Metabolite Profile of Treatment-Naive Metabolic Syndrome Subjects in Relation to Cardiovascular Disease Risk
Moritz V. Warmbrunn,
Annefleur M. Koopen,
Nicolien C. de Clercq,
Pieter F. de Groot,
Ruud S. Kootte,
Kristien E. C. Bouter,
Kasper W. ter Horst,
Annick V. Hartstra,
Mireille J. Serlie,
Mariette T. Ackermans,
Maarten R. Soeters,
Daniel H. van Raalte,
Mark Davids,
Max Nieuwdorp,
Albert K. Groen
Affiliations
Moritz V. Warmbrunn
Department of Internal and Vascular Medicine, Amsterdam University Medical Centers, Location AMC, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
Annefleur M. Koopen
Department of Internal and Vascular Medicine, Amsterdam University Medical Centers, Location AMC, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
Nicolien C. de Clercq
Department of Internal and Vascular Medicine, Amsterdam University Medical Centers, Location AMC, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
Pieter F. de Groot
Department of Internal and Vascular Medicine, Amsterdam University Medical Centers, Location AMC, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
Ruud S. Kootte
Department of Internal and Vascular Medicine, Amsterdam University Medical Centers, Location AMC, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
Kristien E. C. Bouter
Department of Internal and Vascular Medicine, Amsterdam University Medical Centers, Location AMC, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
Kasper W. ter Horst
Department of Endocrinology and Metabolism, Amsterdam UMC, Location AMC at University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
Annick V. Hartstra
Department of Internal and Vascular Medicine, Amsterdam University Medical Centers, Location AMC, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
Mireille J. Serlie
Department of Endocrinology and Metabolism, Amsterdam UMC, Location AMC at University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
Mariette T. Ackermans
Department of Endocrinology and Metabolism, Amsterdam UMC, Location AMC at University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
Maarten R. Soeters
Department of Endocrinology and Metabolism, Amsterdam UMC, Location AMC at University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
Daniel H. van Raalte
Diabetes Center, Department of Internal Medicine, Amsterdam UMC, Location VUMC at VU University Medical Centers, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands
Mark Davids
Department of Internal and Vascular Medicine, Amsterdam University Medical Centers, Location AMC, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
Max Nieuwdorp
Department of Internal and Vascular Medicine, Amsterdam University Medical Centers, Location AMC, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
Albert K. Groen
Department of Internal and Vascular Medicine, Amsterdam University Medical Centers, Location AMC, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
Metabolic syndrome (MetSyn) is an important risk factor for type 2 diabetes and cardiovascular diseases (CVD). This study aimed to find distinct plasma metabolite profiles between insulin-resistant and non-insulin resistant subjects with MetSyn and evaluate if MetSyn metabolite profiles are related to CVD risk and lipid fluxes. In a cross-sectional study, untargeted metabolomics of treatment-naive males with MetSyn (n = 132) were analyzed together with clinical parameters. In a subset of MetSyn participants, CVD risk was calculated using the Framingham score (n = 111), and lipolysis (n = 39) was measured by a two-step hyperinsulinemic euglycemic clamp using [1,1,2,3,3-2H5] glycerol to calculate lipolysis suppression rates. Peripheral insulin resistance was related to fatty acid metabolism and glycerolphosphorylcholine. Interestingly, although insulin resistance is considered to be a risk factor for CVD, we observed that there was little correspondence between metabolites associated with insulin resistance and metabolites associated with CVD risk. The latter mainly belonged to the androgenic steroid, fatty acid, phosphatidylethanolamine, and phophatidylcholine pathways. These data provide new insights into metabolic changes in mild MetSyn pathophysiology and MetSyn CVD risk related to lipid metabolism. Prospective studies may focus on the pathophysiological role of the here-identified biomarkers.
