Cross-sectional study examining factors impacting on uptake of postpartum type 2 diabetes screening among women diagnosed with hyperglycaemia in pregnancy.

AIMS: Early postpartum glucose screening of women with hyperglycaemia in pregnancy (HIP) can identify women who have the highest risk of developing impaired glucose tolerance and T2DM. This study examines the association between demographics, events during pregnancy, socioeconomic status and postpartum T2DM screening. METHODS: Using the French National Health Data System, this cross-sectional study included all deliveries where the mother had HIP in France in 2015, (n = 76,862). The odds ratio (OR) for attending postpartum screening was calculated via multi-level logistic regression. RESULTS: T2DM screening uptake at six months postpartum was 42·9% [95 % Confidence Interval: 42·6-43·3]. Several characteristics were associated with lower uptake: living in the most deprived area(OR = 0·78[0·74-0·83]); being < 25 years-old (reference age group 25-29;≤17: 0.53 [0·31-0·90];18-24: 0.73[0·69-0·78]); smoking (0·65[0·62-0·68]); obesity (0·93[0·89-0·97]); caesarean delivery (0·95[0·92-0·99]). Factors associated with higher uptake included primiparity (1·30[1·26-1·34]); having followed the French recommendations for HIP screening (1·24[1·20-1·28]); insulin prescription (1·75[1·69-1·81]) and pre-eclampsia (1·30[1·19-1·42]). p < 0.01 is justified due to sample size. CONCLUSION: Improving identification of factors affecting postpartum T2DM screening uptake, such as demographics, socioeconomic context and events during pregnancy, may lead to development of target interventions to aide adherence to screening regime and thereby diagnosis of women with prediabetes or diabetes, for whom secondary and tertiary prevention is crucial.

Pre-gestational diabetes and the risk of congenital heart defects in the offspring: A French nationwide study.

AIM: To compare the frequencies and types of congenital heart defects for infants of women without and with pre-gestational diabetes, type 1 and type 2 diabetes (T1DM, T2DM) and to identify risk factors. METHODS: All live births between 2012 and 2020 were screened for maternal diabetes and infant congenital heart defects using the French Medical Information System Program in Medicine, Surgery and Obstetrics database (PMSI-MCO). Incidences of these defects were estimated, and a logistic model evaluated maternal and fetal prognostic risk factors. RESULTS: Overall, 6,038,703 mothers did not have pre-gestational diabetes (no-diabetes), 23,147 had T1DM, and 14,401 had T2DM. The incidence of infant congenital disease was 6.2% for the no-diabetes group, 8.0%, for women with T1DM, and 8.4% for women with T2DM (P < 0.001); for congenital heart defects, incidences were respectively 0.8%, 3.0% and 2.7% (P < 0.001). In comparison with the no-diabetes group, the odds ratios (95%CI) of coronary heart defects were 2.07 (1.91;2.24) (P < 0.001) for women with T1DM and 2.20 (1.99;2.44) (P < 0.001) for women with T2DM, with no difference between T1DM and T2DM (P = 0.336). cesarian section, small and large for gestational age, and prematurity were also associated with an increased risk of congenital heart defects. CONCLUSION: In this study we observed higher incidences of congenital heart defects in infants of women with pre-gestational diabetes compared to women without pre-gestational diabetes, with no difference between women with T1DM or T2DM. These data call for intensifying preconception care and justify systematic cardiac echography in selected fetuses.

Diabetes is associated with high risk of severe adverse events during chemotherapy for cancer patients: A single-center study.

Diabetes mellitus (DM) is a common comorbidity among cancer patients, but its impact on chemotherapy tolerance has not been widely studied. We aimed to compare the occurrence of severe grade 3/4 adverse events (G3/4 AEs) within 90 days of starting chemotherapy between patients with and without diabetes. We conducted a retrospective single-center study in Lille University Hospital Oncology Department, France. Patients who received the first cycle of chemotherapy for gastrointestinal, gynecological or cancer of unknown primary source between 1 May 2013 and 1 May 2016, were included. Overall, 609 patients were enrolled: 490 patients without diabetes (80.5%) and 119 patients with diabetes (19.5%). Within 90 days of starting chemotherapy, patients with diabetes had a significantly higher occurrence of AEs G3/4 compared to those with no diabetes (multivariate odds ratio [OR]: 1.57 [1.02-2.42], P = .04). More frequent G3/4 AEs in patients with diabetes were infection (26%), hematological disorders (13%), endocrine disorders (13%) and deterioration of the general condition (13%). In the year following the beginning of chemotherapy, patients with diabetes were twice as likely to be hospitalized as those without diabetes (univariate OR: 2.1 [1.40-3.15], P = .0003). After multivariate adjustment, diabetes was no longer significantly associated with the risk of hospitalization (P = .051). There were no differences between patients with and without diabetes regarding dose reduction and chemotherapy treatment delays (P = .61 and P = .30, respectively). Our study suggests the need for better consideration of DM in the personalized care plan to improve chemotherapy tolerance and quality of life of patients with DM.

Adipose tissue macrophages (ATM) of obese patients are releasing increased levels of prolactin during an inflammatory challenge: a role for prolactin in diabesity?

BACKGROUND: Obesity, characterized by low grade inflammation, induces adipose tissue macrophage (ATM) infiltration in white adipose tissue (AT) in both humans and rodents, thus contributing to insulin resistance. Previous studies have shown altered prolactin secretion in obesity, however, studies linking ATM infiltration and prolactin (PRL) secretion to the pathogenesis of the metabolic syndrome, obesity and diabetes are lacking. METHODS/RESULTS: In vivo, qPCR and Western blot analysis demonstrated that prolactin expression was increased in AT of obese rats and also in human AT from obese, obese pre-diabetic and obese diabetic compared to lean counterparts. Immunohistochemistry of obese rat and human AT sections demonstrated a specific expression of prolactin in macrophages. In vitro, we demonstrated that hyperglycemia and inflammation stimulated macrophages (human THP-1 cell line and sorted rat ATM) to express PRL, when challenged with different glucose concentrations with or without IL1ß. In in vivo and in vitro experiments, we assessed the expression of Pit-1 (PRL-specific transcription factor) and found that its expression was parallel to PRL expression. CONCLUSIONS: In this study, we show that rodent and human macrophages synthesize prolactin in response to inflammation and high glucose concentrations. GENERAL SIGNIFICANCE: Our data shed new light on the potential role of macrophages in the physiopathology of diabesity via the PRL expression and on its expression mechanism and regulation.

Diabetes during pregnancy influences Hofbauer cells, a subtype of placental macrophages, to acquire a pro-inflammatory phenotype.

Growing evidence indicates that maternal pathophysiological conditions, such as diabetes, influence fetal growth and could program metabolic disease in adulthood. Placental cells, particularly Hofbauer cells (HBCs), which are placental macrophages characterized by an anti-inflammatory profile (M2), can sense the modified maternal environment. The goal of this study was to investigate the direct effect of hyperglycemia on HBCs. We studied, at mRNA and protein levels, some markers of M2 and M1 (pro-inflammatory) macrophages in placentae from control and diabetic patients to assess the balance between pro- and anti-inflammatory macrophages: an imbalance of M2 to M1 macrophages has been observed in humans. We used pregnant rats, receiving a single injection of streptozotocin (STZ), as a model of maternal diabetes. We noticed a M2-to-M1 macrophage unbalance as we observed in human. An in vitro model of isolated rat HBCs was used to identify the direct effects of high glucose. We found that high glucose stimulation activated genes belonging to TLR (Toll-Like Receptor)-dependent inflammatory pathways. Moreover, the HBCs stimulated by high glucose switched their M2 profile towards M1, with increased expression of pro-inflammatory cytokines and markers. We also noticed that the oxidative-stress pathway was activated in response to high glucose driven by Hif-1α. In this study, we demonstrated that diabetes/hyperglycemia affect the anti-inflammatory profile of HBCs, by stimulating these cells to acquire an inflammatory profile leading to adverse consequences for the fetal-placental-maternal axis.

Hormonal contraception in women at risk of vascular and metabolic disorders: guidelines of the French Society of Endocrinology.

Hormonal contraceptive methods are widely used in France, including not only oral estrogen-progestin combinations but also non-oral estrogen-progestin delivery methods (patches, vaginal rings), as well as oral forms, implants and intra-uterine devices that deliver only a progestin. Hormonal contraception has only a modest impact on lipid and carbohydrate metabolism, but estrogen-progestin contraceptives have been linked to a variety of vascular risks. Overall, the risk of venous thrombosis is multiplied by a factor of about 4, depending on age, the compounds used, and other risk factors (including biological thrombophilia and a personal history of thrombosis), whereas the risk of arterial events is only increased in women with risk factors. Available data suggest there is no excess risk with progestin-based contraceptives, but far fewer studies have been conducted. At the initiative of the French Society of Endocrinology, an expert group met in 2010 in order to reach a consensus on the use of hormonal contraceptive methods in women with vascular or metabolic risk factors, based on available data and international guidelines published by WHO in 2009 and subsequently adapted to the United States context. The following text, intentionally limited to hormonal contraception, is intended to serve as a guide when prescribing in specific clinical situations, such as a family or personal history of arterial or venous thromboembolism, or the existence of cardiovascular risk factors (hypertension, smoking, diabetes, dyslipidemia, obesity).