Abstract
BACKGROUND: Advanced glycation end-products (AGEs) are one of the mechanisms related to diabetic vascular complications. However, since AGEs are multiple and heterogeneous moieties, there is no universally accepted method to measure them for clinical purposes. The aim of this work was to study the utility of a simple fluorimetric assay as predictor of complications. METHODS: Blood samples from 102 type 2 diabetic patients were obtained to assess glucose, glycosylated haemoglobin, creatinine, lipoproteins and C Reactive Protein (CRP), fluorescent AGES by spectrophotofluorimetry and non-fluorescent AGEs by measurement of N(ε)-carboxymethyl-Lysine (CML) using an ELISA kit in a subsample of 82 patients. Urinary fluorescent AGEs, albumin and creatinine were also measured in a morning urine sample. Microvascular complications were studied by ophthalmologic examination, albuminuria and peripheral nerve conduction velocity. RESULTS: Patients without microvascular complications had significantly lower levels of both serum and urinary AGEs. CML was associated with retinopathy. Multiple regression analysis confirmed that AGEs, length of diabetes and glycosylated haemoglobin were all variables associated with diabetic complications, in this sample. CONCLUSIONS: A simple fluorimetric assay to measure low molecular weight fluorescent AGEs, and CML could be employed as screening tools to predict diabetic complications, at a primary care setting. AGEs should probably be considered as another therapeutic target in diabetes management.
Highlights
Advanced glycation end-products (AGEs) are moieties formed endogenously by the non-enzymatic “browning” or Maillard biochemical reaction of a ketone or aldehyde group from reducing sugars such as glucose, with free amino groups from proteins,with further rearrangements, to form stable and undigestible compounds, which crosslink to lysine residues of long-lived proteins, such as collagen
In this study we treated the serum and urine samples as for flow injection assay (FIA), but measured flurescence and photometry of the remaining low molecular weight fraction, in a 96 plate spectro-photofluorimeter, to see if this simpler method was able to discriminate between patients with or without microvascular complications. Less sensitive, this methodology could represent a simple way to screen for microvascular complications in type 2 diabetics
When separating according to number of microvascular complications, serum fluorescent AGEs were found to be significantly lower among uncomplicated diabetics (Table 1)
Summary
Advanced glycation end-products (AGEs) are moieties formed endogenously by the non-enzymatic “browning” or Maillard biochemical reaction of a ketone or aldehyde group from reducing sugars such as glucose, with free amino groups from proteins,with further rearrangements, to form stable and undigestible compounds, which crosslink to lysine residues of long-lived proteins, such as collagen. Intracellular sugars such as glucose 6-phosphate and fructose, originate AGEs faster than glucose. AGEs should probably be considered as another therapeutic target in diabetes management
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