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Effect of etanercept on insulin secretion and insulin sensitivity in a randomized trial with psoriatic patients at risk for developing type 2 diabetes mellitus

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Abstract

Tumor necrosis factor-alpha (TNF-alpha) inhibitors have been used in the treatment of psoriasis, which is associated with the insulin resistance syndrome. The purpose of this study was to determine the effect of etanercept, a TNF-alpha inhibitor, on insulin secretion and insulin sensitivity in psoriatic patients with high risk factors to develop type 2 diabetes mellitus. Randomized double blind clinical trial with 2 weeks of follow-up. The allocation was done by simple randomization. The investigation was performed in 12 psoriatic patients with indication of systemic treatment and 2 or more risk factors for type 2 diabetes mellitus. Patients with infections, topical corticosteroids or salicylic acid ointments for 6 weeks before the study, diabetes, acromegaly, cancer and other systemic diseases were excluded. All subjects gave written informed consent to participate in the study and the protocol was approved by the hospital-based Ethical Committee. Etanercept was injected in a subcutaneous dose of 25 mg in 1 ml twice by week for 2 weeks or 1 ml of saline solution as placebo. Insulin secretion was estimated with the formula for the homeostasis model analysis β-cell function index and insulin sensitivity was assessed using the euglycemic-hyperinsulinemic clamp technique. There was no significant difference in insulin secretion and insulin sensitivity with etanercept. Fasting serum insulin levels were decreased in the etanercept group (146 ± 117–111 ± 87 pmol/l, P = 0.04). Etanercept did not modify insulin secretion and insulin sensitivity in psoriatic patients with risk factors for type 2 diabetes mellitus.

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References

  1. Bloomgarden Z (2003) Inflammation and insulin resistance. Diabetes Care 26:1619–1623

    Article  PubMed  CAS  Google Scholar 

  2. Cottet S, Dupraz P, Hamburger F, Dolci W, Jaquet M, Thorens B (2002) cFLIP Protein prevents tumor necrosis factor-[alpha]-mediated induction of caspase-8-dependent apoptosis in insulin-secreting [beta]Tc-Tet cells. Diabetes 51:1805–1814

    Article  PubMed  CAS  Google Scholar 

  3. Culy C, Keating G (2002) Etanercept. Drugs 2:2493–2437

    Google Scholar 

  4. DeFronzo RA, Tobin J, Andres R (1979) Glucose clamp technique: a method for quantifying insulin secretion and resistance. Am J Physiol 6:E214–E223

    Google Scholar 

  5. Gellfand J, Neimann A, Shin D, Wang X, Margolis D, Troxel A (2006) Risk of myocardial infarction in patients with psoriasis. JAMA 296:1735–1741

    Article  Google Scholar 

  6. González-Ortiz M, Martínez-Abundis E, Balcázar-Muñoz B, Robles-Cervantes J (2001) Inhibition of cyclooxygenase-1 or -2 on insulin sensitivity in healthy subjects. Horm Metab Res 33:250–253

    Article  PubMed  Google Scholar 

  7. González-Ortiz M, Martínez-Abundis E, Lifshitz A (1998) Insulin sensitivity and sex steroid hormone levels during the menstrual cycle in healthy women with non-insulin-dependent diabetic parents. Gynecol Obstet Invest 46:187–190

    Article  PubMed  Google Scholar 

  8. Gottlieb A (2001) Psoriasis: immunopathology and immunomodulation. Dermatol Clin 19:649–655

    Article  PubMed  CAS  Google Scholar 

  9. Hotamisligil G, Shargill N, Spiegelman B (1993) Adipose expression of tumor necrosis factor-α: direct role in obesity-linked insulin resistance. Science 259:7–90

    Article  Google Scholar 

  10. Iyer S, Yamauchi P, Lowe N (2002) Etanercept for severe psoriasis and psoriatic arthritis: observations on combination therapy. Br J Dermatol 146:118–121

    Article  PubMed  CAS  Google Scholar 

  11. Jeyasseelan L, Rao P (1989) Methods of determining sample sizes in clinical trials. Indian Pediatr 26:115–121

    Google Scholar 

  12. Kormeili T, Lowe N, Yamauchi P (2004) Psoriasis: immunopathogenesis and evolving immunomodulators and systemic therapies: US experiencies. Br J Dermatol 151:3–15

    Article  PubMed  CAS  Google Scholar 

  13. Korth-Bradley JM, Sue-Rubin A, Hanna RK, Simcoe DK, Lebsack ME (2000) The pharmacokinetics of etanercept in healthy volunteer. Ann Pharmacother 34:161–164

    Article  PubMed  CAS  Google Scholar 

  14. Krueger G, Callis K (2004) Potential of tumor necrosis factor inhibitor in psoriasis and psoriatic arthritis. Arch Dermatol 140:218–225

    Article  PubMed  CAS  Google Scholar 

  15. LaDuca J, Gaspari A (2001) Targeting tumor necrosis factor alpha. New drugs used to modulate inflammatory diseases. Dermatol Clin 19:617–635

    Article  PubMed  CAS  Google Scholar 

  16. Ludwig R, Herzog C, Rostock A, Ochsendorf F, Zollner T, Thaci D, Kaufmann R, Vogl T, Boehncke W (2007) Psoriasis: a possible risk factor for development of coronary artery calcification. Br J Dermatol 56:2761–2627

    Google Scholar 

  17. Miyazaki Y, Pipek R, Mandarino L, DeFronzo R (2003) Tumor necrosis factor α and insulin resistance in obese type 2 diabetic patients. Int J Obes 27:88–94

    Article  CAS  Google Scholar 

  18. Ofei F, Hurel S, Newkirk J, Sopwith M Taylor R (1996) Effects of an engineered human anti-TNF-alpha antibody (CDP571) on insulin sensitivity and glycemic control in patients with NIDDM. Diabetes 45:881–885

    Article  PubMed  Google Scholar 

  19. Pakala S, Chivetta M, Kelly C, Katz J (1999) In autoimmune diabetes the transition from benign to pernicious insulitis requires an islet cell response to tumor necrosis factor alpha. J Exp Med 189:1053–1062

    Article  PubMed  CAS  Google Scholar 

  20. Paquot N, Castillo M, Lefèbvre P, Scheen A (2000) No increased insulin sensitivity after a single intravenous administration of a recombinant human tumor necrosis factor receptor: Fc fusion protein in obese insulin-resistant patients. J Clin Endocrinol Metab 85:1316–1319

    Article  PubMed  CAS  Google Scholar 

  21. Rask-Madsen C, Domínguez H, Ihlemann N, Hermann T, Køber L, Torp-Pedersen C (2002) Tumor necrosis factor-[alpha] inhibits insulin’s stimulating effect on glucose uptake and endothelium-dependent vasodilatation in humans. Circulation 108:1815–1821

    Article  Google Scholar 

  22. Spranger-Joachim K, Möhlig M, Hoffmann K, Bergmann MM, Ristow M, Boeing H, Pfeiffer AFH (2003) Inflammatory cytokines and the risk to develop type 2 diabetes. Results of the prospective population-based european prospective investigation into cancer and nutrition (EPIC)-potsdam study. Diabetes 52:812–817

    Article  CAS  Google Scholar 

  23. von Eckardstein A, Schulte H, Assmann G (2000) Risk for diabetes mellitus in middle-aged caucasian male participants of the PROCAM study: implications for the definition of impaired fasting glucose by the American Diabetes Association. J Clin Endocrinol Metab 85:3101–3108

    Article  Google Scholar 

  24. Weir G, Laybutt D, Kaneto H, Bonner-Weir S, Sharma A (2001) Beta-cell adaptation and decompensation during the progression of diabetes. Diabetes 50:S154–S159

    Article  PubMed  CAS  Google Scholar 

  25. Winkler G, Lakatos P, Salamon F, Speer G, Baranyi E, Melczer Z, Karoly C (1999) Response to Fernandez-Real et al. Contribution of tumor necrosis factor-alpha in insulin resistance in patients with android type obesity. Diabetes Care 22:870

    Article  Google Scholar 

  26. Yoshitaka S, Hiroaki D, Shuji M, Masayuki I, Satoshi T, Tomohiko T, Toshihiko I (2004) Infliximab (anti-tnf alpha antibody) improved insulin resistance in rheumatoid arthritis patients. Diabetes 53:A160–A161

    Google Scholar 

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Correspondence to Esperanza Martínez-Abundis.

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Martínez-Abundis, E., Reynoso-von Drateln, C., Hernández-Salazar, E. et al. Effect of etanercept on insulin secretion and insulin sensitivity in a randomized trial with psoriatic patients at risk for developing type 2 diabetes mellitus. Arch Dermatol Res 299, 461–465 (2007). https://doi.org/10.1007/s00403-007-0784-3

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  • DOI: https://doi.org/10.1007/s00403-007-0784-3

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