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

BACKGROUND: China 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 A(2) (Lp-PLA(2)) and secretory phospholipase A(2) (sPLA(2)) 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-PLA(2) and sPLA(2) levels after early intensive insulin treatment and its relevance with insulin resistance and pancreatic β-cell function. METHODS: In 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-PLA(2) and sPLA(2) were measured before and after CSII. RESULTS: Levels of Lp-PLA(2) and sPLA(2) were significantly higher in diabetic patients with macroangiopathy than in those without (P < 0.05). After CSII, the sPLA(2) 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 (AIR(3–5)), 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 (ISI(ced), IAI, and QUICKI) were higher after treatment (P < 0.05). Correlation analysis showed that the decrease in the Lp-PLA(2) and sPLA(2) levels was positively correlated with a reduction in HOMA-IR after CSII (P < 0.05). Additionally, multiple linear regression analysis showed that Lp-PLA(2) and sPLA(2) independently correlated with HOMA-IR (P < 0.05). CONCLUSIONS: Lp-PLA(2) and sPLA(2) 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-PLA(2) and sPLA(2) levels. TRIAL REGISTRATION: ChiCTR-TRC-10001618 2010 September 16.