OBJECTIVE
Salsalate is a nonacetylated
salicylate that lowers
glucose levels in people with
type 2 diabetes (T2D). Here we examined whether
salsalate also lowered
serum-protein-bound levels of early and
advanced glycation end products (AGEs) that have been implicated in
diabetic vascular complications. RESEARCH DESIGN AND METHODS Participants were from the Targeting
Inflammation Using
Salsalate for
Type 2 Diabetes (TINSAL-T2D) study, which examined the impact of
salsalate treatment on
hemoglobin A1c (HbA1c) and a wide variety of other parameters. One hundred eighteen participants received
salsalate, 3.5 g/day for 48 weeks, and 109 received placebo. Early glycation product levels (HbA1c and
fructoselysine [measured as
furosine]) and AGE levels (
glyoxal and
methylglyoxal hydroimidazolones [G-(1)H, MG-(1)H],
carboxymethyllysine [CML],
carboxyethyllysine [CEL],
pentosidine) were measured in patient serum samples. RESULTS Forty-eight weeks of
salsalate treatment lowered levels of HbA1c and serum
furosine (P < 0.001) and CML compared with placebo. The AGEs CEL and G-(1)H and MG-(1)H levels were unchanged, whereas
pentosidine levels increased more than twofold (P < 0.001). Among
salsalate users, increases in
adiponectin levels were associated with lower HbA1c levels during follow-up (P < 0.001). Changes in renal and
inflammation factor levels were not associated with changes in levels of early or late glycation factors.
Pentosidine level changes were unrelated to changes in levels of renal function,
inflammation, or
cytokines. CONCLUSIONS
Salsalate therapy was associated with a reduction in early but not late glycation end products. There was a paradoxical increase in serum
pentosidine levels suggestive of an increase in oxidative stress or decreased clearance of
pentosidine precursor.