Yonsei Med J.  2011 Mar;52(2):242-248. 10.3349/ymj.2011.52.2.242.

Changes of Body Weight and Inflammatory Markers after 12-Week Intervention Trial: Results of a Double-Blind, Placebo-Control Pilot Study

• Joo NS
• Kim SM
• Kim KM
• Kim CW
• Kim BT
• Lee DJ

• KMID: 1779658
• DOI: http://doi.org/10.3349/ymj.2011.52.2.242

Abstract

PURPOSE
Low grade inflammation is a well-known characteristic in obese subjects. We investigated body weight changes and inflammatory markers after 12-week intervention trial.
MATERIALS AND METHODS
Twenty-six obese subjects were enrolled and 19 (13 men and 6 women) completed the study. Sibutramine is an FDA-approved drug for body weight control; therefore, we chose this drug as the standard treatment medication in this study. Patients were randomly allocated to receive an anti-inflammatory agent (Diacerein treatment group; n = 12) or placebo (n = 7) for 12 weeks. Anthropometry, body proportion by dual-energy X-ray absorptiometry, and metabolic parameters at the beginning and end of study were measured and compared.
RESULTS
The treatment group had a tendency towards more reduction in anthropometry as compared to the placebo group, in body weight reduction (- 7.0 kg vs. - 4.6 kg), body mass index (- 2.51 kg/m2 vs. - 1.59 kg/m2), and waist circumference (- 7.3 cm vs. - 4.4 cm). These reductions were not statistically significant. Changes in levels of high-sensitivity C-reactive protein and adiponectin in the treatment group were more favorable than in the placebo group.
CONCLUSION
This small pilot study showed no statistical difference for changes in anthropometry, and inflammatory markers between the two groups. Therefore, we could not find any additional effects of Diacerein on weight loss and inflammatory variables in this study.

Keyword

Inflammation; anti-inflammatory agent; adiponectin; TNF-alpha

MeSH Terms

Absorptiometry, Photon
Adiponectin/blood
Adult
Anthraquinones/*therapeutic use
Anti-Inflammatory Agents/*therapeutic use
Appetite Depressants/therapeutic use
C-Reactive Protein/analysis
Cyclobutanes/*therapeutic use
Double-Blind Method
Female
Humans
Inflammation
Lipoproteins, LDL/blood
Male
Obesity/*drug therapy/immunology
Pilot Projects
Tumor Necrosis Factor-alpha/blood
Waist Circumference/drug effects/immunology
Weight Loss/drug effects/*immunology

Figure

• 

  Fig. 1 Response rate: weight reduction of ≥ 5% and ≥ 10% in the two groups. The top panel shows the response rate of ≥ 5% or < 5% weight reduction subjects after the 12-week intervention. The lower panel shows the response rate of ≥ 10% or < 10% weight reduction.

Reference

1. Korean Ministry of Health and Welfare. Report on National Health and Nutrition Survey 2005. 2006. Seoul: Korean Ministry of Health and Welfare.

2. Jee SH, Sull JW, Park J, Lee SY, Ohrr H, Guallar E, et al. Body mass index and mortality in Korean men and women. N Engl J Med. 2006. 355:779–787.

3. Visser M, Bouter LM, McQuillan GM, Wener MH, Harris TB. Elevated C-reactive protein levels in overweight and obese adults. JAMA. 1999. 282:2131–2135.

4. Cook DG, Mendall MA, Whincup PH, Carey IM, Ballam L, Morris JE, et al. C-reactive protein concentration in children: relationship to adiposity and other cardiovascular risk factors. Atherosclerosis. 2000. 149:139–150.

5. Wisse BE. The inflammatory syndrome: the role of adipose tissue cytokines in metabolic disorders linked to obesity. J Am Soc Nephrol. 2004. 15:2792–2800.

6. Bastard JP, Maachi M, Lagathu C, Kim MJ, Caron M, Vidal H, et al. Recent advances in the relationship between obesity, inflammation, and insulin resistance. Eur Cytokine Netw. 2006. 17:4–12.

7. Ramalho R, Guimarães C. [The role of adipose tissue and macrophages in chronic inflammation associated with obesity]. Acta Med Port. 2008. 21:489–496.

8. Ford ES. The metabolic syndrome and mortality from cardiovascular disease and all-causes: findings from the National Health and Nutrition Examination Survey II Mortality Study. Atherosclerosis. 2004. 173:309–314.

9. Hu G, Qiao Q, Tuomilehto J, Balkau B, Borch-Johnsen K, Pyorala K. Prevalence of the metabolic syndrome and its relation to all-cause and cardiovascular mortality in nondiabetic European men and women. Arch Intern Med. 2004. 164:1066–1076.

10. Thompson D, Brown JB, Nichols GA, Elmer PJ, Oster G. Body mass index and future healthcare costs: a retrospective cohort study. Obes Res. 2001. 9:210–218.

11. Tamura T, Ohmori K. Diacerein suppresses the increase in plasma nitric oxide in rat adjuvant-induced arthritis. Eur J Pharmacol. 2001. 419:269–274.

12. Tamura T, Shirai T, Kosaka N, Ohmori K, Takafumi N. Pharmacological studies of diacerein in animal models of inflammation, arthritis and bone resorption. Eur J Pharmacol. 2002. 448:81–87.

13. Pelletier JP, Yaron M, Haraoui B, Cohen P, Nahir MA, Choquette D, et al. Efficacy and safety of diacerein in osteoarthritis of the knee: a double-blind, placebo-controlled trial. The Diacerein Study Group. Arthritis Rheum. 2000. 43:2339–2348.

14. Nguyen M, Dougados M, Berdah L, Amor B. Diacerein in the treatment of osteoarthritis of the hip. Arthritis Rheum. 1994. 37:529–536.

15. Haffner SM, Greenberg AS, Weston WM, Chen H, Williams K, Freed MI. Effect of rosiglitazone treatment on nontraditional markers of cardiovascular disease in patients with type 2 diabetes mellitus. Circulation. 2002. 106:679–684.

16. Mohanty P, Aljada AS, Ghanim H, Hofmeyer D, Tripathy D, Syed T, et al. Evidence for a potent antiinflammatory effect of rosiglitazone. J Clin Endocrinol Metab. 2004. 89:2728–2735.

17. Chu NV, Kong AP, Kim DD, Armstrong D, Baxi S, Deutsch R, et al. Differential effects of metformin and troglitazone on cardiovascular risk factors in patients with type 2 diabetes. Diabetes Care. 2002. 25:542–549.

18. Kasim-Karakas SE, Tsodikov A, Singh U, Jialal I. Responses of inflammatory markers to a low-fat, high-carbohydrate diet: effects of energy intake. Am J Clin Nutr. 2006. 83:774–779.

19. Seshadri P, Iqbal N, Stern L, Williams M, Chicano KL, Daily DA, et al. A randomized study comparing the effects of a low-carbohydrate diet and a conventional diet on lipoprotein subfractions and C-reactive protein levels in patients with severe obesity. Am J Med. 2004. 117:398–405.

20. Manigrasso MR, Ferroni P, Santilli F, Taraborelli T, Guagnano MT, Michetti N, et al. Association between circulating adiponectin and interleukin-10 levels in android obesity: effects of weight loss. J Clin Endocrinol Metab. 2005. 90:5876–5879.

21. Caballero AE, Delgado A, Aguilar-Salinas CA, Herrera AN, Castillo JL, Cabrera T, et al. The differential effects of metformin on markers of endothelail activation and inflammation in subjects with impaired glucose tolerance: a placebo-controlled randomized clinical trial. J Clin Endocrinol Metab. 2004. 89:3943–3948.

22. Nicklas BJ, Ambrosius W, Messier SP, Miller GD, Penninx BW, Loeser RF, et al. Diet-induced weight loss, exercise, and chronic inflammation in older, obese adults: a randomized controlled clinical trial. Am J Clin Nutr. 2004. 79:544–551.

23. Risérus U, Vessby B, Arnlöv J, Basu S. Effects of cis-9, trans-11 conjugated linoleic acid supplementation on insulin sensitivity, lipid peroxidation, and proinflammatory markers in obese men. Am J Clin Nutr. 2004. 80:279–283.

24. Esposito K, Pontillo A, Di Palo C, Giugliano G, Masella M, Marfella R, et al. Effect of weight loss and lifestyle changes on vascular inflammatory markers in obese women: a randomized trial. JAMA. 2003. 289:1799–1804.

25. Kumada M, Kihara S, Sumitsuji S, Kawamoto T, Matsumoto S, Ouchi N, et al. Association of hypoadiponectinemia with coronary artery disease in men. Arterioscler Thromb Vasc Biol. 2003. 23:85–89.

26. Ridker PM, Hennekens CH, Buring JE, Rifai N. C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. N Engl J Med. 2000. 342:836–843.

27. Ridker PM, Rifai N, Stampfer MJ, Hennekens CH. Plasma concentrations of interleukin-6 and the risk of future myocardial infarction among apparently healthy men. Circulation. 2000. 101:1767–1772.

28. Stefan N, Stumvoll M. Adiponectin--its role in metabolism and beyond. Horm Metab Res. 2002. 34:469–474.