Plasma Exosomal miRNAs Associated With Metabolism as Early Predictor of Gestational Diabetes Mellitus.

To date, the miRNA expression profile of plasma exosomes in women whose pregnancy is complicated by gestational diabetes mellitus (GDM) has not been fully clarified. In this study, differentially expressed miRNAs in plasma exosomes were identified by high-throughput small-RNA sequencing in 12 pregnant women with GDM and 12 with normal glucose tolerance (NGT) and validated in 102 pregnant women with GDM and 101 with NGT. A total of 22 exosomal miRNAs were found, five of which were verified by real-time qPCR. Exosomal miR-423-5p was upregulated, whereas miR-122-5p, miR-148a-3p, miR-192-5p, and miR-99a-5p were downregulated in women whose pregnancy was complicated by GDM. IGF1R and GYS1 as target genes of miR-423-5p, and G6PC3 and FDFT1 as target genes of miR-122-5p were associated with insulin and AMPK signaling pathways and may participate in the regulation of metabolism in GDM. The five exosomal miRNAs had an area under the curve of 0.82 (95%CI, 0.73, ∼0.91) in early prediction of GDM. Our study demonstrates that dysregulated exosomal miRNAs in plasma from pregnant women with GDM might influence the insulin and AMPK signaling pathways and could contribute to the early prediction of GDM.

Early Diagnosed Gestational Diabetes Mellitus Is Associated With Adverse Pregnancy Outcomes: A Prospective Cohort Study.

CONTEXT: The significance of an early diagnosis of gestational diabetes mellitus (GDM) with oral glucose tolerance test (OGTT) has not been determined. OBJECTIVE: The objective of this work is to investigate GDM diagnosed by early and standard OGTTs and determine adverse maternal and neonatal outcomes associated with early GDM diagnosis. RESEARCH DESIGN AND METHODS: The Early Diagnosis of Gestational Diabetes Mellitus study is a prospective cohort study. Each participant in the study underwent 2 OGTTs, an early OGTT at 18 to 20 gestational weeks (gws) and a standard OGTT at 24 to 28 gws. The reproduciblity between early and standard OGTT were analyzed. Maternal and neonatal metabolic disorders and pregnancy outcomes were compared across groups. RESULTS: A total of 522 participants completed both the early and standard OGTTs. The glucose values in the early OGTT were not significantly different from those in the standard OGTT (fasting: 4.31 ± 0.41 mmol/L vs 4.29 ± 0.37 mmol/L, P = .360; 1-hour: 7.68 ± 1.71 mmol/L vs 7.66 ± 1.59 mmol/L, P = .826; 2-hour: 6.69 ± 1.47 mmol/L vs 6.71 ± 1.39 mmol/L, P = .800). The reproducibility of early and standard OGTT results was 74.9%. Pregnant women in the GDM group had higher glycated hemoglobin, C-peptide, and homeostasis model assessment of insulin resistance in the late gestational period. Neonates born to mothers in the GDM group were at a higher risk of being large for gestational age (odds ratio [OR]: 3.665; 95% CI, 1.006-11.91) and were also more prone to neonatal hyperinsulinemia (OR: 3.652; 95% CI, 1.152-10.533). CONCLUSION: Early-onset GDM diagnosed by OGTT at 18 to 20 gws is associated with maternal and neonatal metabolic disorders and adverse pregnancy outcomes. Further randomized controlled trials on the therapeutic efficacy for early-onset GDM will confirm the significance of early screening for GDM.

Continuous elevation of plasma asprosin in pregnant women complicated with gestational diabetes mellitus: A nested case-control study.

INTRODUCTION: To investigate the expression of asprosin, a novel insulin resistance-related factor, in plasma and placenta of pregnant women with and without gestational diabetes mellitus (GDM). METHODS: This is a nested case-control study within the prospective study named Early Diagnosis of Gestational Diabetes Mellitus (EDoGDM). Forty pregnant women with GDM and forty control cases with normal glucose tolerance (NGT) were recruited in the present study. Asprosin levels were tested by ELISA in maternal plasma at 18-20 and 24-28 gestational weeks and before delivery, as well as in umbilical plasma. Asprosin concentrations were compared between GDM and NGT groups, and the relationship between asprosin and other parameters were analyzed. Expression of asprosin in placenta was examined by Western blot and immunohistochemistry. RESULTS: Asprosin was elevated in plasma of GDM pregnant women and their offspring, after adjusted by maternal and neonatal clinical characteristics and lipid profiles. Asprosin was expressed in placenta from both GDM and NGT pregnant women. DISCUSSION: Protein asprosin is expressed in human placenta and is elevated in the plasma of pregnant women complicated with GDM and their offspring. As an insulin resistance-related factor increased before 20 gestational weeks, asprosin may play a role as a potential early biomarker of GDM.

The role of elevated serum procalcitonin in neuroendocrine neoplasms of digestive system.

INTRODUCTION: Elevated serum procalcitonin (PCT) was reported in patients with certain type of neuroendocrine neoplasms (NENs). OBJECTIVE: The aim of this study was to assess the role of elevated serum PCT in NENs from digestive system. PATIENTS AND METHODS: Serum PCT and serum CgA level were measured in 155 patients with NENs from digestive system. RESULTS: Elevated serum PCT was found in 63 patients (40.6%). Grade 3 disease was a significant factor associated with elevated serum PCT (OR, 9.24; 95%CI, 3.04-28.08; P<0.001). Serum PCT level was significantly decreased after treatment both in patients with stable disease (P=0.003) and patients with partial remission (P=0.001). In these patients, serum PCT level significantly increased again at the time of progression disease (P=0.001). Elevated serum PCT was a significant factor of worse survival (HR, 2.86; 95%CI, 1.36-6.03; P=0.006). Compared with patients with normal serum PCT and CgA level, patients with either PCT or CgA elevated and patients with both PCT and CgA elevated had progressively worse survival. Additionally, PCT expression in tumor cells was found in 24.0% of patients but did not correlate with other clinicopathological factors, including serum PCT. CONCLUSIONS: Serum PCT is elevated in part of patients with NENs of digestive system, especially in patients with grade 3 disease. Serum PCT level can help evaluate treatment response and its elevation indicates poor prognosis. Combination of serum PCT and CgA can improve outcome prediction.

Early Diagnosis of Gestational Diabetes Mellitus (EDoGDM) study: a protocol for a prospective, longitudinal cohort study.

INTRODUCTION: A diagnosis of gestational diabetes mellitus (GDM) in low-risk pregnant women is based on an oral glucose tolerance test (OGTT) between 24 and 28 gestational weeks. However, there is insufficient evidence for why the test is performed in this time period. Moreover, the fetus may be exposed to hyperglycaemia prior to the current testing time frame, making earlier administration potentially advantageous. The main purpose of the present study is to investigate the GDM diagnostic value of an OGTT performed at 18-20 gestational weeks. The results of the study may provide scientific insight into the most beneficial time of OGTT for pregnant women. METHODS AND ANALYSIS: As a prospective, longitudinal cohort study, the Early Diagnosis of Gestational Diabetes Mellitus (EDoGDM) study will recruit 570 pregnant women who meet the inclusion and exclusion criteria outlined below. OGTTs will be performed between 18 and 20 gestational weeks (early OGTT) and 24-28 gestational weeks (regular OGTT). Clinical and laboratory information of the mother and their offspring will be collected for analysis. The prevalence of GDM at 18-20 gestational weeks will be described, and the sensitivity, specificity, positive predictive value and negative predictive value of early OGTT on diagnosis of GDM will be studied. Clinical outcomes associated with hyperglycaemia will be compared between groups diagnosed by early or regular OGTT. ETHICS AND DISSEMINATION: The study was approved by The Ethical Committees of The First Affiliated Hospital of Sun Yat-sen University (number 2016-042). Signed informed consent will be obtained from all participants. The results of this study will be disseminated in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT02740283.

Early pregnancy fasting plasma glucose and lipid concentrations in pregnancy and association to offspring size: a retrospective cohort study.

BACKGROUND: Hyperlipidemia and high fasting plasma glucose levels at the first prenatal visit (First Visit FPG) are both related to gestational diabetes mellitus, maternal obesity/overweight and fetal overgrowth. The purpose of the present study is to investigate the correlation between First Visit FPG and lipid concentrations, and their potential association with offspring size at delivery. MATERIALS AND METHODS: Pregnant women that received regular prenatal care and delivered in our center in 2013 were recruited for the study. Fasting plasma glucose levels were tested at the first prenatal visit (First Visit FPG) and prior to delivery (Before Delivery FPG). HbA1c and lipid profiles were examined at the time of OGTT test. Maternal and neonatal clinical data were collected for analysis. Data was analyzed by independent sample t test, Pearson correlation, and Chi-square test, followed by partial correlation and multiple linear regression analyses to confirm association. Statistical significance level was α =0.05. RESULTS: Analyses were based on 1546 mother-baby pairs. First Visit FPG was not correlated with any lipid parameters after adjusting for maternal pregravid BMI, maternal age and gestational age at First Visit FPG. HbA1c was positively correlated with triglyceride and Apolipoprotein B in the whole cohort and in the NGT group after adjusting for maternal age and maternal BMI at OGTT test. Multiple linear regression analyses showed neonatal birth weight, head circumference and shoulder circumference were all associated with First Visit FPG and triglyceride levels. CONCLUSION: Fasting plasma glucose at first prenatal visit is not associated with lipid concentrations in mid-pregnancy, but may influence fetal growth together with triglyceride concentration.

Serum Enzyme Profiles Differentiate Five Types of Muscular Dystrophy.

BACKGROUND: Differentiation among types of muscular dystrophy (MD) has remained challenging. In this retrospective study, we sought to develop a methodology for differentiation of MD types using analysis of serum enzyme profiles. METHODS: The serum levels of enzymes from 232 patients, including 120 with DMD, 36 with BMD, 36 with FSHD, 46 with LGMD, and 11 with EDMD, were evaluated. RESULTS: The characteristic profiles of serum enzymes facilitated differentiation of these five types of MD. DMD was characterized by simultaneous elevation of ALT, AST, LDH, and ALP; BMD and LGMD were characterized by elevation of ALT, AST, and LDH; and FSHD and EDMD were characterized by a lack of abnormal serum enzyme levels. We further developed discriminant functions to distinguish BMD and LGMD. For LGMD, LGMD2B patients had significantly higher ALP levels than non-LGMD2B patients (98 ± 59 U/L versus 45 ± 9 U/L, resp., p < 0.05). CONCLUSIONS: Our approach enabled the determination of MD subtypes using serum enzyme profiles prior to genetic testing, which will increase the chance a mutation will be found in the first gene analyzed.

Serum creatinine level: a supplemental index to distinguish Duchenne muscular dystrophy from Becker muscular dystrophy.

BACKGROUND: To improve assessment of dystrophinopathy, the aim of this study was to identify whether serum creatinine (Crn) level reflects disease severity. METHODS: Biochemical, Vignos score, and genetic data were collected on 212 boys with dystrophinopathy. RESULTS: Serum Crn level had a strong inverse correlation with Vignos score by simple correlation (r = -0.793) and partial correlation analysis after adjustment for age, height, and weight (r = -0.791; both P < 0.01). Serum Crn level was significantly higher in patients with in-frame than out-of-frame mutations (Z = -4.716, P < 0.01) and in Becker muscular dystrophy (BMD) patients than Duchenne muscular dystrophy (DMD) patients at ages 4, 5, 7, and 9 yr (all P < 0.0125). After adjusting for age, height, and weight, BMD patients still had a significantly higher serum Crn level than DMD patients (ß = 7.140, t = 6.277, P < 0.01). CONCLUSIONS: Serum Crn level reflected disease severity and may serve as a supplemental index to distinguish DMD from BMD in clinical practice.