1092-P: sRAGE—A Biomarker of Kidney Disease in Youth-Onset Type 2 Diabetes (T2D)

The circulating soluble receptor for advanced glycation end products (sRAGE) has been proposed as a biomarker of diabetes complications in adults. In the TODAY study of youth with T2D, we measured sRAGE 3 times at: randomization (T1), glycemic failure (HbA1c≥8%) on randomized treatment or midpoint in study (T2), and end of follow-up (T3). Of TODAY subjects, 165 lost glycemic control with HbA1c ≥ 8% (G1) and 135 maintained HbA1c < 8% (G2)]. Controls [n=99, HbA1 5% (4.9, 5.2), with similar obesity, sex (60% female), race-ethnicity, median age 24 (21, 27) years as the TODAY cohort at T3] had sRAGE measured once. Multivariable models examined the relationship of sRAGE with nephropathy [urine albumin: creatinine (UACR) ≥30 mg/g, hyperfiltration (eGFR ≥135 ml/min/1.73m²)] and vascular measures [pulse wave velocity (PWV), augmentation index (AI)], adjusting for treatment, diabetes duration, HbA1c, BMI, age, sex, and race-ethnicity. At T1, the T2D youth groups had similar age (13.9 yrs), diabetes duration (0.7 yrs), and sex (60% female). sRAGE concentrations were lower in T2D vs. controls (752.8±308.3 vs. 954.4 ± 356.7 pg/ml, p<0.0001) at T3. By T3 (mean duration 7 yrs), sRAGE levels decreased compared with T1 and T2 in G1 vs. G2 (p<0.05). sRAGE concentrations were 711.9±294.1 vs. 802.7±318.9 pg/ml, p=0.0032 in G1 vs. G2 at T3, with no significant difference by treatment. HbA1c was inversely related with sRAGE. Higher sRAGE concentrations were associated with a lower risk of hyperfiltration (HR=0.93, 95% CI 0.86-0.99, p=0.03) and inversely related to eGFR (p<0.001); no relationships were observed with UACR, PWV, or AI. sRAGE levels decline overtime in youth with T2D, are inversely related to glycemia, and may serve as a biomarker of kidney function.