Journal ArticleDOI
GDF15 reflects beta cell function in obese patients independently of the grade of impairment of glucose metabolism.
Marie Helene Schernthaner-Reiter,Bianca K. Itariu,Michael Krebs,Miriam Promintzer-Schifferl,Thomas M. Stulnig,Andrea Tura,Christian Anderwald,Martin Clodi,Bernhard Ludvik,Giovanni Pacini,Anton Luger,Greisa Vila +11 more
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TLDR
It is concluded that in patients with severe obesity, GDF15 strongly relates to beta cell function and should be further investigated as a potential therapeutic target and biomarker guiding treatment options.Abstract:
Background and aims Growth differentiation factor 15 (GDF15) is a strong predictor of cardiovascular morbidity and mortality found to be both marker and target of impaired glucose metabolism. GDF15 increases following glucose administration and is up-regulated in obesity and diabetes. We investigate here the relationship between GDF15 and beta cell function. Methods and results In this cross-sectional study we evaluated GDF15 concentrations in 160 obese subjects (BMI 35–63 kg/m2, age 39.4 ± 18.6 years, m/f 38/122) who underwent a 75 g oral glucose tolerance test (OGTT). Based on the OGTT results, the cohort was divided into two groups: 1) normal fasting glucose and normal glucose tolerance (n = 80), 2) impaired fasting glucose, impaired glucose tolerance or type 2 diabetes (n = 80). The relationship of GDF15 to fasting and OGTT-based dynamic insulin sensitivity and insulin secretion parameters was evaluated. GDF15 was higher in the prediabetes and diabetes groups and correlated with HbA1c, glucose, insulin as well as baseline and dynamic indices of insulin sensitivity and estimated beta cell function. Multiple regression analysis revealed that age, waist-to-height ratio, glomerular filtration rate and prehepatic beta cell function, but not the grade of impairment of glucose metabolism, were independent predictors of GDF15. Subgroup analysis showed that of all parameters of glucose metabolism only C-peptide, fasting prehepatic beta cell function and insulinogenic index remained significantly related to GDF15 in both groups. Conclusion We conclude that in patients with severe obesity, GDF15 strongly relates to beta cell function and should be further investigated as a potential therapeutic target and biomarker guiding treatment options.read more
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Journal ArticleDOI
GDF15: emerging biology and therapeutic applications for obesity and cardiometabolic disease.
Dongdong Wang,Emily A. Day,Logan K Townsend,Djordje Djordjevic,Sebastian Beck Jørgensen,Gregory R. Steinberg +5 more
TL;DR: Growth differentiation factor 15 (GDF15) is a member of the TGFβ superfamily whose expression is increased in response to cellular stress and disease as well as by metformin this article.
Journal ArticleDOI
The clinical impact of growth differentiation factor-15 in heart disease: A 2019 update
Maria Arkoumani,Maria Arkoumani,Nektaria Papadopoulou-Marketou,Nektaria Papadopoulou-Marketou,Nicolas C. Nicolaides,Christina Kanaka-Gantenbein,Nikolaos Tentolouris,Ioannis Papassotiriou +7 more
TL;DR: GDF-15 can be used as a marker of prognosis in patients with cardiovascular disorders, in combination with conventional prognostic factors, such as N-terminal pro B-type natriuretic peptide (NT-proBNP) and high-sensitivity troponin T (hs-TnT).
Journal ArticleDOI
Circulating Cardiac Biomarkers in Diabetes Mellitus: A New Dawn for Risk Stratification—A Narrative Review
TL;DR: It was found that NPs and hs-cTnT are still the most important tools that have an affordable price as well as high sensitivity and specificity to predict clinical outcomes among patients with pre-DM and DM in routine clinical practice, but other circulating biomarkers need to be carefully investigated in large trials in the future.
Journal ArticleDOI
Pathophysiological role of growth differentiation factor 15 (GDF15) in obesity, cancer, and cachexia
TL;DR: Growth differentiation factor 15 or macrophage inhibitory cytokine-1 (GDF15/MIC-1) is a divergent member of the transforming growth factor β superfamily and has diverse pathophysiological roles in cancers, cardiometabolic disorders, and other diseases as discussed by the authors .
Journal ArticleDOI
Pathophysiological role of growth differentiation factor 15 (GDF15) in obesity, cancer, and cachexia.
Jawed A. Siddiqui,Ramesh Pothuraju,Parvez Khan,Gunjan Sharma,Sakthivel Muniyan,Parthasarathy Seshacharyulu,Maneesh Jain,Mohd W. Nasser,Surinder K. Batra,Surinder K. Batra +9 more
TL;DR: Growth differentiation factor 15 or macrophage inhibitory cytokine-1 (GDF15/MIC-1) is a divergent member of the transforming growth factor β superfamily and has a diverse pathophysiological roles in cancers, cardiometabolic disorders, and other diseases as discussed by the authors.
References
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Journal ArticleDOI
MIC-1, a novel macrophage inhibitory cytokine, is a divergent member of the TGF-β superfamily
Michelle Bootcov,Asne R. Bauskin,Stella M. Valenzuela,Anthony G. Moore,Mohinder Bansal,Xiao Yan He,Hong Ping Zhang,Melissa Donnellan,Stephen M. Mahler,Kimberley Pryor,Bradley J. Walsh,Richard C. Nicholson,W. Douglas Fairlie,S B Por,Joan M. Robbins,Samuel N. Breit +15 more
TL;DR: Purified recombinant MIC-1 is able to inhibit lipopolysaccharide -induced macrophage TNF-alpha production, suggesting that MIC- 1 acts in macrophages as an autocrine regulatory molecule.
Journal ArticleDOI
A Model-Based Method for Assessing Insulin Sensitivity From the Oral Glucose Tolerance Test
TL;DR: A glucose-insulin model was used to derive an OGTT-based IS (oral glucose insulin sensitivity [OGIS]) index, which predicts glucose clearance in a glucose clamp and yielded results similar to Cl CLAMP and fully consistent with established physiological principles.
Journal ArticleDOI
GFRAL is the receptor for GDF15 and is required for the anti-obesity effects of the ligand
Linda Yang,Chih-Chuan Chang,Zhe Sun,Dennis Madsen,Haisun Zhu,Søren Berg Padkjær,Xiaoai Wu,Tao Huang,Karin Hultman,Sarah J Paulsen,Jishu Wang,Anne Bugge,Jane Boesen Frantzen,Per Nørgaard,Jacob Jeppesen,Zhiru Yang,Anna Secher,Haibin Chen,Xun Li,Linu M. John,Bing Shan,Zhenhua He,Xiang Gao,Jing Su,Kristian Tage Hansen,Wei Yang,Sebastian Beck Jørgensen +26 more
TL;DR: It is shown that GDF15 binds specifically to GDNF family receptor α-like (GFRAL) with high affinity, and that GFRAL requires association with the coreceptor RET to elicit intracellular signaling in response to GDF 15 stimulation.
Journal ArticleDOI
The metabolic effects of GDF15 are mediated by the orphan receptor GFRAL
Paul J. Emmerson,Feng Wang,Yong Du,Qian Liu,Richard Todd Pickard,Malgorzata Donata Gonciarz,Tamer Coskun,Matthew J Hamang,Dana Sindelar,Kimberly K Ballman,Lisa A Foltz,Avinash Muppidi,Jorge Alsina-Fernandez,Gavin C. Barnard,Jason X. Tang,Xilin Liu,Xudong Mao,Robert W. Siegel,John H. Sloan,Pamela Jean Mitchell,Bei B Zhang,Ruth E. Gimeno,Bei Shan,Xinle Wu +23 more
TL;DR: It is demonstrated that GDNF-family receptor α-like (GFRAL), an orphan member of the GFR-α family, is a high-affinity receptor for GDF15 that mediates the metabolic effects of GDF12 and binds to GDF 15 in vitro and is required for the metabolic actions of G DF15 with respect to body weight and food intake in vivo in mice.
Journal ArticleDOI
Growth Differentiation Factor 15 as a Biomarker in Cardiovascular Disease.
TL;DR: GDF-15 captures distinct aspects of CV disease development, progression, and prognosis, which are not represented by clinical risk predictors and other biomarkers, and may become useful for decision support.
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