The presence of polycystic ovary syndrome increases the risk of maternal but not neonatal complications in women with type 2 diabetes in pregnancy.

AIMS: Our aims were, in the setting of type 2 diabetes mellitus (T2DM) in pregnancy, to investigate the association of polycystic ovary syndrome (PCOS) with perinatal outcomes and to examine whether treatment with metformin had a differential effect in those with and without PCOS. MATERIALS AND METHODS: We performed a retrospective cohort study using the metformin in women with type 2 diabetes in pregnancy (MiTy) trial data. We examined differences in maternal and neonatal outcomes among MiTy participants with and without PCOS using linear and logistic regression to adjust for potential confounders. We additionally examined the relative difference in the effect of metformin treatment on pregnancy outcomes among MiTy participants with PCOS versus those without PCOS. RESULTS: Among women with T2DM in pregnancy, PCOS was significantly associated with higher excess gestational weight gain (unadjusted 12.0 vs. 11.4 kg, adjusted mean difference 2.1 kg [0.3, 3.9], p = 0.021) and higher total insulin dose at 34-36 weeks (unadjusted 172 vs. 124 units per day, adjusted mean difference 44 units [15, 73], p = 0.004), but no difference was seen in neonatal outcomes. Unlike the non-PCOS subgroup, metformin treatment versus placebo in the PCOS subgroup was associated with an increase in extremely large-for-gestational-age infants (28.6 vs. 14.0%, p = 0.008 for interaction) and an increase in worsened pre-existing maternal hypertension (16.7 vs. 4.5%, p = 0.046 for interaction). CONCLUSIONS: Clinicians should be alerted to the potential for high insulin requirements and excess weight gain in pregnant patients with T2DM and comorbid PCOS. Moreover, metformin may not be as beneficial in this population as previously understood.

The Antioxidant Capacity of Breast Milk and Plasma of Women with or without Gestational Diabetes Mellitus.

Women with gestational diabetes (GD) have reduced antioxidant capacity; however, the relationship between maternal diet, maternal biochemical capacity, breast milk concentration, and infant intake has not been adequately explored in the literature. An exploration of underlying mechanism(s) is warranted, particularly for nutrient antioxidants impacted by maternal intake. These nutrients may provide a means for modifying maternal and infant antioxidant capacity. Oxygen radical absorbance capacity (ORAC), alpha-tocopherol, ascorbic acid, and beta-carotene concentrations were measured in breast milk of women with and without GD. Plasma, three-day diet records, and breast milk were collected at 6 to 8 weeks postpartum. Student's t-test was used to compare breast milk ORAC, nutrient antioxidant concentration and plasma ORAC between women with and without GD. Pearson correlations were used to determine associations among antioxidant concentrations in breast milk and dietary antioxidant intake. Breast milk antioxidant concentrations were associated with maternal intake of beta-carotene (r = 0.629, p = 0.005). Breast milk and plasma ORAC and antioxidant vitamin concentrations were not significantly different between GD and NG women. Breast milk ORAC associated with breast milk alpha-tocopherol for NG (r = 0.763, p = 0.010), but not GD women (r = 0.385, p = 0.35), and with breast milk ascorbic acid for GD (r = 0.722, p = 0.043) but not NG women (r = 0.141, p = 0.70; interaction p = 0.041). In GD participants, breast milk ORAC was significantly associated with plasma ORAC (r = 0.780, p = 0.039). ORAC and antioxidant vitamin concentrations in breast milk in women with GD were comparable to women with NG; however, the relationships between breast milk ORAC and vitamin concentrations differed in GD versus NG women for alpha-tocopherol and ascorbic acid.

Associations Among Biomarkers of Inflammation, Tubular Injury and Lipid Metabolism With Gestational Diabetes Mellitus Status, Microalbuminuria and Retinopathy in the Microalbuminuria and Retinopathy in Gestational Diabetes Study.

OBJECTIVES: Pregnancy may be complicated by gestational diabetes mellitus (GDM) and/or microvascular complications like albuminuria, retinopathy and pre-eclampsia. In this study we aimed to identify whether mechanistic pathways associated with microvascular complications are active in pregnant women with GDM or microvascular disease. METHODS: Urinary albumin excretion and biomarkers of inflammation, lipoprotein metabolism and tubular injury were quantified in 355 pregnant women with and without GDM. Participants underwent fundus photography graded for retinopathy. Adjusted associations between individual biomarkers and each outcome variable of interest, including GDM status, albuminuria and retinopathy, were performed using logistic regression. RESULTS: After adjusting for age, systolic blood pressure, body mass index and ethnicity, significant associations between GDM status and apolipoprotein A1, interleukin (IL)-6, IL-8, soluble tumour necrosis factor receptor-I and -II (sTNFR-I and -II), vascular endothelial growth factor and von Willebrand factor were observed. Increased high-sensitivity C-reactive protein (hsCRP) and sTNFR-II were associated with higher levels of albuminuria. hsCRP and previous GDM were associated with retinopathy. CONCLUSION: Mechanistic pathways associated with microvascular complications appear to be active in pregnant women with GDM or microvascular disease.

Can placental growth factors explain birthweight variation in offspring of women with type 1 diabetes?

AIMS/HYPOTHESIS: Maternal hyperglycaemia alone does not explain the incidence of large offspring amongst women with type 1 diabetes. The objective of the study was to determine if there is an association between placental function, as measured by angiogenic factors, and offspring birthweight z score in women with type 1 diabetes. METHODS: This cohort study included samples from 157 Continuous Glucose Monitoring in Pregnant Women with Type 1 Diabetes (CONCEPTT) trial participants. Correlations were estimated between birthweight z score and placental growth factor (PlGF) and soluble fms-like tyrosine kinase (sFlt-1) levels measured at baseline and at 24 and 34 weeks of gestation. Linear regression was used to assess the relationship between birthweight z score and placental health, as measured by PlGF and sFlt-1/PlGF ratio, stratified by glycaemic status (continuous glucose monitoring and HbA1c measures) and adjusted for potential confounders of maternal BMI, smoking and weight gain. Higher PlGF levels and lower sFlt-1/PlGF ratios represent healthy placentas, while lower PlGF levels and higher sFlt-1/PlGF ratios represent unhealthy placentas. RESULTS: Among CONCEPTT participants, the slopes relating PlGF levels to birthweight z scores differed according to maternal glycaemia at 34 weeks of gestation (p = 0.003). With optimal maternal glycaemia (HbA1c < 48 mmol/mol [6.5%]/ or continuous glucose monitoring time above range ≤ 30%), birthweight z scores were reduced towards zero (normal weight) with increasing PlGF values (representing a healthy placenta), and increased with decreasing PlGF values. With suboptimal glycaemic status (HbA1c ≥ 48 mmol/mol [6.5%] or time above range > 30%), increasing PlGF values were associated with heavier infants. Those with a healthy placenta (PlGF > 100) and suboptimal glycaemic control had a higher mean z score (2.45) than those with an unhealthy placenta (mean z score = 1.86). Similar relationships were seen when using sFlt-1/PlGF ratio as a marker for a healthy vs unhealthy placenta. CONCLUSIONS/INTERPRETATION: In women with type 1 diabetes, infant birthweight is influenced by both glycaemic status and placental function. In women with suboptimal glycaemia, infant birthweight was heavier when placentas were healthy. Suboptimal placental function should be considered in the setting of suboptimal glycaemia and apparently 'normal' birthweight.

BMI and risk of gestational diabetes among women of South Asian and Chinese ethnicity: a population-based study.

AIMS/HYPOTHESIS: The aim of this study was to examine how BMI influences the association between Asian ethnicity and risk of gestational diabetes (GDM). METHODS: This population-based cohort study included pregnant women without pre-existing diabetes mellitus in Ontario, Canada between 2012 and 2014. Women of Chinese and South Asian ethnicity were identified using a validated surname algorithm. GDM was ascertained using hospitalisation codes. The relationship between ethnicity and GDM was modelled using modified Poisson regression, adjusted for maternal age, pre-pregnancy BMI, parity, previous GDM, long-term residency status, income quintile and smoking status. An interaction term between ethnicity and pre-pregnancy BMI was tested. RESULTS: Of 231,618 pregnant women, 9289 (4.0%) were of South Asian ethnicity and 12,240 (5.3%) were of Chinese ethnicity. Relative to women from the general population, in whom prevalence of GDM was 4.3%, the adjusted RR of GDM was higher among those of South Asian ethnicity (1.81 [95% CI 1.64, 1.99]) and Chinese ethnicity (1.66 [95% CI 1.53, 1.80]). The association between GDM and Asian ethnicity remained significant across BMI categories but differed according to BMI. The prevalence of GDM exceeded 5% at an estimated BMI of 21.5 kg/m2 among South Asian women, 23.0 kg/m2 among Chinese women and 29.5 kg/m2 among the general population. CONCLUSIONS/INTERPRETATION: The risk of GDM is significantly higher in South Asian and Chinese women, whose BMI is lower than that of women in the general population. Accordingly, targeted GDM prevention strategies may need to consider lower BMI cut-points for Asian populations.

Characteristics of Women With Gestational Diabetes From Non-Caucasian Compared With Caucasian Ethnic Groups.

OBJECTIVES: Short- and long-term outcomes in women after gestational diabetes mellitus (GDM) vary by ethnicity. Understanding differences in baseline diabetes risk factors is important for informing choice of risk-reducing interventions. We aimed to compare maternal and pregnancy-related characteristics in Caucasian and non-Caucasian women with GDM. METHODS: Using a large multicentre Canadian cohort of women diagnosed with GDM and recruited between 2009 and 2013, we compared demographic, clinical and behavioural characteristics in women with GDM across 7 ethnic groups. Data were obtained from chart reviews and surveys, and logistic and linear regression models were used to compare binary and continuous variables, respectively, between Caucasian and non-Caucasian ethnic groups. RESULTS: Of the 1,332 women with GDM, 911 were eligible for inclusion. Of these, 41.4% were white Caucasian, 17.1% were South Asian, 18.4% were East Asian, 5.8% were black, 8.8% were Filipina, 5.2% were Middle Eastern and 3.3% were Hispanic. Non-Caucasian women were diagnosed with GDM at a younger age and were more likely to have a family history of diabetes compared with Caucasian women. With the exception of East Asians, non-Caucasian women were more likely to be overweight using ethnicity-specific body mass index cutoffs and have higher oral glucose tolerance test values than Caucasian women. Prepregnancy smoking and alcohol consumption prevalence were highest in Caucasian women. CONCLUSIONS: Several important ethnicity-specific differences in clinical and behavioural characteristics of women with GDM were identified. These differences need to be considered when offering interventions for reducing risk of adverse perinatal outcomes and subsequent type 2 diabetes.

Maternal and neonatal outcomes after bariatric surgery; a systematic review and meta-analysis: do the benefits outweigh the risks?

OBJECTIVE DATA: Obesity during pregnancy is associated with a number of adverse obstetric outcomes that include gestational diabetes mellitus, macrosomia, and preeclampsia. Increasing evidence shows that bariatric surgery may decrease the risk of these outcomes. Our aim was to evaluate the benefits and risks of bariatric surgery in obese women according to obstetric outcomes. STUDY: We performed a systematic literature search using MEDLINE, Embase, Cochrane, Web of Science, and PubMed from inception up to December 12, 2016. Studies were included if they evaluated patients who underwent bariatric surgery, reported subsequent pregnancy outcomes, and compared these outcomes with a control group. STUDY APPRAISAL AND SYNTHESIS METHODS: Two reviewers extracted study outcomes independently, and risk of bias was assessed with the use of the Newcastle-Ottawa Quality Assessment Scale. Pooled odds ratios for each outcome were estimated with the Dersimonian and Laird random effects model. RESULTS: After a review of 2616 abstracts, 20 cohort studies and approximately 2.8 million subjects (8364 of whom had bariatric surgery) were included in the metaanalysis. In our primary analysis, patients who underwent bariatric surgery showed reduced rates of gestational diabetes mellitus (odds ratio, 0.20; 95% confidence interval, 0.11-0.37, number needed to benefit, 5), large-for-gestational-age infants (odds ratio, 0.31; 95% confidence interval, 0.17-0.59; number needed to benefit, 6), gestational hypertension (odds ratio, 0.38; 95% confidence interval, 0.19-0.76; number needed to benefit, 11), all hypertensive disorders (odds ratio, 0.38; 95% confidence interval, 0.27-0.53; number needed to benefit, 8), postpartum hemorrhage (odds ratio, 0.32; 95% confidence interval, 0.08-1.37; number needed to benefit, 21), and caesarean delivery rates (odds ratio, 0.50; 95% confidence interval, 0.38-0.67; number needed to benefit, 9); however, group of patients showed an increase in small-for-gestational-age infants (odds ratio, 2.16; 95% confidence interval, 1.34-3.48; number needed to harm, 21), intrauterine growth restriction (odds ratio, 2.16; 95% confidence interval, 1.34-3.48; number needed to harm, 66), and preterm deliveries (odds ratio, 1.35; 95% confidence interval, 1.02-1.79; number needed to harm, 35) when compared with control subjects who were matched for presurgery body mass index. There were no differences in rates of preeclampsia, neonatal intensive care unit admissions, stillbirths, malformations, and neonatal death. Malabsorptive surgeries resulted in a greater increase in small-for-gestational-age infants (P=.0466) and a greater decrease in large-for-gestational-age infants (P=<.0001) compared with restrictive surgeries. There were no differences in outcomes when we used administrative databases vs clinical charts. CONCLUSION: Although bariatric surgery is associated with a reduction in the risk of several adverse obstetric outcomes, there is a potential for an increased risk of other important outcomes that should be considered when bariatric surgery is discussed with reproductive-age women.

Oral hypoglycemic therapy: understanding the mechanisms of transplacental transfer.

The current trend towards an increase in the rate of Type 2 diabetes in women of childbearing age will inevitably result in an increasing number of women requiring hypoglycemic therapy throughout pregnancy. For patients with Type 2 diabetes or gestational diabetes, oral hypoglycemic agents (OHAs) represent an attractive alternative to insulin therapy. However, there exists some apprehension regarding the use of OHAs during pregnancy. Although the current accepted understanding is that most drugs administered during pregnancy can permeate the placental barrier, there is sufficient evidence to suggest that the placenta is capable of limiting fetal exposure to drugs. In particular, large sets of data on the transplacental transfer and clinical use of glyburide in pregnancy have suggested that glyburide may be a safe alternative to insulin therapy. Glyburide's limited fetal transfer has been attributed to its high protein binding, rapid clearance rate and the role of placental efflux transporters such as the breast cancer resistance protein. However, there are a number of maternal, placental and fetal factors that may alter the transplacental passage of drugs used in pregnancy. Therefore, it is essential that OHAs are further investigated to determine their safety with confidence and provide better treatment options for diabetes in pregnancy.

Does the presence of polycystic ovary syndrome increase the risk of obstetrical complications in women with gestational diabetes?

OBJECTIVE: To determine whether women with both polycystic ovary syndrome (PCOS) and gestational diabetes mellitus (GDM) have an increased risk of obstetric complications compared with women with GDM alone. METHODS: A retrospective cohort study of maternal/fetal outcomes in women with GDM and PCOS was compared with women with GDM alone. Outcomes were compared using Fisher's exact test for categorical variables and t-test for continuous variables. Logistic regression models allowed for the calculation of odds ratios and 95% confidence intervals (CIs) for each outcome, adjusted for confounding. RESULTS: One hundred seventy one women were included in the study. Significantly more women with both GDM and PCOS had pregnancy-induced hypertension/preeclampsia (15.9% vs. 3.9%, p = 0.019, OR = 4.62, 95% CI = 1.38-15.41). Multiple logistic regression revealed that this increase persisted after controlling for body mass index (p = 0.028, OR = 4.43, 95% CI = 1.17-16.72) and parity (p = 0.050, OR = 3.45, 95% CI = 1.00-11.92). Women with GDM and PCOS tended to have more preterm deliveries (25.0% vs. 11.8%, p = 0.063). More infants of women with GDM and PCOS required phototherapy treatment for hyperbilirubinemia (25.0% vs. 7.9%, p = 0.0066, OR = 3.90, 95% CI = 1.52-9.98). Logistic regression revealed that this association persisted after controlling for preterm delivery (OR = 3.18, 95% CI = 1.14-8.82, p = 0.026). CONCLUSIONS: Mothers with both disorders should be monitored more carefully and counseled regarding their increased risk of both maternal and fetal complications.

Risk of development of diabetes mellitus after diagnosis of gestational diabetes.

BACKGROUND: It is generally appreciated that gestational diabetes is a risk factor for type 2 diabetes. However, the precise relation between these 2 conditions remains unknown. We sought to determine the incidence of diabetes mellitus after diagnosis of gestational diabetes. METHODS: We used a population-based database to identify all deliveries in the province of Ontario over the 7-year period from Apr. 1, 1995, to Mar. 31, 2002. We linked these births to mothers who had been given a diagnosis of gestational diabetes through another administrative database that records people with diabetes on the basis of either physician service claims or hospital admission records. We examined database records for these women from the time of delivery until Mar. 31, 2004, a total of 9 years. We determined the presence of diabetes mellitus according to a validated administrative database definition for this condition. RESULTS: We identified 659 164 pregnant women who had no pre-existing diabetes. Of these, 21 823 women (3.3%) had a diagnosis of gestational diabetes. The incidence of gestational diabetes rose significantly over the 9-year study period, from 3.2% in 1995 to 3.6% in 2001 (p < 0.001). The probability of diabetes developing after gestational diabetes was 3.7% at 9 months after delivery and 18.9% at 9 years after delivery. After adjustment for age, urban or rural residence, neighbourhood income quintile, whether the woman had a previous pregnancy, whether the woman had hypertension after the index delivery, and primary care level before the index delivery, the most significant risk factor for diabetes was having had gestational diabetes during the index pregnancy (hazard ratio 37.28, 95% confidence interval 34.99-40.88; p < 0.001). Age, urban residence and lower income were also important factors. When analyzed by year of delivery, the rate of development of diabetes was higher among the latest subcohort of women with gestational diabetes (delivery during 1999-2001) than among the earliest subcohort (delivery during 1995 or 1996) (16% by 4.7 years after delivery v. 16% by 9.0 years). INTERPRETATION: In this large population-based study, the rate of development of diabetes after gestational diabetes increased over time and was almost 20% by 9 years. This estimate should be used by clinicians to assist in their counselling of pregnant women and by policy-makers to target these women for screening and prevention.