Longitudinal analysis of low-molecular weight fluorophores in type 1 diabetes mellitus

Objectives : Circulating low molecular weight (<10 kDa) fluorophores (LMW-F) measured by non-specific fluorescence spectroscopy may detect small advanced glycation end-products (AGEs) not recognized by other assays. This longitudinal study assessed correlates of LMW-F and predictive power of LMW-F levels for vascular health in Type 1 diabetes (T1DM) patients. Methods : Fasting patients with T1DM (n=37) were studied twice at intervals of 12-60 months (mean±SD, 33±15 months). LMW-F levels were also measured once in 112 healthy control subjects. Results : Relative to controls, LMW-F levels were higher in diabetic subjects at initial and final time points (mean±SD), 5.4±1.9 AU/ml and 4.5±1.8 AU/ml respectively vs. 3.8±2.1 AU/ml ; p=0.0001 and p=0.06). Baseline LMW-F levels predicted subsequent hs-CRP and oxLDL/LDL values. LMW-F levels decreased significantly over time in diabetes (5.4 ± 1.9 vs. 4.5 ± 1.8 AU/ml ; p=0.02). Rises in LMW-F levels in individual diabetic subjects correlated significantly with worsening renal function (BUN), glycemia (HbA1c) and with vascular dysfunction (systemic vascular resistance). Conclusions : LMW-F levels predict levels of inflammation and oxidation in T1DM. Changes in LMW-F levels in T1DM reflect variations in glycemia and renal function. Biochemical characterization of LMW-F would facilitate understanding of the potential utility of LMW-F as a therapeutic target.