Glycation of apoA-I and Diabetic Atherogenesis

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.

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.

Eligibility Criteria:
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.