title: Levels of atherogenic lipoproteins are unexpectedly reduced in interstitial fluid from type 2 diabetes patients.
abstract: At a given level of serum cholesterol, patients with T2D have an increased risk of developing atherosclerosis compared with nondiabetic subjects. We hypothesized that T2D patients have an increased interstitial fluid (IF)-to-serum gradient ratio for LDL, due to leakage over the vascular wall. Therefore, lipoprotein profiles in serum and IF from 35 T2D patients and 35 healthy controls were assayed using fast performance liquid chromatography. The IF-to-serum gradients for VLDL and LDL cholesterol, as well as for apoB, were clearly reduced in T2D patients compared with healthy controls. No such differences were observed for HDL cholesterol. Contrary to our hypothesis, the atherogenic VLDL and LDL particles were not increased in IF from diabetic patients. Instead, they were relatively sparser than in healthy controls. The most probable explanation to our unexpected finding is that these lipoproteins are more susceptible to retainment in the extravascular space of these patients, reflecting a more active uptake by, or adhesion to, tissue cells, including macrophages in the vascular wall. Further studies are warranted to further characterize the mechanisms underlying these observations, which may be highly relevant for the understanding of why the propensity to develop atherosclerosis is increased in T2D.
authors.affiliation: Metabolism Unit Karolinska Institutet at Karolinska University Hospital Huddinge, C2-84, S-141 86 Stockholm, Sweden KI/AZ Integrated CardioMetabolic Center, Department of Medicine, Karolinska Institutet at Karolinska University Hospital Huddinge, C2-84, S-141 86 Stockholm, Sweden Molecular Nutrition Unit, Center for Innovative Medicine, Department of Biosciences and Nutrition, Karolinska Institutet at Karolinska University Hospital Huddinge, S-141 86 Stockholm, Sweden.
authors.forename: Johanna
authors.initials: J
authors.lastname: Apro
authors.affiliation: Division of Clinical Chemistry, Department of Laboratory Medicine, Karolinska Institutet at Karolinska University Hospital Huddinge, C1-74, S-141 86 Stockholm, Sweden.
authors.forename: Paolo
authors.initials: P
authors.lastname: Parini
authors.affiliation: Metabolism Unit Karolinska Institutet at Karolinska University Hospital Huddinge, C2-84, S-141 86 Stockholm, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Broijersén
authors.affiliation: Metabolism Unit Karolinska Institutet at Karolinska University Hospital Huddinge, C2-84, S-141 86 Stockholm, Sweden KI/AZ Integrated CardioMetabolic Center, Department of Medicine, Karolinska Institutet at Karolinska University Hospital Huddinge, C2-84, S-141 86 Stockholm, Sweden Molecular Nutrition Unit, Center for Innovative Medicine, Department of Biosciences and Nutrition, Karolinska Institutet at Karolinska University Hospital Huddinge, S-141 86 Stockholm, Sweden.
authors.forename: Bo
authors.initials: B
authors.lastname: Angelin
authors.affiliation: Metabolism Unit Karolinska Institutet at Karolinska University Hospital Huddinge, C2-84, S-141 86 Stockholm, Sweden KI/AZ Integrated CardioMetabolic Center, Department of Medicine, Karolinska Institutet at Karolinska University Hospital Huddinge, C2-84, S-141 86 Stockholm, Sweden Molecular Nutrition Unit, Center for Innovative Medicine, Department of Biosciences and Nutrition, Karolinska Institutet at Karolinska University Hospital Huddinge, S-141 86 Stockholm, Sweden.
authors.forename: Mats
authors.initials: M
authors.lastname: Rudling
mesh_terms: D050197:Atherosclerosis / Q000150:complications / Q000378:metabolism*; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000378:metabolism* / Q000473:pathology*; D045604:Extracellular Fluid / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D008074:Lipoproteins / Q000097:blood / Q000378:metabolism*; D008297:Male; D008875:Middle Aged
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008074:Lipoproteins
keywords: apolipoproteins; cholesterol; high density lipoprotein; low density lipoprotein; statins; triglycerides; very low density lipoprotein