Impaired HDL cholesterol efflux in metabolic syndrome is unrelated to glucose tolerance status: the CODAM study.
Type 2 diabetes mellitus (T2DM) and metabolic syndrome (MetS) increase atherosclerotic cardiovascular disease risk. Cholesterol efflux capacity (CEC) is a key metric of the anti-atherosclerotic functionality of high-density lipoproteins (HDL). The present study aimed to delineate if T2DM and MetS cross-sectionally associate with altered CEC in a large high cardiometabolic risk population. CEC was determined from THP-1 macrophage foam cells towards apolipoprotein B-depleted plasma from 552 subjects of the CODAM cohort (288 controls, 126 impaired glucose metabolism [IGM], 138 T2DM). MetS was present in 297 participants. CEC was not different between different glucose tolerance categories but was lower in MetS (P < 0.001), at least partly attributable to lower HDL cholesterol (HDL-C) and apoA-I levels (P < 0.001 for each). Low grade inflammation was increased in IGM, T2DM and MetS as determined by a score comprising 8 different biomarkers (P < 0.05-< 0.001; n = 547). CEC inversely associated with low-grade inflammation taking account of HDL-C or apoA-I in MetS (P < 0.02), but not in subjects without MetS (interaction: P = 0.015). This study demonstrates that IGM and T2DM do not impact the HDL CEC function, while efflux is lower in MetS, partly dependent on plasma HDL-C levels. Enhanced low-grade inflammation in MetS may conceivably impair CEC even independent of HDL-C and apoA-I.
Department of Pediatrics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.|Top Institute Food and Nutrition, Wageningen, The Netherlands.
Wijtske
W
Annema
Department of Pediatrics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Arne
A
Dikkers
Department of Pediatrics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Jan Freark
JF
de Boer
Laboratory for Metabolism and Vascular Medicine, Department of Internal Medicine, Maastricht University Medical Centre (MUMC), Maastricht, The Netherlands.|CARIM School for Cardiovascular Diseases, Maastricht University, Maastricht, The Netherlands.
Marleen M J
MMJ
van Greevenbroek
Laboratory for Metabolism and Vascular Medicine, Department of Internal Medicine, Maastricht University Medical Centre (MUMC), Maastricht, The Netherlands.|CARIM School for Cardiovascular Diseases, Maastricht University, Maastricht, The Netherlands.
Carla J H
CJH
van der Kallen
Laboratory for Metabolism and Vascular Medicine, Department of Internal Medicine, Maastricht University Medical Centre (MUMC), Maastricht, The Netherlands.|CARIM School for Cardiovascular Diseases, Maastricht University, Maastricht, The Netherlands.
Casper G
CG
Schalkwijk
Laboratory for Metabolism and Vascular Medicine, Department of Internal Medicine, Maastricht University Medical Centre (MUMC), Maastricht, The Netherlands.|CARIM School for Cardiovascular Diseases, Maastricht University, Maastricht, The Netherlands.
Coen D A
CDA
Stehouwer
Department of Endocrinology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Robin P F
RPF
Dullaart
Department of Pediatrics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Uwe J F
UJF
Tietge
D016632:Apolipoprotein A-I / Q000097:blood; D001055:Apolipoproteins B / Q000097:blood; D001692:Biological Transport / Q000502:physiology; D002784:Cholesterol / Q000009:adverse effects* / Q000378:metabolism*; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000473:pathology*; D005260:Female; D005487:Foam Cells / Q000473:pathology; D005947:Glucose / Q000378:metabolism; D018149:Glucose Intolerance / Q000473:pathology*; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007249:Inflammation / Q000473:pathology; D008075:Lipoproteins, HDL / Q000097:blood; D008297:Male; D024821:Metabolic Syndrome / Q000473:pathology*; D014280:Triglycerides / Q000097:blood
D016632:Apolipoprotein A-I; D001055:Apolipoproteins B; D002784:Cholesterol; D005947:Glucose; D006442:Glycated Hemoglobin; D008075:Lipoproteins, HDL; D014280:Triglycerides; C517652:hemoglobin A1c protein, human