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Growth‐differentiation factor 15 (GDF15) is an inflammatory cytokine involved in energy homeostasis that is being pursued as a drug target for obesity. Its circulating levels are acutely increased by the type 2 diabetes medication metformin, resulting in reduced appetite and weight loss. We identified a genetic variant at the GDF15 gene to proxy a small, lifelong increase in circulating GDF15 levels, and leveraged it in colocalization and Mendelian randomization analyses to investigate the effects of chronically elevated GDF15 levels on body mass index (BMI) and type 2 diabetes liability. The results provide human genetic evidence supporting that chronically elevated GDF15 levels increase BMI. There was no genetic evidence to support bi‐directional effects, or that chronically elevated GDF15 levels directly affect liability to type 2 diabetes. Our results contrast the BMI‐lowering effects of an acute increase in GDF15 levels observed after metformin use. These findings have direct implications for informing pharmacological strategies aimed at targeting GDF15 levels for weight loss. [ABSTRACT FROM AUTHOR]

Context: Patients presenting with heart failure symptoms are categorized into heart failure (HF) with reduced and preserved ejection fraction. Objective: Aim is to investigate the additional use of candidate biomarkers to characterize patients with either sub-type of HF. Methods: Literature search was conducted in the electronic databases MEDLINE and Cochrane Central Register of Controlled Trials from inception through November 2014. Results: The results of 47 diseased and general population cohorts were included. Conclusion: Current studies could outline the additional use of candidate biomarkers especially GDF-15, MR-proADM and high-sensitive determined troponin, although major outcome studies are still missing. [ABSTRACT FROM AUTHOR]

Aims This study investigates the role of osteoprotegerin ( OPG) and growth-differentiation factor 15 ( GDF-15) as predictors of outcome in cardiogenic shock ( CS) complicating acute myocardial infarction. The novel biomarkers OPG and GDF-15 have shown prognostic impact in various cardiovascular diseases including myocardial infarction. In acute myocardial infarction complicated by CS, the diagnostic and prognostic impact of these biomarkers has not been investigated yet. OPG and GDF-15 may have additional prognostic impact on early prognosis assessment, being potentially useful for decision-making in CS. Methods and results In the randomized Intra-aortic Balloon Pump in cardiogenic Shock II ( IABP-SHOCK II)-trial, 600 patients with CS complicating acute myocardial infarction undergoing early revascularization were assigned to therapy with or without IABP. Within a pre-defined substudy, blood samples were collected from 190 patients during PCI. GDF-15 and OPG serum levels were measured with standard enzyme-linked immunosorbent assay kits. Patients with GDF-15 and OPG levels greater than the median showed higher rates of death at 30 days by χ2 testing ( OPG, 51% vs. 32%, P = 0.01; GDF-15, 52% vs. 31%, P = 0.005) and log rank testing [ GDF-15, hazard ratio ( HR) 1.88, 95% confidence interval ( CI) 1.21-2.94; P = 0.005; OPG, HR 1.74, 95% CI 1.11-2.71; P = 0.01]. Both markers were significantly predictive of 30-day mortality in univariable logistic regression analysis. In a multivariable logistic stepwise regression model, GDF-15, TIMI (Thrombolysis In Myocardial Infarction) flow grade <3 after PCI, age, LVEF, and serum lactate remained significant predictors of 30-day mortality. Conclusion GDF-15 on admission is a significant independent predictor of short-term mortality in infarct-related CS. Trail registration: NCT00491036 [ABSTRACT FROM AUTHOR]