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

OBJECTIIVE- To study the distribution of high-density lipoprotein (HDL ) subclasses in insulin-dependent diabetes mellitus (IDDM) patients wi th nephropathy and factors involved in the regulation of HDL, includin g plasma cholesteryl ester transfer protein (CETP) and postheparin pla sma lipoprotein lipase (LPL) and hepatic lipase (HL) activities. RESEA RCH DESIGN AND METHODS- Participants included 52 microalbuminuric IDDM patients (with a urinary albumin excretion rate [UAER] of 20-200 mu g /min), 37 macroalbuminuric IDDM patients (UAER >200 mu g/min), and 64 normoalbuminuric IDDM patients (UAER <20 mu g/min). Groups were matche d for age, body mass index, duration of diabetes, and glycemic control (HbA(1),). RESULTS- Median concentrations of HDL and HDL, cholesterol were 11.6 (P = 0.01) and 22.7% (P = 0.01) less in microalbuminuric pa tients and 5.1 and 15.5% less in macroalbuminuric patients compared wi th 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 cholestero l: 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). Posthepari n plasma LPL:HL ratio was lower in microalbuminuric patients compared with normoalbuminuric patients (1.65 vs. 1.05 [median],P < 0.01). Plas ma CETP activity was higher in the macroalbuminuric patients than in m icro- (P < 0.05) and normoalbuminuric patients (P < 0.05) bur did not correlate with HDL, HDL(2), or HDL(3) cholesterol. LPL:HL ratio correl ated positively with HDL cholesterol(r = 0.372, P < 0.001), HDL(2) cho lesterol (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). CONCLUSI ONS- IDDM patients with micro- and macroalbuminuria show only trivial changes in concentrations of different HDL parameters, which cannot ex plain che excess risk of coronary heart disease in these patients. Dat a also indicate that elevation of CETP activity in IDDM patients with nephropathy is probably not responsible for the lowering