scholarly journals Growth differentiation factor 15 increases in both cerebrospinal fluid and serum during pregnancy

2021 ◽  
Author(s):  
Ulrika Andersson-Hall ◽  
Pernilla Svedin ◽  
Carina Mallard ◽  
Kaj Blennow ◽  
Henrik Zetterberg ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Cell Function ◽  
Physiological State ◽  
Elective Caesarean Section ◽  
Serum Levels ◽  
Model Assessment ◽  
Female Fetus ◽  
Growth Differentiation Factor 15 ◽  
Differentiation Factor ◽  
Pregnant State

AbstractAimGrowth differentiation factor 15 (GDF15) increases in serum during pregnancy to levels not seen in any other physiological state and is suggested to be involved in pregnancy-induced nausea, weight regulation and glucose metabolism. The main action of GDF15 is regulated through a receptor of the brainstem, i.e., through exposure of GDF15 in both blood and cerebrospinal fluid (CSF). The aim of the current study was to measure GDF15 in both CSF and serum during pregnancy, and to compare it longitudinally to non-pregnant levels.MethodsWomen were sampled at elective caesarean section (n=45, BMI=28.1±5.0) and were followed up 5 years after pregnancy (n=25). GDF15, insulin and leptin were measured in CSF and serum. In addition, glucose, adiponectin and Hs-CRP were measured in blood.ResultsGDF15 levels were higher during pregnancy compared with follow-up in both CSF (385±128 vs. 115±32 ng/l, p<0.001) and serum (73789±29198 vs. 404±102 ng/l, p<0.001). CSF levels correlated with serum levels during pregnancy (p<0.001), but not in the non-pregnant state (p=0.98). Both CSF and serum GDF15 were highest in women carrying a female fetus (p<0.001), previously linked to pregnancy-induced nausea. Serum GDF15 correlated with the homeostatic model assessment for beta-cell function and placental weight, and CSF GDF15 correlated inversely with CSF insulin levels.ConclusionThis, the first study to measure CSF GDF15 during pregnancy, demonstrated increased GDF15 levels in both serum and CSF during pregnancy. The results suggest that effects of GDF15 during pregnancy can be mediated by increases in both CSF and serum levels.

scholarly journals Growth differentiation factor 15 increases in both cerebrospinal fluid and serum during pregnancy

PLoS ONE ◽  
2021 ◽  
Vol 16 (5) ◽  
pp. e0248980
Author(s):  
Ulrika Andersson-Hall ◽  
Pernilla Svedin ◽  
Carina Mallard ◽  
Kaj Blennow ◽  
Henrik Zetterberg ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Cell Function ◽  
Physiological State ◽  
Elective Caesarean Section ◽  
Serum Levels ◽  
Model Assessment ◽  
Female Fetus ◽  
Growth Differentiation Factor 15 ◽  
Differentiation Factor ◽  
Pregnant State

Aim Growth differentiation factor 15 (GDF15) increases in serum during pregnancy to levels not seen in any other physiological state and is suggested to be involved in pregnancy-induced nausea, weight regulation and glucose metabolism. The main action of GDF15 is regulated through a receptor of the brainstem, i.e., through exposure of GDF15 in both blood and cerebrospinal fluid (CSF). The aim of the current study was to measure GDF15 in both CSF and serum during pregnancy, and to compare it longitudinally to non-pregnant levels. Methods Women were sampled at elective caesarean section (n = 45, BMI = 28.1±5.0) and were followed up 5 years after pregnancy (n = 25). GDF15, insulin and leptin were measured in CSF and serum. Additional measurements included plasma glucose, and serum adiponectin and Hs-CRP. Results GDF15 levels were higher during pregnancy compared with follow-up in both CSF (385±128 vs. 115±32 ng/l, P<0.001) and serum (73789±29198 vs. 404±102 ng/l, P<0.001). CSF levels correlated with serum levels during pregnancy (P<0.001), but not in the non-pregnant state (P = 0.98). Both CSF and serum GDF15 were highest in women carrying a female fetus (P<0.001). Serum GDF15 correlated with the homeostatic model assessment for beta-cell function and placental weight, and CSF GDF15 correlated inversely with CSF insulin levels. Conclusion This, the first study to measure CSF GDF15 during pregnancy, demonstrated increased GDF15 levels in both serum and CSF during pregnancy. The results suggest that effects of GDF15 during pregnancy can be mediated by increases in both CSF and serum levels.

Decreased Serum Growth Differentiation Factor 15 Levels After Lifestyle Intervention in Patients With Newly Diagnosed Type 2 Diabetes Mellitus

2020 ◽  
Author(s):  
Xingxing He ◽  
Jiaorong Su ◽  
Xiaojing Ma ◽  
Jingyi Lu ◽  
Yufei Wang ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Lifestyle Intervention ◽  
Enzyme Linked Immunosorbent Assay ◽  
Oral Glucose ◽  
Model Assessment ◽  
Newly Diagnosed ◽  
Serum Samples ◽  
Growth Differentiation Factor 15 ◽  
Differentiation Factor

Abstract Background: Recent studies noted that circulating growth differentiation factor 15 (GDF15) were closely related to metabolic states. The study aimed to explore the changes of GDF15 levels and their influencing factors after 4 weeks of lifestyle intervention (LI) or LI combined with breakfast meal replacement (LI+MR) in newly diagnosed type 2 diabetes patients. Methods: A total of 84 patients with available serum samples at both baseline and Week 4 were enrolled in this biomarker substudy. All subjects underwent a 2-hour 75g oral glucose tolerance test at baseline and Week 4. Serum GDF15 levels were determined by a sandwich enzyme-linked immunosorbent assay. Results: After 4-weeks of LI, GDF15 levels overall significantly decreased compared with baseline (P<0.05). ∆GDF15 levels were significantly and negatively associated with baseline GDF15 levels (r=–0.450, P<0.001). The optimal cut-off point of baseline GDF15 levels for predicting a GDF15 decrease after 4-weeks of LI was 904.57 pg/ml, with an area under curve of 0.699. Based on the cut-off point of 900 pg/ml, patients with baseline GDF15 ≥900 pg/ml had significantly decreased GDF15 levels after LI, while those <900 pg/ml had no significant changes. Regression models showed that baseline GDF15 level was an independent positive factor for the improvement of fasting plasma glucose and homeostasis model assessment for insulin resistance only in patients with baseline GDF15 levels ≥900 pg/ml. Conclusions: LI led to significantly decreased GDF15 levels among patients with newly diagnosed type 2 diabetes and its effect was more significant among patients with baseline GDF15 levels ≥900 pg/ml.Trial registration: ClinicalTrials.gov, NCT02248714. Registered 25 September 2014 - Retrospectively registered, https://www.clinicaltrials.gov/ct2/show/NCT02248714?term=NCT02248714&draw=2&rank=1

Abstract PO-001: Increased growth differentiation factor 15 serum levels in pancreatic cancer patients

2020 ◽  
Author(s):  
Veronica R. Placencio-Hickok ◽  
Arsen Osipov ◽  
Sejal Mehta ◽  
Subhash D. Katewa ◽  
Jiping Zha ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Patients ◽  
Serum Levels ◽  
Growth Differentiation Factor 15 ◽  
Differentiation Factor

scholarly journals Association between Circulating Growth Differentiation Factor 15 and Cirrhotic Primary Biliary Cholangitis

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Zhanyi Li ◽  
Yu Liu ◽  
Xiangyong Li ◽  
Yuankai Wu ◽  
Fangji Yang ◽  
...  
Keyword(s):  
Serum Levels ◽  
Response To Treatment ◽  
Primary Biliary Cholangitis ◽  
Strongly Correlated ◽  
Weight Changes ◽  
Adequate Treatment ◽  
Growth Differentiation Factor 15 ◽  
Reactive Protein ◽  
Differentiation Factor ◽  
End Stage

Primary biliary cholangitis (PBC) is a common condition that usually shows a progressive course towards cirrhosis without adequate treatment. Growth differentiation factor 15 (GDF15) plays multiple roles in various pathological conditions. The overall role of circulating GDF15 in cirrhotic PBC requires further investigation. Twenty patients with cirrhotic PBC, 26 with non-cirrhotic PBC, and 10 healthy subjects were enrolled between 2014 and 2018, and the serum levels of GDF15 were measured via enzyme immunoassay. The correlations between serum GDF15, weight, biochemical parameters, and the prognosis were analysed. Serum levels of GDF15 were significantly higher in cirrhotic PBC patients than in non-cirrhotic PBC patients or healthy controls ( p = 0.009 and p < 0.001 , respectively). The circulating GDF15 levels strongly correlated with weight changes ( r = − 0.541 , p = 0.0138 ), albumin ( r = − 0.775 , p < 0.0001 ), direct bilirubin ( r = − 0.786 , p < 0.0001 ), total bile acids ( r = 0.585 , p = 0.007 ), and C-reactive protein ( r = 0.718 , p = 0.0005 ). Moreover, circulating GDF15 levels strongly correlated with the Mayo risk score ( r = 0.685 , p = 0.0009 ) and Model for End-stage Liver Disease score ( r = 0.687 , p = 0.0008 ). Determined by the area under the receiver operating characteristic curves, the overall diagnostic accuracies of GDF15 were as follows: cirrhosis = 0.725 (>3646.55 pg/mL, sensitivity: 70.0%, specificity: 69.2%), decompensated   cirrhosis = 0.956 (>4073.30 pg/mL, sensitivity: 84.62%, specificity: 100%), and cirrhotic biochemical non-responders = 0.835 (>3479.20 pg/mL, sensitivity: 71.43%, specificity: 92.31%). GDF15 may be a useful and integrated biochemical marker to evaluate not only the disease severity and prognosis but also the nutrition and response to treatment of cirrhotic PBC patients, and its overall performance is satisfactory. Therapy targeting GDF15 is likely to benefit cirrhotic PBC patients and is worth further research.

scholarly journals Serum Levels of Growth Differentiation Factor-15 as an Inflammatory Marker in Patients with Unstable Angina Pectoris

2021 ◽  
Author(s):  
Fariba Raygan ◽  
Aniseh Etminan ◽  
Hanieh Mohammadi ◽  
Hossein Akbari ◽  
Hassan Nikoueinejad
Keyword(s):  
Angina Pectoris ◽  
Serum Level ◽  
Unstable Angina ◽  
Serum Levels ◽  
Unstable Angina Pectoris ◽  
Risk Scores ◽  
Growth Differentiation Factor 15 ◽  
Differentiation Factor ◽  
The Mean ◽  
And Control

Background: Growth differentiation factor-15 (GDF-15), a member of transforming growth factors, is a stress-responsive marker whose levels may significantly increase in response to pathological stresses associated with inflammatory tissue injuries such as unstable angina pectoris (USAP). This study evaluated the diagnostic value of GDF-15 in patients with USAP. Methods: The present cross-sectional study recruited 39 patients with USAP criteria and 30 patients with stable angina pectoris (SAP), referred to Shahid Beheshti Hospital, Kashan, Iran. All the patients with USAP had at least 1 coronary artery stenosis (>50%) in angiography. The control group comprised 42 healthy individuals. The serum levels of GDF-15 were measured in all the participants by ELISA. Also analyzed were the relationship between GDF-15 levels and thrombolysis in myocardial infarction (TIMI) and the Global Registry of Acute Coronary Events (GRACE) risk scores in the patients with USAP to determine the severity of the disease. Result: The study population consisted of 111 subjects, 62 women and 49 men, divided into 3 groups of USAP (n=39, mean age=60.07±14.10 y), SAP (n=30, mean age=67.56±9.88 y), and control (n=42, mean age=61.21±7.76 y). The mean serum level of GDF-15 in the USAP group was significantly different from the other 2 groups (P<0.001), while no significant difference was observed in this regard between the SAP and control groups (P=0.797). No correlation was found between the mean GDF-15 serum level and the GRACE (P=0.816) and TIMI (P=0.359) risk scores in the USAP group. Conclusion:  The mean serum level of GDF-15 exhibited a rise in our patients with USAP. GDF-15 may be a diagnostic biomarker of USAP and its severity.

scholarly journals Clinical and Tumor Characteristics of Patients with High Serum Levels of Growth Differentiation Factor 15 in Advanced Pancreatic Cancer

Cancers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 4842
Author(s):  
Hidetaka Suzuki ◽  
Shuichi Mitsunaga ◽  
Masafumi Ikeda ◽  
Takao Aoyama ◽  
Kazumi Yoshizawa ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Liver Metastasis ◽  
Group Performance ◽  
Performance Status ◽  
Advanced Pancreatic Cancer ◽  
Serum Levels ◽  
Pancreatic Disease ◽  
High Serum ◽  
Growth Differentiation Factor 15 ◽  
Differentiation Factor

We aimed to evaluate the association of circulating growth differentiation factor 15 (GDF-15) with cachexia symptoms and the biological activity of advanced pancreatic cancer (APC). Treatment-naïve patients with liver metastasis of APC or with benign pancreatic disease were retrospectively analyzed. Clinical data, blood samples, and biopsy specimens of liver metastasis were collected prior to anti-cancer treatment. Serum GDF-15 levels and multiple protein expressions in lysates extracted from liver metastasis were measured by enzyme-linked immuno-sorbent assay and reverse-phase protein array, respectively. The cut-off for serum GDF-15 was determined as 3356.6 pg/mL, the mean plus two standard deviations for benign pancreatic disease. The high-GDF-15 group was characterized as showing low Karnofsky performance status (KPS) (p = 0.037), poor Eastern Cooperative Oncology Group performance status (ECOG-PS) (p = 0.049), severe appetite loss (p = 0.011), and high serum levels of carbohydrate antigen 19-9 (p = 0.019) and C-reactive protein (p = 0.009). Tumors of the high-GDF-15 group expressed high levels of phosphorylated (p)JNK (p = 0.007) and pAkt (p = 0.040). APC patients with high serum GDF-15 showed signatures of cachexia and activation of the signaling pathways involving Akt and JNK in the tumor. This study indicated circulating GDF-15 could be associated with cachectic symptoms in APC.

High Levels of Growth Differentiation Factor 15 in Patients with Congenital Dyserythtopoietic Anemia Type I

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3456-3456
Author(s):  
Hannah Tamary ◽  
Hanna Shalev ◽  
Galit Avraham ◽  
Meira Zoldan ◽  
Itai Levi ◽  
...  
Keyword(s):  
Transferrin Receptor ◽  
Elevated Serum ◽  
Serum Levels ◽  
High Serum ◽  
Type I ◽  
Soluble Transferrin Receptor ◽  
Ineffective Erythropoiesis ◽  
Growth Differentiation Factor 15 ◽  
Differentiation Factor ◽  
A Minor

Abstract Growth differentiation factor 15 (GDF15) is a member of the TGF-beta superfamily of cytokines previously found to suppress hepcidin in primary human hepatocytes. GDF15 is secreted from human erythroblasts, and extremely high serum levels are present in β-thalassemia patients (Tanno et al., Nat. Med. 2007, 13, 1096–1101). To determine if elevated GDF15 levels are unique for thalassemia or more generally associated with iron-loading related to ineffective erythropoiesis, we determined the GDF15 levels, as well as, serum hepcidin (Swinkels DW et al, PLoS ONE PLoS ONE. 2008;3:e2706), ferritin, erythropoietin (EPO) and soluble transferrin receptor (sTfR) in patients with the congenital dyserythropoietic anemia type I (CDA I). Seventeen Israeli Bedouins with CDA I were studied, all homozygous for the founder R1040W mutation in the CDAN1 gene. All of the patients studied were young adults with a mean age of 29 years. Two patients previously underwent splenectomy, and one patient is currently transfusion-dependent. For comparison, ten healthy volunteers (HV) were studied. The mean level of GDF15 in CDA I patients was significantly elevated [10,239 ± 3,049 pg/ml (range 5,530–17,008) compared to 269 ± 238 pg/ml in healthy controls; p = 1.5×10−10]. Consistent with a previous study of dyserythropoietic anemia patients, significantly higher levels of soluble transferrin receptor were detected among the CDA I population (sTfR; CDA I, 86.4 ± 14.0 nmol/L; HV, 21.4 ± 6.2 nmol/L, p = 7.4×10−15). Serum EPO levels were also elevated (EPO; CDA I, 118 ± 59 IU/dL; HV, 2.0 ± 1.5 IU/dL, p = 2.3×10−7). For iron analyses, three patients with extensive transfusion histories were excluded. Among the remaining 14 patients, iron overload was demonstrated by elevated serum ferritin (CDA I, 916 ± 507 ng/ml; HV, 72 ± 60 ng/ml, p = 1.4×10−5). Despite the significant elevation in iron stores, significantly elevated levels of hepcidin 25 (Hep25) were not detected in the CDA I patients. Instead, a minor decrease in serum Hep25 levels were detected (Hep25; CDA I, 3.3 ± 2.8 nM; HV, 4.1 ± 3.0 nM, p = 0.27). Correlation analyses were performed between the iron parameters (Ferritin and Hep25) and GDF15, sTfR, or EPO levels. Only GDF15 demonstrated a significant positive correlation with ferritin and significant inverse correlations with Hep25 and the Hep25/Ferritin ratio. Weaker correlations with EPO were identified. Unexpectedly, the correlation trends for sTfR were opposite those of GDF15 in this group. These results demonstrate that GDF15 is immensely over-expressed in CDA I, and further suggest this cytokine contributes to hepcidin dysregulation and secondary hemochromatosis in humans with ineffective erythropoiesis.

scholarly journals Growth differentiation factor 15 predicts future insulin resistance and impaired glucose control in obese nondiabetic individuals: results from the XENDOS trial

2012 ◽  
Vol 167 (5) ◽  
pp. 671-678 ◽  
Author(s):  
Tibor Kempf ◽  
Anja Guba-Quint ◽  
Jarl Torgerson ◽  
Maria Chiara Magnone ◽  
Carolina Haefliger ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Body Weight ◽  
Glucose Control ◽  
Univariate Analysis ◽  
Model Assessment ◽  
Waist To Hip Ratio ◽  
Growth Differentiation Factor 15 ◽  
Differentiation Factor ◽  
Unit Increase ◽  
Design And Methods

Objective Growth differentiation factor-15 (GDF-15) is a stress-responsive cytokine that is increased in obesity and established type 2 diabetes. We assessed whether GDF-15 can predict future insulin resistance and impaired glucose control in obese nondiabetic individuals. Design and methods Plasma GDF-15 concentrations were measured with an automated electrochemiluminescent immunoassay at baseline and after 4 years in 496 obese nondiabetic individuals (52% men, median age 48 years, median body mass index (BMI) 37.6 kg/m2) enrolled in the XENical in the prevention of Diabetes in Obese subjects (XENDOS) trial. Results The median GDF-15 concentration at baseline was 869 ng/l (interquartile range 723–1064 ng/l). GDF-15 was related to body weight, BMI, waist-to-hip ratio, and insulin resistance (homeostasis model assessment of insulin resistance (HOMA-IR)) (all P<0.01). Changes in GDF-15 from baseline to 4 years were related to changes in body weight, BMI, waist-to-hip ratio, and HOMA-IR (all P<0.05). Baseline GDF-15 was associated with the risk to have prediabetes or diabetes at 4 years by univariate analysis (odds ratio (OR) for 1 unit increase in ln GDF-15, 3.2; 95% confidence interval (CI): 1.7–6.1; P<0.001), and after multivariate adjustment for age, gender, treatment allocation (orlistat vs placebo), BMI, waist-to-hip ratio, and glucose control at baseline (OR 2.2; 95% CI: 1.1–4.7; P=0.026). Similarly, baseline GDF-15 was independently associated with HOMA-IR at 4 years (P=0.024). Conclusions This first longitudinal study of GDF-15 in a large cohort of obese individuals indicates that GDF-15 is related to abdominal obesity and insulin resistance and independently associated with future insulin resistance and abnormal glucose control.

Sign in / Sign up

Export Citation Format

Share Document