Longitudinal analysis of low-molecular weight fluorophores in type 1 diabetes mellitus.
OBJECTIVE
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.
Januszewski
Andrzej S
AS
University of Melbourne, Department of Medicine, St Vincent's Hospital, Melbourne, Australia.
Thomas
Merlin C
MC
Karschimkus
Connie S
CS
Chung
Jasmine S
JS
Rowley
Kevin G
KG
Nelson
Craig L
CL
O'Neal
David N
DN
Dragicevic
George
G
Harper
Colin A
CA
Best
James D
JD
Jenkins
Alicia J
AJ
D000328:Adult; D015415:Biomarkers / Q000097:blood; D003922:Diabetes Mellitus, Type 1 / Q000175:diagnosis* / Q000628:therapy; D003925:Diabetic Angiopathies / Q000175:diagnosis / Q000628:therapy; D003928:Diabetic Nephropathies / Q000175:diagnosis / Q000628:therapy; D005260:Female; D017127:Glycation End Products, Advanced / Q000097:blood*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D008970:Molecular Weight; D018384:Oxidative Stress; D013050:Spectrometry, Fluorescence; D013194:Staining and Labeling
D015415:Biomarkers; D017127:Glycation End Products, Advanced