Session: SUN 758-779-Cardiometabolic Risk & Vascular Biology
Poster Board SUN-766
Subjects and Methods: T2DM subjects in the present study were selected from the ongoing SMART2D study (Singapore study of MAcro-angiopathy and micro-vascular Reactivity in Type 2 Diabetes). By the cut-off time of this sub-study (August 31, 2012), 486 T2DM with normal albuminuria (urine ACR < 30 μg/mg and eGFR>60 ml/min/1.73m2; age 55.6 ± 11.1 yrs, male 47.9%, T2DM duration 8.9 ± 7.5 yrs), 253 T2DM with microalbuminuria (ACR >=30 μg/mg but < 300 μg/ml and eGFR> 60 ml/min/1.73m2; age 57.3 ± 11.3 yrs, male 46.8%, T2DM duration 12.2 ± 9.8 yrs) and 269 T2DM with overt diabetic nephropathy (DN, ACR>=300 μg/mg and/or eGFR < 60 ml/min/1.73m2 ; age 60.6 ± 9.9 yrs, male 55.8% , T2DM duration 15.0 ± 9.7 yrs) were recruited. Within each group, 200 subjects were randomly selected for this sub-study (n=600 total). Carotid-femoral pulse wave velocity (PWV) was measured by SphygmoCor (AtCor Medical, Australia) and total sRAGE was quantified by ELISA (R&D Systems, Minneapolis, MN).
Results: Plasma sRAGE was increased with the deterioration of renal function (918 ± 411 pg/ml, 975 ± 423 pg/ml and 1437 ± 916 pg/ml in T2DM with normalbuminuria, microalbuminuria and overt DN, respectively. p<0.0001 after adjustment for age and gender). Stepwise linear regression showed that sRAGE was associated with eGFR, logACR, age and BMI, but not PWV, which was also increased with the progression of renal impairment (9.2±2.6 m/s, 9.8±2.7 m/s and 11.0±2.9 m/s in T2DM with normalbuminuria, microalbuminuria and overt DN, respectively. P<0.0001). Cognizant of potential confounding by impaired renal function, we analyzed the association between PWV and sRAGE by stratifying the subjects based on severity of renal impairment. Pearson bivariate correlation analysis showed that PWV and sRAGE was significantly correlated only in T2DM with normalbuminuria (r=-0.177, p=0.012). Further analysis by linear regression revealed that PWV was independently associated with age, SBP, duration of diabetes and sRAGE in T2DM with normalbuminuria after adjustment for multiple covariates (R2=0.436, p<0.0001).
Conclusions: In T2DM, plasma sRAGE was increased with progressive deterioration in renal function. Soluble RAGE was significantly associated with PWV only in normalbuminuric T2DM. Our finding that sRAGE was inversely associated with arterial stiffness in early stage of T2DM might have clinical implications.
Nothing to Disclose: ECKY, JJL, LYY, ST, CFS, XWN, WCT, SP, SCL
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