Glycation of apoA-I and Diabetic Atherogenesis

Diabetes Mellitus, Type 2 Clinical Trial

Official title:

The Impact of Glycation Modification of apoA-I on HDL Function and Atherogenesis in Type Diabetes Mellitus

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05659043
• Other study ID #: 81870357
• Status: Active, not recruiting
• Start date: January 2017
• Est. completion date: December 2023

Study information

• Verified date: December 2022
• Source: Ruijin Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The goal of this study is to determine the relationship of apoprotein A-1 (apoA-I) glycation and development of diabetic atherosclerosis.

ApoA-I is crucial for reverse cholesterol transport and anti-inflammation/anti-atherosclersis functions of HDL. However, apoA-I is easily subjected to non-enzymatic glycation modification in diabetic milleu. Our preliminary study has shown that apoA-I in HDL from type 2 diabetes mellitus (T2DM) patients with coronary artery disease (CAD) is significantly glycated, and site specific glycation of apoA-I impairs HDL function and is related to the development of atherosclerosis. To the best of our knowledge, less clinical information regarding apoA-I glycation and CAD has been reported. In this cross-sectional study, by consecutively enrolling diabetic patients with (two to three hundred) or without CAD (controls, six to eight hundred) in our hospital, we will isolate their serum HDL and perform a qualitative and quantitative proteomic analysis of apoA-I glycation. The relation of apoA-I glycation and HDL function and angiography-determined severity of CAD will be evaluated. Later, we will follow these diabetic patients to analyze the influence of apoA-I glycation on the outcome including plaque progression.

Description:

The goal of this study is to determine the relationship of apoprotein A-1 (apoA-I) glycation and development of diabetic atherosclerosis.

ApoA-I is crucial for reverse cholesterol transport and anti-inflammation/anti-atherosclersis functions of HDL. However, apoA-I is easily subjected to non-enzymatic glycation modification in diabetic milleu. Our preliminary study has shown that apoA-I in HDL from type 2 diabetes mellitus (T2DM) patients with coronary artery disease (CAD) is significantly glycated, and site specific glycation of apoA-I impairs HDL function and is related to the severity of atherosclerosis. To the best of our knowledge, less clinical information regarding apoA-I glycation and CAD has been reported. In this cross-sectional study, we will consecutively enroll several hundred diabetic patients (two to three hundred) with no CAD (less than stenosis of 25% in coronary CTA) as controls. And we will also consecutively enroll several hundred (six to eight hundred) angiographically established T2DM patients with CAD (stenosis of >50% in coronary angiography). Serum HDL of all participants will be isolated and a qualitative and quantitative proteomic analysis of apoA-I glycation will be performed by mass spectrometry. The relation of apoA-I glycaiton and HDL function and angioraphy-determined severity of CAD will be evaluated. Later, we will follow these diabetic patients for approximately two years to analyze the influence of apoA-I glycation on the clinical outcomes (stroke, myocardial infarction, hospitalization for heart failure, death due to cardiovascular causes, etc) including plaque progression.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 2000
• Est. completion date: December 2023
• Est. primary completion date: December 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

Inclusion Criteria:

Type 2 diabetes diagnosed by one of the following criteria:

HbA1c >/= 6.5% Fasting plasma glucose >/= 7.0 mmol/l (confirmed) 2h plasma glucose value during OGTT >/= 11.1 mmol/l Already receiving glucose-lowering agents; Receiving coronary angiography for clinically suspected CAD (T2DM with CAD), Receiving CCTA for suspected CAD or other causes (T2DM without CAD).

Exclusion Criteria:

Severe liver failure (Child-Pugh grade B to C); Severe anemia (hemoglobin < 60g/L); Familial hypercholesterolemia; Active malignant tumor; Active autoimmune diseases on corticosteroids; Acute or chronic infection; Death.

Related Conditions & MeSH terms

• Atherosclerosis
• Diabetes Mellitus
• Diabetes Mellitus, Type 2

Intervention

Other:
• overnight fasting
All blood samples were taken on the day of cardiac catheterization after overnight fasting.

Locations

Country	Name	City	State
China	Ruijin Hospital, Shanghai Jiaotong University School of Medicine	Shanghai	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Ruijin Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Qualitative and Quantitative Mapping ApoA-I Glycation Modification Profiles	One of aims is understanding the importance of apoA-I glycation modification in HDL dysfunction and the progression of diabetic CAD, a comprehensive analysis of apoA-I glycation modification requires numerous levels of information, including (1) the type of glycation modification, (2) glycation localization, (3) glycation frequency in the subject cohort, and (4) the extent of glycation. The other aim is identifying the crucial pathogenic glycation sites of apoA-I based on apoA-I glycation modification profiles. Defining the chemistry of the pathologic glycation sites of apoA-I during progression of CAD will allow us to target specific epitopes using therapeutic antibodies or small molecules at every stage of disease.	completion date - December 2021
Secondary	Individual ApoA-I Glycation Profiles Variability and Cardiovascular Events	Individual ApoA-I Glycation Profiles Variability is evaluated annually,and The incidence of MACCE (major adverse cardio and cerebral vascular events), lesion associated events (target lesion myocardial infarction, target lesion faliure, target vessel Revascularization, etc. observed continuously for 3 years.	December 2023