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Published on: October 12, 2017
High-density lipoprotein composition and paraoxonase activity in Type I diabetes
J Valabhji1, A J McColl, M Schachter
1Department of Endocrinology and Metabolic Medicine, Imperial College School of Medicine, St Mary's Hospital, Praed Street, London W2 1NY, UK. j.valabhji@ic.ac.uk
Clinical Science (London, England : 1979)
|November 29, 2001
Summary
Type I diabetes increases coronary heart disease (CHD) risk despite normal high-density lipoprotein (HDL) cholesterol. Paraoxonase (PON1) activity in HDL particles did not explain this increased risk in diabetic patients.
Area of Science:
- Biochemistry
- Cardiovascular Medicine
- Endocrinology
Background:
- Type I diabetes is linked to increased coronary heart disease (CHD) risk, a paradox given normal or elevated high-density lipoprotein (HDL) cholesterol levels.
- Paraoxonase (PON1) activity, an antioxidant enzyme associated with HDL, is hypothesized to influence HDL's protective role against CHD.
Purpose of the Study:
- To investigate the relationship between HDL composition, paraoxonase (PON1) activity, and coronary heart disease (CHD) risk in Type I diabetes.
- To determine if altered PON1 activity in specific HDL fractions contributes to the increased CHD incidence observed in diabetic individuals.
Main Methods:
- Isolated seven HDL fractions from diabetic and non-diabetic subjects using density-gradient ultracentrifugation.
- Measured PON1 activity in serum and isolated HDL fractions using phenyl acetate.
- Assessed CHD risk by measuring carotid artery intima-media thickness (IMT) via B-mode ultrasound.
Main Results:
- Diabetic subjects exhibited increased carotid IMT and higher HDL cholesterol concentrations compared to controls.
- HDL particles in diabetic subjects showed qualitative differences, including reduced triacylglycerol content and increased large, buoyant particles.
- PON1 activity was similar between diabetic and non-diabetic subjects and did not correlate with carotid IMT, suggesting it does not mediate the increased CHD risk.
Conclusions:
- HDL particle density, size, and composition influence PON1 activity.
- Despite altered HDL characteristics in Type I diabetes, PON1 activity does not appear to be a significant factor in the elevated risk of coronary heart disease.
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