Impact of maternal diabetes mellitus on fetal atrial strain.

While Maternal Diabetes Mellitus (DM) is well known to affect the size and function of multiple fetal organ systems, effects on developing heart chamber function remain difficult to assess. We sought to determine the independent impact of maternal DM on fetal cardiac function in middle pregnancy. We prospectively recruited mothers with all categories of DM and non-diabetic healthy controls (NDC). Echocardiograms were optimized for chamber quantification and strain analysis. Left atrial area (LAA), LA strain (LAS), right atrial strain (RAS), global longitudinal ventricular strain (GLS) and Right ventricular free wall strain (RV FWS) were evaluated by 2 blinded operators. After excluding 9 mothers with poor fetal image quality, images from 104 mothers with DM and 47 NDC were analyzed. Mothers with DM and NDCs were well matched for age, blood pressure, smoking prevalence, and gestational age. Fetal heart rate (FHR) was significantly higher in fetuses of mothers with DM compared to NDC (147 ± 10 bpm vs. 144 ± 8, p = 0.04). LAA in fetuses of mothers with DM trended towards being larger in size (1.68 ± 0.4cm2 vs. 1.56 ± 0.4cm2, p = 0.08). Fetal septal diameters were larger in maternal DM compared to NDC (2.7 ± 0.5 cm vs. 2.5 ± 0.5 cm, p = 0.001). GLS was similar between the groups. Fetal LAS was lower in maternal DM (28.8 ± 8.8% vs. 33.3 ± 10.4%, p = 0.007) and was independently associated with maternal DM after adjusting for GLS and FHR. Fetal RAS was lower in maternal DM (27.7 ± 10.4% vs. 31.8 ± 10.3%, p = 0.007), however only determinates were estimated fetal weight and RV FWS. Maternal DM independently impairs fetal LA function in mid pregnancy. These early functional changes in the developing heart warrant future studies investigating impact on cardiovascular health.

Downregulation of AMP-activated protein kinase by Cidea-mediated ubiquitination and degradation in brown adipose tissue.

We previously showed that Cidea(-/-) mice are resistant to diet-induced obesity through the upregulation of energy expenditure. The AMP-activated protein kinase (AMPK), consisting of catalytic alpha subunit and regulatory subunits beta and gamma, has a pivotal function in energy homoeostasis. We show here that AMPK protein levels and enzymatic activity were significantly increased in the brown adipose tissue of Cidea(-/-) mice. We also found that Cidea is colocalized with AMPK in the endoplasmic reticulum and forms a complex with AMPK in vivo through specific interaction with the beta subunit of AMPK, but not with the alpha or gamma subunit. When co-expressed with Cidea, the stability of AMPK-beta subunit was dramatically reduced due to increased ubiquitination-mediated degradation, which depends on a physical interaction between Cidea and AMPK. Furthermore, AMPK stability and enzymatic activity were increased in Cidea(-/-) adipocytes differentiated from mouse embryonic fibroblasts or preadipocytes. Our data strongly suggest that AMPK can be regulated by Cidea-mediated ubiquitin-dependent proteosome degradation, and provide a molecular explanation for the increased energy expenditure and lean phenotype in Cidea-null mice.

Maternal diabetes independent of BMI is associated with altered accretion of adipose tissue in large for gestational age fetuses.

AIM: To analyse the effects of maternal diabetes mellitus (DM) and body mass Index (BMI) on central and peripheral fat accretion of large for gestational age (LGA) offspring. METHODS: This retrospective study included LGA fetuses (n = 595) with ultrasound scans at early (19.23 ± 0.68 weeks), mid (28.98 ± 1.62 weeks) and late (36.20 ± 1.59 weeks) stages of adipogenesis and measured abdominal (AFT) and mid-thigh (TFT) fat as surrogates for central and peripheral adiposity. Women were categorised according to BMI and DM status [pre-gestational (P-DM; n = 59), insulin managed (I-GDM; n = 132) and diet managed gestational diabetes (D-GDM; n = 29)]. Analysis of variance and linear regressions were applied. RESULTS: AFT and TFT did not differ significantly between BMI categories (normal, overweight and obese). In contrast, AFT was significantly higher in pregnancies affected by D-GDM compared to non-DM pregnancies from mid stage (0.44 mm difference, p = 0.002) and for all DM categories in late stage of adipogenesis (≥ 0.49 mm difference, p < 0.008). Late stage TFT accretion was higher than controls for P-DM and I-GDM but not for D-GDM (0.67 mm difference, p < 0.001; 0.49 mm difference, p = 0.001, 0.56 mm difference, p = 0.22 respectively). In comparison to the early non-DM group with an AFT to TFT ratio of 1.07, the I-GDM group ratio was 1.25 (p < 0.001), which normalised by 28 weeks becoming similar to control ratios. CONCLUSIONS: DM, independent of BMI, was associated with higher abdominal and mid-thigh fat accretion in fetuses. Use of insulin improved central to peripheral fat ratios in fetuses of GDM mothers.

Sonographic and other nonglycemic factors can predict large-for-gestational-age infants in diet-managed gestational diabetes mellitus: A retrospective cohort study.

BACKGROUND: Gestational diabetes mellitus (GDM) is one of the most common complications of pregnancy. Left untreated or poorly controlled, GDM results in adverse infant outcomes such as large for gestational age (LGA). This study aims to identify nonglycemic maternal and fetal factors predictive of LGA outcomes in pregnancies complicated by diet-managed GDM. METHODS: This was a retrospective cohort study of singleton pregnancies complicated by diet-managed GDM from 2004 to 2015. Multiple logistic regression analysis was performed on maternal and perinatal factors to identify risk factors for LGA. In addition, a subset univariate analysis was conducted for pregnancies in which fetal ultrasound abdominal circumference measurements were available at gestational weeks 18 to 22, 24 to 28, and 29 to 33. RESULTS: A total of 1064 women were included, delivering 123 LGA infants. Women with higher parity (odds ratio [OR] 1.44; CI, 1.23-1.68; P < .001) and higher prepregnancy body mass index (BMI) (OR 1.09; CI, 1.06-1.12; P < .001) were more likely to have LGA infants. Maternal smoking (OR 0.30; CI, 0.14-0.62; P = .001) and higher gestational age at birth (OR 0.91; CI, 0.84-0.99; P = .018) were associated with reduced risk. Subset univariate analysis showed that fetal abdominal circumference measurements at weeks 24 to 28 and 29 to 33 beyond the 75th percentile (OR 5.92 and 13.74, respectively) and 90th percentile (OR 4.57 and 15.89, respectively) were highly predictive of LGA. CONCLUSIONS: Parity, smoking status, maternal BMI, gestational age, and ultrasound fetal abdominal circumference measurements were identified as useful predictors of LGA. Presence of these predictors may prompt closer monitoring of pregnancy and early therapeutic intervention to improve management and reduce the risk of adverse fetal and maternal outcomes.

The effect of preliminary training on quantitative evaluation of sonographer performance in the fetal morphology ultrasound examination.

Introduction: The aim of this study is to provide a quantitative scoring system to assess sonographer performance by reviewing images from the fetal morphology examination. Methods: Ten ultrasound images from patients at 18-22 weeks gestation were assessed and scored for quality according to predefined criteria. One hundred normal cases were randomly selected and 10 images from each case were analysed by four experienced reviewers. The preliminary training incorporated the first 25 cases and involved a training period for reviewers; the remaining 75 cases were allocated to post training. The scores acquired by each reviewer were statistically analysed using Pearson's and intra-class correlations to determine the reproducibility of the results. Results: The preliminary training results were calculated separately and compared to the post training study. The preliminary intra-class correlation coefficient was 0.12. In the post training study the intra-class correlation coefficient was doubled at 0.24. The greatest correlation was observed between reviewers 1 and 4 with a coefficient of 0.71. Reviewers 3 and 4 demonstrated the lowest correlation coefficient of 0.30. Discussion: A significant increase in the intra-class correlation coefficient indicated that training reviewers achieves more reproducible results. Suggested improvements to the study include recording fetal position, maternal BMI and assessing individual reviewer variability. An instruction manual defining each criterion might also yield better results. Conclusion: The quantitative method used in this study assessed ultrasound images by placing a numerical value on image quality. Analysis of the preliminary training period demonstrates improved reproducibility of the results. Further investigation into the criteria is necessary to refine the quantitative method.