Predictors of preeclampsia in women in the metformin in gestational diabetes (MiG) study

Background: Gestational Diabetes Mellitus (GDM), maternal obesity and pregnancy weight gain are associated with an increased risk of developing Preeclampsia (PE). The aim of this study was to examine the predictors of PE in women commencing pharmacotherapy for GDM in the Metformin in Gestational diabetes trial.Methods: Descriptive and logistic regression analyses examined the relationship between maternal enrolment characteristics and later development of PE.Results: 46 (6.3%) of 703 women developed PE. At enrolment ((30 (SD3.2) weeks gestation), women who later developed PE had higher HbA1c (6.14% (95% CI 5.84, 6.45) vs. 5.73% (95% CI 5.67, 5.78), P = 0.003), fasting triglycerides (2.93 mmol/L (95% CI 2.57, 3.29) vs. 2.55mmol/L (95% CI 2.47, 2.62), P = 0.03) and blood pressure. Their infants were born 9 days earlier (P < 0.001) but were otherwise not different. In univariate analysis, the strongest positive predictors for PE were Polynesian ethnicity (OR 2.75 (95% CI 1.48, 5.09), P= 0.001), personal or family history of PE (OR 2.65 (95% CI 1.36, 5.16), P=0.004), maternal HbA1c (OR 1.96 (95% CI 1.35, 2.89), P< 0.001), triglycerides (OR 1.45 (95% CI 1.07,1.97), P=0.002), and weight gain from early pregnancy (OR 1.09 (95% CI 1.03,1.17), P=0.01). HDL-C was a negative predictor of PE (OR 0.29 (95% CI 0.09, 0.94), P= 0.04).Following adjustment for Polynesian ethnicity and personal or family history of PE, and when further adjusted for HbA1c or early pregnancy BMI, these variables remained significant.Conclusion: Treatment allocation and BMI were not associated with risk of PE. Personal or family history of PE, Polynesian ethnicity, degree of hyperglycemia, maternal triglycerides and weight gain prior to treatment signal increased risk of subsequent PE in women needing pharmacotherapy for GDM

SPRING: an RCT study of probiotics in the prevention of gestational diabetes mellitus in overweight and obese women

Background: Obesity is increasing in the child-bearing population as are the rates of gestational diabetes. Gestational diabetes is associated with higher rates of Cesarean Section for the mother and increased risks of macrosomia, higher body fat mass, respiratory distress and hypoglycemia for the infant. Prevention of gestational diabetes through life style intervention has proven to be difficult. A Finnish study showed that ingestion of specific probiotics altered the composition of the gut microbiome and thereby metabolism from early gestation and decreased rates of gestational diabetes in normal weight women. In SPRING (the Study of Probiotics IN the prevention of Gestational diabetes), the effectiveness of probiotics ingestion for the prevention of gestational diabetes will be assessed in overweight and obese women

Enhanced mitochondrial metabolism may account for the adaptation to insulin resistance in islets from C57BL/6J mice fed a high-fat diet

Aim/hypothesis: Hyperinsulinaemia maintains euglycaemia in insulin-resistant states. The precise cellular mechanisms by which the beta cells adapt are still unresolved. A peripherally derived cue, such as increased circulating fatty acids, may instruct the beta cell to initiate an adaptive programme to maintain glucose homeostasis. When this fails, type 2 diabetes ensues. Because mitochondria play a key role in beta cell pathophysiology, we tested the hypothesis that mitochondrial metabolism is critical for beta cell adaptation to insulin resistance. Methods: C57BL/6J mice were given high-fat (HF) diet for 12 weeks. We then analysed islet hormone secretion, metabolism in vivo and in vitro, and beta cell morphology. Results: HF diet resulted in insulin resistance and glucose intolerance but not frank diabetes. Basal insulin secretion was elevated in isolated islets from HF mice with almost no additional response provoked by high glucose. In contrast, a strong secretory response was seen when islets from HF mice were stimulated with fuels that require mitochondrial metabolism, such as glutamate, glutamine, alpha-ketoisocaproic acid and succinate. Moreover, while glucose oxidation was impaired in islets from HF mice, oxidation of glutamine and palmitate was enhanced. Ultrastructural analysis of islets in HF mice revealed an accumulation of lipid droplets in beta cells and a twofold increase in mitochondrial area. Conclusions/interpretation: We propose that beta cells exposed to increased lipid flux in insulin resistance respond by increasing mitochondrial volume. This expansion is associated with enhanced mitochondrial metabolism as a means of beta cell compensation

Re-assessing microbiomes in the low-biomass reproductive niche

The female reproductive tract represents a continuum between the vagina and the upper genital tract. New evidence from cultivation-independent studies suggests that the female upper genital tract is not sterile, however the significance of this for reproductive health and disease remains to be fully elucidated. Further, diagnosis and treatment of infectious reproductive tract pathologies using cultivation-independent technologies represents a largely unchartered area of modern medical science. The challenge now is to design well-controlled experiments to account for the ease of contamination known to confound molecular based studies of low-biomass niches, including the uterus and placenta. This will support robust assessment of the potential function of microorganisms, microbial metabolites and cell-free bacterial DNA on reproductive function in health and disease.J.L. O’Callaghan, R. Turner, M. Dekker Nitert, H.L. Barrett, V. Clifton, E.S. Pelze

Preconception care and barriers to addressing overweight and obesity: a focus on weight loss advice and weight loss strategies

Obesity in women of childbearing age is on the rise. Obesity in pregnancy is associated with an increased risk of pregnancy complications for the mother, and macrosomia for the baby. Reducing maternal weight prior to pregnancy is difficult to achieve, but reduces the risk for these complications. Diet and lifestyle interventions are usually successful only in the short term. Bariatric surgery has proved to be successful in weight loss prior to pregnancy although it is recommended that maternal weight is stable for more than six months prior to conception. Preconception care visits are opportunities to make women aware of the risks of their body weight on complications of pregnancy, to provide them with accurate information about their body weight and successful weight loss strategies. Current preconception care varies widely in content and health care provider and is currently attracting women higher education levels and a higher disposable income than the general obstetric population. Future preconception care strategies should focus on alternative ways of providing all women with information about the risks of obesity on pregnancy complications but ensure that women with lower levels of education are especially catered for