Advertisement

Acta Diabetologica

, Volume 50, Issue 4, pp 537–543 | Cite as

Salsalate improves glycemic control in patients with newly diagnosed type 2 diabetes

  • Elham Faghihimani
  • Ashraf Aminorroaya
  • Hassan Rezvanian
  • Peyman Adibi
  • Faramarz Ismail-Beigi
  • Masoud Amini
Original Article

Abstract

Chronic inflammation contributes to insulin resistance and type 2 diabetes mellitus (T2DM). We investigated whether treatment with salsalate, an anti-inflammatory medication, improves glycemia in a group of newly diagnosed drug-naïve patients with T2DM. The study was a randomized, double-blind, placebo-controlled trial. Diagnosis of T2DM was made within 2 months of enrollment, and participants had not received any anti-glycemic agent. Sixty adults were randomized to receive salsalate (3 g/day) or placebo for 12 weeks. Fasting plasma glucose and insulin, glucose 2 h after 75 g oral glucose, HbA1C, lipid profile, HOMA-IR, and HOMA-B were determined before and after treatment. Salsalate reduced fasting glucose from 6.3 ± 0.2 mmol/l to 5.4 ± 0.2 mmol/l (P < 0.01) and TG from 1.9 ± 0.2 mmol/l to 1.5 ± 0.2 mmol/l (P < 0.03). Fasting insulin levels were increased in the salsalate group from 18.8 ± 1.6 to 21.6 ± 3.9, while they decreased in the placebo group. HbA1c rose in the placebo group from 6.2% ± 0.2 to 7.9% ± 1.1 mmol/mol, but decreased in the intervention group from 6.1% ± 0.5 to 5.6% ± 0.2 mmol/mol (P < 0.04 for between-group comparison). HOMA-IR did not change but HOMA-B increased ~1.7-fold (P = 0.06) in the salsalate group. The results show that salsalate is effective in improving glycemic control in newly diagnosed naïve patients with T2DM. The optimal duration of treatment with salsalate and sustainability of its effect requires further study (IRCT138709011465N1).

Keywords

Salsalate Type 2 diabetes Glycemic control 

Notes

Acknowledgments

No potential conflicts of interest relevant to this article were reported. E.F. wrote the manuscript and researched data. A.A. reviewed/edited the manuscript. H.R. And P.A. reviewed/edited the manuscript. F.I-B. contributed to the discussion and reviewed/edited the manuscript. M.A. researched data and contributed to discussion. The authors thank Majid Abyar, Maryam Zare, Atsa Noruzi and all the staff of the Isfahan Endocrinology and Metabolism Research Center. The authors acknowledge Isfahan University of Medical Sciences for the financial support of this study as a dissertation for E.F.

Conflicts of interest

Nothing to declare.

References

  1. 1.
    King H, Aubert RE, Herman WH (1998) Global burden of diabetes, 1995–2025: prevalence, numerical estimates, and projections. Diabetes 21:1414–1431CrossRefGoogle Scholar
  2. 2.
    zachary t. bloomgarden (2003) Inflammation and insulin resistance. Diabetes Care 26(6):1922–1926Google Scholar
  3. 3.
    Duncan BB, Schmidt MI (2006) The epidemiology of low-grade chronic systemic inflammation and type 2 diabetes. Diabetes Technol Ther 8:7–17PubMedCrossRefGoogle Scholar
  4. 4.
    Burke AP, Tracy RP, Kolodgie F, Malcom GT, Zieske A, Kutys R, Pestaner J, Smialek J, Virmani R (2002) Elevated C-reactive protein values and atherosclerosis in sudden coronary death: association with different pathologies. Circulation 105:2019–2023PubMedCrossRefGoogle Scholar
  5. 5.
    Thorand B, Lowel H, Schneider A, Kolb H, Meisinger C, Frohlich M, Koenig W (2003) C-reactive protein as a predictor for incident diabetes mellitus among middle aged men: results from the MONICA Ausburg cohort study. Arch Intern Med 163:93–99PubMedCrossRefGoogle Scholar
  6. 6.
    Han TS, Sattar N, Williams K, Gonzalez-Villalpando C, Lean ME, Haffner SM (2002) Prospective study of C-reactive protein in relation to the development of diabetes and metabolic syndrome in the Mexico City Diabetes Study. Diabetes Care 25:2016–2021PubMedCrossRefGoogle Scholar
  7. 7.
    Festa A, D’Agostino R Jr, Howard G, Mykkanen L, Tracy RP, Haffner SM (2002) Chronic subclinical inflammation as part of the insulin resistance syndrome: the insulin resistance atherosclerosis study (IRAS). Circulation 102:42–47CrossRefGoogle Scholar
  8. 8.
    Romano M, Guagnano MT, Pacini G, Vigneri S, Falco A, Marinopiccoli M, Manigrasso MR, Basili S, Davi G (2003) Association of inflammation markers with impaired insulin sensitivity and coagulative activation in obese healthy women. J Clin Endocrinol Metab 88:5321–5326PubMedCrossRefGoogle Scholar
  9. 9.
    Duncan BB et al (2003) Low-grade systemic inflammation and the development of type 2 diabetes: the atherosclerosis risk in communities study. Diabetes 52:1799–1805PubMedCrossRefGoogle Scholar
  10. 10.
    Kolb H, Mandrup-Poulsen T (2005) An immune origin of type 2 diabetes? Diabetologia 48:1038–1050PubMedCrossRefGoogle Scholar
  11. 11.
    Shoelson SE, Lee J, Yuan M (2003) Inflammation and the IKKβ/IκB/NF-κB axis in obesity and diet-induced insulin resistance. Int J Obes Relat Metab Disord 27(Suppl. 3):S49–S52Google Scholar
  12. 12.
    Shoelson SE, Lee J, Goldfine AB (2006) Inflammation and insulin resistance. J Clin Invest 116:1793–1801PubMedCrossRefGoogle Scholar
  13. 13.
    Cai D et al (2005) Local and systemic insulin resistance resulting from hepatic activation of IKKβ and NF-κB. Nat Med 11:183–190PubMedCrossRefGoogle Scholar
  14. 14.
    Tilg H, Moschen AR (2008) Inflammatory mechanisms in the regulation of insulin resistance. Mol Med 14(3–4):222–231PubMedGoogle Scholar
  15. 15.
    Rumore MM, Kim KS (2010) Potential role of salicylates in type 2 diabetes. Ann Pharmacol 44:1207–1221CrossRefGoogle Scholar
  16. 16.
    Koska J, Ortega E, Bunt JC, Gasser A, Impson J, Hanson RL, Forbes J, de Courten B, Krakoff J (2009) The effect of salsalate on insulin action and glucose tolerance in obese non-diabetic patients: results of a randomized double-blind placebo-controlled study. Diabetologia 52:385–393PubMedCrossRefGoogle Scholar
  17. 17.
    Fleischman A, Shoelson SE, Bernier R, Goldfine AB (2008) Salsalate improves glycemia and inflammatory parameters in obese young adults. Diabetes Care 31:289–294PubMedCrossRefGoogle Scholar
  18. 18.
    Yuan M, Konstantopoulos N, Lee J, Hansen L, Li ZW, Karin M, Shoelson SE (2001) Reversal of obesity- and diet-induced insulin resistance with salicylates or targeted disruption of IkkB. Science 293:1673–1677PubMedCrossRefGoogle Scholar
  19. 19.
    Hundal RS, Petersen KF, Mayerson AB, Randhawa PS, Inzucchi S, Shoelson SE, Shulman GI (2002) Mechanism by which highdose aspirin improves glucose metabolism in type 2 diabetes. J Clin Invest 109:1321–1326PubMedGoogle Scholar
  20. 20.
    Yin MJ, Yamamoto Y, Gaynor RB (1998) The anti-inflammatory agents aspirin and salicylate inhibit the activity of IκB kinase-β. Nature 396:77–80PubMedCrossRefGoogle Scholar
  21. 21.
    Stevenson MA, Zhao MJ, Asea A, Coleman CN, Calderwood SK (1999) Salicylic acid and aspirin inhibit the activity of RSK2 kinase and repress RSK2-dependent transcription of cyclic AMP response element binding protein- and NF-kappa B-responsive genes. J Immunol 163:5608–5616PubMedGoogle Scholar
  22. 22.
    Anonymous (2010) Diagnosis and classification of diabetes mellitus. Diabetes Care 33:S62, 8 ppGoogle Scholar
  23. 23.
    Goldfine AB, Fonseca V, Jablonski KA, Pyle L, Staten MA, Shoelson SE, for the TINSAL-T2D (Targeting Inflammation Using Salsalate in Type 2 Diabetes) Study Team (2010) The effects of Salsalate on glycemic control in patients with type 2 diabetes: a randomized trial. Ann Intern Med 152:346–357PubMedCrossRefGoogle Scholar
  24. 24.
    Festa A, D’Agostino R Jr, Tracy RP, Haffner SM (2002) Elevated levels of acute-phase proteins and plasminogen activator inhibitor-1 predict the development of type 2 diabetes: the insulin resistance atherosclerosis study. Diabetes 51:1131–1137PubMedCrossRefGoogle Scholar
  25. 25.
    Hostamisligil GS et al (1996) IRS-1 mediated inhibition of insulin receptor tyrosine kinase activity in TNF-α- and obesity-induced insulin resistance. Science 271:665–668CrossRefGoogle Scholar
  26. 26.
    Vozarova B et al (2002) High white blood cell count is associated with a worsening of insulin sensitivity and predicts the development of type 2 diabetes. Diabetes 51:455–461PubMedCrossRefGoogle Scholar
  27. 27.
    Haiyan Xu, Barnes GT, Yang Q, Tan G, Yang D, Chou CJ, Sole J, Nichols A, Ross JS, Tartaglia LA, Hong Chen J (2003) Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. Clin Invest 112:1821–1830Google Scholar
  28. 28.
    Fernandez-Real J-M, Lopez-Berejo A et al (2008) Salicylates increase insulin secretion in healthy obese subjects. J Clin Endocrinol Met 93:2523–2530CrossRefGoogle Scholar
  29. 29.
    Bratusch-Marrain PR, Vierhapper H, Komjati M, Waldhäusl WK (1985) Acetyl-salicylic acid impairs insulin-mediated glucose utilization and reduces insulin clearance in healthy and non-insulin-dependent diabetic man. Diabetologia 28:671–676PubMedCrossRefGoogle Scholar
  30. 30.
    Wallace TA, Levy JC, Mathews DR (2004) Use and abuse of HOMA modeling. Diabetes Care 27:1487–1495PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Elham Faghihimani
    • 1
  • Ashraf Aminorroaya
    • 1
  • Hassan Rezvanian
    • 1
  • Peyman Adibi
    • 2
  • Faramarz Ismail-Beigi
    • 3
  • Masoud Amini
    • 1
  1. 1.Isfahan Endocrinology and Metabolism Research Center, Isfahan University of Medical SciencesIsfahanIran
  2. 2.Isfahan University of Medical SciencesIsfahanIran
  3. 3.Department of MedicineCase Western Reserve UniversityClevelandUSA

Personalised recommendations