PMID- 34663793 OWN - NLM STAT- MEDLINE DCOM- 20211203 LR - 20221207 IS - 2044-4052 (Electronic) IS - 2044-4052 (Linking) VI - 11 IP - 1 DP - 2021 Oct 18 TI - Growth differentiation factor-15 and the association between type 2 diabetes and liver fibrosis in NAFLD. PG - 32 LID - 10.1038/s41387-021-00170-3 [doi] LID - 32 AB - BACKGROUND: Type 2 diabetes mellitus (T2DM) is a strong risk factor for liver fibrosis in non-alcoholic fatty liver disease (NAFLD). It remains uncertain why T2DM increases the risk of liver fibrosis. It has been suggested that growth differentiation factor-15 (GDF-15) concentrations increase the risk of liver fibrosis. We aimed to investigate (a) whether GDF-15 concentrations were associated with liver fibrosis and involved in the relationship between T2DM and liver fibrosis and (b) what factors linked with T2DM are associated with increased GDF-15 concentrations. METHODS: Ninety-nine patients with NAFLD (61% men, 42.4% T2DM) were studied. Serum GDF-15 concentrations were measured by electro-chemiluminescence immunoassay. Vibration-controlled transient elastography (VCTE)-validated thresholds were used to assess liver fibrosis. Regression modelling, receiver operator characteristic curve analysis and Sobel test statistics were used to test associations, risk predictors and the involvement of GDF-15 in the relationship between T2DM and liver fibrosis, respectively. RESULTS: Patients with NAFLD and T2DM (n = 42) had higher serum GDF-15 concentrations [mean (SD): 1271.0 (902.1) vs. 640.3 (332.5) pg/ml, p < 0.0001], and a higher proportion had VCTE assessed >/=F2 fibrosis (48.8 vs. 23.2%, p = 0.01) than those without T2DM. GDF-15 was independently associated with liver fibrosis (p = 0.001), and GDF-15 was the most important single factor predicting >/=F2 or >/=F3 fibrosis (>/=F2 fibrosis AUROC 0.75, (95% CI 0.63-0.86), p < 0.001, with sensitivity, specificity, positive predictive (PPV) and negative predictive (NPV) values of 56.3%, 86.9%, 69.2% and 79.1%, respectively). GDF-15 was involved in the association between T2DM and >/=F2 fibrosis (Sobel test statistic 2.90, p = 0.004). Other factors associated with T2DM explained 60% of the variance in GDF-15 concentrations (p < 0.0001). HbA1c concentrations alone explained 30% of the variance (p < 0.0001). CONCLUSIONS: GDF-15 concentrations are a predictor of liver fibrosis and potentially involved in the association between T2DM and liver fibrosis in NAFLD. HbA1c concentrations explain a large proportion of the variance in GDF-15 concentrations. CI - (c) 2021. The Author(s). FAU - Bilson, Josh AU - Bilson J AUID- ORCID: 0000-0003-4665-3886 AD - Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK. AD - National Institute for Health Research Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton National Health Service Foundation Trust, Southampton, UK. FAU - Scorletti, Eleonora AU - Scorletti E AD - Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK. AD - National Institute for Health Research Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton National Health Service Foundation Trust, Southampton, UK. AD - Division of Gastroenterology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA. FAU - Bindels, Laure B AU - Bindels LB AUID- ORCID: 0000-0003-3747-3234 AD - Metabolism and Nutrition Research Group, Louvain Drug Research Institute, Universite Catholique de Louvain, Brussels, Belgium. FAU - Afolabi, Paul R AU - Afolabi PR AD - Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK. AD - National Institute for Health Research Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton National Health Service Foundation Trust, Southampton, UK. FAU - Targher, Giovanni AU - Targher G AUID- ORCID: 0000-0002-4325-3900 AD - Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy. FAU - Calder, Philip C AU - Calder PC AD - Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK. AD - National Institute for Health Research Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton National Health Service Foundation Trust, Southampton, UK. AD - Institute for Life Sciences, University of Southampton, Southampton, UK. FAU - Sethi, Jaswinder K AU - Sethi JK AUID- ORCID: 0000-0003-4157-0475 AD - Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK. J.Sethi@soton.ac.uk. AD - National Institute for Health Research Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton National Health Service Foundation Trust, Southampton, UK. J.Sethi@soton.ac.uk. AD - Institute for Life Sciences, University of Southampton, Southampton, UK. J.Sethi@soton.ac.uk. FAU - Byrne, Christopher D AU - Byrne CD AUID- ORCID: 0000-0001-6322-7753 AD - Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK. C.D.Byrne@soton.ac.uk. AD - National Institute for Health Research Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton National Health Service Foundation Trust, Southampton, UK. C.D.Byrne@soton.ac.uk. LA - eng GR - WT_/Wellcome Trust/United Kingdom GR - 206453/Z/17/Z/WT_/Wellcome Trust/United Kingdom GR - 206453/Z/17/Z/Wellcome Trust (Wellcome)/ GR - IS-BRC-20004/DH | National Institute for Health Research (NIHR)/ PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20211018 PL - England TA - Nutr Diabetes JT - Nutrition & diabetes JID - 101566341 RN - 0 (GDF15 protein, human) RN - 0 (Glycated Hemoglobin A) RN - 0 (Growth Differentiation Factor 15) SB - IM MH - Adult MH - Aged MH - Diabetes Mellitus, Type 2/*blood/epidemiology MH - Elasticity Imaging Techniques/methods MH - Female MH - Glycated Hemoglobin/analysis MH - Growth Differentiation Factor 15/*blood MH - Humans MH - Immunoassay/methods MH - Liver Cirrhosis/*blood/epidemiology/metabolism MH - Logistic Models MH - Male MH - Middle Aged MH - Non-alcoholic Fatty Liver Disease/*blood/epidemiology MH - ROC Curve MH - Randomized Controlled Trials as Topic MH - Risk Factors MH - Young Adult PMC - PMC8523689 COIS- The authors declare no competing interests. EDAT- 2021/10/20 06:00 MHDA- 2021/12/15 06:00 PMCR- 2021/10/18 CRDT- 2021/10/19 05:57 PHST- 2021/02/15 00:00 [received] PHST- 2021/08/19 00:00 [accepted] PHST- 2021/08/12 00:00 [revised] PHST- 2021/10/19 05:57 [entrez] PHST- 2021/10/20 06:00 [pubmed] PHST- 2021/12/15 06:00 [medline] PHST- 2021/10/18 00:00 [pmc-release] AID - 10.1038/s41387-021-00170-3 [pii] AID - 170 [pii] AID - 10.1038/s41387-021-00170-3 [doi] PST - epublish SO - Nutr Diabetes. 2021 Oct 18;11(1):32. doi: 10.1038/s41387-021-00170-3.