Timing of gestational diabetes diagnosis and progression to type 2 Diabetes: A comparative analysis.

AIM: To evaluate and compare the risk of progressing to type 2 diabetes (T2DM) based on the timing of gestational diabetes (GDM) diagnosis during pregnancy. METHODS: Retrospective analysis of pregnant individuals with gestational diabetes and post-pregnancy follow up. Data sourced from Meuhedet HMO's computerized laboratory system, cross-tabulated with the Israeli National Diabetes Registry. The cohort was divided into normoglycemic, early GDM (diagnosed by fasting plasma glucose 92-125 mg/dL (5.1-6.9 mM) at < 15 weeks), 2nd trimester GDM (diagnosed at 24-28 weeks), and late GDM (diagnosed after 29 weeks). Statistics included univariate analysis followed by survival analysis. Risk was further analyzed for individuals by obesity status. RESULTS: 75,459 entered the analysis: 90 % normoglycemic, 7.9 % early GDM, 1.4 % 2nd trimester GDM, and 0.7 % late GDM. Median post-pregnancy follow-up time was 4.3 (IQR 3.3-5.1). 2nd trimester GDM showed the highest T2DM risk annually after pregnancy. Cox regression analysis, adjusted for confounders, revealed a significantly higher T2DM risk for 2nd-trimester GDM compared to early and late GDM. Late GDM did not confer additional significant T2DM risk. Stratification by obesity status highlighted that early GDM increased the risk of T2DM only in individuals without obesity. CONCLUSIONS: GDM diagnosis timing significantly impacts T2DM risk. 2nd trimester GDM carries the highest T2DM risk.

Hypoglycemia in Oral Glucose Tolerance Test during Pregnancy and Risk for Type 2 Diabetes-A Five-Year Cohort Study.

Objective: To evaluate the risk of progression to type 2 diabetes (T2D) following reactive hypoglycemia in 100 g oral glucose tolerance test (oGTT). Methods: A retrospective analysis of parturients with up to 5-year follow-up postpartum. Data were extracted from the computerized laboratory system of Meuhedet, an Israeli HMO and cross-linked with the Israeli National Registry of Diabetes. Included were parturients with no prior diabetesand available oGTT values during pregnancy. Reactive hypoglycemia was defined as glucose levels lower than 60 mg/dL in at least one of 3 post-glucose load values in oGTT. The cohort was divided into 3 groups: normal glucose status, reactive hypoglycemia, and GDM. Maternal characteristics, laboratory data, and progression to T2D over 5 years were compared. Univariate and survival analyses assessed the adjusted hazard ratio for T2D, stratified by obesity Results: Among 14,122 parturients, 16.8% had reactive hypoglycemia, 71% had normal glucose status, and 12.2% had GDM. Adjusted for age, obesity, and hypertension, Parturients with reactive hypoglycemia had similar T2D risk compared to normal glucose status and a lower risk compared to GDM patients, regardless of obesity status. Conclusions: Reactive hypoglycemia during oGTT does not increase the risk of progressing to T2D.

External validation of vaginal birth after cesarean delivery calculator in Israeli cohort of parturients and construction of an improved model.

OBJECTIVE: To validate the Maternal Fetal Medicine Unit's (MFMU) vaginal birth after cesarean delivery (VBAC) calculator in an Israeli cohort, and to detect other variables associated with VBAC and construct an improved VBAC calculator. METHODS: A retrospective cohort study was performed at a single university-affiliated medical center. Women carrying a singleton, term, cephalic-presenting fetus, with previous one low transverse cesarean delivery who opted for trial of VBAC were included. Demographic and obstetric characteristics were incorporated into the MFMU's calculator, to predict probabilities of VBAC and compare prediction performance with the original publication utilizing receiver operating characteristic (ROC) statistics. Logistic regression analysis was used to investigate other variables and construct an improved model for success of VBAC. RESULTS: Of 490 parturients, 396 (80.8%) had a successful vaginal delivery. Compared to the original publication, the MFMU's calculator underperformed: area under the ROC curve (AUC) was 0.709 (95% confidence interval [CI] 0.652-0.766, P < 0.001). Sensitivity, specificity, positive and negative predictive values, and overall accuracy were 67.42%, 65.96%, 89.30%, 32.46%, and 32.46%, respectively. An improved model that included previous VBAC, prior vaginal delivery, spontaneous onset of delivery, and maternal diabetes resulted in improved prediction performance with an AUC of 0.771 (95% CI 0.723-0.82, P < 0.001). CONCLUSION: MFMU's VBAC calculator needs to be validated in different populations before implementation.

The Accuracy of Sonographically Estimated Fetal Weight and Prediction of Small for Gestational Age in Twin Pregnancy-Comparison of the First and Second Twins.

Accurate sonographic estimation of fetal weight is essential for every pregnancy, especially in twin gestation. We conducted a retrospective analysis of the sonographically estimated fetal weight (sEFW) of all twin gestations performed within 14 days of delivery in a single center that aimed to evaluate the accuracy of sEFW in predicting neonatal weight and small for gestational age (SGA) by comparing the first fetus to the second. A total of 190 twin gestations were evaluated for the study. There was no statistically significant difference in the sEFW between the first and the second twins, but the second twin had a statistically significant lower birth weight (2434 vs. 2351 g, p = 0.028). No difference was found in median absolute systematic error (p = 0.450), random error, or sEFW evaluations that were within 10% of the birth weight between the fetuses (65.3% vs. 67.9%, p = 0.587). Reliability analysis demonstrated an excellent correlation between the sEFW and the birth weight for both twins; however, the Euclidean distance was slightly higher for the first twin (12.21%). For SGA prediction, overall, there was a low sensitivity and a high specificity for all fetuses, with almost no difference between the first and second twins. We found that sEFW overestimated the birth weight for the second twin, with almost no other difference in accuracy measures or SGA prediction.

miR-103 inhibits proliferation and sensitizes hemopoietic tumor cells for glucocorticoid-induced apoptosis.

Glucocorticoid (GC) hormones are an important ingredient of leukemia therapy since they are potent inducers of lymphoid cell apoptosis. However, the development of GC resistance remains an obstacle in GC-based treatment. In the present investigation we found that miR-103 is upregulated in GC-sensitive leukemia cells treated by the hormone. Transfection of GC resistant cells with miR-103 sensitized them to GC induced apoptosis (GCIA), while miR-103 sponging of GC sensitive cells rendered them partially resistant. miR-103 reduced the expression of cyclin dependent kinase (CDK2) and its cyclin E1 target, thereby leading to inhibition of cellular proliferation. miR-103 is encoded within the fifth intron of PANK3 gene. We demonstrate that the GC receptor (GR) upregulates miR-103 by direct interaction with GC response element (GRE) in the PANK3 enhancer. Consequently, miR-103 targets the c-Myc activators c-Myb and DVL1, thereby reducing c-Myc expression. Since c-Myc is a transcription factor of the miR-17~92a poly-cistron, all six miRNAs of the latter are also downregulated. Of these, miR-18a and miR-20a are involved in GCIA, as they target GR and BIM, respectively. Consequently, GR and BIM expression are elevated, thus advancing GCIA. Altogether, this study highlights miR-103 as a useful prognostic biomarker and drug for leukemia management in the future.