Discovery of Novel Proteomic Biomarkers for the Prediction of Kidney Recovery from Dialysis-Dependent AKI Patients

Background: Acute kidney injury requiring dialysis (AKI-D) is associated with prolonged hospitalization, mortality, and progressive chronic kidney disease (CKD) among survivors. Previous studies have examined only select urine or serum biomarkers for predicting kidney recovery from AKI. Methods: Serum samples collected on day 8 of randomized renal replacement therapy from 72 patients enrolled in the Veteran's Affairs/National Institutes of Health Acute Renal Failure Trial Network study were analyzed by the SOMAscan proteomic platform to profile 1305 proteins in each sample. Of these patients, 38 recovered kidney function and dialysis was discontinued, while another 34 patients remained on dialysis by day 28. Results: Differential serum levels of 119 proteins, with 53 higher and 66 lower, were detected in samples from patients who discontinued dialysis compared to patients who remained on dialysis by day 28. Patients were classified into tertiles based on SOMAscan protein measurements for the 25 proteins most differentially expressed. The association of serum levels of each protein with kidney recovery was further evaluated using logistic regression analysis. Higher serum levels of CXCL11, CXCL2/CXCL3, CD86, Wnt-7a, BTK, c-Myc, TIMP-3, CCL5, ghrelin, PDGF-C, survivin, CA2, IL-9, EGF, and neuregulin-1, and lower levels of soluble CXCL16, IL1RL1, stanniocalcin-1, IL-6, and FGF23 when classified in tertiles, were significantly associated with better kidney recovery. This significant association persisted for each of these proteins after adjusting for potential confounding risk factors including age, gender, cardiovascular SOFA score, congestive heart failure, diabetes, modality of intensive dialysis treatment, cause of AKI, baseline serum creatinine, day-8 urine volume, and estimated 60-day mortality risk. Conclusions: These results suggest concerted changes between survival-related proteins and immune-regulatory chemokines in regulating angiogenesis, endothelial and epithelial remodeling, and kidney cell regeneration, illustrating potential mechanisms of kidney recovery. Thus, this study identifies potential novel predictive biomarkers of kidney recovery in AKI-D patients.

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Interleukin-6, Hepcidin, and Other Biomarkers in Anemia of Chronic Disease (ACD) and Chemotherapy-Induced Anemia (CIA): Potential Therapeutic Targets.

Blood ◽

10.1182/blood.v120.21.2086.2086 ◽

2012 ◽

Vol 120 (21) ◽

pp. 2086-2086 ◽

Cited By ~ 1

Author(s):

Saroj Vadhan-Raj ◽

Xiao Zhou ◽

Carlos E. Bueso-Ramos ◽

Shreyaskumar Patel ◽

Robert S Benjamin ◽

...

Keyword(s):

Chronic Disease ◽

Inflammatory Cytokines ◽

Linear Regression Analysis ◽

Transferrin Saturation ◽

Serum Levels ◽

Serum Samples ◽

Anemia Of Chronic Disease ◽

Baseline Serum ◽

Tnf Α ◽

Pro Inflammatory Cytokines

Abstract Abstract 2086 Background: Anemia in patients with malignancies can be multifactorial including anemia of chronic disease (ACD), also known as anemia of inflammation (AI), and chemotherapy (CT)-induced anemia (CIA) from myelosuppression. Although, exact mechanism for ACD is not known, induction of hepcidin, a key iron-regulatory hormone, by Interleukin (IL)-6 and other pro-inflammatory cytokines with resulting hypoferremia and limitation of iron supply to the bone marrow appear to be major contributors to pathogenesis of anemia. Hepcidin reduces iron levels by inducing degradation of the cellular iron exporter, ferroportin. The objective of this study was to examine the levels of various cytokines/regulators that may play role in ACD. Methods: Chemo-naïve patients with sarcoma scheduled to initiate first-line doxorubicin-based chemotherapy had blood samples drawn at baseline, and following chemotherapy (post cycles1, 3 and 6) for analysis of pro-inflammatory cytokines/other biomarkers of anemia. Serum samples were analyzed for IL-1β, IL-6, TNF-α, Hepcidin, hemojuvelin, ferroportin, soluble transferrin receptor (sTFR), and C-reactive protein (CRP) using ELISA techniques (R&D Diagnostics, Uscn Life Science Inc, or Abnova). Correlations between these biomarkers and Hgb levels at baseline and during the study period were calculated by linear regression analysis (SAS 9.2). Results: Of the 49 patients enrolled on to the clinical trial, there were 26 (53%) women and 23 (47%) men, with median age 45 years (range 19–65 years). Twenty-five percent of the patients had Hgb less than 12g/dL (range, 8.9–15.9 g/dL) prior to CT. At baseline, 50% of the pts had hypoferremia with low serum iron and transferrin saturation <20%. Baseline serum levels of IL-6 (r= −0.73, p<0.0001), hepcidin (r= −0.46, p=0.005), CRP (r= −0.46, p=0.003), sTFR (r= −0.32, p=0.064) inversely correlated with hemoglobin levels prior to CT, supporting their role in ACD. During CT (median 4, range; 1–6 cycles), Hgb declined in all pts with 55% requiring PRBC transfusions (77% of pts starting with baseline Hgb < 12 g/dL vs 47% of pts with baseline Hgb > 12 g/dL). Interestingly, as shown below, Hepcidin, IL-6, and sTFR all significantly negatively correlated with Hgb levels during CT. No significant correlation was found for IL-1β, TNF-α, ferroportin, or hemojuvelin levels with Hgb. Conclusions: IL-6 and Hepcidin pathway appears to play an important role in anemia in cancer patients before and during CT. Treatment with novel agents targeting this pathway may provide effective strategies for prevention and treatment of ACD and CIA. Disclosures: Vadhan-Raj: JNJ: Research Funding.

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Correlation of lactate dehydrogenase (LDH) isoenzyme profile with outcome in advanced colorectal cancer (CRC) patients (pts) treated with chemotherapy and bevacizumab (BEV) or cediranib (CED).

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.e13541 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. e13541-e13541

Author(s):

Jair Bar ◽

Stuart Spencer ◽

Shethah Morgan ◽

Laura Pike ◽

David Cunningham ◽

...

Keyword(s):

Predictive Biomarkers ◽

Progression Free Survival ◽

Predictive Biomarker ◽

Total Serum ◽

Serum Samples ◽

Baseline Serum ◽

Ldh Isoenzymes ◽

Hypoxic Conditions ◽

Ldh Isoenzyme ◽

Agarose Electrophoresis

e13541 Background: There is a clinical need for predictive biomarkers of efficacy of VEGF signaling inhibitors (VSIs). LDH is a tetramer that can include any combination of the M and H subunits. LDH4 and 5 isoenzymes are composed mostly of the M subunit and are more abundant in hypoxic conditions. We speculated that the levels of LDH isoenzymes in pts serum may correlate with outcome of pts treated with VSIs. HORIZON I trial enrolled pts that were randomized to mFOLFOX6 with BEV or CED. A retrospective exploratory analysis was performed on baseline serum samples of these pts. Methods: Total serum LDH was tested on fresh samples during the conduct of the trial. About 2 years after the trial, frozen samples stored at -70 degrees were tested for total serum LDH and LDH isoenzymes, measured by agarose electrophoresis and a colorimetric enzymatic assay. Relative levels of M and H subunits were derived based on the known structure of each isoenzyme. Progression free survival (PFS) and overall survival (OS) were compared by subgroups of total LDH and LDH isoenzyme levels. P values were not calculated for these exploratory analyses. Results: Baseline total LDH levels from fresh serum were available for 207 pts. Total and isoenzyme LDH levels were available for frozen serum samples of 189 pts. Total LDH in the frozen and fresh samples correlated (R=0.9). Distant isoenzymes (e.g. LDH1 and 5) were negatively correlated. High M/H subunits ratio correlated with poor OS (HR=1.804, 95%CI 1.24-2.620). A non-significant trend for better OS to CED-treated vs. BEV-treated pts was seen in pts with high M/H ratio (e.g., CED 30mg vs BEV HR=0.685, 95%CI 0.382-1.23). Conclusions: Evaluation of LDH isoenzymes is feasible using serum samples kept frozen for 2 years. A negative correlation is seen between hypoxic-related and oxic-related isoenzymes. In CRC pts treated with a VSI, LDH isoenzyme hypoxia-associated profile correlates with poorer outcome. LDH isoenzyme profile as a possible predictive biomarker for benefit from CED vs. BEV requires further investigation.

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Role of serum matrix metalloproteinase in the diagnosis of gastric cancer

Pakistan Journal of Medical Sciences ◽

10.12669/pjms.36.5.2059 ◽

2020 ◽

Vol 36 (5) ◽

Author(s):

Jian Liu ◽

Liya Zhou ◽

Sanren Lin ◽

Bei Yao

Keyword(s):

Gastric Cancer ◽

Matrix Metalloproteinase ◽

Serum Levels ◽

Gastric Disease ◽

Antibody Array ◽

Clinical Value ◽

Serum Samples ◽

Creative Commons ◽

Related Proteins

Objective: To determine the clinical value of a matrix metalloproteinase (MMP) antibody array in diagnosing gastric cancer (GC). Methods: In this prospective study, serum samples of patients with GC (n=66) and non-neoplastic gastric disease (NGD; n=34) were collected between November 2017 and July 2018. The quantitative measurement of 10 MMP-related proteins was done using MMP arrays and compared between the two groups. Results: The serum levels of MMPs 3, 8, 9 and tissue inhibitor of metalloproteinases (TIMPs) 1 and 2 were significantly higher in the GC group than in the NGD group (p<0.05). The area under curve (AUC) of the 10 MMP proteins for the diagnosis of GC varied between 0.500 and 0.658. The total AUC of all MMPs was 0.897 (95% CI: 0.837-0.957). The total AUC of the five MMPs (MMPs 3, 8, 9, and TIMPs 1 and 2) was 0.821 (95% CI: 0.733-0.909) for diagnosing GC. Also, the 10-factor and 5-factor predictive models had good diagnostic ability for early GC with an AUC of 0.865 (95% CI: 0.753-0.977) and 0.749 (95% CI: 0.600-0.898), respectively. Conclusions: The detection of multiple serum MMPs with protein biochip technology is promising to be used as a novel non-invasive tool for facilitating early diagnosis or screening of GC. doi: https://doi.org/10.12669/pjms.36.5.2059 How to cite this:Liu J, Zhou L, Lin S, Yao B. Role of serum matrix metalloproteinase in the diagnosis of gastric cancer. Pak J Med Sci. 2020;36(5):1025-1031. doi: https://doi.org/10.12669/pjms.36.5.2059 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Low Serum Levels of Myeloid Progenitor Inhibitory Factor-1 Predict Good Response to Methotrexate in Rheumatoid Arthritis

ISRN Inflammation ◽

10.1155/2013/460469 ◽

2013 ◽

Vol 2013 ◽

pp. 1-4 ◽

Cited By ~ 3

Author(s):

Varun Dhir ◽

Amit Sandhu ◽

Nidhi Gupta ◽

Veena Dhawan ◽

Shefali Sharma ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Disease Activity ◽

Predictive Biomarkers ◽

Serum Levels ◽

Inhibitory Factor ◽

Poor Responders ◽

Serum Samples ◽

Myeloid Progenitor ◽

Lower Baseline ◽

Inhibitory Factor 1

Background. Although the benchmark in the treatment of rheumatoid arthritis remains methotrexate, only 70% of patients respond. Thus, there is a need for predictive biomarkers. This study planned to evaluate serum levels of myeloid progenitor inhibitory factor-1 (MPIF-1) and monocyte chemoattractant protein 2 (MCP-2)—as biomarkers. Methods. Patients with rheumatoid arthritis (RA) having high disease activity (DAS28-3v ≥ 5.1) were treated with oral methotrexate (MTX) for 12 weeks. Disease activity was measured by DAS28-3v (Modified Disease Activity Score 3 variables). Serum samples were stored at baseline and 12 weeks. Results. This study included 46 patients (F : M = 35 : 11) having mean (±SD) age of 42.6 ± 11.3 yrs, disease duration of 4.7 ± 4.5 yrs, and DAS28-3v of 6.1 ± 0.8. Serum MPIF1 was elevated in patients compared to controls (1636.7 ± 1009.7, 441.2 ± 173.8 pg/mL, P<0.001), but there was no difference in MCP2 levels (31.4 ± 11.9, 33.8 ± 24.0 pg/mL). Baseline MPIF-1 level was lower in good responders (ΔDAS28-3v ≥ 1.2, N=9) compared to poor responders (ΔDAS28-3v < 0.6, N=27) (1171.0 ± 670.8, 1816.7 ± 1154.1 pg/mL, P=0.05). On ROC analysis, baseline MPIF1 performed reasonably to predict good response; that is, ΔDAS28-3v ≥ 1.2 (AUC 0.68, 95% CI 0.50–0.87). Conclusions. Lower baseline MPIF1 level predicted a good response to methotrexate at 12 weeks.

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A novel biomarker panel examining response to adjuvant pancreatic cancer therapy in RTOG 9704.

Journal of Clinical Oncology ◽

10.1200/jco.2014.32.3_suppl.176 ◽

2014 ◽

Vol 32 (3_suppl) ◽

pp. 176-176 ◽

Cited By ~ 2

Author(s):

Gregory M. Heestand ◽

James Don Murphy ◽

Jennifer Moughan ◽

William Regine ◽

Jia Luo ◽

...

Keyword(s):

Pancreatic Cancer ◽

Disease Free Survival ◽

High Sensitivity ◽

Serum Levels ◽

Proximity Ligation Assay ◽

P Value ◽

Serum Samples ◽

Multivariate Statistical ◽

Baseline Serum ◽

Clinical Endpoints

176 Background: RTOG 9704 was an adjuvant pancreatic adenocarcinoma trial. Patients with resected stage I-III disease were randomized to receive 5-FU vs. gemcitabine (GEM) chemotherapy pre and post 5-FU chemoradiation. Prior to adjuvant therapy, patients had baseline serum samples drawn and archived for future study. Methods: To better understand the biology of pancreatic cancer, investigators involved with this project have evaluated numerous proteins of interest via literature review and gene expression data. By using the multiplex capabilities and high sensitivity detection of the proximity ligation assay (PLA), a probe panel was built from commercially available antibodies capable of quantifying 42 key proteins from 24 uL of patient serum. To determine if any of these proteins corresponded with survival or predicted response, the baseline serum specimens were obtained for assay with our PLA panel. Clinical endpoints were overall (OS) and disease-free survival (DFS). Univariate and multivariate statistical techniques were used. Using a Bonferroni correction, a p-value of <0.0012 was considered statistically significant. Results: Of the 451 eligible patients, 213 had samples available for study – 112 (53%) in the 5-FU arm and 101 (47%) in the GEM arm. As expected, decreased levels of CEA and CA 19-9 were prognostic for improved OS in all patients. Low levels of matrix metalloproteinase-7 (MMP-7) predicted an OS benefit from adjuvant GEM, but not 5-FU. Conclusions: PLA is a powerful tool for identifying potential biomarkers from archived, small volume serum samples. These data suggest that pancreatic cancer patients with low MMP-7 serum levels were most likely to benefit from adjuvant GEM. Supported by RTOG grants U10 CA21661, CCOP grant U10 CA37422, and RTOG Biospecimen Resource grant U24 CA114734 from the National Cancer Institute. [Table: see text]

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Clinical Significance of Serum NEDD9 Levels in Patients with Pancreatic Cancer

Biomolecules ◽

10.3390/biom8040169 ◽

2018 ◽

Vol 8 (4) ◽

pp. 169 ◽

Cited By ~ 1

Author(s):

Cigdem Usul Afsar ◽

Mehmet Karabulut ◽

Senem Karabulut ◽

Safiye Tokgoz Ozal ◽

Murat Cikot ◽

...

Keyword(s):

Pancreatic Cancer ◽

Performance Status ◽

Progression Free Survival ◽

Serum Levels ◽

Enzyme Linked Immunosorbent Assay ◽

Control Group ◽

Serum Samples ◽

Baseline Serum ◽

Free Survival ◽

The Relationship

Introduction: Pancreatic cancer (PC) is a lethal malignancy. Various diagnostic, predictive, and prognostic biomarkers have been evaluated. This study was conducted to investigate the serum levels of neural precursor cell expressed developmentally downregulated protein 9 (NEDD9) in patients with PC and the relationship between tumor progression and known prognostic parameters. Materials and Methods: Serum samples were obtained on first admission before any treatment. Serum NEDD9 levels were determined using enzyme-linked immunosorbent assay (ELISA). Age- and sex-matched healthy controls were included in the analysis. Results: In a three year period, 32 patients with a pathologically-confirmed diagnosis of PC were enrolled in this study. The median age at diagnosis was 61 years, range 38 to 84 years; the majority of the patients in the group were men (n = 20, 62.5%). The tumor was located in the head of pancreas in 21 (65.6%) patients. Forty-one percent of 17 metastatic patients who received palliative CTx (chemotherapy) were CTx-responsive. The baseline serum NEDD9 levels were significantly higher in patients with PA than in the control group (p = 0.03). Median OS of the whole group were 27 ± 7.3 weeks. Alcohol intake, performance status, and LDH levels were found to be significant prognostic factors (p = 0.006, p < 0.001, and p < 0.001, respectively). However, serum NEDD9 levels had no significantly effect on progression free survival (PFS) and overall survival (OS) (p = 0.71 and p = 0.58, respectively). Conclusions: NEDD9 is identified as a secretory biomarker for PC but it has no prognostic role.

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Dexamethasone enhances the efficacy of atorvastatin in inhibiting excessively inflammation-induced abnormal angiogenesis by regulating macrophages

Journal of Neuroinflammation ◽

10.1186/s12974-021-02257-1 ◽

2021 ◽

Vol 18 (1) ◽

Author(s):

Zhitao Gong ◽

Daqiang Zhan ◽

Meng Nie ◽

Xiaochun Li ◽

Chuang Gao ◽

...

Keyword(s):

Combined Therapy ◽

Serum Levels ◽

Chronic Subdural Haematoma ◽

High Dose ◽

Serum Samples ◽

Drug Treatments ◽

Anti Inflammatory ◽

Underlying Mechanisms ◽

Related Proteins ◽

First Time

Abstract Background We have recently showed that atorvastatin (ATO) combined with low dose of dexamethasone (DEX) was more efficacious in treating patients with chronic subdural haematoma (CSDH) than ATO monotherapy. This study was designed to investigate the underlying mechanisms of the improved efficacy of this combined therapy. Methods Mass spectrometry was performed to quantitatively detect drugs in haematoma fluids and serum samples from CSDH patients and also in cultured macrophages after treatment with either ATO alone or in combination with DEX. The differentiation and apoptosis of macrophages were evaluated using flow cytometry. The expression of cytokines, chemokines and angiogenesis-related proteins was evaluated using proteome profile arrays, immunoblots and ELISA, respectively. Results ATO was detected in haematoma fluids and serum samples, whose levels were increased significantly in samples collected from patients treated with both ATO and DEX. ATO was also increased in cultured macrophages treated with ATO and DEX. The numbers of M1-polarized macrophages were higher than the M2 phenotype in the haematoma fluids of patients. Cultured macrophages treated with ATO and DEX had reduced numbers of M1-polarized macrophages, increased numbers of M2-polarized macrophages as compared to monotherapies, and decreased rate of apoptosis induced by high-dose DEX. DEX enhanced the anti-inflammatory and anti-angiogenic activity of ATO by suppressing VEGFA and other inflammatory angiogenic factors. Consistent with the finding, patients responded well to the drug treatments had lower serum levels of VEGFA. Conclusions We have shown for the first time that ATO given orally was detected in CSDH haematoma fluids. DEX enhances the anti-inflammatory and anti-angiogenic effects of ATO, primarily by increasing the presence of ATO in haematoma and macrophages and by regulating the functions of macrophages.

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Serum Levels Of CD178 (Soluble FasL) Predict Treatment Response and Survival In Chronic Lymphocytic Leukaemia (CLL)

Blood ◽

10.1182/blood.v122.21.2866.2866 ◽

2013 ◽

Vol 122 (21) ◽

pp. 2866-2866

Author(s):

Peter Mollee ◽

Melinda Burgess ◽

Nigel McMillan ◽

Nicholas Saunders ◽

Catherine Cheung ◽

...

Keyword(s):

Critical Role ◽

Serum Levels ◽

Response To Therapy ◽

Clinical Feature ◽

Study Group ◽

Serum Samples ◽

Baseline Serum ◽

Cytokines And Chemokines ◽

Soluble Fasl

Abstract Background CLL cells have prolonged survival in vivo, but rapidly undergo apoptosis when cultured ex vivo indicating the importance of the tumour microenvironment in resistance to apoptosis. Chemokines and their receptors have been identified as playing a critical role in the CLL microenvironment and we have previously identified CCL2, CXCL2, IL-6 and IL-8 as pro-survival factors in our in vitro long-term CLL culture model. We examined the in vivo significance of these and other chemokines by examining serum levels in a cohort of uniformly treated patients with CLL. Methods Serum samples were collected from 32 Australian patients participating in the German CLL Study Group CLL8 trial prior to treatment and were assessed for circulation levels of several cytokines and chemokines. Serum samples from 7 age matched healthy donors were used as controls. Serum concentration of CCL21, CXCL12, CXCL13, CCL19 and CXCL2 were examined using enzyme-linked immunosorbent assays (ELISA) and levels of CCL2, CCL3, CCL4, sCD54, sCD178, IL6 and IL-8 were examined using flex sets of BD Cytometric Bead Arrays System. Levels of these cytokines and chemokines were compared both to the healthy donor control samples and correlated with known prognostic and clinical factors. The levels were also evaluated in respect to response to therapy, progression-free survival (PFS) and overall survival (OS). Results 32 patients were studied: median age 62yrs, 84% male, Binet stage B 63%, stage C 37%. 15 received FCR and 17 FC with a median PFS of 45 months and median OS not reached. Compared to controls, patients with CLL had significantly higher serum levels of CXCL13 (117pg/ml vs 15pg/ml, p=0.0001), CCL3 (273pg/ml vs 103pg/ml, p=0.0007), CCL4 (13pg/ml vs 0pg/ml, p=0.0057), CD178 (45pg/ml vs 26pg/ml, p=0.01) and IL-6 (5pg/ml vs 0, p=0.02) and significantly lower levels of CXCL12 (803pg/ml vs 1177pg/ml, p=0.003) and sCD154 (345pg/ml vs 2121pg/ml p=0.0004). CCL2 levels did not correlate with any baseline clinical feature, response to therapy, PFS or OS. CXCL2 levels reduced with more advanced Rai stage disease (p=0.0083) but did not predict PFS or OS. CD178 levels did not correlate with any baseline clinical feature but predicted response to therapy with lower levels predicting improved response (p=0.04). Higher CD178 also strongly predicted worse PFS (HR 1.026, p<0.001) and OS (HR 1.02, p=0.018), a consistent effect whether treated with FC (HR 1.023, p=0.024) or FCR (HR 1.026, p=0.026). No other chemokine levels predicted PFS. Conclusion Baseline serum levels of CD178 (soluble FasL) may be a useful predictor of response to therapy and outcome in CLL. Further studies to confirm these findings and to define the biological mechanism of FasL overexpression and function are required. Acknowledgments We thank the German CLL Study Group and Roche for access to patient samples and data from the CLL8 study, and the Leukaemia Foundation of Australia for grant support. Disclosures: Mollee: Roche Australia: Sponsorship for attending ICML Lugano 2013 Other.

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The Predictive Value of miR-16, -29a and -134 for Early Identification of Gestational Diabetes: A Nested Analysis of the DALI Cohort

Cells ◽

10.3390/cells10010170 ◽

2021 ◽

Vol 10 (1) ◽

pp. 170 ◽

Cited By ~ 1

Author(s):

Anja Sørensen ◽

Mireille van Poppel ◽

Gernot Desoye ◽

Peter Damm ◽

David Simmons ◽

...

Keyword(s):

Gestational Diabetes ◽

Early Identification ◽

Perinatal Outcomes ◽

Predictive Biomarkers ◽

Normal Glucose Tolerance ◽

Serum Samples ◽

Baseline Serum ◽

Individual Mirnas ◽

Normal Glucose ◽

Nested Case Control

Early identification of gestational diabetes mellitus (GDM) aims to reduce the risk of adverse maternal and perinatal outcomes. Currently, no circulating biomarker has proven clinically useful for accurate prediction of GDM. In this study, we tested if a panel of small non-coding circulating RNAs could improve early prediction of GDM. We performed a nested case-control study of participants from the European multicenter ‘Vitamin D and lifestyle intervention for GDM prevention (DALI)’ trial using serum samples from obese pregnant women (BMI ≥ 29 kg/m2) entailing 82 GDM cases (early- and late- GDM), and 41 age- and BMI-matched women with normal glucose tolerance (NGT) throughout pregnancy (controls). Anthropometric, clinical and biochemical characteristics were obtained at baseline (<20 weeks of gestation) and throughout gestation. Baseline serum microRNAs (miRNAs) were measured using quantitative real time PCR (qPCR). Elevated miR-16-5p, -29a-3p, and -134-5p levels were observed in women, who were NGT at baseline and later developed GDM, compared with controls who remained NGT. A combination of the three miRNAs could distinguish later GDM from NGT cases (AUC 0.717, p = 0.001, compared with fasting plasma glucose (AUC 0.687, p = 0.004)) as evaluated by area under the curves (AUCs) using Receiver Operator Characteristics (ROC) analysis. Elevated levels of individual miRNAs or a combination hereof were associated with higher odds ratios of GDM. Conclusively, circulating miRNAs early in pregnancy could serve as valuable predictive biomarkers of GDM.

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386-P: Acute Hypoglycemia Does Not Alter Serum Levels of Amyloid-Related Proteins Associated with Dementia

Diabetes ◽

10.2337/db20-386-p ◽

2020 ◽

Vol 69 (Supplement 1) ◽

pp. 386-P

Author(s):

ABU MOIN ◽

THOZHUKAT SATHYAPALAN ◽

STEPHEN ATKIN ◽

ALEXANDRA E. BUTLER

Keyword(s):

Serum Levels ◽

Acute Hypoglycemia ◽

Related Proteins

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