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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

View Article: PubMed Central - PubMed

ABSTRACT

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 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.

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-PLA2 and sPLA2 were measured before and after CSII.

Results: Levels 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).

Conclusions: Lp-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.

No MeSH data available.


Concentrations of blood glucose and insulin during IVGTT and OGTT before and after CSII (n = 90). a Means ± SD for glucose concentrations during IVGTT before (■) and after CSII (▲). The AUCGlu in IVGTT decreased significantly (89.43 ± 17.38 mmol · min vs. 67.01 ± 11.74 mmol · min, P < 0.01) after CSII. b Median (interquartile range) for insulin concentrations during IVGTT before (■) and after CSII (▲). The AUCIns in IVGTT was significantly elevated (11.91 [8.00, 29.05] mU · min vs. 25.64 [10.32, 46.79] mU · min, P < 0.01) after CSII. c Means ± SD for glucose concentrations during OGTT before (■) and after CSII (▲). AUCGlu in OGTT decreased significantly (79.57 ± 18.88 mmol · min vs. 46.49 ± 9.28 mmol · min, P < 0.01) after CSII. d Median (interquartile range) for insulin concentrations during OGTT before (■) and after CSII (▲). AUCIns in OGTT was significantly elevated (27.60 [12.20, 64.37] mU · min vs. 75.45 [46.37, 123.53] mU · min, P < 0.01) after CSII. Values of P < 0.05 are statistically significant. CSII, continuous subcutaneous insulin infusion; IVGTT, intravenous glucose-tolerance test; OGTT, oral glucose-tolerance test; SD, standard deviation; AUCGlu, area under the curve of glucose; AUCIns, area under the curve of insulin
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Fig1: Concentrations of blood glucose and insulin during IVGTT and OGTT before and after CSII (n = 90). a Means ± SD for glucose concentrations during IVGTT before (■) and after CSII (▲). The AUCGlu in IVGTT decreased significantly (89.43 ± 17.38 mmol · min vs. 67.01 ± 11.74 mmol · min, P < 0.01) after CSII. b Median (interquartile range) for insulin concentrations during IVGTT before (■) and after CSII (▲). The AUCIns in IVGTT was significantly elevated (11.91 [8.00, 29.05] mU · min vs. 25.64 [10.32, 46.79] mU · min, P < 0.01) after CSII. c Means ± SD for glucose concentrations during OGTT before (■) and after CSII (▲). AUCGlu in OGTT decreased significantly (79.57 ± 18.88 mmol · min vs. 46.49 ± 9.28 mmol · min, P < 0.01) after CSII. d Median (interquartile range) for insulin concentrations during OGTT before (■) and after CSII (▲). AUCIns in OGTT was significantly elevated (27.60 [12.20, 64.37] mU · min vs. 75.45 [46.37, 123.53] mU · min, P < 0.01) after CSII. Values of P < 0.05 are statistically significant. CSII, continuous subcutaneous insulin infusion; IVGTT, intravenous glucose-tolerance test; OGTT, oral glucose-tolerance test; SD, standard deviation; AUCGlu, area under the curve of glucose; AUCIns, area under the curve of insulin

Mentions: With regard to the insulin-secretory function of islets, none of the diabetic patients showed first-phase insulin secretion, and the peak of second-phase secretion appeared later than it normally does (120 min vs. 60 min, respectively). After 2 weeks of CSII, the levels of insulin at each time point in both IVGTT and OGTT were significantly elevated (P < 0.001) and the first-phase insulin secretion was recovered, whereas the peak of second-phase secretion was delayed (Fig. 1). Indicators of β-cell function including AIR3–5, ΔINS30/ΔG30, HOMA-β, and MBCI significantly improved after treatment (P < 0.05). The results remained the same when they were divided by HOMA-IR to exclude the influence of insulin resistance (P < 0.001) (Table 1).Fig. 1


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
Concentrations of blood glucose and insulin during IVGTT and OGTT before and after CSII (n = 90). a Means ± SD for glucose concentrations during IVGTT before (■) and after CSII (▲). The AUCGlu in IVGTT decreased significantly (89.43 ± 17.38 mmol · min vs. 67.01 ± 11.74 mmol · min, P < 0.01) after CSII. b Median (interquartile range) for insulin concentrations during IVGTT before (■) and after CSII (▲). The AUCIns in IVGTT was significantly elevated (11.91 [8.00, 29.05] mU · min vs. 25.64 [10.32, 46.79] mU · min, P < 0.01) after CSII. c Means ± SD for glucose concentrations during OGTT before (■) and after CSII (▲). AUCGlu in OGTT decreased significantly (79.57 ± 18.88 mmol · min vs. 46.49 ± 9.28 mmol · min, P < 0.01) after CSII. d Median (interquartile range) for insulin concentrations during OGTT before (■) and after CSII (▲). AUCIns in OGTT was significantly elevated (27.60 [12.20, 64.37] mU · min vs. 75.45 [46.37, 123.53] mU · min, P < 0.01) after CSII. Values of P < 0.05 are statistically significant. CSII, continuous subcutaneous insulin infusion; IVGTT, intravenous glucose-tolerance test; OGTT, oral glucose-tolerance test; SD, standard deviation; AUCGlu, area under the curve of glucose; AUCIns, area under the curve of insulin
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC5120429&req=5

Fig1: Concentrations of blood glucose and insulin during IVGTT and OGTT before and after CSII (n = 90). a Means ± SD for glucose concentrations during IVGTT before (■) and after CSII (▲). The AUCGlu in IVGTT decreased significantly (89.43 ± 17.38 mmol · min vs. 67.01 ± 11.74 mmol · min, P < 0.01) after CSII. b Median (interquartile range) for insulin concentrations during IVGTT before (■) and after CSII (▲). The AUCIns in IVGTT was significantly elevated (11.91 [8.00, 29.05] mU · min vs. 25.64 [10.32, 46.79] mU · min, P < 0.01) after CSII. c Means ± SD for glucose concentrations during OGTT before (■) and after CSII (▲). AUCGlu in OGTT decreased significantly (79.57 ± 18.88 mmol · min vs. 46.49 ± 9.28 mmol · min, P < 0.01) after CSII. d Median (interquartile range) for insulin concentrations during OGTT before (■) and after CSII (▲). AUCIns in OGTT was significantly elevated (27.60 [12.20, 64.37] mU · min vs. 75.45 [46.37, 123.53] mU · min, P < 0.01) after CSII. Values of P < 0.05 are statistically significant. CSII, continuous subcutaneous insulin infusion; IVGTT, intravenous glucose-tolerance test; OGTT, oral glucose-tolerance test; SD, standard deviation; AUCGlu, area under the curve of glucose; AUCIns, area under the curve of insulin
Mentions: With regard to the insulin-secretory function of islets, none of the diabetic patients showed first-phase insulin secretion, and the peak of second-phase secretion appeared later than it normally does (120 min vs. 60 min, respectively). After 2 weeks of CSII, the levels of insulin at each time point in both IVGTT and OGTT were significantly elevated (P < 0.001) and the first-phase insulin secretion was recovered, whereas the peak of second-phase secretion was delayed (Fig. 1). Indicators of β-cell function including AIR3–5, ΔINS30/ΔG30, HOMA-β, and MBCI significantly improved after treatment (P < 0.05). The results remained the same when they were divided by HOMA-IR to exclude the influence of insulin resistance (P < 0.001) (Table 1).Fig. 1

View Article: PubMed Central - PubMed

ABSTRACT

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 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 &beta;-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&nbsp;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.

Results: Levels of Lp-PLA2 and sPLA2 were significantly higher in diabetic patients with macroangiopathy than in those without (P&thinsp;&lt;&thinsp;0.05). After CSII, the sPLA2 level decreased significantly in all diabetic patients (P&thinsp;&lt;&thinsp;0.05), while the Lp-PLA2 level changed only in those with macroangiopathy (P&thinsp;&lt;&thinsp;0.05). The area under the curve of insulin in IVGTT and OGTT, the acute insulin response (AIR3&ndash;5), early phase of insulin secretion (&Delta;Ins30/&Delta;G30), modified &beta;-cell function index, and homeostatic model assessment for &beta;-cell function (HOMA-&beta;) increased after treatment even when adjusted for the influence of insulin resistance (IR; P&thinsp;&lt;&thinsp;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&thinsp;&lt;&thinsp;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&thinsp;&lt;&thinsp;0.05). Additionally, multiple linear regression analysis showed that Lp-PLA2 and sPLA2 independently correlated with HOMA-IR (P&thinsp;&lt;&thinsp;0.05).

Conclusions: Lp-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.

No MeSH data available.