METABOLISM OF HDL APOLIPOPROTEIN-A-I AND APOLIPOPROTEIN-A-II IN TYPE-1 (INSULIN-DEPENDENT) DIABETES-MELLITUS

Concentrations of HDL cholesterol and apolipoprotein A-I are commonly increased in Type 1 (insulin-dependent) diabetes mellitus but the mech anisms whereby diabetes influences HDL metabolism have not been studie d. We investigated the metabolism of HDL apoproteins A-I and II in nor molipidaemic Type 1 diabetic men (n = 17, HbA1 6.4-11.9%) without micr oalbuminuria but with a wide range of HDL cholesterol (0.85-2.10 mmol/ l) and in non-diabetic men (n = 18) matched for body mass index and th e range of HDL cholesterol. Input rates and fractional catabolic rates for apolipoproteins A-I and II were determined following injection of I-125-apolipoprotein A-I and I-131-apolipoprotein A-I tracers. Additi onal multicompartmental analysis was performed using a model to descri be the kinetics of HDL particles containing only apolipoprotein A-I (L p A-I) and apolipoprotein A-I and apolipoprotein A-II (Lp A-I/A-II). N o gross differences from normal subjects were observed in the mean lev els of lipids, lipoproteins, apoproteins and the lipolytic enzymes in the diabetic men as a result of the selection process. Furthermore, th e relationship between apolipoprotein A kinetics and plasma HDL choles terol levels appeared to be preserved in the diabetic group. However, some normal interrelationships were disrupted in the diabetic men. Fir stly, the rate of apolipoprotein A-II synthesis was 22% lower than in control subjects (p < 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 p articles was similar in the two groups. Secondly, there was no correla tion between VLDL triglyceride and HDL cholesterol or VLDL triglycerid e and the fractional catabolic rate of apolipoproteins A-I and A-II in diabetic men in contrast to that seen in control subjects. We conclud e that there is a disruption in the normal association between VLDL an d HDL metabolism in Type 1 diabetic men and postulate that the observe d differences may be due to the therapeutic use of exogenous insulin.