Oxylipins in triglyceride-rich lipoproteins of dyslipidemic subjects promote endothelial inflammation following a high fat meal.

Elevated triglyceride-rich lipoproteins (TGRL) in circulation is a risk factor for atherosclerosis. TGRL from subjects consuming a high saturated fat test meal elicited a variable inflammatory response in TNFα-stimulated endothelial cells (EC) that correlated strongly with the polyunsaturated fatty acid (PUFA) content. This study investigates how the relative abundance of oxygenated metabolites of PUFA, oxylipins, is altered in TGRL postprandially, and how these changes promote endothelial inflammation. Human aortic EC were stimulated with TNFα and treated with TGRL, isolated from subjects' plasma at fasting and 3.5 hrs postprandial to a test meal high in saturated fat. Endothelial VCAM-1 surface expression stimulated by TNFα provided a readout for atherogenic inflammation. Concentrations of esterified and non-esterified fatty acids and oxylipins in TGRL were quantified by mass spectrometry. Dyslipidemic subjects produced TGRL that increased endothelial VCAM-1 expression by ≥35%, and exhibited impaired fasting lipogenesis activity and a shift in soluble epoxide hydrolase and lipoxygenase activity. Pro-atherogenic TGRL were enriched in eicosapentaenoic acid metabolites and depleted in esterified C18-PUFA-derived diols. Abundance of these metabolites was strongly predictive of VCAM-1 expression. We conclude the altered metabolism in dyslipidemic subjects produces TGRL with a unique oxylipin signature that promotes a pro-atherogenic endothelial phenotype.

Clinical impact of sample interference on intensive insulin therapy in severely burned patients: a pilot study.

Severely burned patients benefit from intensive insulin therapy (IIT) for tight glycemic control (TGC). The authors evaluated the clinical impact of automatic correction of hematocrit and ascorbic acid interference for bedside glucose monitoring performance in critically ill burn patients. The performance of two point-of-care glucose monitoring systems (GMSs): 1) GMS1, an autocorrecting device, and 2) GMS2, a noncorrecting device were compared. Sixty remnant arterial blood samples were collected in a prospective observational study to evaluate hematocrit and ascorbic acid effects on GMS1 vs GMS2 accuracy paired against a plasma glucose reference. Next, we enrolled 12 patients in a pilot randomized controlled trial. Patients were randomized 1:1 to receive IIT targeting a TGC interval of 111 to 151 mg/dl and guided by either GMS1 or GMS2. GMS bias, mean insulin rate, and glycemic variability were calculated. In the prospective study, GMS1 results were similar to plasma glucose results (mean bias, -0.75 [4.0] mg/dl; n = 60; P = .214). GMS2 results significantly differed from paired plasma glucose results (mean bias, -5.66 [18.7] mg/dl; n = 60; P = .048). Ascorbic acid therapy elicited significant GMS2 performance bias (29.2 [27.2]; P < .001). Randomized controlled trial results reported lower mean bias (P < .001), glycemic variability (P < .05), mean insulin rate (P < .001), and frequency of hypoglycemia (P < .001) in the GMS1 group than in the GMS2 group. Anemia and high-dose ascorbic acid therapy negatively impact GMS accuracy and TGC in burn patients. Automatic correction of confounding factors improves glycemic control. Further studies are warranted to determine outcomes associated with accurate glucose monitoring during IIT.