title: High-density lipoprotein composition and paraoxonase activity in Type I diabetes.
abstract: Type I diabetes is associated with a high incidence of coronary heart disease (CHD), despite a normal or even increased concentration of high-density lipoprotein (HDL) cholesterol. This paradox may be explained by changes in the antioxidant capacity of HDL, related to paraoxonase (PON1) activity. HDL compositional changes in subjects with Type I diabetes may result in changes in PON1 activity that are associated with a higher incidence of CHD. Single-vertical-spin density-gradient ultracentrifugation was used to isolate seven HDL fractions from serum according to density. PON1 activity was measured in serum and in the HDL fractions using phenyl acetate as substrate. The mean recovery of PON1 activity in the HDL fractions was 87% (S.D. 12%). CHD risk was assessed using B-mode ultrasound to measure carotid artery intima-media thickness (IMT). Groups of 35 subjects with Type I diabetes [duration of diabetes 18 years (12-32 years) [median (interquartile range)]; glycated haemoglobin 7.67% (1.17%)] and 24 non-diabetic control subjects were studied. Carotid IMT was greater in the diabetic subjects [0.60 (0.55-0.70) compared with 0.55 (0.45-0.64) mm; P=0.042] and HDL cholesterol concentration was higher [1.53 (0.36) compared with 1.32 (0.34) mmol/l; P=0.031]. There were qualitative differences in HDL in subjects with Type I diabetes: HDL particles were triacylglycerol-deplete, and there were greater numbers of the larger, more buoyant HDL particles. These properties were not those found to determine PON1 activity. PON1 activity increased as HDL particle density increased and particle size decreased; the increase in PON1 activity was associated with an increase in the ratio of the two HDL surface lipid components, phospholipid and unesterified cholesterol, as particle density increased. PON1 activity was similar in diabetic and non-diabetic subjects [121 (28) and 120 (36) micromol x min(-1) x ml(-1) respectively; P=0.887]. PON1 activity was not associated with carotid IMT in either group. Our results suggest that the PON1 activities of HDL particles relate to the density, size and composition of the particles. However, PON1 activity does not appear to contribute to the greater risk of CHD in subjects with Type I diabetes.
authors.affiliation: Department 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
authors.forename: J
authors.initials: J
authors.lastname: Valabhji
authors.forename: A J
authors.initials: AJ
authors.lastname: McColl
authors.forename: M
authors.initials: M
authors.lastname: Schachter
authors.forename: S
authors.initials: S
authors.lastname: Dhanjil
authors.forename: W
authors.initials: W
authors.lastname: Richmond
authors.forename: R S
authors.initials: RS
authors.lastname: Elkeles
mesh_terms: D000328:Adult; D043303:Aryldialkylphosphatase; D002339:Carotid Arteries / Q000473:pathology; D008076:Cholesterol, HDL / Q000097:blood; D003327:Coronary Disease / Q000097:blood / Q000201:enzymology; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000201:enzymology / Q000473:pathology; D003925:Diabetic Angiopathies / Q000097:blood / Q000201:enzymology; D004950:Esterases / Q000097:blood*; D005260:Female; D006801:Humans; D008075:Lipoproteins, HDL / Q000097:blood*; D008297:Male; D008875:Middle Aged; D017539:Tunica Intima / Q000473:pathology; D017540:Tunica Media / Q000473:pathology
chemical_list: D008076:Cholesterol, HDL; D008075:Lipoproteins, HDL; D004950:Esterases; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human