3p expression with a MedDiet-based nutritional intervention.

Hypothesis: Gestational diabetes mellitus (GDM) entails a complex underlying pathogenesis, with a specific genetic background and the effect of environmental factors. This study examines the link between a set of single nucleotide polymorphisms (SNPs) associated with diabetes and the development of GDM in pregnant women with different ethnicities, and evaluates its potential modulation with a clinical intervention based on a Mediterranean diet.Methods: 2418 women from our hospital-based cohort of pregnant women screened for GDM from January 2015 to November 2017 (the San Carlos Cohort, randomized controlled trial for the prevention of GDM ISRCTN84389045 and real-world study ISRCTN13389832) were assessed for evaluation. Diagnosis of GDM was made according to the International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria. Genotyping was performed by IPLEX MassARRAY PCR using the Agena platform (Agena Bioscience, SanDiego, CA). 110 SNPs were selected for analysis based on selected literature references. Statistical analyses regarding patients’ characteristics were performed in SPSS (Chicago, IL, USA) version 24.0. Genetic association tests were performed using PLINK v.1.9 and 2.0 software. Bioinformatics analysis, with mapping of SNPs was performed using STRING, version 11.5.Results: Quality controls retrieved a total 98 SNPs and 1573 samples, 272 (17.3%) with GDM and 1301 (82.7%) without GDM. 1104 (70.2%) were Caucasian (CAU) and 469 (29.8%) Hispanic (HIS). 415 (26.4%) were from the control group (CG), 418 (26.6%) from the nutritional intervention group (IG) and 740 (47.0%) from the real-world group (RW). 40 SNPs (40.8%) presented some kind of significant association with GDM in at least one of the genetic tests considered. The nutritional intervention presented a significant association with GDM, regardless of the variant considered. In CAU, variants rs4402960, rs7651090, IGF2BP2; rs1387153, rs10830963, MTNR1B; rs17676067, GLP2R; rs1371614, DPYSL5; rs5215, KCNJ1; and rs2293941, PDX1 were significantly associated with an increased risk of GDM, whilst rs780094, GCKR; rs7607980, COBLL1; rs3746750, SLC17A9; rs6048205, FOXA2; rs7041847, rs7034200, rs10814916, GLIS3; rs3783347, WARS; and rs1805087, MTR, were significantly associated with a decreased risk of GDM, In HIS, variants significantly associated with increased risk of GDM were rs9368222, CDKAL1; rs2302593, GIPR; rs10885122, ADRA2A; rs1387153, MTNR1B; rs737288, BACE2; rs1371614, DPYSL5; and rs2293941, PDX1, whilst rs340874, PROX1; rs2943634, IRS1; rs7041847, GLIS3; rs780094, GCKR; rs563694, G6PC2; and rs11605924, CRY2 were significantly associated with decreased risk for GDM.Conclusions: We identify a core set of SNPs in their association with diabetes and GDM in a large cohort of patients from two main ethnicities from a single center. Identification of these genetic variants, even in the setting of a nutritional intervention, deems useful to design preventive and therapeutic strategies.

A pre-gestational thyroid reserve of iodine is crucial to guarantee the increased demand for thyroid hormone production of early pregnancy. An iodine intake ≥150 µg/day is currently recommended. The objective of this study was to assess average pre-gestational food-based iodine consumption in pregnant women at their first prenatal visit (p = 0.026), a lower miscarriage rate, and a decrease in the composite of materno-fetal adverse events (0.81; 0.67–0.98). Reaching the recommended iodine pre-pregnancy intake with foods could benefit the progression of pregnancy.

Gestational diabetes mellitus (GDM) is the most frequent morbidity found in pregnancy, and it increases the risk for several maternal-fetal complications. Hispanic women are considered at high risk. The St. Carlos GDM prevention study is a randomized controlled trial (RCT) conducted from 2016–2017. Normoglycemic women were randomized at 12–14 Gestation week (WG) to an intervention group (IG) receiving recommendations based on the MedDiet (supplemented with ExtraVirgin Olive Oil/pistachios), or to a control group (CG), recommended to limit fat intake. After RCT conclusion, IG recommendations were applied to a real-world group (RW) in routine clinical practice. The primary endpoint of the current study is an assessment of the GDM rate in Hispanic participants of the aforementioned studies: 132 RCT, 128 CT, 284 RW participants. The GDM rate was lower in IG: 19/128(14.8%), p = 0.021, and RW: 38/284(13.4%), p = 0.029) than in CG: 34/132(25.8%). Adjusted RR (95%CI) for GDM: 0.72 (0.50–0.97), p = 0.037 in IG and 0.77 (0.61–0.97), p = 0.008 in RW. Rates of urinary tract infections, emergency caesarean-sections and perineal trauma were also lower in IG and RW. Other adverse outcomes were lower in IG vs. CG. In conclusion, a MedDiet-based intervention reduces the rate of GDM and several adverse maternal-fetal outcomes in Hispanic women residing in Spain.

The intrauterine environment may be related to the future development of chronic diseases in the offspring. The St. Carlos gestational diabetes mellitus (GDM) prevention study, is a randomized controlled trial that evaluated the influence of the early (before 12th gestational week) Mediterranean diet (MedDiet) on the onset of GDM and adverse gestational outcomes. Out of 874 women assessed after delivery (440 control group (CG)/434 intervention group (IG)), 703 children were followed (365/338; CG/IG), with the aim to assess whether the adherence to a MedDiet during pregnancy induces health benefits for the offspring during the first two years of life. Logistic regression analysis showed that the IG in children of mothers with pre-gestational body mass index (BMI) < 25 kg/m² and normal glucose tolerance (NGT), was associated with a lower risk (RR(95% CI)) of suffering from severe events requiring hospitalization due to bronchiolitis/asthma (0.75(0.58–0.98) and 0.77(0.59–0.99), respectively) or other diseases that required either antibiotic (0.80(0.65–0.98) and 0.80(0.65–0.99), respectively), corticosteroid treatment (0.73(0.59–0.90) and 0.79(0.62–1.00) respectively) or both (all p < 0.05). A nutritional intervention based on the MedDiet during pregnancy is associated with a reduction in offspring’s hospital admissions, especially in women with pre-gestational BMI < 25 kg/m² and NGT.

Background The consumption of dairy products in pregnancy is widely extended. However, whether the consumption of low or high fat dairy produce is more beneficial for maternofetal health has yet to be established. Research design and methods This prospective cohort study evaluated the effect of consumption of dairy products during pregnancy on the frequency of gestational diabetes mellitus (GDM) and a composite of adverse maternofetal outcomes (CMFO). Pregnant women receiving obstetric care between 2014 and 2017 were eligible. Those who consumed ≥3 servings/day of dairy products at 24–28 gestational weeks (GWs) were included and analyzed (n=2004). The population was stratified into three groups according to intake of fat-free dairy products—skimmed milk and fat-free yoghurt and cheese—(days/week): infrequent (1–2), average (3–6) and regular (7). Logistic regression analysis compared ORs (95% CI) for GDM and CMFO between the three groups (where the group of reference was the ‘infrequent’ intake group). Results After adjusting for confounding factors, no significant associations were found between the degree of consumption of fat-free dairy products and the risk of GDM and a CMFO. Moreover, when categorized by the degree of adherence to the Mediterranean diet (above or below the median score), associations were found between the ‘regular’ intake group and an increased risk of having a CMFO in women with a high adherence to the Mediterranean diet (OR: 1.50; 95% CI: 1.01 to 2.22; pConclusions The consumption of fat-free dairy products during pregnancy does not seem to be beneficial for maternofetal health.

An early antenatal dietary intervention could play an important role in the prevention of metabolic diseases postpartum. The aim of this study is to evaluate whether an early, specific dietary intervention reduces women’s cardiovascular risk in the “fourth trimester”. This prospective cohort study compares 1675 women from the standard-care group (ScG/n = 676), who received standard-care dietary guidelines, with the intervention group (IG/n = 999), who received Mediterranean diet (MedDiet)-based dietary guidelines, supplemented with extra-virgin olive oil and nuts. Cardiovascular risk was determined by the presence of metabolic syndrome (MetS) and insulin resistance syndrome (IrS) (HOMA-IR 3.5) at 12–14 weeks postpartum. MetS was less frequent in the IG (11.3 vs. 19.3%, p < 0.05). The intervention was associated with a reduction in the relative risk of having MetS: 0.74 (95% CI, 0.60–0.90), but not in the risk of IrS. When analyzing the presence of having one or more components of the MetS, the IG had significantly higher rates of having 0 components and lower rates of having ≥1 (p-trend = 0.029). An early MedDiet-based nutritional intervention in pregnancy is associated with reductions in postpartum rates of MetS.

Background: A high adherence (adh.) to a MedDiet pattern was associated with a reduced GDM risk. Studies have shown associations between MTNR1B rs10830963, TCF7L2 rs7903146, MC4R rs17782313 SNPs and GDM risk. The conferring risk could be modified by a MedDiet. This study’s aim was to investigate if the association between the degree of adh. to a MedDiet and GDM incidence is modulated by MTNR1B rs10830963 C>G, TCF7L2 rs7903146 C>T and MC4R rs17782313 T>C polymorphisms. Methods and Findings: 874 women were stratified into 3 groups defined as high, moderate or low adh. according to late first-trimester (>12 gestational weeks) compliance with 6 food targets: vegetables >12 s/w, fruits >12 s/w, juice 3 s/w, consumption of extra virgin olive oil (EVOO) >6 d/w and 40 mL/d EVOO. High adh. was defined as complying with 5-6 targets; moderate 2-4 targets and low 0-1 targets. Patients were genotyped for rs10830963, rs7903146 and rs17782313. Logistic regression analysis was adjusted for ethnicity, age, parity and BMI. Results: There was a significant association between rs10830963 risk allele G and GDM risk (OR) 1.87(1.29-2.73); and fasting 1.77(0.88-2.66) and 1 h glycaemia 6.27 (1.72-10.83) during 75g OGTT (all p<0.0001). Subjects with rs10830963 G allele who had low adh. had higher fasting glucose (mg/dL) compared to carriers with high adh. (88.24±0.93 vs. 84.59±0.85, p inter< 0.05). For T carriers of rs7903146 and C carriers of rs17782313 the genetic risk for GDM was significantly lower in women with high adh. 0.43 (0.23-0.80) compared to low adh. 0.2 (0.14-0.99), p-inter <0.01. The genetic risk score confirmed a significant gene-MedDiet interaction (p=0,05) for GDM. There was no effect in non-risk genotype carriers for the 3 SNPs. Conclusions: MTNR1B, TCF7L2, MC4R genes modulate the effect of a DietMed on the development of impaired glucose metabolism and GDM. Disclosure: A. Barabash: None. J. Valerio Deogracia: None. C. Assaf-Balut: None. L. Del Valle: None. N. Garcia de la Torre: None. E. Bordiu: None. A. Duran: None. M. Fuentes: None. J. Ines: None. M. Cuesta: None. M.A. Rubio: None. A.L. Calle: None. Funding: Instituto de Salud Carlos III of Spain; Fondo Europeo de Desarrollo Regional; Sociedad de Endocrinolog?a Nutrici?n y Diabetes de la Comunidad de Madrid (IPI/2017/NR2)

We reported that a Mediterranean Diet (MedDiet), supplemented with extra-virgin olive oil (EVOO) and pistachios, reduces GDM incidence and several other adverse outcomes. In order to assess its translational effects in the real world we evaluated the effect of MedDiet from 1st gestational visit in GDM rate compared with control (CG) and intervention (IG) groups from the previously referred trial. As secondary objective we also compared adverse perinatal outcomes between normoglycemic and diabetic women. This trial is a prospective, clinic-based, interventional study with a single group. 1066 eligible normoglycaemic women before 12 gestational weeks were assessed. 932 women (32.4 ± 5.2 years old, pre-gestational BMI 22.5 ± 3.5 kg/m²) received a motivational lifestyle interview with emphasis on daily consumption of EVOO and nuts, were followed-up and analysed. Binary regression analyses were used to examine the risk for each pregnancy outcome, pregnancy-induced hypertension, preeclampsia, gestational weight gain (GWG), caesarean-section, perineal trauma, preterm delivery, small (SGA) and large for gestational age (LGA), and Neonatal Intensive Care Unit admissions. GDM was diagnosed in 13.9%. This rate was significantly lower than the CG: RR 0.81 (0.73–0.93), p < 0.001 and no different from the IG: RR 0.96 (0.85–1.07), p = 0.468. GWG was lower in diabetic women (10.88 ± 6.46 vs. 12.30 ± 5.42 Kg; p = 0.013). Excessive weight gain (EWG) was also lower in GDM [RR 0.91 (0.86–0.96); p < 0.001] without a significant increase of insufficient weight gain. LGA were also lower (1 (0.8%) vs. 31 (3.9%); p < 0.05)), and SGA were similar (5 (3.8%) vs. 30 (3.7%)). LGA were associated to EWG (RR 1.61 (1.35–1.91), p < 0.001). Differences in other maternal-foetal outcomes were not found. In conclusions an early MedDiet nutritional intervention reduces GDM incidence and maternal-foetal adverse outcomes and should be universally applied as 1st line therapy. GDM might not be consider as a high risk pregnancy any longer.