The hemostatic parameters in pregnant women with different types of diabetes mellitus

BACKGROUND: The prevalence of diabetes mellitus (DM) in pregnancy is on the rise. Despite that gestational hypercoagulability is a physiological condition, diabetic pregnancy is associated with a high risk of venous thromboembolic complications (VTEC). There are many surveys related to the hemostatic parameters in non-pregnant women, but studies in pregnant women are not enough.AIMS: To assess the coagulation and vascular-platelet hemostasis parameters in pregnant women with various types of diabetes mellitus, taking into account its correction method. The data were compared with these indicators in women with preeclampsia and healthy pregnant women at the same gestational age.MATERIALS AND METHODS: An observational, single-center, retrospective cohort study was carried out at D.O. Ott ­Research Institute of Obstetrics, Gynecology, and Reproductive Medicine. The study included 1994 pregnant women who presented several groups taking into account the type of DM and its correction method, a group of women with preeclampsia (PE), and healthy women. The analysis of clinical data was carried out at 28–32 gestational weeks from 2012 to 2017. The study’s primary endpoint was taken as indicators of fibrinogen content, prothrombin index, thrombin time, activated partial thromboplastin time (APTT), and international normalized ratio (INR) antithrombin III, D-dimer, von Willebrand factor, and fibronectin. Additionally, the incidence of VTEC during pregnancy and within six weeks after delivery, gestational arterial hypertension, preeclampsia, fetal growth restriction, premature birth, and stillbirth cases was assessed.RESULTS: in pregnant women with various types of diabetes mellitus and preeclampsia, a state of pathological hypercoagulation was observed compared to the control group. These changes were characterized by an increase and activation of the following blood parameters: fibrinogen, the degree and rate of platelet aggregation, D-dimer, homocysteine, von Willebrand factor, and fibronectin. At the same time, the content of antithrombin III was significantly reduced in patients with DM. Correlation analysis established a direct relationship between the range of the studied factors with the degree of glycemic control and the frequency of obstetric complications.CONCLUSIONS: Diabetes mellitus in pregnancy is associated with a hypercoagulation condition and overexpression in the synthesis of endothelial dysfunction markers. Moreover, the severity of these processes depends on the type of DM and the severity of metabolic disorders. In diabetic pregnancy, exceptional attention to coagulation indicators, regular monitoring, and preventive treatment is required in order to improve the perinatal outcomes.

Diabetic pregnancy as a novel risk factor for cardiac dysfunction in the offspring—the heart as a target for fetal programming in rats

Aims/hypothesis The impact of diabetic pregnancy has been investigated extensively regarding offspring metabolism; however, little is known about the influence on the heart. We aimed to characterise the effects of a diabetic pregnancy on male adult offspring cardiac health after feeding a high-fat diet in an established transgenic rat model. Methods We applied our rat model for maternal type 2 diabetes characterised by maternal insulin resistance with hyperglycaemia and hyperinsulinaemia. Diabetes was induced preconceptionally via doxycycline-induced knock down of the insulin receptor in transgenic rats. Male wild-type offspring of diabetic and normoglycaemic pregnancies were raised by foster mothers, followed up into adulthood and subgroups were challenged by a high-fat diet. Cardiac phenotype was assessed by innovative speckle tracking echocardiography, circulating factors, immunohistochemistry and gene expression in the heart. Results When feeding normal chow, we did not observe differences in cardiac function, gene expression and plasma brain natriuretic peptide between adult diabetic or normoglycaemic offspring. Interestingly, when being fed a high-fat diet, adult offspring of diabetic pregnancy demonstrated decreased global longitudinal (−14.82 ± 0.59 vs −16.60 ± 0.48%) and circumferential strain (−23.40 ± 0.57 vs −26.74 ± 0.34%), increased relative wall thickness (0.53 ± 0.06 vs 0.37 ± 0.02), altered cardiac gene expression, enlarged cardiomyocytes (106.60 ± 4.14 vs 87.94 ± 1.67 μm), an accumulation of immune cells in the heart (10.27 ± 0.30 vs 6.48 ± 0.48 per fov) and higher plasma brain natriuretic peptide levels (0.50 ± 0.12 vs 0.12 ± 0.03 ng/ml) compared with normoglycaemic offspring on a high-fat diet. Blood pressure, urinary albumin, blood glucose and body weight were unaltered between groups on a high-fat diet. Conclusions/interpretation Diabetic pregnancy in rats induces cardiac dysfunction, left ventricular hypertrophy and altered proinflammatory status in adult offspring only after a high-fat diet. A diabetic pregnancy itself was not sufficient to impair myocardial function and gene expression in male offspring later in life. This suggests that a postnatal high-fat diet is important for the development of cardiac dysfunction in rat offspring after diabetic pregnancy. Our data provide evidence that a diabetic pregnancy is a novel cardiac risk factor that becomes relevant when other challenges, such as a high-fat diet, are present. Graphical abstract

Hypoglycaemia in non-diabetic pregnancy

Hypoglycaemia in non-diabetic pregnancy is rare, the majority of reported cases being due to insulinoma, acute fatty liver of pregnancy, malaria and inborn errors of metabolism. A case of hypoglycaemia in a woman with previous laparoscopic sleeve gastrectomy, and hypothalamic-pituitary-adrenal axis insufficiency in the setting of opioid dependence is presented. The timing of low interstitial glucose levels was atypical for late dumping syndrome following bariatric surgery, and a change in the woman’s glucocorticoid replacement resulted in resolution of hypoglycaemic symptoms. The incidence of opioid dependence in pregnancy is increasing rapidly. Health professionals should be aware of the possibility of opioids causing hypothalamic-pituitary-adrenal axis insufficiency, and the additional mechanisms by which opioids may cause hypoglycaemia.

A Proposed Fetal Risk Scoring System for Gestational Diabetes to assist in optimizing Timing of Delivery

Background: Gestational diabetes is characterized by three main factors: macrosomia, increased metabolic rate and large vascular cross sections. A critical and crucial finding in diabetic pregnancies is that significant acidaemia and hyperlacticemia can occur in fetuses in the absence of hypoxaemia. The increased metabolic rate results in significant increases in oxidative metabolism but this capacity is reduced in fetuses due to low pyruvate dehydrogenase activity increasing the risk for acidosis. This pathophysiology is not recognized by standard monitoring models which revolves around placental insufficiency which is in fact not the problem in a gestational diabetic pregnancy. A proposed risk scoring system has been developed based on our previous studies to risk categorise gestational diabetics in terms of fetal outcome.Methods: The diabetic cases from four case-control studies were combined to form a total sample of 159 cases for validation of the risk scoring system. Univariate logistic regression was used to assess the effect of individual risk factors with proposed cutoffs on adverse pregnancy outcome. The diagnostic accuracy of the total summative score, was assessed by computing the area under the ROC curve.Results: Four potential parameters were identified to risk- categorise fetuses in a gestational diabetic pregnancy ie the myocardial performance index (MPI), E/A ratio (marker of diastolic dysfunction), increasing fetal weight (macrosomia) and increased amniotic fluid index (AFI). The total score, obtained by summation of the composite scores for parameters ranged from 0 to 11. The total score performed as an excellent predictor of adverse outcome, evidenced by the ROC area under the curve of 0.94. A cutpoint of 6 on the score confers a sensitivity of 84.2% and specificity of 90.2% for detection of adverse outcome. Conclusion: To our knowledge this is the first Gestational Diabetic Scoring system proposed to predict an adverse outcome.