Study of glycemic fluctuation impact on angiopoietin-2 and endoplasmic reticulum stress in type 2 diabetes complicated with acute phase of acute coronary syndrome / 中华内分泌代谢杂志

ABSTRACT

Objective To investigate the changes in angiopoietin 2 and endoplasmic reticulum stress,and the prognosis of acute phase of coronary syndrome (ACS) in type 2 diabetic patients with glycemic fluctuations.Methods Seventy-eight cases of consecutive diabetic patients with ACS within 7 days were enrolled.Another 78 cases of non-diabetic patients with ACS were selected as control.Risk assessment with global acute coronary events (GRACE) score in patients with ACS,dynamic blood glucose monitoring system (CGMS) for three days,realtime PCR analysis of angiopoietin-2,within the reticulum stress-related heavy chain binding protein (Bip),inositol kinase demand Ⅰ (IREI),endoplasmic reticulum class should PKR kinase (PERK),oxygen-regulated protein 150 (ORP150),activating transcription factor 6 (ATF6),X-box binding protein 1 (XBP1)mRNA expression change,phosphorylation of eukaryotic translation initiation factor 2oα (p-eIF2α) by western blotting angiopoietin-2,parameters were compared between the two groups.Correlation analysis with GRACE score ; while angiopoietin-2 parameters and glycemic fluctuation,endoplasmic reticulum stress-related genes correlation analysis were made.Results (1) ACS group average daily blood glucose fluctuations(MAGE),mean absolute difference daytime blood glucose (MODD),and postprandial blood glucose fluctuation (MPPGE) and the maximum amplitude of glycemic excursions (LAGE) were significantly higher [MAGE(5.13 ± 1.19) vs (3.19 ± 0.55) mmol/L,MODD (2.59 ± 0.72) vs (1.72 ± 0.63) mmol/L; MPPGE (3.51 ± 1.01) vs (2.58 ± 0.55) mmol/L and LAGE (7.75 ± 2.39) vs (4.34 ± 0.85) mmol/L,all P＜0.05].(2)In ACS group angiopoietin-2,endoplasmic reticulum associated genes Bip,IREI,PERK,ORP150,ATF6,XBP1,and monocyte chemoattractant protein 1 (MCP-1) mRNA expression levels as compared with the control group were statistically significant(all P＜0.05) ; Angiopoietin-2,protein p-eIF2α were higher(P＜0.05).(3) In the ACS group with pearson correlation analysis,angiopoietin-2 and MAGE,LAGE,MPPGE correlation (r =0.432,0.279,0.386,all P＜0.05),Bip and MAGE,LAGE,MPPGE correlation(r =0.783,0.589,0.887,all P＜ 0.05) ; IREI and MAGE,LAGE,MPPGE,MODD correlation (r =0.567,0.783,0.569,0.823,all P＜0.05) ; PERK and MAGE,MPPGE,MODD correlation(r =0.687,0.902,0.709,all P＜0.05) ; ORP150 and MAGE,LAGE,MPPGE,MODD correlation(r=0.779,0.871,0.775,0.689,all P＜0.05) ; ATF6 and MAGE,LAGE,MPPGE,MODD correlation(r =0.873,0.675,0.893,0.884,all P＜0.05),while XBP1 with no correlation with glycemic fluctuations (P＞0.05).(4) The endoplasmic reticulum stress gene was related to MCP-1 and blood glucose fluctuation parameters.(5) Multiple Logistic regression analysis revealed that LAGE,MPPGE,Bip,IREI,PERK,ORP150,ATF6 were risk factors affecting angiopoietin-2,and angiopoietin-2,ages,MAGE,homeostasis model assessment for insulin resistance,Bip,ATF6 were risk factors affecting GRACE.(6) The ejection fractions of the ACS patients showed negative correlation with MAGE and LAGE,multiple linear regression analysis showed that age,HOMA-IR,Ang-2,and MAGE,Bip,ATF6 established the linear regression relation with ejection fraction.Conclusion Glycemic fluctuations cause angiopoietin-2 to rise and lead to increased endoplasmic reticulum stress and affect the prognosis of diabetic patients with ACS.