REduction in the incidence of GEstational DIAbetes mellitus (GDM) with MEDDiet/Lifestyle

INTERVENTION: Eligible women will be randomly assigned to one of two groups: 1. Control group: Women are assigned to standard treatment with recommendations to reduce all types of fat from both animal and vegetable sources including nuts and olive oil, and a training program. This prudent diet recommendation represents a contribution of total fat less than 30% of the total energy intake, and carbohydrate intake of more than 50%. Women will be followed up by the Obstetric Department 2. MedDiet group: Women receive free virgin olive oil (1 litre/week) and mixed nuts (150 g/week) and the training program. Dietitians will give personalized dietary advice to participants with instructions regarding use of olive oil for cooking and dressing, increased consumption of fruit, vegetables, legumes, fish and avoidance of red or processed meat, butter, cream, fast food, sweets, pastries, and sugar‐sweetened beverages. This intervention diet is comprised of an intake of approximately 35‐40% of the total fat (predominantly unsaturated fatty acids) and 40‐45% of the low glycemic index carbohydrates, maintaining a protein intake of 20%, similar to the control diet. Nutrition interventions are aimed to achieve a lifestyle score >10 based on Diabetes Nutrition and Complications Trial (DNCT) previously reported. Women will be followed up by the Endocrinology Department. Added 30/08/2017: To diagnose GDM a single 2‐h 75‐g oral glucose tolerance test was performed, applying IADPSG criteria. One impaired value above the thresholds was enough to diagnose GDM: fasting glucose =92mg/dL, 1‐hour glucose =180mg/dL and 2‐hours glucose =153mg/dL. Women diagnosed with GDM were followed‐up at the Pregnancy and Diabetes Unit and the Obstetrics Department. GDM was treated with diet alone or in combination with insulin therapy, when diet alone was incapable of controlling glucose excursions. Nutritional treatment of GDM was based on a Mediterranean diet, with recommendations very similar to the ones provided to th CONDITION: Gestational Diabetes Mellitus ; Nutritional, Metabolic, Endocrine ; Diabetes mellitus arising in pregnancy INCLUSION CRITERIA: 1. Women aged over 18 2. With normal fasting glucose values (< 92 mg/dl) in the 1st gestational assessment (8‐12 GWs) 3. Who sign the informed consent Added 30/08/2017: 4. Having attended GDM screening at 24‐28 gestational weeks Added 26/01/2018: 5. Who did not develop GDM PRIMARY OUTCOME: To define the prevention of GDM (evaluated at 24‐28 GWs with HAPO criteria) after the lifestyle intervention based on MedDiet and physical activity/exercise, as compared to standard treatment, in women with normal FPG at the 1st gestational visit (8‐12 GWs).; ; Added 26/01/2018:; The primary outcome will be to compare the incidence of composite maternofoetal outcomes in normoglycemic women who followed two different nutritional recommendations ? guidelines based on a MedDiet with an enhanced consumption of extra virgin olive oil and nuts versus guidelines provided in regular clinical practice that limit fat consumption. Composite maternofoetal outcomes assessed were emergency c‐section, perineal trauma, pregnancy induced hypertension, preeclampsia, prematurity, large‐for‐gestational‐age, and small‐for‐gestational‐age. ; ; Added 30/08/2017:; Follow up study:; To evaluate normoglycemia (HbA1c and glycemia levels) and gestational weight gain in both groups of women.; SECONDARY OUTCOME: 1. To define the parameters of gestation length, fetal development, delivery characteristics such as cesarean delivery and instrumental vaginal birth, placental weight, and newborn data such as newborn weight, Apgar test values, and cord blood pH. Timepoint: at delivery, Visit 4.; 2. To define functional genetic risk of developing GDM focusing on obese and non‐obese pregnant women. Method and timepoint: HumanOmniExpress Infinium Illumina Exome v1.0, which allows the genotyping of approximately 950,000 markers in total sample. Of these, 700,000 are included in the common variants HumanOmniExpress Infinium (MAF> 5%) and 250,000 variants are included in the Human Exon Exome BeadChip. Eight samples can be hybridized per chip. Measured at Visit 0.; 3. To investigate the effects of MedDiet and scheduled physical exercise/activity on inflammatory biomarkers in pregnant women. Method and timepoint: adiponectin, leptin, insulin and proinsulin will be determined by radioimmunoassay (Linco SA). hsCRP, sCD40L and Lp‐PLA2 will be determined by specific ELISA kits. Visit 0‐6.; 4. To investigate the effects of MedDiet and scheduled physical exercise/activity on epigenetic mechanisms (DNA methylation and miRNA expression) in pregnant women and their offspring. If confirmed, it would represent a novel epigenetic mechanism for regulation of gene expression in the offspring (method and timepoint: we will perform a genome‐wide DNA methylation analysis with the Illumina HumanMethylation450 BeadChip, following the Illumina Infinium HD Methylation protocol, using DNA obtained from whole blood. Quantitative methylation‐specific PCR assay [qMSP]: validation of the most significant loci. Quantitative MSP will be performed with a 7500 Real‐Time PCR System (Applied Biosystems). The primers will be designed using the MethPrimer website. Visit 0‐2‐4‐6.; 5. To investigate whether the MedDiet and scheduled physical exercise/activity alters the composition of the gut microbial flora both in the women and their offspring (method and timepoint: fecal collection and bacterial DNA quantification: DNA of microbial flora contained in the stool samples will be isolated using the PSP Spin Stool DNA PLUS Kit (Invitek Biotechnology and Biodesign). Visit 0‐2‐4‐6.; 6. To evaluate the impact of all of these parameters on the health of newborns in the first year of life; 7. To estimate changes in HbA1c, insulin, HOMA, lipid profile, body weight, blood pressure, adherence to changes in lifestyle estimated by Med Score and urinary hydroxytyrosol levels and plasma alpha‐linolenic acid levels (to confirm compliance in the group receiving MedDiet (extra‐virgin olive oil and mixed nuts). Timepoint: Visit 0‐2‐4‐6; 8. To estimate the conversion rate to abnormal glucose tolerance (type 2 diabetes mellitus, IFG and IGT) of women with prior gestational diabetes mellitus (GDM) between 6 and 12 weeks after delivery. Method: oral glucose tolerance test (OGTT) measured at Visit 5.; ; Added 26/01/2018:; Follow up study:; 1. To compare clinical parameters (glucose, Insulin, HOMA‐IR and blood pressure).; 2. To compare maternal dietary and physical activity habits throughout pregnancy; 3. To compare body weight and weight gain. ; ; Added 30/08/2017:; Follow up study:; 1. To compare clinical and anthropometric parameters (insulin, HOMA‐IR, lipid profile, blood pressure...) of women with and without GDM; 2. Gestational and maternal outcomes: To define rates of urinary tract infections (UTI), perineal trauma, preeclampsia, pregnancy‐induced hypertension, albuminuria, type of delivery (vaginal, instrumental and C‐sections); 3. Infant outcomes: prematurity, shoulder dystocia, newborns weight LGA and SGA, admission to Neonatal Intensive Care Unit (NICU), Hypoglycemia, Respiratory distress and Hiperbilirrubinemia.