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The impact of salsalate treatment on serum levels of advanced glycation end products in type 2 diabetes.

Abstract

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.

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    Corresponding author: Joshua I. Barzilay, joshua.barzilay@kp.org.

    , , , , , ,

    Source

    Diabetes care 37:4 2014 Apr pg 1083-91

    MeSH

    Adiponectin
    Adult
    Anti-Inflammatory Agents, Non-Steroidal
    Arginine
    Diabetes Mellitus, Type 2
    Diabetic Angiopathies
    Female
    Glycated Hemoglobin A
    Glycation End Products, Advanced
    Humans
    Lysine
    Male
    Middle Aged
    Pyruvaldehyde
    Salicylates

    Pub Type(s)

    Clinical Trial, Phase II
    Journal Article
    Randomized Controlled Trial
    Research Support, N.I.H., Extramural

    Language

    eng

    PubMed ID

    24255104

    Citation

    Barzilay, Joshua I., et al. "The Impact of Salsalate Treatment On Serum Levels of Advanced Glycation End Products in Type 2 Diabetes." Diabetes Care, vol. 37, no. 4, 2014, pp. 1083-91.
    Barzilay JI, Jablonski KA, Fonseca V, et al. The impact of salsalate treatment on serum levels of advanced glycation end products in type 2 diabetes. Diabetes Care. 2014;37(4):1083-91.
    Barzilay, J. I., Jablonski, K. A., Fonseca, V., Shoelson, S. E., Goldfine, A. B., Strauch, C., & Monnier, V. M. (2014). The impact of salsalate treatment on serum levels of advanced glycation end products in type 2 diabetes. Diabetes Care, 37(4), pp. 1083-91. doi:10.2337/dc13-1527.
    Barzilay JI, et al. The Impact of Salsalate Treatment On Serum Levels of Advanced Glycation End Products in Type 2 Diabetes. Diabetes Care. 2014;37(4):1083-91. PubMed PMID: 24255104.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - The impact of salsalate treatment on serum levels of advanced glycation end products in type 2 diabetes. AU - Barzilay,Joshua I, AU - Jablonski,Kathleen A, AU - Fonseca,Vivian, AU - Shoelson,Steven E, AU - Goldfine,Allison B, AU - Strauch,Christopher, AU - Monnier,Vincent M, AU - ,, Y1 - 2013/11/19/ PY - 2013/11/21/entrez PY - 2013/11/21/pubmed PY - 2015/1/23/medline SP - 1083 EP - 91 JF - Diabetes care JO - Diabetes Care VL - 37 IS - 4 N2 - 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. SN - 1935-5548 UR - https://www.unboundmedicine.com/medline/citation/24255104/The_impact_of_salsalate_treatment_on_serum_levels_of_advanced_glycation_end_products_in_type_2_diabetes_ L2 - http://care.diabetesjournals.org/cgi/pmidlookup?view=long&amp;pmid=24255104 DB - PRIME DP - Unbound Medicine ER -