Effect of intensive insulin treatment on plasma levels of lipoprotein-associated phospholipase A and secretory phospholipase A 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 (Lp-PLA) and secretory phospholipase A (sPLA) 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 and sPLA 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 and sPLA were measured before and after CSII.

Results: Levels of Lp-PLA and sPLA were significantly higher in diabetic patients with macroangiopathy than in those without (P < 0.05). After CSII, the sPLA 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), 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, IAI, and QUICKI) were higher after treatment (P < 0.05). Correlation analysis showed that the decrease in the Lp-PLA and sPLA levels was positively correlated with a reduction in HOMA-IR after CSII (P < 0.05). Additionally, multiple linear regression analysis showed that Lp-PLA and sPLA independently correlated with HOMA-IR (P < 0.05).

Conclusions: Lp-PLA and sPLA 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 and sPLA levels.

Trial Registration: ChiCTR-TRC-10001618 2010 September 16.