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- Title
Paraoxonase 1 Mass (PON1) and Microvascular Complications in Type 2 Diabetes (DM).
- Authors
Hanley, Anthony J.; Zinman, Bernard; Maguire, Graham; Mamakeesick, Mary; Harris, Stewart B.; Hegele, Robert; Retnakaran, Ravi; Klein, Ronald; Connelly, Phillip W.
- Abstract
PON1, an anti-inflammatory / antioxidant enzyme associated with HDL-containing apolipoprotein A1 (apoA1), is reduced in subjects with DM, although limited data are available regarding PON1 and microvascular complications. Our objective was to evaluate the association of PON1 mass with microvascular disease in 107 subjects with DM (age, 46±12y; DM duration, 9±7y; A1c, 8±2%) in a community-based study. Microalbuminuria was assessed using the urine albumin/creatinine ratio (ACR); kidney dysfunction using the estimated glomerular filtration rate (eGFR, Cockcroft-Gault) and plasma cystatin C concentration; and neuropathy with the Michigan Neuropathy Screening Instrument. Retinopathy was graded from digital photographs using standard methods. A1c, blood pressure, lipids, waist, and DM treatment and duration were assessed. PON1 was measured after separation of plasma by SDS electrophoresis and Western blot with anti-human PON1 monoclonal antibody 4C10 and detection with Alexa Fluor 680 anti-mouse IgG, and was analyzed using the PON1/HDL and PON1/APO A1 ratios. PON1/HDL and PON1/apoA1 were associated positively with eGFR (r=0.32, r=0.25, both p<0.001) and inversely with cystatin C (r= -0.26, r= -0.27, both p<0.001). After adjustment for age, sex, waist, DM duration, A1c, and DM treatment in multiple regression, the inverse association of PON1/apoA1 with cystatin C remained significant β= -0.002, t=-2.13, p=0.037). In addition, 1 SD differences in both PON1/HDL and PON1/apoA1 were inversely associated with the presence of retinopathy (PON/HDL: odds ratio (OR) = 0.4 (95% CI 0.2-0.9), p=0.02); PON/apoA1: OR=0.5 (0.3-1.0), 13=0.049). After adjustment for age, sex: DM duration, systolic BP and A1c, the inverse association with PON1/HDL was of borderline statistical significance (OR = 0.5 (0.2-1.0), p=0.06). There was no association of PON1 with ACR or neuropathy. In conclusion, these data support a possible role for inflammation and/or oxidative stress in the development of microvascular disease.
- Subjects
PARAOXONASE; DIABETES complications; TYPE 2 diabetes; APOLIPOPROTEINS; MICROCIRCULATION disorders; GLOMERULAR filtration rate; DIABETIC retinopathy
- Publication
Diabetes, 2007, Vol 56, pA213
- ISSN
0012-1797
- Publication type
Article