Suzette Coat

Maternal and Neonatal Circulating Markers of Metabolic and Cardiovascular Risk in the Metformin in Gestational Diabetes (MiG) Trial: Responses to maternal metformin versus insulin treatment

OBJECTIVE This study was designed to compare glucose, lipids, and C-reactive protein (CRP) in women with gestational diabetes mellitus treated with metformin or insulin and in cord plasma of their offspring and to examine how these markers relate to infant size at birth. RESEARCH DESIGN AND METHODS Women with gestational diabetes mellitus were randomly assigned to metformin or insulin in the Metformin in Gestational Diabetes trial. Fasting maternal plasma glucose, lipids, and CRP were measured at randomization, 36 weeks’ gestation, and 6–8 weeks postpartum as well as in cord plasma. Women with available cord blood samples (metformin n = 236, insulin n = 242) were included. RESULTS Maternal plasma triglycerides increased more from randomization to 36 weeks’ gestation in women treated with metformin (21.93%) versus insulin (9.69%, P < 0.001). Maternal and cord plasma lipids, CRP, and neonatal anthropometry did not differ between treatments. In logistic regression analyses adjusted for confounders, the strongest associations with birth weight >90th centile were maternal triglycerides and measures of glucose control at 36 weeks. CONCLUSIONS There were few differences in circulating maternal and neonatal markers of metabolic status and no differences in measures of anthropometry between the offspring of women treated with metformin and the offspring of women treated with insulin. There may be subtle effects of metformin on maternal lipid function, but the findings suggest that treating gestational diabetes mellitus with metformin does not adversely affect lipids or CRP in cord plasma or neonatal anthropometric measures.

Neurodevelopmental outcome at 2 years in offspring of women randomised to metformin or insulin treatment for gestational diabetes

Objective Gestational diabetes mellitus (GDM) is a common complication of pregnancy and is increasingly being treated with metformin that crosses the placenta rather than insulin, which does not. This study seeks to examine the neurodevelopment of offspring of women treated with metformin or insulin for GDM. Design We performed a prospective follow-up study of children whose mothers had been randomly assigned at 20–33 weeks gestation to treatment with metformin or insulin for GDM. Of the 211 children followed up at 2 years, 128 were from Auckland, New Zealand (64 metformin vs 64 insulin), and 83 from Adelaide, Australia (39 metformin vs 49 insulin). Neurodevelopment was examined with the Bayley Scales of Infant Development V.2 mental development index (MDI) and psychomotor development index (PDI). Clinical and demographic background characteristics were obtained at enrolment, birth and follow-up. Results No significant differences were found between treatment groups in clinical or demographic characteristics. The MDI and PDI composite scores were tested with general linear models. No significant differences were found between metformin and insulin, respectively, in New Zealand (MDI, M=83.6 vs 86.9 and PDI, M=83.4 vs M=85.2) or Australia (MDI, M=102.5 vs M=98.4 and PDI, M=105.6 vs M=99.9) and no interactions observed. The differences in neurodevelopmental outcomes between the Auckland and Adelaide cohorts were explained by parental ethnicity, infant birth weight >4000 g, neonatal hypoglycaemia, maternal glycaemia and smoking in the household. Conclusions This study provides additional data supporting the safety of metformin in the treatment of GDM. Trial registration number ACTRN 12605000311651.

Determinants of Maternal Triglycerides in Women With Gestational Diabetes Mellitus in the Metformin in Gestational Diabetes (MiG) Study

OBJECTIVE Factors associated with increasing maternal triglyceride concentrations in late pregnancy include gestational age, obesity, preeclampsia, and altered glucose metabolism. In a subgroup of women in the Metformin in Gestational Diabetes (MiG) trial, maternal plasma triglycerides increased more between enrollment (30 weeks) and 36 weeks in those treated with metformin compared with insulin. The aim of this study was to explain this finding by examining factors potentially related to triglycerides in these women. RESEARCH DESIGN AND METHODS Of the 733 women randomized to metformin or insulin in the MiG trial, 432 (219 metformin and 213 insulin) had fasting plasma triglycerides measured at enrollment and at 36 weeks. Factors associated with maternal triglycerides were assessed using general linear modeling. RESULTS Mean plasma triglyceride concentrations were 2.43 (95% CI 2.35–2.51) mmol/L at enrollment. Triglycerides were higher at 36 weeks in women randomized to metformin (2.94 [2.80–3.08] mmol/L; +23.13% [18.72–27.53%]) than insulin (2.65 [2.54–2.77] mmol/L, P = 0.002; +14.36% [10.91–17.82%], P = 0.002). At 36 weeks, triglycerides were associated with HbA1c (P = 0.03), ethnicity (P = 0.001), and treatment allocation (P = 0.005). In insulin-treated women, 36-week triglycerides were associated with 36-week HbA1c (P = 0.02), and in metformin-treated women, they were related to ethnicity. CONCLUSIONS At 36 weeks, maternal triglycerides were related to glucose control in women treated with insulin and ethnicity in women treated with metformin. Whether there are ethnicity-related dietary changes or differences in metformin response that alter the relationship between glucose control and triglycerides requires further study.

Vitamin B12 and homocysteine status during pregnancy in the metformin in gestational diabetes trial: responses to maternal metformin compared with insulin treatment†

The aim of the study is to compare the effects of metformin and insulin treatment for gestational diabetes mellitus (GDM) on vitamin B12 and homocysteine (Hcy) status.

Metformin in gestational diabetes: The offspring follow-up (MiG TOFU): Body composition and metabolic outcomes at 7-9 years of age

Objective To compare body composition and metabolic outcomes at 7–9 years in offspring of women with gestational diabetes (GDM) randomized to metformin (±insulin) or insulin treatment during pregnancy. Research design and methods Children were assessed at 7 years in Adelaide (n=109/181) and 9 years in Auckland (n=99/396) by anthropometry, bioimpedance analysis (BIA), dual-energy X-ray absorptiometry (DXA), magnetic resonance imaging (MRI) (n=92/99) and fasting bloods (n=82/99). Results In the Adelaide subgroup, mothers were similar at enrollment. Women randomized to metformin versus insulin had higher treatment glycemia (p=0.002) and more infants with birth weight >90th percentile (20.7% vs 5.9%; p=0.029). At 7 years, there were no differences in offspring measures. In Auckland, at enrollment, women randomized to metformin had a higher body mass index (BMI) (p=0.08) but gained less weight during treatment (p=0.07). Offspring birth measures were similar. At 9 years, metformin offspring were larger by measures of weight, arm and waist circumferences, waist:height (p<0.05); BMI, triceps skinfold (p=0.05); DXA fat mass and lean mass (p=0.07); MRI abdominal fat volume (p=0.051). Body fat percent was similar between treatment groups by DXA and BIA. Abdominal fat percentages (visceral adipose tissue, subcutaneous adipose tissue and liver) were similar by MRI. Fasting glucose, triglyceride, insulin, insulin resistance, glycosylated hemoglobin (HbA1c), cholesterol, liver transaminases, leptin and adiponectin were similar. Conclusions Metformin or insulin for GDM was associated with similar offspring total and abdominal body fat percent and metabolic measures at 7–9 years. Metformin-exposed children were larger at 9 years. Metformin may interact with fetal environmental factors to influence offspring outcomes.

Consulting parents on childhood obesity and implications for medical student learning.

Aim:  It is important that medical schools take some account of community expectations for health care when planning curricula. This is particularly important for emerging public health problems such as childhood obesity. The aim of this study was to explore parent attitudes to the role of the doctor in childhood obesity and implications for medical student learning.

Increasing health‐care options: The perspectives of parents who use complementary and alternative medicines

Aim:  To explore the relationship between conventional medicine and complementary and alternative medicine (CAM) with parents who use CAM, and to consider factors that may contribute to parent non‐disclosure of CAM usage to their doctor.

The Medical Education Priorities of Parents Who Use Complementary and Alternative Medicine

Many parents use complementary and alternative medicine (CAM) for their children. A number of medical schools are introducing CAM teaching, and this study was undertaken to explore the medical education priorities of parents who use CAM for their children. A total of 27 parents (25 females, 2 males) participated in 1 of 6 focus group discussions. Transcripts were analyzed using an iterative process of concept identification, hypothesis testing, and detailed comparisons. Participant preferences for health care for their children were complex and informed by previous health care experiences and current family health care needs. Using CAM allowed parents choice and control in managing their family’s health care. Many participant priorities for medical education in CAM echoed key principles of patient-centered care in addition to specific suggestions for curriculum development. Participating parents believed that it was important to increase medical students’ knowledge and understanding of both CAM modalities and the perspectives of parents.

Reduced Cortical Excitability, Neuroplasticity, and Salivary Cortisol in 11–13-Year-Old Children Born to Women with Gestational Diabetes Mellitus

Background Children exposed to gestational diabetes mellitus (GDM) in utero are at increased risk of neurodevelopmental difficulties, including autism and impaired motor control. However, the underlying neurophysiology is unknown. Methods Using transcranial magnetic stimulation, we assessed cortical excitability, long-term depression (LTD)-like neuroplasticity in 45 GDM-exposed and 12 control children aged 11–13 years. Data were analysed against salivary cortisol and maternal diabetes severity and treatment (insulin [N = 22] or metformin [N = 23]) during pregnancy. Findings GDM-exposed children had reduced cortical excitability (p = .003), LTD-like neuroplasticity (p = .005), and salivary cortisol (p < .001) when compared with control children. Higher maternal insulin resistance (IR) before and during GDM treatment was associated with a blunted neuroplastic response in children (p = .014) and this was not accounted for by maternal BMI. Additional maternal and neonatal measures, including fasting plasma glucose and inflammatory markers, predicted neurophysiological outcomes. The metformin and insulin treatment groups had similar outcomes. Interpretation These results suggest that GDM can contribute to subtle differences in child neurophysiology, and possibly cortisol secretion, persisting into early adolescence. Importantly, these effects appear to occur during second trimester, before pharmacologic treatment typically commences, and can be predicted by maternal insulin resistance. Therefore, earlier detection and treatment of GDM may be warranted. Metformin appears to be safe for these aspects of neurodevelopment.