Characterization of Glyoxal Modified LDL: Role in the Generation of Circulating Autoantibodies in Type 2 Diabetes Mellitus and Coronary Artery Disease

2021 ◽  
Vol 22 ◽  
Author(s):  
Md Masum Rizwee ◽  
Minhal Abidi ◽  
Safia Habib ◽  
Abdul Rouf Mir ◽  
Asif Ali ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Antigenic Determinants ◽  
Modified Ldl ◽  
Circulating Antibodies ◽  
Artery Disease

Aims: To investigate role of glyoxal modified LDL in immunopathology of diabetes and cardiovascular disease. Background: Glycoxidation of proteins is widely studied in relation to diabetes and cardiovascular disease. Objective: This study probed the glyoxal mediated modifications in LDL, analyzed the immunogenicity of the glycated LDL and ascertained the presence of circulating antibodies against modified LDL in patients with type 2 diabetes mellitus (T2DM), coronary artery disease (CAD) and patients with both (T2DM+CAD). Methods: Glyoxal mediated modifications in LDL were studied by multiple spectroscopic techniques, high performance liquid chromatography and electron microscopy. Immunization studies were carried in New Zealand rabbits. Presence of antibodies against glyoxal modified LDL in immunized rabbits and human subjects were analyzed by ELISA. Results: Glyoxal altered the structural integrity of LDL and lead to the formation of AGEs. It decreased the alpha helix content of LDL; increased β sheet formation; increased carbonyl content and decreased free lysine and arginine content. Modified LDL showed aggregation, generation of of Nε-(Carboxymethyl) lysine and the formation of amorphous type aggregates. It exhibited high antigenicity and generated specific immune response that shared common antigenic determinants with other glycated proteins. Direct binding data showed the presence of anti- glyoxal modified LDL antibodies in patients with T2DM, CAD and patients with both T2DM and CAD. Further analysis in competitive binding assay revealed specific binding characteristics of auto-antibodies. Sera from patients with T2DM+CAD exhibited highest binding with glyoxal modified LDL. Conclusion: Glyoxal modified LDL has neo-antigenic determinants that cause the generation of circulating antibodies in diabetes and coronary artery disease. The study might have potential relevance in biomarker development.

Characterization of Glyoxal Modified LDL: Role in the Generation of Circulating Autoantibodies in Type 2 Diabetes Mellitus and Coronary Artery Disease

2021 ◽  
Vol 18 ◽  
Author(s):  
Md Masum Rizwee ◽  
Minhal Abidi ◽  
Safia Habib ◽  
Abdul Rouf Mir ◽  
Asif Ali ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Coronary Artery Disease ◽  
Type 2 Diabetes Mellitus ◽  
Coronary Artery ◽  
Antigenic Determinants ◽  
Modified Ldl ◽  
Circulating Antibodies ◽  
Artery Disease

Aims: To investigate the role of glyoxal modified LDL in the immunopathology of diabetes and cardiovascular disease. Background: Glycoxidation of proteins is widely studied in relation to diabetes and cardi-ovascular disease. Objective: This study probed the glyoxal mediated modifications in LDL, analyzed the im-munogenicity of the glycated LDL and ascertained the presence of circulating antibodies against modified LDL in patients with type 2 diabetes mellitus (T2DM), coronary artery disease (CAD) and patients with both (T2DM+CAD). Methods: Glyoxal mediated modifications in LDL were studied by multiple spectroscopic techniques, high-performance liquid chromatography and electron microscopy. Immuniza-tion studies were carried in New Zealand rabbits. The presence of antibodies against glyoxal modified LDL in immunized rabbits and human subjects was analyzed by ELISA. Results: Glyoxal altered the structural integrity of LDL and lead to the formation of AGEs. It decreased the alpha-helix content of LDL; increased β sheet formation; increased carbon-yl content and decreased free lysine and arginine content. Modified LDL showed aggrega-tion, generation of Nε-(Carboxymethyl) lysine and the formation of amorphous type aggre-gates. It exhibited high antigenicity and generated specific immune responses that shared common antigenic determinants with other glycated proteins. Direct binding data showed the presence of anti-glyoxal modified LDL antibodies in patients with T2DM, CAD and patients with both T2DM and CAD. Further analysis in competitive binding assay revealed specific binding characteristics of auto-antibodies. Sera from patients with T2DM+CAD exhibited the highest binding with glyoxal modified LDL. Conclusion: Glyoxal modified LDL has neo-antigenic determinants that cause the genera-tion of circulating antibodies in diabetes and coronary artery disease. The study might have potential relevance in biomarker development.

scholarly journals A study of prevalence of silent coronary artery disease in asymptomatic type II diabetes mellitus

2021 ◽  
Vol 9 (1) ◽  
pp. 1-4
Author(s):  
Moogaambiga S ◽  
Kirubhakaran K ◽  
Devi PL ◽  
Santhosh P
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Diabetic Patients ◽  
Treadmill Test ◽  
Silent Coronary Artery Disease ◽  
Artery Disease

Background: Cardiovascular disease is a major cause of morbidity and mortality in diabetics. However diabetic patients do not present with typical anginal symptoms or may be even asymptomatic and silent coronary artery disease (CAD) is prevalent in diabetics. Moreover silent CAD is not different from symptomatic CAD with respect to prognosis and adverse effects. Aim: The study was done to demonstrate the prevalence of silent myocardial ischemic changes in asymptomatic type 2 diabetes mellitus patients with normal resting ECG by doing a stress exercise test. Methodology: This descriptive study was done in 100 patients with type 2 diabetes more than 2 years who did not have any history of cardiovascular disease or symptoms. Detailed history was taken and investigations such as HbA1c, fasting and postprandial blood sugar, serum creatinine, urine examination were done. Resting ECG, Echocardiogram was found to be normal and they were subjected to a treadmill test. Results: Among the 100 participants 18 persons (18%) had positive ECG findings in treadmill test. A positive association was found between the duration of diabetes and prevalence of positive treadmill test. Conclusion: There is significant prevalence of silent CAD in diabetic patients and they tend to present with advanced disease at presentation and have poorer prognosis compared to non diabetic population. Hence it is necessary to screen early for silent CAD in diabetics to improve disease outcomes.

scholarly journals Screening for Asymptomatic Coronary Artery Disease in People With Type2 Diabetes Mellitus in a Tertiary Care Center

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A419-A419
Author(s):  
Ajoy Tewari
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
High Risk ◽  
Risk Score ◽  
Artery Disease ◽  
Asymptomatic Coronary Artery Disease

Abstract Cardiovascular disease is the biggest driver of mortality in people with diabetes. Cardiovascular disease and diabetes share the same risk factors, the so-called “common soil” hypothesis. Asians and more specifically Indians are predisposed to cardiovascular disease, that too at an earlier age. The cost of management of cardiovascular disease in India is prohibitive. Thus, screening for asymptomatic coronary artery disease in people with type 2 diabetes and referring them for further evaluation will go a long way in preventing cardiovascular mortality. 560 consenting previously diagnosed people with type 2 diabetes, undergoing treatment for type 2 diabetes at our center, were recruited in the study. We used the risk score model for the assessment of coronary artery disease in asymptomatic patients with type 2 diabetes (1) because it was easy to use, specific for Asian population and validated with coronary computed tomographic angiography in asymptomatic people with type 2 diabetes. Questions regarding smoking, past history of stroke and duration of diabetes were recorded as per the risk score and accordingly the subjects were labelled low, intermediate and high risk. Anthropometric measurements were recorded, lipid profile was measured, neuropathy assessment was done using the DNS score. Results: 48.9%subjects were females,51.1% were males, mean duration of diabetes was 3.5 years, mean HbA1c was 8.5%, mean BMI 26.5kg/m2, mean age was 51.4 years, mean CAD score was 4.1 44.2% of the subjects were in a low risk category, 44.9% were in the intermediate risk category and 10.9% in the high-risk category. The maximum people had intermediate to high risk and were in the age group of 50–60 years (21.3%), followed by 13% in the 60–70 age group. Surprisingly, 12.6% people in the 40-50year age group had an intermediate to high risk score for ASCVD. The high prevalence of intermediate to high risk in relatively younger populations with shorter duration of diabetes (mean duration of diabetes 3.5 years) mandates universal screening for asymptomatic coronary artery disease in all people with type 2 diabetes mellitus. Our study highlights the importance of identifying asymptomatic coronary artery disease using locally relevant risk models and their timely referral to prevent excessive cardiovascular mortality in people with type 2 diabetes mellitus. This would ensure optimum utilization and prioritization of scarce resources in resource crunch situations. Keywords: Screening, asymptomatic CAD, type 2 diabetes mellitus. References: 1. Park G-M, An H, Lee S-W, Cho Y-R, Gil EH, Her SH, et al. Risk Score Model for the Assessment of Coronary Artery Disease in Asymptomatic Patients With Type 2 Diabetes. Medicine [Internet]. 2015 Jan [cited 2020 Oct 14];94(4):e508. Available from: https://journals.lww.com/md-journal/Fulltext/2015/01040/Risk_Score_Model_for_the_Assessment_of_Coronary.44.aspx

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