Effect of intensive insulin treatment on plasma levels of lipoprotein-associated phospholipase A2 and secretory phospholipase A2 in patients with newly diagnosed type 2 diabetes

Abstract

BackgroundChina has the highest absolute disease burden of diabetes worldwide. For diabetic patients, diabetes-related vascular complications are major causes of morbidity and mortality. The roles of lipoprotein-associated phospholipase A2 (Lp-PLA2) and secretory phospholipase A2 (sPLA2) as inflammatory markers have been recently evaluated in the pathogenesis of both diabetes and atherosclerosis. We aimed to determine the mechanism through which patients with newly diagnosed type 2 diabetes gain long-term vascular benefit from intensive insulin therapy by evaluating the change in Lp-PLA2 and sPLA2 levels after early intensive insulin treatment and its relevance with insulin resistance and pancreatic β-cell function.MethodsIn total, 90 patients with newly diagnosed type 2 diabetes mellitus were enrolled. All patients received continuous subcutaneous insulin infusion (CSII) for approximately 2 weeks. Intravenous glucose-tolerance test (IVGTT) and oral glucose-tolerance test (OGTT) were performed, and plasma concentrations of Lp-PLA2 and sPLA2 were measured before and after CSII.ResultsLevels of Lp-PLA2 and sPLA2 were significantly higher in diabetic patients with macroangiopathy than in those without (P < 0.05). After CSII, the sPLA2 level decreased significantly in all diabetic patients (P < 0.05), while the Lp-PLA2 level changed only in those with macroangiopathy (P < 0.05). The area under the curve of insulin in IVGTT and OGTT, the acute insulin response (AIR3–5), early phase of insulin secretion (ΔIns30/ΔG30), modified β-cell function index, and homeostatic model assessment for β-cell function (HOMA-β) increased after treatment even when adjusted for the influence of insulin resistance (IR; P < 0.001). The HOMA-IR was lower after treatment, and the three other indicators adopted to estimate insulin sensitivity (ISIced, IAI, and QUICKI) were higher after treatment (P < 0.05). Correlation analysis showed that the decrease in the Lp-PLA2 and sPLA2 levels was positively correlated with a reduction in HOMA-IR after CSII (P < 0.05). Additionally, multiple linear regression analysis showed that Lp-PLA2 and sPLA2 independently correlated with HOMA-IR (P < 0.05).ConclusionsLp-PLA2 and sPLA2 are closely related to insulin resistance and macroangiopathy in diabetic patients. Intensive insulin therapy might help improve IR and protect against diabetic macroangiopathy by influencing the Lp-PLA2 and sPLA2 levels.Trial registration ChiCTR-TRC-10001618 2010 September 16.

Carbohydrate intake attenuates post-exercise plasma levels of cytochrome P450-generated oxylipins

“…Cytosolic PLA 2 (cPLA 2 ) exhibits preference for hydrolysis of ARA from phospholipid substrates, and expression is induced through a number of signaling pathways activated by acute exercise including MAPK/ERK (mitogen-activated protein kinases/ extracellular signal-regulated kinases), and transcriptional activators such as nuclear factor-kappa B (NF-κB) and proinflammatory cytokines [ 35 , 36 ]. Post-exercise plasma ARA levels were significantly reduced with carbohydrate intake, and these data imply that PLA 2 activity was attenuated, perhaps in part due to higher glucose and insulin levels as extrapolated from diabetes-based investigations [ 26 , 37 ]. In a previous study conducted by our research group utilizing the same exercise model, we showed that serum insulin levels increased 29% after 75-km cycling with carbohydrate compared to a decrease of 28% with water only [ 20 ].…”

“…We sought to determine if carbohydrate intake during exercise countered other PUFA-derived oxylipins, a likely finding given their important immune and inflammation regulatory roles. One potential mechanism for the influence of carbohydrate intake on lipid-related metabolites during exercise is the associated increase in insulin that inhibits tissue triacylglycerol lipase, hormone sensitive lipase, and PLA 2 , thus reducing triacylglycerol breakdown and the release of free fatty acids into circulation [ 26 , 27 ]. Prolonged exercise increases PLA 2 activity in muscle tissue, and the potential countermeasure influence of acute carbohydrate ingestion through related increases in insulin and other factors should result in a reduced release of oxylipins and inflammatory lipid mediators.…”

Atypical Antipsychotic Administration in Schizophrenic Patients Leads to Elevated Lipoprotein‐Associated Phospholipase A2 Levels and Increased Cardiovascular Risk: A Retrospective Cohort Study

“…Lp‐PLA2 activity significantly rose in patients of type 2 diabetes during the early stages of the disease. T2DM patients in whom Lp‐PLA2 activity was elevated were also more likely to develop CAD than those without elevated levels . Therefore, it is indicated that AAP tend to produce high CVD risk in the early stages of treatment and before hyperglycaemia.…”

Lipoprotein‐associated phospholipase A2: The story continues

“…Furthermore, positive correlations between Lp‐PLA2 and several atherogenic factors in patients with newly diagnosed diabetes as well as the cardio‐ankle vascular index, a recently developed marker of arterial stiffness, in long‐term T2DM patients were demonstrated recently . Lin et al proposed that Lp‐PLA2 might affect the incidence of atherosclerosis in diabetic patients and the decline in Lp‐PLA2 levels through intensive insulin therapy might contribute to protection from diabetic atherosclerotic complications . Additional studies are essential to clarify the role of Lp‐PLA2 in modifying the atherosclerotic process of T2DM patients.…”