ABSTRACT
The aim of this study was to evaluate the impact of the Dietary Approaches to Stop Hypertension (DASH) diet on glycaemic control and consumption of processed (PF) and ultraprocessed (UPF) foods in pregnant women with pre-gestational diabetes mellitus (PGDM). This is a randomised, controlled, single-blind clinical trial with forty-nine adult women with PGDM, followed at a public maternity hospital in Rio de Janeiro, Brazil. The control group (CG) received a standard diet consisting of 45-55 % of the total energy intake of carbohydrates, 15-20 % of proteins and 25-30 % of lipids. The DASH group (DG) received an adapted DASH diet, which did not differ from the standard diet in the percentage of macronutrients, but had higher contents of fibre, unsaturated fats and minerals such as Ca, Mg and K; and lower contents of Na and saturated fats than the standard diet. In the analysis by protocol, the DG presented a higher incidence of glycaemic control after 12 weeks of intervention (57·1 v. 8·3 %, P = 0·01, moderate effect size) and a lower mean consumption of UPF (-9·9 %, P = 0·01) compared with the CG. There was no statistically significant difference in fasting and postprandial blood glucose concentrations, or in the consumption of PF between the groups (P > 0·05). The DASH diet may be a strategy for glycaemic control in pregnant women with PGDM, favouring the adoption of a nutritionally adequate diet with lower consumption of UPF. Further studies are needed to investigate the effect of the DASH diet on glycaemic profile, and maternal and perinatal outcomes in women with PGDM.
Subject(s)
Diabetes, Gestational , Dietary Approaches To Stop Hypertension , Glycemic Control , Hypertension , Adult , Brazil , Diabetes, Gestational/diet therapy , Diet , Female , Humans , Hypertension/prevention & control , Pregnancy , Pregnant Women , Single-Blind MethodABSTRACT
O diabetes mellitus gestacional (DMG) é uma complicação que atinge o metabolismo da gestante, resultando em intolerância à glicose e consequente hiperglicemia, originada pela insuficiência de insulina materna. Este estudo tem como objetivo identificar os tratamentos disponíveis e mais utilizados para o DMG. Trata-se de um uma revisão de literatura, feita a partir de 22 referências, acerca dos tratamentos para o DMG. As bases de dados escolhidas foram Google Acadêmico, UpToDate, SciELO e o acervo da Universidade do Planalto Catarinense. Estudos apontam a insulina humana NPH e regular como a principal escolha, quando comparada aos seus análogos, apesar de ainda existirem muitas controvérsias quanto ao início do tratamento, o esquema terapêutico e os ajustes das doses. Pesquisas têm demonstrado bons resultados sobre a eficácia e a segurança dos hipoglicemiantes orais gliburida e metformina no tratamento de gestantes diabéticas, mas é evidente a necessidade de mais estudos para confirmar a efetividade deles e garantir um bom desenvolvimento do concepto. Concluiu-se que o controle dietético e o exercício físico são a primeira opção de tratamento para o DMG. Todavia, caso a euglicemia não seja atingida, opta-se pelo tratamento medicamentoso por meio da insulinoterapia ou hipoglicemiantes orais, o que possibilita a redução da incidência dos efeitos adversos ao binômio materno-fetal.(AU)
Gestational diabetes mellitus (DMG) is a complication that affects the pregnant woman's metabolism, resulting in glucose intolerance and consequent hyperglycemia, caused by insufficient maternal insulin. This study aims to identify the available and most used treatments for DMG. This is a literature review, based on 22 references, about treatments for Gestational Diabetes; the databases chosen were Google Scholar, UpToDate, SciELO and the collection of the Universidade do Planalto Catarinense. Studies point to human insulin NPH and regular as the main choice when compared to its analogues, although there are still many controversies about the beginning of treatment, therapeutic scheme and dose adjustments. Researches have shown good results on the efficacy and safety of oral hypoglycemic agents glyburide and metformin in the treatment of diabetic pregnant women, but it is evident the need for further studies to confirm their effectiveness and to guarantee a good development of the fetus. It was concluded that dietary control and physical exercise are the first treatment option for DGM. However, if euglycemia is not achieved, drug treatment is chosen through insulin therapy or oral hypoglycemic agents, which makes it possible to reduce the incidence of adverse effects to the maternal-fetal binomial.(AU)
Subject(s)
Humans , Female , Pregnancy , Diabetes, Gestational/diet therapy , Diabetes, Gestational/drug therapy , Diabetes, Gestational/therapy , Diabetes Mellitus/drug therapy , Exercise , Databases, Bibliographic , Glyburide/adverse effects , Glyburide/therapeutic use , Hypoglycemic Agents/adverse effects , Hypoglycemic Agents/therapeutic use , Insulin/administration & dosage , Insulin/therapeutic use , Metformin/adverse effects , Metformin/therapeutic useABSTRACT
AIMS: To address the effect of a diet enriched in extra virgin olive oil (EVOO) on maternal metabolic parameters and placental proinflammatory markers in Gestational diabetes mellitus (GDM) patients. METHODS: Pregnant women at 24-28 weeks of gestation were enrolled: 33 GDM patients which were randomly assigned or not to the EVOO-enriched group and 17 healthy controls. Metabolic parameters were determined. Peroxisome proliferator activated receptor (PPAR) γ and PPARα protein expression, expression of microRNA (miR)-130a and miR-518d (which respectively target these PPAR isoforms) and levels of proinflammatory markers were evaluated in term placentas. Matrix metalloproteinases (MMPs) activity was evaluated in term placentas and umbilical cord blood. RESULTS: GDM patients that received the EVOO-enriched diet showed reduced pregnancy weight gain (GDM-EVOO:10.3 ± 0.9, GDM:14.2 ± 1.4, P = .03) and reduced triglyceridemia (GDM-EVOO:231 ± 14, GDM:292 ± 21, P = .02) compared to the non-EVOO-enriched GDM group. In GDM placentas, the EVOO-enriched diet did not regulate PPARγ protein expression or miR-130a expression, but prevented the reduced PPARα protein expression (P = .02 vs GDM) and the increased miR-518d expression (P = .009 vs GDM). Increased proinflammatory markers (interleukin-1ß, tumour necrosis factor-α and nitric oxide overproduction) in GDM placentas were prevented by the EVOO-enriched diet (respectively P = .001, P = .001 and P = .01 vs GDM). MMPs overactivity was prevented in placenta and umbilical cord blood in the EVOO-enriched GDM group (MMP-9: respectively P = .01 and P = .001 vs GDM). CONCLUSIONS: A diet enriched in EVOO in GDM patients reduced maternal triglyceridemia and weight gain and has antiinflammatory properties in placenta and umbilical cord blood, possibly mediated by the regulation of PPAR pathways.
Subject(s)
Biomarkers/blood , Blood Glucose/analysis , Diabetes, Gestational/diet therapy , Diet , Fetal Blood/metabolism , Olive Oil/pharmacology , Placenta/metabolism , Adult , Case-Control Studies , Diabetes, Gestational/metabolism , Diabetes, Gestational/pathology , Female , Follow-Up Studies , Glycated Hemoglobin/analysis , Humans , Olive Oil/administration & dosage , Pregnancy , PrognosisABSTRACT
In a rat model of gestational diabetes mellitus (GDM) programmed in the offspring of neonatal streptozotocin-induced (nSTZ) diabetic rats, lipids are accumulated in the fetal liver in a sex-dependent way. Here, we evaluated whether maternal diets enriched in olive oil in rats that will develop GDM ameliorate lipid metabolic impairments in the fetal livers. Pregnant offspring of control and nSTZ diabetic rats (F0) were fed a 6% olive oil-supplemented diet throughout the F1 gestation. We evaluated maternal metabolic parameters as well as lipid content, expression of lipid metabolizing enzymes and protein expression of PLIN2, PPARs and PPAR coactivators in the fetal livers. The offspring of nSTZ diabetic rats developed GDM regardless of the maternal treatment. Hypertriglyceridemia in GDM rats was prevented by the olive oil-enriched maternal treatment. In the livers of male fetuses of GDM rats, the maternal olive oil-supplemented diet prevented lipid overaccumulation and prevented the increase in PPARγ and PPARδ levels. In the livers of female fetuses of GDM rats, the maternal olive oil supplementation prevented the increase in PPARδ levels and the reduction in PGC1α levels, but did not prevent the reduced lipid content. Control and GDM rats showed a reduction of lipid metabolic enzymes in the fetal livers, which was associated with reduced levels of the PPAR coactivators PGC-1α and SRC-1 in males and of SRC-1 in females. These results suggest powerful effects of a maternal olive oil-supplemented diet in the fetal liver, possibly providing benefits in the fetuses and offspring from GDM rats.
Subject(s)
Diabetes Mellitus, Experimental/diet therapy , Diabetes, Gestational/diet therapy , Diet , Lipid Metabolism , Liver/embryology , Olive Oil/administration & dosage , PPAR gamma/metabolism , Animals , Dietary Supplements , Female , Ligands , Lipids/chemistry , Liver/metabolism , Male , Perilipin-2/metabolism , Pregnancy , Pregnancy, Animal , Rats , Rats, Wistar , Sex FactorsABSTRACT
: Gestational diabetes mellitus (GDM) associates with fetal endothelial dysfunction (ED), which occurs independently of adequate glycemic control. Scarce information exists about the impact of different GDM therapeutic schemes on maternal dyslipidemia and obesity and their contribution to the development of fetal-ED. The aim of this study was to evaluate the effect of GDM-treatments on lipid levels in nonobese (N) and obese (O) pregnant women and the effect of maternal cholesterol levels in GDM-associated ED in the umbilical vein (UV). O-GDM women treated with diet showed decreased total cholesterol (TC) and low-density lipoproteins (LDL) levels with respect to N-GDM ones. Moreover, O-GDM women treated with diet in addition to insulin showed higher TC and LDL levels than N-GDM women. The maximum relaxation to calcitonin gene-related peptide of the UV rings was lower in the N-GDM group compared to the N one, and increased maternal levels of TC were associated with even lower dilation in the N-GDM group. We conclude that GDM-treatments modulate the TC and LDL levels depending on maternal weight. Additionally, increased TC levels worsen the GDM-associated ED of UV rings. This study suggests that it could be relevant to consider a specific GDM-treatment according to weight in order to prevent fetal-ED, as well as to consider the possible effects of maternal lipids during pregnancy.
Subject(s)
Diabetes, Gestational/diet therapy , Dyslipidemias/diet therapy , Maternal-Fetal Exchange/physiology , Obesity/diet therapy , Umbilical Veins/physiopathology , Adult , Birth Weight/physiology , Blood Glucose/analysis , Body Mass Index , Body Weight/physiology , Cholesterol/blood , Cholesterol/metabolism , Cross-Sectional Studies , Diabetes, Gestational/blood , Diabetes, Gestational/diagnosis , Diabetes, Gestational/metabolism , Diet, Carbohydrate-Restricted , Dyslipidemias/blood , Dyslipidemias/etiology , Dyslipidemias/physiopathology , Endothelium, Vascular/physiopathology , Female , Humans , Infant, Newborn , Lipoproteins, LDL/blood , Lipoproteins, LDL/metabolism , Male , Middle Aged , Obesity/blood , Obesity/metabolism , Obesity/physiopathology , Placental Circulation/physiology , Pregnancy , Retrospective Studies , Young AdultABSTRACT
OBJECTIVE: To evaluate the factors associated with the need for insulin as a complementary treatment to metformin in pregnant women with gestational diabetes mellitus (GDM). METHODS: A case-control study was performed from April 2011 to February 2016 with pregnant women with GDM who needed complementary treatments besides diet and physical exercise. Those treated with metformin were compared with those who, in addition to metformin, also needed the combination with insulin. Maternal characteristics and glycemic control were evaluated. Multinomial logistic regression models were developed to evaluate the influence of different therapies on neonatal outcomes. RESULTS: A total of 475 pregnant women who needed pharmacological therapy were evaluated. Of these, 366 (77.05%) were submitted to single therapy with metformin, and 109 (22.94%) needed insulin as a complementary treatment. In the analysis of the odds ratio (OR), fasting glucose (FG) < 90 mg/dL reduced the odds of needing the combination (OR: 0.438 [0.235-0.815]; p = 0.009], as well as primiparity (OR: 0.280 [0.111-0.704]; p = 0.007]. In obese pregnant women, an increased chance of needing the combination was observed (OR: 2,072 [1,063-4,039]; p = 0,032). CONCLUSION: Obesity resulted in an increased chance of the mother needing insulin as a complementary treatment to metformin, while FG < 90 mg/dL and primiparity were protective factors.
OBJETIVO: Avaliar os fatores associados à necessidade de insulina como tratamento complementar à metformina em gestantes com diabetes mellitus gestacional (DMG). MéTODOS: Um estudo caso-controle foi realizado de abril de 2011 a fevereiro de 2016 com gestantes portadoras de DMG que necessitaram de tratamentos complementares além de dieta e exercícios físicos. Aquelas tratadas com metformina foram comparadas com aquelas que, além da metformina, também precisaram de combinação com insulina. Foram avaliadas as características maternas e de controle glicêmico. Modelos de regressão logística multinomial foram construídos para avaliar a influência das diferentes terapias nos desfechos neonatais. RESULTADOS: Foram avaliadas 475 gestantes que necessitaram de terapia farmacológica. Destas, 366 (77,05%) utilizaram terapia única com metformina, e 109 (22,95%) necessitaram de insulina como tratamento complementar. Na análise da razão de possibilidades (RP), a glicemia de jejum (GJ) < 90 mg/dL reduziu as chances de necessidade da combinação (RP: 0,438 [0,2350,815]; p = 0,009), bem como a primiparidade (RP: 0,280 [0,1110,704]; p = 0,007). Em gestantes obesas, foi observada uma chance maior de necessidade da combinação (RP: 2.072 [1.0634.039]; p = 0,032). CONCLUSãO: A obesidade resultou em um aumento na chance de a mãe precisar de insulina como tratamento complementar à metformina, enquanto a GJ < 90 mg/dL e a primiparidade foram fatores de proteção.
Subject(s)
Diabetes, Gestational/drug therapy , Hypoglycemic Agents/therapeutic use , Insulin/therapeutic use , Metformin/therapeutic use , Adult , Blood Glucose/metabolism , Case-Control Studies , Diabetes, Gestational/blood , Diabetes, Gestational/diet therapy , Drug Therapy, Combination , Exercise Therapy , Female , Humans , Obesity, Maternal/blood , Obesity, Maternal/complications , Obesity, Maternal/diet therapy , Parity , PregnancyABSTRACT
Abstract Objective To evaluate the factors associated with the need for insulin as a complementary treatment to metformin in pregnant women with gestational diabetes mellitus (GDM). Methods A case-control study was performed from April 2011 to February 2016 with pregnant women with GDM who needed complementary treatments besides diet and physical exercise. Those treated with metformin were compared with those who, in addition to metformin, also needed the combination with insulin. Maternal characteristics and glycemic control were evaluated. Multinomial logistic regression models were developed to evaluate the influence of different therapies on neonatal outcomes. Results A total of 475 pregnant women who needed pharmacological therapy were evaluated. Of these, 366 (77.05%) were submitted to single therapy with metformin, and 109 (22.94%) needed insulin as a complementary treatment. In the analysis of the odds ratio (OR), fasting glucose (FG)<90 mg/dL reduced the odds of needing the combination (OR: 0.438 [0.235-0.815]; p=0.009], as well as primiparity (OR: 0.280 [0.111-0.704]; p=0.007]. In obese pregnant women, an increased chance of needing the combination was observed (OR: 2,072 [1,063-4,039]; p=0,032). Conclusion Obesity resulted in an increased chance of the mother needing insulin as a complementary treatment to metformin, while FG<90 mg/dL and primiparity were protective factors.
Resumo Objetivo Avaliar os fatores associados à necessidade de insulina como tratamento complementar à metformina em gestantes com diabetes mellitus gestacional (DMG). Métodos Um estudo caso-controle foi realizado de abril de 2011 a fevereiro de 2016 comgestantes portadoras de DMG que necessitaram de tratamentos complementares além de dieta e exercícios físicos. Aquelas tratadas commetformina foram comparadas com aquelas que, além da metformina, também precisaram de combinação com insulina. Foram avaliadas as características maternas e de controle glicêmico. Modelos de regressão logística multinomial foram construídos para avaliar a influência das diferentes terapias nos desfechos neonatais. Resultados Foram avaliadas 475 gestantes que necessitaram de terapia farmacológica. Destas, 366 (77,05%) utilizaram terapia única com metformina, e 109 (22,95%) necessitaram de insulina como tratamento complementar. Na análise da razão de possibilidades (RP), a glicemia de jejum (GJ)<90mg/dL reduziu as chances de necessidade da combinação (RP: 0,438 [0,235-0,815]; p=0,009), bem como a primiparidade (RP: 0,280 [0,111-0,704]; p=0,007). Em gestantes obesas, foi observada uma chance maior de necessidade da combinação (RP: 2.072 [1.063-4.039]; p=0,032). Conclusão A obesidade resultou em um aumento na chance de a mãe precisar de insulina como tratamento complementar à metformina, enquanto a GJ<90 mg/dL e a primiparidade foram fatores de proteção.
Subject(s)
Humans , Female , Pregnancy , Adult , Diabetes, Gestational/drug therapy , Hypoglycemic Agents/therapeutic use , Insulin/therapeutic use , Metformin/therapeutic use , Parity , Blood Glucose/metabolism , Case-Control Studies , Diabetes, Gestational/diet therapy , Diabetes, Gestational/blood , Drug Therapy, Combination , Exercise Therapy , Obesity, Maternal/complications , Obesity, Maternal/diet therapy , Obesity, Maternal/bloodABSTRACT
BACKGROUND: Gestational Diabetes Mellitus (GDM), defined as glucose intolerance with onset or first recognition during pregnancy, represents one of the most common maternal-fetal complications during pregnancy and it is associated with poor perinatal outcomes. To date, GDM is a rising condition over the last decades coinciding with the ongoing epidemic of obesity and Type 2 Diabetes Mellitus (T2DM). OBJECTIVE: The aim of this review is to discuss the role of diet and nutritional interventions in preventing GDM with the explanation of the special role of myo-inositol (MI) in this matter. METHODS: We performed an overview of the most recent literature data on the subject with particular attention to the effectiveness of diet and nutritional interventions in the prevention of GDM with the special role of MI. RESULTS: Nutritional intervention and physical activity before and during pregnancy are mandatory in women affected by GDM. Moreover, the availability of insulin-sensitizers such as different forms of inositol has dramatically changed the scenario, allowing the treatment of several metabolic diseases, such as those related to glucose dysbalance. Although the optimal dose, frequency, and form of MI administration need to be further investigated, diet supplementation with MI appears to be an attractive alternative for the GDM prevention as well as for the reduction of GDM-related complications. CONCLUSIONS: More studies should be conducted to prove the most effective nutritional intervention in GDM. Regarding the potential effectiveness of MI, further evidence in multicenter, randomized controlled trials is needed to draw firm conclusions.
Subject(s)
Diabetes, Gestational/diet therapy , Diabetes, Gestational/prevention & control , Inositol/administration & dosage , Female , Humans , PregnancyABSTRACT
BACKGROUND: Trials have examined on the benefits of vitamin D supplementation in pregnant women. OBJECTIVE: This review aimed to evaluate whether oral vitamin D supplements, when given to pregnant women with gestational diabetes mellitus (GDM), would improve maternal and neonatal outcomes, compared with no treatment or placebo. METHOD: We performed a systematic review following Cochrane methodology, and randomized trials were included where pregnant women with GDM received vitamin D supplementation versus placebo/no treatment or vitamin D and calcium versus placebo/no treatment. Primary outcomes were preeclampsia, preterm birth, cesarean delivery, gestational hypertension, and adverse events related to vitamin D supplementation. The search strategies were applied to the following databases: MEDLINE, Embase, LILACS, and CENTRAL. Similar outcomes in at least two trials were plotted using Review Manager 5.3 software. The quality of evidence was generated according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE). RESULTS: The total of 1224 references were identified, eleven trials were potentially eligible, and six were included in this review (totaling 456 women). The meta-analysis of frequency of cesarean deliveries did not show significant differences between groups, none of the trials evaluated the remaining primary outcomes. For secondary outcomes, our results suggest that vitamin D supplementation in pregnant women with GDM may reduce newborn complications such as hyperbilirubinemia, polyhydramnios (RR: 0.40, 95% CI: 0.23 to 0.68; RR: 0.17, 95% CI: 0.03 to 0.89; respectively), and the need for maternal or infant hospitalization (RR: 0.13; 95% CI: 0.02 to 0.98; RR: 0.40, 95% CI: 0.23 to 0.69). However, the evidence was of low or very low quality. CONCLUSION: We did not find moderate or high quality evidence indicating that vitamin D supplementation, when compared with placebo, improves glucose metabolism, adverse maternal and neonatal outcomes related to GDM in pregnant women.
Subject(s)
Diabetes, Gestational/diet therapy , Dietary Supplements , Vitamin D/administration & dosage , Cesarean Section/statistics & numerical data , Female , Hospitalization/statistics & numerical data , Humans , Infant Health/statistics & numerical data , Infant, Newborn , Infant, Newborn, Diseases/epidemiology , Infant, Newborn, Diseases/prevention & control , Maternal Health/statistics & numerical data , Placebos/administration & dosage , Pregnancy , Premature Birth/etiology , Premature Birth/prevention & control , Randomized Controlled Trials as Topic , Treatment OutcomeABSTRACT
Objective: Undetected diabetes in pregnancy (DiP) can lead to deleterious consequences. Strengthening health systems and implementing national standardized protocols for screening and management can improve outcomes. This study aimed to achieve consensus on clinical guidelines and facilitate universal screening using standardized testing and an app. Design and Methodology: An integrated care model was developed and antenatal caregivers were trained on screening and management of DiP. A secure Information and Communication Technologies (ICT) solution for real-time communication of results was designed and piloted as the reporting system. The app provided automatic alerts to patients and doctors facilitating timely intervention and offered self-management tools. Pregnant women ≥ 18 years, n = 655 at two antenatal clinics in Trinidad (1 public and 1 private hospital) were screened using a standard 75g 2-hour oral glucose tolerance test (OGTT) after an overnight fast. Seven lab technologists and 24 doctors were trained to use the app. Cost-effectiveness was assessed. Results: National consensus was achieved with 197 antenatal caregivers, for universal screening for DiP. The app facilitated a reporting system of blood glucose results and delivered real-time SMS text and e-mail alerts to participants. 10.1% of participants had abnormal fasting glucose and 14.1% had at least one abnormal reading between 0hr to 2hrs. Universal screening for GDM was cost-effective in the local setting. Results: National consensus was achieved with 197 antenatal caregivers, for universal screening for DiP. The app facilitated a reporting system of blood glucose results and delivered real-time SMS text and e-mail alerts to participants. 10.1% of participants had abnormal fasting glucose and 14.1% had at least one abnormal reading between 0hr to 2hrs. Universal screening for GDM was cost-effective in the local setting. Conclusions: The high prevalence of DiP in T&T justifies the need for universal screening and related health systems change. Training healthcare teams in DiP screening and ICT-enabled management are essential elements of a standardized health system which features real-time reporting.
Subject(s)
Humans , Female , Pregnancy , Adult , Diabetes, Gestational , Trinidad and Tobago , Diabetes, Gestational/diagnosis , Diabetes, Gestational/diet therapy , Diabetes, Gestational/drug therapyABSTRACT
The aim of the study was to evaluate the food intake of pregnant women with gestational diabetes mellitus (GDM) according to two methods of dietary guidance. A randomised controlled clinical trial was conducted by appointment with a nutritionist and by using data from hospital records (2011-2014). The study population comprised adult women diagnosed with GDM treated in a public maternity hospital in Rio de Janeiro, Brazil. The control group (CG) received nutritional advice by the traditional method and the intervention group (IG) were instructed on carbohydrate counting. The analysis of food intake and the consumption of processed foods (PF) and ultra-processed foods (UPF) were evaluated in the second and third trimester. A total of 286 pregnant women were initially assessed (145 in the CG and 141 in the IG). It was observed that 89/120 (74·2 %) and 183/229 (79·9 %) consumed PF daily in the second and third trimesters, respectively, whereas 117/120 (97·5 %) and 225/231 (97·4 %) consumed UPF daily in the second and third trimesters, respectively. When analysing the intake of macronutrients (%) by quartiles, women who had fat intake in the third quartile had the highest average postprandial blood glucose compared with those who consumed fat in the second quartile (P=0·02). The consumption of PF and UPF was high and dietary intake was similar in both groups, regardless of dietary guidance method deployed, suggesting that both methods tested in the study can be used for monitoring the nutritional status of pregnant women with GDM.
Subject(s)
Diabetes, Gestational/diet therapy , Eating , Nutrition Therapy/methods , Adult , Brazil , Counseling , Diet , Dietary Carbohydrates/administration & dosage , Female , Gestational Age , Humans , Nutrition Assessment , Pregnancy , Single-Blind MethodABSTRACT
Gestational diabetes mellitus (GDM) is a disease characterised by glucose intolerance and first diagnosed in pregnancy. This condition relates to an anomalous placental environment and aberrant placental vascular function. GDM-associated hyperglycaemia changes the placenta structure leading to abnormal development and functionality of this vital organ. Aiming to avoid the GDM-hyperglycaemia and its deleterious consequences in the mother, the foetus and newborn, women with GDM are firstly treated with a controlled diet therapy; however, some of the women fail to reach the recommended glycaemia values and therefore they are passed to the second line of treatment, i.e., insulin therapy. The several protocols available in the literature regarding insulin therapy are variable and not a clear consensus is yet reached. Insulin therapy restores maternal glycaemia, but this beneficial effect is not reflected in the foetus and newborn metabolism, suggesting that other factors than d-glucose may be involved in the pathophysiology of GDM. Worryingly, insulin therapy may cause alterations in the placenta and umbilical vessels as well as the foetus and newborn additional to those seen in pregnant women with GDM treated with diet. In this review, we summarised the variable information regarding indications and protocols for administration of the insulin therapy and the possible outcomes on the function and structure of the foetoplacental unit and the neonate parameters from women with GDM.
Subject(s)
Blood Glucose/drug effects , Diabetes, Gestational/drug therapy , Fetal Macrosomia/prevention & control , Insulin/therapeutic use , Placenta/drug effects , Diabetes, Gestational/blood , Diabetes, Gestational/diet therapy , Female , Fetal Macrosomia/epidemiology , Fetal Macrosomia/etiology , Glucose Tolerance Test , Humans , Incidence , Infant, Newborn , PregnancyABSTRACT
SCOPE: Offspring from rats with mild diabetes develop gestational diabetes mellitus (GDM). We tested the hypothesis that an olive oil-supplemented diet attenuates placental oxidative stress/inflammation, activation of mTOR signaling, and inhibition of peroxisome proliferator-activated receptor γ (PPARγ) and fetal overgrowth in GDM offspring from mild diabetic rats. METHODS AND RESULTS: Female offspring from rats with mild diabetes (group that developed GDM) and controls were fed with either a standard diet or a 6% olive oil-supplemented diet during pregnancy. On day 21 of pregnancy, plasma glucose levels in mothers and fetuses were increased in the GDM group independently of the diet. Fetal overgrowth and activation of placental mTOR signaling were partially prevented in the olive oil-treated GDM group. Placental PPARγ protein expression was decreased in GDM rats, independently of the diet. However, increases in placental lipoperoxidation, connective tissue growth factor, and matrix metalloproteinase 2 levels were prevented by the olive oil-enriched diet. CONCLUSION: Diets enriched with olive oil attenuate placental dysfunction and fetal overgrowth in rats with GDM induced by intrauterine programming.
Subject(s)
Diabetes, Gestational/diet therapy , Olive Oil/pharmacology , Placenta/physiopathology , Animals , Diabetes Mellitus, Experimental/diet therapy , Diabetes, Gestational/physiopathology , Dietary Supplements , Female , Organ Size/drug effects , Oxidative Stress/drug effects , PPAR gamma/metabolism , Placenta/drug effects , Placenta/metabolism , Pregnancy , Rats, Wistar , Signal Transduction/drug effects , TOR Serine-Threonine Kinases/metabolismABSTRACT
En Cuba se desarrolla una importante actividad de diabetes y embarazo y existe un programa nacional acerca de esto. Con el objetivo de actualizar los aspectos más importantes relacionados con estos 2 elementos, se realizó, en abril de 2017, el Segundo Consenso Cubano de Diabetes y Embarazo, para lo cual se constituyeron 6 comisiones de trabajo: Atención preconcepcional a la mujer con diabetes pregestacional, Tamizaje y diagnóstico de la diabetes gestacional, Tratamiento dietético de la mujer embarazada con diabetes, Manejo obstétrico y metabólico de la mujer embarazada con diabetes y Seguimiento y riesgo posparto de la mujer con diabetes. Se aprobaron, entre otros aspectos: la posibilidad de diagnosticar diabetes franca al inicio del embarazo, la búsqueda de diabetes gestacional con prueba diagnóstica a las 26 semanas, el uso de metformina durante el embarazo y de la curva de Hadlock para determinar el peso fetal, y un algoritmo de pesquisa de diabetes para mujeres que han tenido diabetes gestacional(AU)
In Cuba there is an important activity of diabetes and pregnancy, and there is a national program in this regard. The Second Cuban Consensus on Diabetes and Pregnancy was held in April 2017 with the aim of updating the most important aspects related to these 2 elements, for which 6 work commissions were established: Preconceptional care for women with pre-pregnancy diabetes, Screening and diagnosis of gestational diabetes, Dietary treatment of pregnant women with diabetes, Obstetric and metabolic management of pregnant women with diabetes, and Follow-up and postpartum risk of women with diabetes. Among other aspects, these were approved: the possibility of diagnosing diabetes at the beginning of pregnancy, the search for gestational diabetes with a diagnostic test at week 26, the use of metformin during pregnancy and the Hadlock curves to determine fetal weight; and a diabetes screening algorithm for women who have had gestational diabetes(AU)
Subject(s)
Humans , Female , Pregnancy , Consensus Development Conferences as Topic , Diabetes, Gestational/diagnosis , Diabetes, Gestational/diet therapyABSTRACT
En Cuba se desarrolla una importante actividad de diabetes y embarazo y existe un programa nacional acerca de esto. Con el objetivo de actualizar los aspectos más importantes relacionados con estos 2 elementos, se realizó, en abril de 2017, el Segundo Consenso Cubano de Diabetes y Embarazo, para lo cual se constituyeron 6 comisiones de trabajo: Atención preconcepcional a la mujer con diabetes pregestacional, Tamizaje y diagnóstico de la diabetes gestacional, Tratamiento dietético de la mujer embarazada con diabetes, Manejo obstétrico y metabólico de la mujer embarazada con diabetes y Seguimiento y riesgo posparto de la mujer con diabetes. Se aprobaron, entre otros aspectos: la posibilidad de diagnosticar diabetes franca al inicio del embarazo, la búsqueda de diabetes gestacional con prueba diagnóstica a las 26 semanas, el uso de metformina durante el embarazo y de la curva de Hadlock para determinar el peso fetal, y un algoritmo de pesquisa de diabetes para mujeres que han tenido diabetes gestacional(AU)
In Cuba there is an important activity of diabetes and pregnancy, and there is a national program in this regard. The Second Cuban Consensus on Diabetes and Pregnancy was held in April 2017 with the aim of updating the most important aspects related to these 2 elements, for which 6 work commissions were established: Preconceptional care for women with pre-pregnancy diabetes, Screening and diagnosis of gestational diabetes, Dietary treatment of pregnant women with diabetes, Obstetric and metabolic management of pregnant women with diabetes, and Follow-up and postpartum risk of women with diabetes. Among other aspects, these were approved: the possibility of diagnosing diabetes at the beginning of pregnancy, the search for gestational diabetes with a diagnostic test at week 26, the use of metformin during pregnancy and the Hadlock curves to determine fetal weight; and a diabetes screening algorithm for women who have had gestational diabetes(AU)
Subject(s)
Humans , Female , Pregnancy , Consensus Development Conferences as Topic , Diabetes, Gestational/diagnosis , Diabetes, Gestational/diet therapyABSTRACT
Maternal diabetes impairs fetoplacental development and programs metabolic diseases in the offspring. We have previously reported that female offspring of pregnant rats with mild diabetes develop gestational diabetes mellitus (GDM) when they become pregnant. Here, we studied the effects of supplementation with polyunsaturated fatty acids (PUFAs) in pregnant mild diabetic rats (F0) by feeding a 6% safflower-oil-enriched diet from day 1 to 14 followed by a 6% chia-oil-enriched diet from day 14 of pregnancy to term. We analyzed maternal metabolic parameters and placental signaling at term in pregnant offspring (F1). The offspring of both PUFAs-treated and untreated mild diabetic rats developed GDM. Although gestational hyperglycemia was not prevented by dietary PUFAs treatment in F0, triglyceridemia and cholesterolemia in F1 mothers were normalized by F0 PUFAs dietary treatment. In the placenta of F1 GDM rats, PPARγ levels were reduced and lipoperoxidation was increased, changes that were prevented by the maternal diets enriched in PUFAs in the F0 generation. Moreover, fetal overgrowth and placental activation of mTOR signaling pathways were reduced in F1 GDM rats whose mothers were treated with PUFAs diets. These results suggest that F0 PUFAs dietary treatment in pregnancies with mild diabetes improves maternal dyslipidemia, fetal overgrowth and placental signaling in female offspring when they become pregnant. We speculate that an increased PUFAs intake in pregnancies complicated by diabetes may prove effective to ameliorate metabolic programming in the offspring, thereby improving the health of future generations.
Subject(s)
Diabetes, Gestational/metabolism , Fatty Acids, Unsaturated/pharmacology , PPAR gamma/metabolism , Placenta/drug effects , TOR Serine-Threonine Kinases/metabolism , Animals , Diabetes Mellitus, Experimental/diet therapy , Diabetes Mellitus, Experimental/metabolism , Diabetes, Gestational/diet therapy , Diabetes, Gestational/etiology , Dietary Supplements , Female , Male , Placenta/metabolism , Pregnancy , Rats, WistarABSTRACT
Pregnant women diagnosed with gestational diabetes mellitus subjected to diet (GDMd) that do not reach normal glycaemia are passed to insulin therapy (GDMi). GDMd associates with increased human cationic amino acid transporter 1 (hCAT-1)-mediated transport of L-arginine and nitric oxide synthase (NOS) activity in foetoplacental vasculature, a phenomenon reversed by exogenous insulin. Whether insulin therapy results in reversal of the GDMd effect on the foetoplacental vasculature is unknown. We assayed whether insulin therapy normalizes GDMd-associated foetoplacental endothelial dysfunction. Primary cultures of human umbilical vein endothelial cells (HUVECs) from GDMi pregnancies were used to assay L-arginine transport kinetics, NOS activity, p44/42mapk and protein kinase B/Akt activation, and umbilical vein rings reactivity. HUVECs from GDMi or GDMd show increased hCAT-1 expression and maximal transport capacity, NOS activity, and eNOS, and p44/42mapk, but not Akt activator phosphorylation. Dilation in response to insulin or calcitonin-gene related peptide was impaired in umbilical vein rings from GDMi and GDMd pregnancies. Incubation of HUVECs in vitro with insulin (1 nmol/L) restored hCAT-1 and eNOS expression and activity, and eNOS and p44/42mapk activator phosphorylation. Thus, maternal insulin therapy does not seem to reverse GDMd-associated alterations in human foetoplacental vasculature.
Subject(s)
Diabetes, Gestational , Endothelium, Vascular/metabolism , Insulin/administration & dosage , Placenta/metabolism , Adult , Cationic Amino Acid Transporter 1/metabolism , Diabetes, Gestational/diet therapy , Diabetes, Gestational/drug therapy , Diabetes, Gestational/metabolism , Diabetes, Gestational/pathology , Endothelium, Vascular/pathology , Female , Gene Expression Regulation/drug effects , Human Umbilical Vein Endothelial Cells/metabolism , Human Umbilical Vein Endothelial Cells/pathology , Humans , Mitogen-Activated Protein Kinase 3/biosynthesis , Nitric Oxide Synthase Type III/biosynthesis , Phosphorylation/drug effects , Placenta/pathology , Pregnancy , Proto-Oncogene Proteins c-akt/metabolismABSTRACT
Gestational diabetes mellitus (GDM) associates with increased L-arginine transport and extracellular concentration of adenosine in human umbilical vein endothelial cells (HUVECs). In this study we aim to determine whether insulin reverses GDM-increased L-arginine transport requiring adenosine receptors expression in HUVECs. Primary cultured HUVECs from full-term normal (n = 38) and diet-treated GDM (n = 38) pregnancies were used. Insulin effect was assayed on human cationic amino acid transporter 1 (hCAT1) expression (protein, mRNA, SLC7A1 promoter activity) and activity (initial rates of L-arginine transport) in the absence or presence of adenosine receptors agonists or antagonists. A1 adenosine receptors (A1AR) and A2AAR expression (Western blot, quantitative PCR) was determined. Experiments were done in cells expressing or siRNA-suppressed expression of A1AR or A2AAR. HUVECs from GDM exhibit higher maximal transport capacity (maximal velocity (V max)/apparent Michaelis Menten constant (K m), V max/K m), which is blocked by insulin by reducing the V max to values in cells from normal pregnancies. Insulin also reversed the GDM-associated increase in hCAT-1 protein abundance and mRNA expression, and SLC7A1 promoter activity for the fragment -606 bp from the transcription start point. Insulin effects required A1AR, but not A2AAR expression and activity in this cell type. In the absence of insulin, GDM-increased hCAT-1 expression and activity required A2AAR expression and activity. HUVECs from GDM pregnancies exhibit a differential requirement of A1AR or A2AAR depending on the level of insulin, a phenomenon that represent a condition where adenosine or analogues of this nucleoside could be acting as helpers of insulin biological effects in GDM.
Subject(s)
Arginine/metabolism , Diabetes, Gestational/drug therapy , Diabetes, Gestational/metabolism , Endothelium, Vascular/metabolism , Hypoglycemic Agents/pharmacology , Insulin/pharmacology , Receptor, Adenosine A1/metabolism , Umbilical Veins/metabolism , Adolescent , Adult , Cationic Amino Acid Transporter 1/biosynthesis , Cationic Amino Acid Transporter 1/genetics , Diabetes, Gestational/diet therapy , Endothelium, Vascular/drug effects , Equilibrative Nucleoside Transporter 1/metabolism , Female , Human Umbilical Vein Endothelial Cells/drug effects , Human Umbilical Vein Endothelial Cells/metabolism , Humans , Infant, Newborn , Male , Pregnancy , Primary Cell Culture , Receptor, Adenosine A1/drug effects , Umbilical Veins/drug effects , Young AdultABSTRACT
BACKGROUND: Gap junctions between ß-cells participate in the precise regulation of insulin secretion. Adherens junctions and their associated proteins are required for the formation, function and structural maintenance of gap junctions. Increases in the number of the gap junctions between ß-cells and enhanced glucose-stimulated insulin secretion are observed during pregnancy. In contrast, protein restriction produces structural and functional alterations that result in poor insulin secretion in response to glucose. We investigated whether protein restriction during pregnancy affects the expression of mRNA and proteins involved in gap and adherens junctions in pancreatic islets. An isoenergetic low-protein diet (6% protein) was fed to non-pregnant or pregnant rats from day 1-15 of pregnancy, and rats fed an isocaloric normal-protein diet (17% protein) were used as controls. RESULTS: The low-protein diet reduced the levels of connexin 36 and ß-catenin protein in pancreatic islets. In rats fed the control diet, pregnancy increased the levels of phospho-[Ser(279/282)]-connexin 43, and it decreased the levels of connexin 36, ß-catenin and beta-actin mRNA as well as the levels of connexin 36 and ß-catenin protein in islets. The low-protein diet during pregnancy did not alter these mRNA and protein levels, but avoided the increase of levels of phospho-[Ser(279/282)]-connexin 43 in islets. Insulin secretion in response to 8.3 mmol/L glucose was higher in pregnant rats than in non-pregnant rats, independently of the nutritional status. CONCLUSION: Short-term protein restriction during pregnancy prevented the Cx43 phosphorylation, but this event did not interfer in the insulin secretion.