PMID- 31717719
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200928
IS  - 2077-0383 (Print)
IS  - 2077-0383 (Electronic)
IS  - 2077-0383 (Linking)
VI  - 8
IP  - 11
DP  - 2019 Oct 25
TI  - Plasma Levels of Retinol Binding Protein 4 Relate to Large VLDL and Small LDL 
      Particles in Subjects with and without Type 2 Diabetes.
LID - 10.3390/jcm8111792 [doi]
LID - 1792
AB  - BACKGROUND: Retinol binding protein 4 (RBP4) carries retinol in plasma, but is 
      also considered an adipokine, as it is implicated in insulin resistance in mice. 
      Plasma RBP4 correlates with total cholesterol, low density lipoprotein 
      (LDL)-cholesterol and triglycerides, and may confer increased cardiovascular 
      risk. However, controversy exists about circulating RPB4 levels in type 2 
      diabetes mellitus (T2DM) and obesity. Here, we analyzed the relationships of RBP4 
      and retinol with lipoprotein subfractions in subjects with and without T2DM. 
      METHODS: Fasting plasma RBP4 (enzyme-linked immunosorbent assay) and retinol 
      (high performance liquid chromatography) were assayed in 41 T2DM subjects and 37 
      non-diabetic subjects. Lipoprotein subfractions (NMR spectroscopy) were measured 
      in 36 T2DM subjects and 27 non-diabetic subjects. Physical interaction of RBP4 
      with lipoproteins was assessed by fast protein liquid chromatography (FPLC). 
      RESULTS: Plasma RBP4 and retinol were strongly correlated (r = 0.881, p < 0.001). 
      RBP4, retinol and the RBP4/retinol ratio were not different between T2DM and 
      non-diabetic subjects (all p > 0.12), and were unrelated to body mass index. 
      Notably, RBP4 and retinol were elevated in subjects with metabolic syndrome (p < 
      0.05), which was attributable to an association with elevated triglycerides (p = 
      0.013). Large VLDL, total LDL and small LDL were increased in T2DM subjects (p = 
      0.035 to 0.003). Taking all subjects together, RBP4 correlated with total 
      cholesterol, non-HDL cholesterol, LDL cholesterol, triglycerides and 
      apolipoprotein B in univariate analysis (p < 0.001 for each). Age-, sex- and 
      diabetes status-adjusted multivariable linear regression analysis revealed that 
      RBP4 was independently associated with large VLDL (beta = 0.444, p = 0.005) and 
      small LDL particles (beta = 0.539, p < 0.001). Its relationship with large VLDL 
      remained after further adjustment for retinol. RBP4 did not co-elute with VLDL 
      nor LDL particles in FPLC analyses. CONCLUSIONS: Plasma RBP4 levels are related 
      to but do not physically interact with large VLDL and small LDL particles. 
      Elevated RBP4 may contribute to a proatherogenic plasma lipoprotein profile.
FAU - Wessel, Hanna
AU  - Wessel H
AD  - Department of Endocrinology, University of Groningen and University Medical 
      Center Groningen, 9700 RB Groningen, The Netherlands.
AD  - Department of Gastroenterology and Hepatology, University of Groningen and 
      University Medical Center Groningen, 9700 RB Groningen, The Netherlands.
FAU - Saeed, Ali
AU  - Saeed A
AD  - Department of Gastroenterology and Hepatology, University of Groningen and 
      University Medical Center Groningen, 9700 RB Groningen, The Netherlands.
AD  - Institute of Molecular Biology and Biotechnology, Bahauddin Zakariya University 
      Multan 66000, Pakistan.
FAU - Heegsma, Janette
AU  - Heegsma J
AD  - Department of Gastroenterology and Hepatology, University of Groningen and 
      University Medical Center Groningen, 9700 RB Groningen, The Netherlands.
AD  - Department of Laboratory Medicine, University of Groningen and University Medical 
      Center Groningen, 9700 RB Groningen, The Netherlands.
FAU - Connelly, Margery A
AU  - Connelly MA
AD  - Laboratory Corporation of America Holdings (LabCorp), Morrisville, NC 27560, USA.
FAU - Faber, Klaas Nico
AU  - Faber KN
AD  - Department of Gastroenterology and Hepatology, University of Groningen and 
      University Medical Center Groningen, 9700 RB Groningen, The Netherlands.
AD  - Department of Laboratory Medicine, University of Groningen and University Medical 
      Center Groningen, 9700 RB Groningen, The Netherlands.
FAU - Dullaart, Robin P F
AU  - Dullaart RPF
AUID- ORCID: 0000-0003-4520-1239
AD  - Department of Endocrinology, University of Groningen and University Medical 
      Center Groningen, 9700 RB Groningen, The Netherlands.
LA  - eng
PT  - Journal Article
DEP - 20191025
PL  - Switzerland
TA  - J Clin Med
JT  - Journal of clinical medicine
JID - 101606588
PMC - PMC6912784
OTO - NOTNLM
OT  - Type 2 diabetes mellitus
OT  - large VLDL
OT  - lipoprotein subfractions
OT  - metabolic syndrome
OT  - nuclear magnetic resonance spectroscopy
OT  - retinol
OT  - retinol binding protein 4
OT  - small LDL
COIS- M.A.C. is an employee of LabCorp. The rest of the authors declare that they have 
      no competing interests.
EDAT- 2019/11/14 06:00
MHDA- 2019/11/14 06:01
PMCR- 2019/10/25
CRDT- 2019/11/14 06:00
PHST- 2019/09/18 00:00 [received]
PHST- 2019/10/17 00:00 [revised]
PHST- 2019/10/22 00:00 [accepted]
PHST- 2019/11/14 06:00 [entrez]
PHST- 2019/11/14 06:00 [pubmed]
PHST- 2019/11/14 06:01 [medline]
PHST- 2019/10/25 00:00 [pmc-release]
AID - jcm8111792 [pii]
AID - jcm-08-01792 [pii]
AID - 10.3390/jcm8111792 [doi]
PST - epublish
SO  - J Clin Med. 2019 Oct 25;8(11):1792. doi: 10.3390/jcm8111792.