Glycation of apoA-I and Diabetic Atherogenesis

NCT05659043 | Unknown

• 1 other identifier: 81870357
• Study Type: observational
• Target: 2,000
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Diabetes Mellitus, Type 2

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Individual ApoA-I Glycation Profiles Variability and Cardiovascular Events

  December 2023

Study Arms (2)

T2DM with CAD

Diagnosis of T2DM was made according to the criteria of the American Diabetes Association. The patients were tested by angiography, with CAD diagnosed if luminal diameter narrowing was estimated visually at ≥50% in a major epicardial coronary artery.

Other: overnight fasting

T2DM without CAD

Diagnosis of T2DM was made according to the criteria of the American Diabetes Association. These subjects had no history of ischemic heart disease (acute myocardial infarction, unstable angina, chronic stable angina, previous percutaneous or surgical coronary revascularization, heart failure) and received CCTA in the outpatient clinics due to suspected CAD or other causes. And the luminal diameter narrowing was estimated by CCTA at ≤30%.

Other: overnight fasting

Interventions

overnight fasting OTHER

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

T2DM with CAD; T2DM without CAD

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

This study is a single-center cohort study. Patients with type 2 diabetes and suspected coronary artery disease undergone coronary angiography at Ruijin Hospital, Shanghai, China are consecutively enrolled.

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Ruijin Hospital: lead

Study Sites (1)

Ruijin Hospital, Shanghai Jiaotong University School of Medicine

Shanghai, Shanghai Municipality, 200025, China

Location

Biospecimen

Retention: SAMPLES WITH DNA

plasma and PBMCs

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 11, 2022
• First Posted: December 21, 2022
• Study Start: January 1, 2017
• Primary Completion: December 1, 2021
• Study Completion: December 1, 2023
• Last Updated: December 21, 2022

Record last verified: 2022-12

Locations

CN (1)