Plasma Cholesteryl Ester Transfer Protein and Its Relationship to Plasma Lipoproteins and Apolipoprotein A-I-Containing Lipoproteins in IDDM Patients With Microalbuminuria and Clinical Nephropathy

OBJECTIVE: To study the distribution of high-density lipoprotein (HDL) subclasses in insulin-dependent diabetes mellitus (IDDM) patients with nephropathy and factors involved in the regulation of HDL, including plasma cholesteryl ester transfer protein (CETP) and postheparin plasma lipoprotein lipase (LPL) and hepatic lipase (HL) activities. RESEARCH DESIGN AND METHODS: Participants included 52 microalbuminuric IDDM patients (with a urinary albumin excretion rate [UAER] of 20-200 micrograms/min), 37 macroalbuminuric IDDM patients (UAER > 200 micrograms/min), and 64 normoalbuminuric IDDM patients (UAER < 20 micrograms/min). Groups were matched for age, body mass index, duration of diabetes, and glycemic control (HbA1). RESULTS: Median concentrations of HDL and HDL2 cholesterol were 11.6 (P = 0.01) and 22.7% (P = 0.01) less in microalbuminuric patients and 5.1 and 15.5% less in macroalbuminuric patients compared with normoalbuminuric patients. No significant differences were observed in the concentrations of apoA-I, apoA-II (apolipoprotein) or LpA-I or LpA-I:A-II (lipoprotein) particles between the groups. HDL cholesterol: apoA-I+apoA-II ratio was significantly lower in micro- (19.7 +/- 4.2 (+/- SD); P < 0.01) and macroalbuminuric patients (20.0 +/- 3.7, P < 0.05) than in normoalbuminuric patients (22.1 +/- 4.4). Postheparin plasma LPL:HL ratio was lower in microalbuminuric patients compared with normoalbuminuric patients (1.65 vs. 1.05 [median], P < 0.01). Plasma CETP activity was higher in the macroalbuminuric patients than in micro- (P < 0.05) and normoalbuminuric patients (P < 0.05) but did not correlate with HDL, HDL2, or HDL3 cholesterol. LPL:HL ratio correlated positively with HDL cholesterol (r = 0.372, P < 0.001), HDL2 cholesterol (r = 0.413, P < 0.001) and with LpA-I particles (r = 0.355, P < 0.001) but not with LpA-I:A-II particles (r = -0.065, NS). CONCLUSIONS: IDDM patients with micro- and macroalbuminuria show only trivial changes in concentrations of different HDL parameters, which cannot explain the excess risk of coronary heart disease in these patients. Data also indicate that elevation of CETP activity in IDDM patients with nephropathy is probably not responsible for the lowering of HDL cholesterol.