Increased urinary loss of high density lipoproteins in albuminuric insulin-dependent diabetic patients

The pathophysiological mechanisms resulting in hyperlipidaemia in albuminuric insulin-dependent diabetic patients are largely unknown. Increased non-specific hepatic protein synthesis as a response to urinary protein loss, has been proposed. However in that case it is unexplained why the plasma concentration of the high density lipoprotein (HDL) subfraction, in contrast to all other lipoprotein subfractions, is normal or even reduced in albuminuric patients. We studied the urinary excretion of HDL-cholesterol in 26 insulin-dependent diabetic patients matched according to sex and age into three groups. I: normal urinary albumin excretion (< 30mg24h-1; n = 8); II: incipient nephropathy (urinary albumin excretion in the range of 30-300 mg24h-1; n = 7); and III: clinical nephropathy (urinary albumin excretion > 300mg24h-1; n= 11). Eight normal subjects served as controls. Lipoproteins in urine were separated by ultracentrifugation, and the daily urinary loss of HDL-cholesterol was 1.30/imol (0.83-2.21) (median and range) in controls, 1.27 μmol (0.56-2.59) in group I, 1.39μmol (0.55-1.97) in group II and 4.02^mol (1.33-42.12) in group HI (p < 0.01). More than 95% of cholesterol in urine was found in the HDL-fraction. The plasma concentrations of total cholesterol, very low density lipoprotein cholesterol, low density lipoprotein cholesterol and triglyceride were 21-94% higher in patients with clinical nephropathy compared with normal controls and group I. The plasma concentration of HDL-cholesterol was unaffected by albuminuria and lipiduria, but we found a positive correlation between the urinary excretion of albumin and the urinary excretion of HDL-cholesterol (p < 0.01). Thus, our finding of selectively increased urinary excretion of HDL-cholesterol may explain, at least in part, why the plasma concentration of this lipoprotein fraction, in contrast to others, is normal or even reduced in albuminuric insulin-dependent diabetic patients.