Association of the novel cardiovascular risk factors paraoxonase 1 and cystatin C in type 2 diabetes * [S]

Paraoxonase 1 (PON1) has been reported to be associated with proteinuria in subjects with type 2 diabetes mellitus (T2DM). Plasma cystatin C is more accurate than creatinine for identifying stage 3 kidney disease in T2DM. We tested the hypothesis that PON1 and cystatin C would be associated in T2DM subjects from an Aboriginal Canadian community, who are at high risk for the development of nephropathy. PON1 A(-162)G and PON2 Ala148Gly genotypes, cystatin C, HbA1c, high density lipoprotein cholesterol (HDLC), waist circumference (waist), and duration of diabetes were included in the regression analysis with log e (ln) of PON1 mass as the dependent variable. A regression model including PON2 Ala148Gly genotype, HDLC, and ln cystatin C explained 25.8% of the variance in PON1 mass. Conversely, waist, age, ln HbA1c, ln duration of diabetes, and ln PON1 mass, but not PON2 genotype, explained 38% of the variance in cystatin C. Subjects with cystatin C estimated glomerular filtration rate (eGFR) <60 ml/min per 1.73 m 2 (stage 3 kidney disease) had significantly lower PON1 mass compared with subjects with cystatin C-eGFR >60 ml/min per 1.73 m 2. The lower mass of PON1, an anti-inflammatory HDL-associated enzyme, in T2DM with cystatin C-eGFR <60 ml/min per 1.73 m 2 may contribute to their increased risk for cardiovascular disease.