Serum Levels of 1,5-Anhydroglucitol and Risk of Incident End-Stage Renal Disease

Glycemic excursions, independent of average glucose, have been implicated in the development of diabetic complications. It is unknown whether low levels of 1,5-anhydroglucitol (1,5-AG) are associated with advanced stages of kidney disease independent of kidney function and glycemia. In the Atherosclerosis Risk in Communities Study (n = 13,277 from 4 US communities), we used structural equation modeling to estimate the association between serum 1,5-AG levels and end-stage renal disease (ESRD) from baseline (1990-1992) through 2013 with adjustment for demographics, risk factors, a latent variable for glycemia (diabetes status, fasting glucose, glycated hemoglobin (HbA_1c), fructosamine, glycated albumin), and a latent variable for kidney function (creatinine, cystatin C, _β2-microglobulin). After adjusting for demographics, risk factors, and the latent variable for kidney function, the linear spline terms representing 1,5-AG levels <6.0 μg/mL (incidence rate ratio (IRR) = 0.79, 95% confidence interval (CI): 0.70, 0.88) and 6.0-9.9 μg/mL (IRR = 0.80, 95% CI: 0.70, 0.92) were significantly associated with ESRD. After additionally adjusting for the latent variable for glycemia, low 1,5-AG levels (<6.0 μg/mL) were no longer significantly associated with ESRD (IRR = 0.92, 95% CI: 0.81, 1.05). In conclusion, low 1,5-AG levels are associated with higher risk of incident ESRD independent of baseline kidney function but not independent of glycemia.