Vitamin C and the risk of gestational diabetes mellitus: a case-control study

OBJECTIVE: To examine whether low maternal dietary intake of vitamin C and low maternal plasma ascorbic acid (AA) concentrations are associated with an increased risk of gestational diabetes mellitus (GDM).
METHODS: Cases were 67 women with GDM meeting National Diabetes Data Group criteria. Controls were 260 women without such a diagnosis. Maternal dietary vitamin C consumption during the periconceptional period and during pregnancy was assessed using a 121-item, semiquantitative food frequency questionnaire. Maternal plasma AA concentrations were determined using automated enzymatic procedures on specimens collected during the intrapartum period.
RESULTS: Mean maternal daily consumption of vitamin C and plasma AA concentrations were 10% and 31% lower, respectively, among GDM cases as compared with controls (130.7 +/- 10.2 vs. 145 +/- 4.9 mg/d, P = .190; 36 +/- 2.0 vs. 53 +/- 1.0 micromol/L, P <.001). After controlling for maternal age, race, prepregnancy adiposity, family history of type 2 diabetes, energy intake and income, women reporting low daily vitamin C intake (< 70 mg/d), as compared with the other women, experienced a 3.7-fold increased risk of GDM (odds ratio [OR] = 3.7, 95% confidence interval [CI] 1.7-8.2). There was a linear relation in risk of GDM with decreasing concentrations of plasma AA (P for linear trend <.001). After adjusting for confounders, women in the lowest quartile (< 42.6 micromol/L), as compared with women in the highest quartile (> 63.3 micromol/L), experienced > 12-fold increased risk of GDM (OR = 12.8, 95% CI 3.5-46.2). CONCLUSION: Low maternal dietary vitamin C intake and low plasma AA concentrations are associated with an increased risk of GDM. Large, prospective, cohort studies are needed to further evaluate the potential beneficial role of vitamin C and other antioxidants in the prevention of impaired glucose tolerance in pregnancy.

Transition to motherhood in type 1 diabetes : design of the pregnancy and postnatal well-being in transition questionnaires

Background : Life transitions are associated with high levels of stress affecting health behaviours among people with Type 1 diabetes. Transition to motherhood is a major transition with potential complications accelerated by pregnancy with risks of adverse childbirth outcomes and added anxiety and worries about pregnancy outcomes. Further, preparing and going through pregnancy requires vigilant attention to a diabetes management regimen and detailed planning of everyday activities with added stress on women. Psychological and social well-being during and after pregnancy are integral for good pregnancy outcomes for both mother and baby. The aim of this study is to establish the face and content validity of two novel measures assessing the well-being of women with type 1 diabetes in their transition to motherhood, 1) during pregnancy and 2) during the postnatal period.

Methods : The approach to the development of the Pregnancy and Postnatal Well-being in T1DM Transition questionnaires was based on a four-stage pre-testing process; systematic overview of literature, items development, piloting testing of questionnaire and refinement of questionnaire. The questionnaire was reviewed at every stage by expert clinicians, researchers and representatives from consumer groups. The cognitive debriefing approach confirmed relevance of issues and identified additional items.

Results : The literature review and interviews identified three main areas impacting on the women’s postnatal self-management; (1) psychological well-being; (2) social environment, (3) physical (maternal and fetal) well-being. The cognitive debriefing in pilot testing of the questionnaire identified that immediate postnatal period was difficult, particularly when the women were breastfeeding and felt depressed.

Conclusions : The questionnaires fill an important gap by systematically assessing the psychosocial needs of women with type 1 diabetes during pregnancy and in the immediate postnatal period. The questionnaires can be used in larger data collection to establish psychometric properties. The questionnaires potentially play a key role in prospective research to determine the self-management and psychological needs of women with type 1 diabetes transitioning to motherhood and to evaluate health education interventions.

Primary prevention of gestational diabetes for women who are overweight and obese : a randomised controlled trial

Background: Gestational Diabetes Mellitus (GDM) has well recognised adverse health implications for the  mother and her newborn that are both short and long term. Obesity is a significant risk factor for developing GDM and the prevalence of obesity is increasing globally. It is a matter of public health importance that clinicians have evidence based strategies to inform practice and currently there is insufficient evidence regarding the impact of dietary and lifestyle interventions on improving maternal and newborn outcomes. The primary aim of this study is to measure the impact of a telephone based intervention that promotes positive lifestyle modifications on the incidence of GDM. Secondary aims include: the impact on gestational weight gain; large for gestational age babies; differences in blood glucose levels taken at the Oral Glucose Tolerance Test (OGTT) and selected factors relating to self-efficacy and psychological wellbeing. 

The challenges and future considerations regarding pregnancy-related outcomes in women with pre-existing diabetes

Ineffective management of blood glucose levels during preconception and pregnancy has been associated with severe maternal and fetal complications in women with pre-existing diabetes. Studies have demonstrated that preconception counseling and pre-pregnancy care can dramatically reduce these risks. However, pregnancy-related outcomes in women with diabetes continue to be less than ideal.

This review highlights and discusses a variety of patient, provider, and organizational factors that can contribute to these suboptimal outcomes. Based on the findings of studies reviewed and authors’ clinical and research experiences, recommendations have been proposed focusing on various aspects of care provided, including improved accessibility to effective preconception and pregnancy-related care and better organized clinic consultations that are sensitive to women’s diabetes and pregnancy needs.

Maternal overnutrition programs changes in the expression of skeletal muscle genes that are associated with insulin resistance and defects of oxidative phosphorylation in adult male rat offspring.

Children of obese mothers have increased risk of metabolic syndrome as adults. Here we report the effects of a high-fat diet in the absence of maternal obesity at conception on skeletal muscle metabolic and transcriptional profiles of adult male offspring. Female Sprague Dawley rats were fed a diet rich in saturated fat and sucrose [high-fat diet (HFD): 23.5% total fat, 9.83% saturated fat, 20% sucrose wt:wt] or a normal control diet [(CD) 7% total fat, 0.5% saturated fat, 10% sucrose wt:wt] for the 3 wk prior to mating and throughout pregnancy and lactation. Maternal weights were not different at conception; however, HFD-fed dams were 22% heavier than controls during pregnancy. On a normal diet, the male offspring of HFD-fed dams were not heavier than controls but demonstrated features of insulin resistance, including elevated plasma insulin concentration [40.1 ± 2.5 (CD) vs 56.2 ± 6.1 (HFD) mU/L; P = 0.023]. Next-generation mRNA sequencing was used to identify differentially expressed genes in the offspring soleus muscle, and gene set enrichment analysis (GSEA) was used to detect coordinated changes that are characteristic of a biological function. GSEA identified 15 upregulated pathways, including cytokine signaling (P < 0.005), starch and sucrose metabolism (P < 0.017), inflammatory response (P < 0.024), and cytokine-cytokine receptor interaction (P < 0.037). A further 8 pathways were downregulated, including oxidative phosphorylation (P < 0.004), mitochondrial matrix (P < 0.006), and electron transport/uncoupling (P < 0.022). Phosphorylation of the insulin signaling protein kinase B was reduced [2.86 ± 0.63 (CD) vs 1.02 ± 0.27 (HFD); P = 0.027] and mitochondrial complexes I, II, and V protein were downregulated by 50-68% (P < 0.005). On a normal diet, the male offspring of HFD-fed dams did not become obese adults but developed insulin resistance, with transcriptional evidence of muscle cytokine activation, inflammation, and mitochondrial dysfunction. These data indicate that maternal overnutrition, even in the absence of prepregnancy obesity, can promote metabolic dysregulation and predispose offspring to type 2 diabetes.

Maternal obesity in females born small: pregnancy complications and offspring disease risk

Obesity is a major public health crisis, with 1.6 billion adults worldwide being classified as overweight or obese in 2014. Therefore, it is not surprising that the number of women who are overweight or obese at the time of conception is increasing. Obesity during pregnancy is associated with the development of gestational diabetes and preeclampsia. The developmental origins of health and disease hypothesis proposes that perturbations during critical stages of development can result in adverse fetal changes, which leads to an increased risk of developing diseases in adulthood. Of particular concern, children born to obese mothers are at a greater risk of developing cardiometabolic disease. One subset of the population who are predisposed to developing obesity are children born small for gestational age, which occurs in 10% of pregnancies worldwide. Epidemiological studies report that these growth restricted children have an increased susceptibility to type 2 diabetes, obesity and hypertension. Importantly during pregnancy, growth restricted females have a higher risk of developing cardiometabolic disease, indicating that they may have an exacerbated phenotype if they are also overweight or obese. Thus the development of early pregnancy interventions targeted to obese mothers may prevent their children from developing cardiometabolic disease in adulthood. This article is protected by copyright. All rights reserved.

Socio-cultural disparities in GDM burden differ by maternal age at first delivery

Aims : Several socio-cultural and biomedical risk factors for gestational diabetes mellitus (GDM) are modifiable. However, few studies globally have examined socio-cultural associations. To eliminate confounding of increased risk of diabetes in subsequent pregnancies, elucidating socio-cultural associations requires examination only of first pregnancies.

Methods : Data for all women who delivered their first child in Victoria, Australia between 1999 and 2008 were extracted from the Victorian Perinatal Data Collection. Crude and adjusted GDM rates were calculated. Multivariate logistic regression was used to examine odds of GDM within and between socio-cultural groups.

Results : From 1999 to 2008, 269,682 women delivered their first child in Victoria. GDM complicated 11,763 (4.4%) pregnancies and burden increased with maternal age, from 2.1% among women aged below 25 years at delivery to 7.0% among those aged 35 years or more. Among younger women, GDM rates were relatively stable across socioeconomic levels. Amongst older women GDM rates were highest in those living in most deprived areas, with a strong social gradient. Asian-born mothers had highest GDM rates. All migrant groups except women born in North-West Europe had higher odds of GDM than Australian-born non-Indigenous women. In all ethnic groups, these differences were not pronounced among younger mothers, but became increasingly apparent amongst older women.

Conclusions : Socio-cultural disparities in GDM burden differ by maternal age at first delivery. Socio-cultural gradients were not evident among younger women. Health and social programs should seek to reduce the risk amongst all older women to that of the least deprived older mothers.

Male sex and pre-existing diabetes are independent risk factors for stillbirth

AIM: To determine whether the risk of stillbirth is associated with male fetal sex, fetal growth and maternal factors in an Australian population. METHODS: A retrospective secondary data analysis of 16 445 singleton births was performed using a tertiary referral centre obstetric database (1995-1999). Univariate and multiple logistic regression analyses were performed. RESULTS: Stillbirth complicated 1% of the pregnancies in the study population, and 59% of stillbirths were associated with a male fetus. Significant characteristics associated with stillbirth were intrauterine growth restriction (IUGR), birth defects, gestational age, Aboriginal ethnicity, previous stillbirth, parity greater than three and placental abruption. Male stillbirths were more likely to occur at a later gestation (median gestation 30.5 weeks, range 20-43 weeks) compared to females (median 25 weeks, range 20-40 weeks), P = 0.01. Sixty per cent of IUGR fetuses were female (P < 0.001). Male sex (odds ratio (OR) 1.5, confidence interval (CI) 1.01, 2.17, P = 0.04) and maternal type 1 diabetes (OR 4.7, CI 1.58, 14.19, P = 0.006) were independently associated with stillbirth. CONCLUSION: Male fetal sex and pre-existing diabetes are independent risk factors for stillbirth. Diabetes remains a significant risk for stillbirth even with contemporary monitoring and clinical management. Those diabetic pregnancies where the fetus is male require appropriate monitoring and timely interventions to achieve an optimal outcome.

Avaliação do retinol em parturientes com diabetes mellitus gestacional no pós parto imediato

Micronutrient deficiencies affect individuals mainly in developing countries, where vitamin A deficiency is a public health problem worldwide more worrying, especially in groups with increased physiological needs such as children and women of reproductive age. Vitamin A is supplied to the body through diet and has an important role in the visual process, cell differentiation, maintenance of epithelial tissue, reproductive and resistance to infection. The literature has demonstrated the relationship between vitamin A and diabetes, including gestational, leading to a risk to both mother and child. Gestational diabetes is any decrease in glucose tolerance of variable magnitude diagnosed each the first time during pregnancy, and may or may not persist after delivery. Insulin resistance during pregnancy is associated with placental hormones, as well as excess fat. Studies have shown that retinol transport protein produced in adipose tissue in high concentrations, this would be associated with resistance by interfering with insulin signaling. Therefore, this study aimed to evaluate the concentration of retinol in serum and colostrum from healthy and diabetic mothers in the immediate postpartum period. One hundred and nine parturient women were recruited, representing seventy-three healthy and thirty-six diabetic. Retinol was extracted and subsequently analyzed by High Performance Liquid Chromatography. Among the results highlights the mothers with gestational diabetes were older than mothers healthy, had more children and a higher prevalence of cases of cesarean section. Fetal macrosomia was present in 1.4% of healthy parturient women and in 22.2% of diabetic mothers. The maternal serum retinol showed an average of 39.7 ± 12.5 mg/dL for healthy parturients 35.12 ± 15 mg/dL for diabetic and showed no statistical difference. It was observed that in the group of diabetic had 17% vitamin A deficiency, whereas in the healthy group, only 4% of the women were deficentes. Colostrum, the concentration of retinol in healthy was 131.3 ± 56.2 mg/dL and 125.3 ± 41.9 mg/dL in diabetic did not differ statistically. This concentration of retinol found in colostrum provides approximately 656.5 mg/day for infants born to healthy mothers and 626.5 mg/day for infants of diabetic mothers, based on a daily consumption of 500 mL of breast milk and need Vitamin A 400 mg/day, thus reaching the requirement of the infant. The diabetic mothers showed significant risk factors and complications related to gestational diabetes. Although no 11 difference was found in serum retinol concentration and colostrum among women with and without gestational diabetes, the individual analysis shows that parturients women with diabetes are 4.9 times more likely to develop vitamin A deficiency than healthy parturients. However, the supply of vitamin A to the newborn was not committed in the presence of gestational diabetes

Glargine vs. NPH insulin therapy in pregnancies complicated by diabetes: An observational cohort study

Aims: The effects of glargine insulin therapy in pregnancies are not well established. We compared maternal and neonatal outcomes of women with pregestational and gestational diabetes treated with glargine or NPH insulin.Methods: A prospective cohort study was conducted analyzing outcomes from 56 women with pregestational and 82 with gestational diabetes treated with either insulin regimen.Results: Comparisons were performed among 138 women: 56 with pregestational and 82 with gestational diabetes. In relation to maternal complications, worsening of retinopathy and nephropathy, preeclampsia, micro and macroalbuminuria, and all kinds of hypoglycemia were found higher in women with pregestational diabetes NPH-treated vs. glargine-treated. In women with gestational diabetes NPH-treated, it was observed increased incidence of prepregnancy and new-onset pregnancy hypertension, micro and macroalbuminuria, as well as mild and frequent hypoglycemia, compared to glargine-treated. Among the neonatal outcomes, 1-min Apgar score <7, necessity of intensive care unit and fetal death in pregestational, while jaundice and congenital malformations in gestational diabetes, respectively, were more frequently observed in infants born to NPH-treated, compared to glargine-treated.Conclusions: Glargine use during pregnancy from preconception through delivery, showed to be safe since it is associated with decreased maternal and neonatal adverse outcomes compared with NPH insulin-treated patients. (C) 2010 Elsevier B.V. All rights reserved.

Association of diabetes and cigarette smoke exposure on the glycemia and liver glycogen of pregnant Wistar rats

Purpose: To evaluate cigarette smoke exposure and/or diabetes association effects on the glycemia and liver glycogen levels of pregnant Wistar rats. Methods: 60 adult rats were randomly distributed into (n= 10/group): non-diabetic exposed to filtered air (G1); non-diabetic exposed to cigarette smoke only before pregnancy (G2); non-diabetic exposed to cigarette smoke before and during pregnancy (G3); diabetic exposed to filtered air (G4); diabetic exposed to cigarette smoke only before pregnancy (G5), and diabetic exposed to cigarette smoke before and during pregnancy (G6). Glycemia was determined at days 0 and 21 of pregnancy. Liver samples were collected for liver glycogen determinations. Results: At day 21 of pregnancy, glycemia was higher in G5 and G6 compared to G4 group. G2 (2.43 +/- 0.43), G3 (3.20 +/- 0.49), G4 (2.62 +/- 0.34), G5 (2.65 +/- 0.27) and G6 groups (1.94 +/- 0.35) presented decreased liver glycogen concentrations compared to G1 (4.20 +/- 0.18 mg/100mg liver tissue) (p<0.05). G5 and G6 groups presented decreased maternal weight gain and litter weight. Conclusions: Severe diabetes and cigarette smoke exposure, alone or associated, caused impairment in liver glycogen storage at term pregnancy. Due to the fact that liver glycogen storages were considered determinant for glucose tolerance, it is relevant to point out a rigid clinical glycemic control and to stop smoking so earlier in pregnancy programming.

Morphometric study of placental villi and vessels in women with mild hyperglycemia or gestational or overt diabetes

In this study, morphometric measures of placental terminal villi and villous vessels were compared in overt, as well as gestational diabetes mellitus, and mild hyperglycemia diagnosed by oral 100 g glucose tolerance test (100 g-OGTT) and glucose profile (GP). At delivery (gestational age >= 34 weeks) a total of 207 placentas were assigned to a control group (n = 56) or to one of three groups complicated by mild hyperglycemia (n = 5 1), gestational diabetes (n = 59) and overt diabetes (n = 4 1). Placenta samples were randomly selected for blind morphometric assessment with an image analyser. Morphometric measures obtained included area and number of terminal villi and their respective villous vessels. Statistical analyses were performed using the chi-square test, ANOVA and stepwise regression (p <= 0.05). Glycemic means were 86.2 mg/dL in controls, 98.9 mg/dL in mild hyperglycemia, 114.1 mg/dL in gestational diabetes and 122.1 mg/dL in overt diabetes. Our results show that abnormal maternal glycemic levels may change the placental morphometric characteristics related to materno-fetal exchanges. (C) 2007 Elsevier B.V.. All rights reserved.

Effect of Bauhinia forficata extract in diabetic pregnant rats: maternal repercussions

Bauhinia forficata, commonly known as paw-of-cow, is widely used in Brazil folk medicine for the treatment of Diabetes mellitus. The purposes of present study were to determine the repercussions of diabetes on the defense system against oxidative stress in pregnant female rats and to characterize the influence of the treatment with Bauhinia forficata extract on the antioxidant system, glycemic control, hepatic glycogen, cholesterol, triglycerides, total proteins and lipids. Virgin female Wistar rats were injected with 40 mg/kg streptozotocin (STZ) before mating. Oral administration of an aqueous extract of Bauhinia forficata leaves was given to non-diabetic and diabetic pregnant rats in 3 doses: 500 mg/kg from 0 to 4(th) day of pregnancy, 600 mg/kg from 5(th) to 14(th) day and 1000 mg/kg from 15(th) to 20(th) day. All the females were killed on the day 21 of pregnancy. A maternal blood sample was collected by venous puncture and the maternal liver was removed for biochemical measurement. The diabetic pregnant rats presented hyperglycemia, hyperlipemia, bypertriglyceridemia, hypercholesterolemia, hyperuricemia, decreased determinations of reduced glutathione (GSH) and superoxide dismutase (SOD). Treatment with B. forficata extract did not interfere in the albumin, total protein and lipid, triglyceride, cholesterol and SOD determinations. Increased hepatic glycogen, decreased uric acid concentration and increased GSH activity was observed. This last fact suggests that the plant may have some action on antioxidant defense system. However, the demonstration of the active component present in B. forficata responsible for its antioxidant effect and the increase in hepatic glycogen deserve further investigation.

Neonatally induced diabetes: liver glycogen storage in pregnant rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Cost-benefit of hospitalization compared with outpatient care for pregnant women with pregestational and gestational diabetes or with mild hyperglycemia, in Brazil

CONTEXTO E OBJETIVO: Gestações complicadas pelo diabetes estão associadas com aumento de complicações maternas e neonatais. Os custos hospitalares aumentam de acordo com a assistência prestada. O objetivo foi calcular o custo-benefício e a taxa de rentabilidade social da hospitalização comparada ao atendimento ambulatorial em gestantes com diabetes ou com hiperglicemia leve. DESENHO do ESTUDO: Estudo prospectivo, observacional, quantitativo, realizado em hospital universitário, sendo incluídas todas as gestantes com diabetes pregestacional e gestacional ou com hiperglicemia leve que não desenvolveram intercorrências clínicas na gestação e que tiveram parto no Hospital das Clínicas, Faculdade de Medicina de Botucatu, Universidade Estadual Paulista (HC-FMB-Unesp). MÉTODOS: Trinta gestantes tratadas com dieta foram acompanhadas em ambulatório e 20 tratadas com dieta e insulina foram abordadas com hospitalizações curtas e frequentes. Foram obtidos custos diretos (pessoal, material e exames) e indiretos (despesas gerais) a partir de dados contidos no prontuário e no sistema de custo por absorção do hospital e posteriormente calculado o custo-benefício. RESULTADOS: O sucesso do tratamento das gestantes diabéticas evitou o gasto de US$ 1.517,97 e US$ 1.127,43 para pacientes hospitalizadas e ambulatoriais, respectivamente. O custo-benefício da atenção hospitalizada foi US$ 143.719,16 e ambulatorial, US$ 253.267,22, com rentabilidade social 1,87 e 5,35 respectivamente. CONCLUSÃO: A análise árvore de decisão confirma que o sucesso dos tratamentos elimina custos no hospital. A relação custo-benefício indicou que o tratamento ambulatorial é economicamente mais vantajoso do que a hospitalização. A rentabilidade social de ambos os tratamentos foi maior que 1, indicando que ambos os tipos de atendimento à gestante diabética têm benefício positivo.