PMID- 37537576 OWN - NLM STAT- MEDLINE DCOM- 20230807 LR - 20231122 IS - 1475-2840 (Electronic) IS - 1475-2840 (Linking) VI - 22 IP - 1 DP - 2023 Aug 3 TI - Plasma lipidic fingerprint associated with type 2 diabetes in patients with coronary heart disease: CORDIOPREV study. PG - 199 LID - 10.1186/s12933-023-01933-1 [doi] LID - 199 AB - OBJECTIVE: We aimed to identify a lipidic profile associated with type 2 diabetes mellitus (T2DM) development in coronary heart disease (CHD) patients, to provide a new, highly sensitive model which could be used in clinical practice to identify patients at T2DM risk. METHODS: This study considered the 462 patients of the CORDIOPREV study (CHD patients) who were not diabetic at the beginning of the intervention. In total, 107 of them developed T2DM after a median follow-up of 60 months. They were diagnosed using the American Diabetes Association criteria. A novel lipidomic methodology employing liquid chromatography (LC) separation followed by HESI, and detection by mass spectrometry (MS) was used to annotate the lipids at the isomer level. The patients were then classified into a Training and a Validation Set (60-40). Next, a Random Survival Forest (RSF) was carried out to detect the lipidic isomers with the lowest prediction error, these lipids were then used to build a Lipidomic Risk (LR) score which was evaluated through a Cox. Finally, a production model combining the clinical variables of interest, and the lipidic species was carried out. RESULTS: LC-tandem MS annotated 440 lipid species. From those, the RSF identified 15 lipid species with the lowest prediction error. These lipids were combined in an LR score which showed association with the development of T2DM. The LR hazard ratio per unit standard deviation was 2.87 and 1.43, in the Training and Validation Set respectively. Likewise, patients with higher LR Score values had lower insulin sensitivity (P = 0.006) and higher liver insulin resistance (P = 0.005). The receiver operating characteristic (ROC) curve obtained by combining clinical variables and the selected lipidic isomers using a generalised lineal model had an area under the curve (AUC) of 81.3%. CONCLUSION: Our study showed the potential of comprehensive lipidomic analysis in identifying patients at risk of developing T2DM. In addition, the lipid species combined with clinical variables provided a new, highly sensitive model which can be used in clinical practice to identify patients at T2DM risk. Moreover, these results also indicate that we need to look closely at isomers to understand the role of this specific compound in T2DM development. Trials registration NCT00924937. CI - (c) 2023. BioMed Central Ltd., part of Springer Nature. FAU - Villasanta-Gonzalez, Alejandro AU - Villasanta-Gonzalez A AD - Lipids and Atherosclerosis Unit, Department of Internal Medicine, Reina Sofia University Hospital, University of Cordoba, Cordoba, Spain. AD - Department of Medical and Surgical Sciences, University of Cordoba, Cordoba, Spain. AD - Instituto Maimonides de Investigacion Biomedica de Cordoba (IMIBIC), Cordoba, Spain. FAU - Mora-Ortiz, Marina AU - Mora-Ortiz M AD - Lipids and Atherosclerosis Unit, Department of Internal Medicine, Reina Sofia University Hospital, University of Cordoba, Cordoba, Spain. AD - Department of Medical and Surgical Sciences, University of Cordoba, Cordoba, Spain. AD - Instituto Maimonides de Investigacion Biomedica de Cordoba (IMIBIC), Cordoba, Spain. FAU - Alcala-Diaz, Juan F AU - Alcala-Diaz JF AD - Lipids and Atherosclerosis Unit, Department of Internal Medicine, Reina Sofia University Hospital, University of Cordoba, Cordoba, Spain. AD - Department of Medical and Surgical Sciences, University of Cordoba, Cordoba, Spain. AD - Instituto Maimonides de Investigacion Biomedica de Cordoba (IMIBIC), Cordoba, Spain. AD - CIBER Fisiopatologia de la Obesidad y Nutricion (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain. FAU - Rivas-Garcia, Lorenzo AU - Rivas-Garcia L AD - Lipids and Atherosclerosis Unit, Department of Internal Medicine, Reina Sofia University Hospital, University of Cordoba, Cordoba, Spain. AD - Department of Medical and Surgical Sciences, University of Cordoba, Cordoba, Spain. AD - Instituto Maimonides de Investigacion Biomedica de Cordoba (IMIBIC), Cordoba, Spain. FAU - Torres-Pena, Jose D AU - Torres-Pena JD AD - Lipids and Atherosclerosis Unit, Department of Internal Medicine, Reina Sofia University Hospital, University of Cordoba, Cordoba, Spain. AD - Department of Medical and Surgical Sciences, University of Cordoba, Cordoba, Spain. AD - Instituto Maimonides de Investigacion Biomedica de Cordoba (IMIBIC), Cordoba, Spain. AD - CIBER Fisiopatologia de la Obesidad y Nutricion (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain. FAU - Lopez-Bascon, Asuncion AU - Lopez-Bascon A AD - Department of Analytical Chemistry and Nanochemistry University Institute, University of Cordoba, Cordoba, Spain. AD - CIBER de Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Salud Carlos III, Madrid, Spain. FAU - Calderon-Santiago, Monica AU - Calderon-Santiago M AD - Department of Analytical Chemistry and Nanochemistry University Institute, University of Cordoba, Cordoba, Spain. AD - CIBER de Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Salud Carlos III, Madrid, Spain. FAU - Arenas-Larriva, Antonio P AU - Arenas-Larriva AP AD - Lipids and Atherosclerosis Unit, Department of Internal Medicine, Reina Sofia University Hospital, University of Cordoba, Cordoba, Spain. AD - Department of Medical and Surgical Sciences, University of Cordoba, Cordoba, Spain. AD - Instituto Maimonides de Investigacion Biomedica de Cordoba (IMIBIC), Cordoba, Spain. FAU - Priego-Capote, Feliciano AU - Priego-Capote F AD - Department of Analytical Chemistry and Nanochemistry University Institute, University of Cordoba, Cordoba, Spain. AD - CIBER de Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Salud Carlos III, Madrid, Spain. FAU - Malagon, Maria M AU - Malagon MM AD - Instituto Maimonides de Investigacion Biomedica de Cordoba (IMIBIC), Cordoba, Spain. AD - CIBER Fisiopatologia de la Obesidad y Nutricion (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain. AD - Department of Cell Biology, Physiology and Immunology, University of Cordoba, Cordoba, Spain. FAU - Eichelmann, Fabian AU - Eichelmann F AD - German Center for Diabetes Research, Munich-Neuherberg, Germany. AD - Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrucke, Nuthetal, Germany. FAU - Perez-Martinez, Pablo AU - Perez-Martinez P AD - Lipids and Atherosclerosis Unit, Department of Internal Medicine, Reina Sofia University Hospital, University of Cordoba, Cordoba, Spain. AD - Department of Medical and Surgical Sciences, University of Cordoba, Cordoba, Spain. AD - Instituto Maimonides de Investigacion Biomedica de Cordoba (IMIBIC), Cordoba, Spain. AD - CIBER Fisiopatologia de la Obesidad y Nutricion (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain. FAU - Delgado-Lista, Javier AU - Delgado-Lista J AD - Lipids and Atherosclerosis Unit, Department of Internal Medicine, Reina Sofia University Hospital, University of Cordoba, Cordoba, Spain. AD - Department of Medical and Surgical Sciences, University of Cordoba, Cordoba, Spain. AD - Instituto Maimonides de Investigacion Biomedica de Cordoba (IMIBIC), Cordoba, Spain. AD - CIBER Fisiopatologia de la Obesidad y Nutricion (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain. FAU - Schulze, Matthias B AU - Schulze MB AD - German Center for Diabetes Research, Munich-Neuherberg, Germany. AD - Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrucke, Nuthetal, Germany. AD - Germany Institute of Nutrition Science, University of Potsdam, Nuthetal, Germany. FAU - Camargo, Antonio AU - Camargo A AD - Lipids and Atherosclerosis Unit, Department of Internal Medicine, Reina Sofia University Hospital, University of Cordoba, Cordoba, Spain. antonio.camargo@imibic.org. AD - Department of Medical and Surgical Sciences, University of Cordoba, Cordoba, Spain. antonio.camargo@imibic.org. AD - Instituto Maimonides de Investigacion Biomedica de Cordoba (IMIBIC), Cordoba, Spain. antonio.camargo@imibic.org. AD - CIBER Fisiopatologia de la Obesidad y Nutricion (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain. antonio.camargo@imibic.org. FAU - Lopez-Miranda, Jose AU - Lopez-Miranda J AD - Lipids and Atherosclerosis Unit, Department of Internal Medicine, Reina Sofia University Hospital, University of Cordoba, Cordoba, Spain. jlopezmir@uco.es. AD - Department of Medical and Surgical Sciences, University of Cordoba, Cordoba, Spain. jlopezmir@uco.es. AD - Instituto Maimonides de Investigacion Biomedica de Cordoba (IMIBIC), Cordoba, Spain. jlopezmir@uco.es. AD - CIBER Fisiopatologia de la Obesidad y Nutricion (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain. jlopezmir@uco.es. LA - eng SI - ClinicalTrials.gov/NCT00924937 PT - Clinical Trial PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230803 PL - England TA - Cardiovasc Diabetol JT - Cardiovascular diabetology JID - 101147637 RN - 0 (Lipids) SB - IM MH - Humans MH - *Coronary Disease/diagnosis MH - *Diabetes Mellitus, Type 2 MH - *Insulin Resistance MH - Lipids MH - Risk Factors PMC - PMC10401778 OTO - NOTNLM OT - Cox OT - LC-MS OT - Lipidomic risk score OT - Random survival forest COIS- The authors declare no competing financial interests. EDAT- 2023/08/04 01:07 MHDA- 2023/08/07 06:42 PMCR- 2023/08/03 CRDT- 2023/08/03 23:37 PHST- 2023/05/21 00:00 [received] PHST- 2023/07/21 00:00 [accepted] PHST- 2023/08/07 06:42 [medline] PHST- 2023/08/04 01:07 [pubmed] PHST- 2023/08/03 23:37 [entrez] PHST- 2023/08/03 00:00 [pmc-release] AID - 10.1186/s12933-023-01933-1 [pii] AID - 1933 [pii] AID - 10.1186/s12933-023-01933-1 [doi] PST - epublish SO - Cardiovasc Diabetol. 2023 Aug 3;22(1):199. doi: 10.1186/s12933-023-01933-1.