title: Metabolism of HDL apolipoprotein A-I and A-II in type 1 (insulin-dependent) diabetes mellitus.
abstract: Concentrations of HDL cholesterol and apolipoprotein A-I are commonly increased in Type 1 (insulin-dependent) diabetes mellitus but the mechanisms whereby diabetes influences HDL metabolism have not been studied. We investigated the metabolism of HDL apoproteins A-I and II in normolipidaemic Type 1 diabetic men (n = 17, HbA1 6.4-11.9%) without microalbuminuria but with a wide range of HDL cholesterol (0.85-2.10 mmol/l) and in nondiabetic men (n = 18) matched for body mass index and the range of HDL cholesterol. Input rates and fractional catabolic rates for apolipoproteins A-I and II were determined following injection of 125I-apolipoprotein A-I and 131I-apolipoprotein A-II tracers. Additional multicompartmental analysis was performed using a model to describe the kinetics of HDL particles containing only apolipoprotein A-I (Lp A-I) and apolipoprotein A-I and apolipoprotein A-II (Lp A-I/A-II). No gross differences from normal subjects were observed in the mean levels of lipids, lipoproteins, apoproteins and the lipolytic enzymes in the diabetic men as a result of the selection process. Furthermore, the relationship between apolipoprotein A kinetics and plasma HDL cholesterol levels appeared to be preserved in the diabetic group. However, some normal interrelationships were disrupted in the diabetic men. Firstly, the rate of apolipoprotein A-II synthesis was 22% lower than in control subjects (p less than 0.05). Modelling indicated that this was due to decreased input of Lp A-I/A-II particles whereas the input of Lp A-I particles was similar in the two groups. Secondly, there was no correlation between VLDL triglyceride and HDL cholesterol or VLDL triglyceride and the fractional catabolic rate of apolipoproteins A-I and A-II in diabetic men in contrast to that seen in control subjects. We conclude that there is a disruption in the normal association between VLDL and HDL metabolism in Type 1 diabetic men and postulate that the observed differences may be due to the therapeutic use of exogenous insulin.
authors.affiliation: Third Department of Medicine, University of Helsinki, Finland.
authors.forename: M R
authors.initials: MR
authors.lastname: Taskinen
authors.forename: J
authors.initials: J
authors.lastname: Kahri
authors.forename: V
authors.initials: V
authors.lastname: Koivisto
authors.forename: J
authors.initials: J
authors.lastname: Shepherd
authors.forename: C J
authors.initials: CJ
authors.lastname: Packard
mesh_terms: D000328:Adult; D016632:Apolipoprotein A-I / Q000378:metabolism*; D016633:Apolipoprotein A-II / Q000378:metabolism*; D001786:Blood Glucose / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008049:Lipase / Q000378:metabolism; D008071:Lipoprotein Lipase / Q000097:blood; D008099:Liver / Q000201:enzymology; D008297:Male; D008954:Models, Biological; D012016:Reference Values
chemical_list: D016632:Apolipoprotein A-I; D016633:Apolipoprotein A-II; D001786:Blood Glucose; D008049:Lipase; D008071:Lipoprotein Lipase