Association of adipokines, leptin/adiponectin ratio and C-reactive protein with obesity and type 2 diabetes mellitus

Diabetology & Metabolic Syndrome

Riyadh Saif-Ali¹  Ali Al-Meeri¹  Molham AL-Habori¹  Zaid Al-Hamodi¹ 

[1] Department of Biochemistry and Molecular Biology, Faculty of Medicine and Health Sciences, University of Sana’a, PO Box 19065, Sana’a, Republic of Yemen

关键词: hs-CRP;    Leptin/Adiponectin ratio;    Leptin;    Adiponectin;    Obesity;    Type 2 DM;   

Others  :  1114995
DOI  :  10.1186/1758-5996-6-99

 received in 2014-06-26, accepted in 2014-09-04,  发布年份 2014

【 摘 要 】

Objective

Alterations in plasma adipokines and/or inflammatory parameters in Type 2 DM remain vague as to whether they are due to obesity and/or directly associated with the diabetic state. Our objective was to compare plasma adiponectin, leptin, leptin/adiponectin ratio (LAR) and hs-CRP in obese non-diabetic subjects and non-obese Type 2 DM patients, as well as determining the association of these adipokines with MetS and diabetes-related quantitative traits.

Methods

In this study, 92 Yemeni male volunteers aged 25–60 years old were enrolled, 31 of whom were healthy subjects with BMI < 25 kg/m² served as control; 30 non-diabetic obese subjects BMI ≥ 30 kg/m² and FBG < 6.1 mmol/l; and 31 non-obese Type 2 DM with FBG > 7 mmol/l and BMI < 25 kg/m².

Results

Adiponectin was lower in obese subjects, with no differences between non-obese Type 2 DM patients and controls. In contrast, leptin, LAR and hs-CRP were higher in both obese subjects and non-obese Type 2 DM patients. Linear regression analysis showed adiponectin to be associated negatively with BMI, waist circumference, insulin, HOMA-β and HOMA-IR; whereas leptin, LAR and hs-CRP were associated positively with BMI, waist circumference, TG, FBG, insulin, HOMA-β and HOMA-IR. Moreover, adiponectin negatively correlated with leptin, LAR and hs-CRP; whereas leptin and LAR positively correlated with hs-CRP and with each other.

Conclusion

Plasma adiponectin is not affected by diabetes per se, suggesting that its alterations in Type 2 DM may be due to obesity and may be an important link between adiposity, IR and Type 2 DM.

【 授权许可】

   
2014 Al-Hamodi et al.; licensee BioMed Central Ltd.

【 参考文献 】

• [1]Stumvoll M, Goldstein B, van Haeften T: Type 2 diabetes: principles of pathogenesis and therapy. Lancet 2005, 365:1333-1346.
• [2]Kahn SE: The relative contributions of insulin resistance and beta-cell dysfunction in the pathophysiology of type 2 diabetes. Diabetologia 2008, 46:3-19.
• [3]Jensen MD: Role of body fat distribution and the metabolic complications of obesity. J Clin Endocrinol Metab 2008, 93:S57-S63.
• [4]Bastard JP, Maachi M, Lagathu C, Kim MJ, Caron M, Vidal H, Capeau J, Feve B: Recent advances in the relationship between obesity, inflammation, and insulin resistance. Eur Cytokine Netw 2006, 17:4-12.
• [5]Rasouli N, Kern PA: Adipocytokines and the metabolic complications of obesity. J Clin Endocrinol Metab 2008, 93:S64-S73.
• [6]Badawi A, Klip A, Haddad P, Cole D, Garcia Bailo B, El-Sohemy A, Karmali M: Type 2 diabetes mellitus and inflammation: prospects for biomarkers of risk and nutritional intervention. Diab Metab Syndr Obesity: Targets and Therapy 2010, 3:173-186.
• [7]Donath MY, Shoelson SE: Type 2 diabetes as an inflammatory disease. Nat Rev Immunol 2011, 11:98-107.
• [8]Mirza S, Hossain M, Mathews C, Martinez P, Pino P, Gay JL, Rentfro A, McCormick JB, Fisher-Hoch SP: Type 2-diabetes is associated with elevated levels of TNF-alpha, IL-6 and adiponectin and low levels of leptin in a population of Mexican Americans: a cross-sectional study. Cytokine 2012, 57(1):136-142.
• [9]Calle MC, Fernandez ML: Inflammation and type 2 diabetes. Diabetes Metab 2012, 38(3):183-191.
• [10]King GL: The role of inflammatory cytokines in diabetes and its complications. J Periodontol 2008, 79:1527-1534.
• [11]Kadowaki T, Yamauchi T, Kubota N, Hara K, Ueki K, Tobe K: Adiponectin and adiponectin receptors in insulin resistance, diabetes, and the metabolic syndrome. J Clin Invest 2006, 116:1784-1792.
• [12]Turer AT, Scherer PE: Adiponectin: mechanistic insights and clinical implications. Diabetologia 2012, 55:2319-2326.
• [13]Skurk T, Alberti-Huber C, Herder C, Hauner H: Relationship between adipocyte size and adipokine expression and secretion. J Clin Endocrinol Metab 2007, 92:1023-1033.
• [14]Herder C, Schneitler S, Rathmann W, Haastert B, Schneitler H, Winkler H, Bredahl R, Hahnloser E, Martin S: Low-grade inflammation, obesity, and insulin resistance in adolescents. J Clin Endocrinol Metab 2007, 92:4569-4574.
• [15]Saltevo J, Laakso M, Jokelainen J, Keinanen-Kiukaanniemi S, Kumpusalo E, Vanhala M: Levels of adiponectin, C-reactive protein and interleukin-1 receptor antagonist are associated with insulin sensitivity: a population based study. Diabetes Metab Res Rev 2008, 24:378-383.
• [16]Ley SH, Harris SB, Connelly PW, Mamakeesick M, Gittelsohn J, Hegele RA, Retnakaran R, Zinman B, Hanley AJG: Adipokines and incident type 2 diabetes in an aboriginal Canadian [corrected] population: the Sandy Lake health and diabetes project. Diabetes Care 2008, 31:1410-1415.
• [17]Tabak AG, Brunner EJ, Miller MA, Karanam S, Mc Ternan PG, Cappuccio FP, Witte DR: Low serum adiponectin predicts 10-year risk of type 2 diabetes and HbA1c independently of obesity, lipids, and inflammation: Whitehall II study. Horm Metab Res 2009, 41:626-629.
• [18]Kishida K, Funahashi T, Shimomura I: Molecular mechanisms of diabetes and atherosclerosis: role of adiponectin. Endocrine Metab Immune Disor - Drug Targets 2012, 12:118-131.
• [19]Ohashi K, Ouchi N, Matsuzawa Y: Anti-inflammatory and anti-atherogenic properties of adiponectin. Biochimie 2012, 94:2137-2142.
• [20]Sharma PK, Bhansali A, Sialy R, Malhotra S, Pandhi P: Effects of pioglitazone and metformin on plasma adiponectin in newly detected type 2 diabetes mellitus. Clin Endocrinol 2006, 65:722-728.
• [21]Miazgowski T, Dziwura-Ogonowska J, Safranow K, Iskierska K, Widecka K: Changes in adiponectin level and fat distribution in patients with type 2 diabetes. Eur J Clin Invest 2014, 44(2):192-199.
• [22]Lindsay RS, Funahashi T, Hanson RL, Matsuzawa Y, Tanaka S, Tataranni A, Knowler WC, Krakoff J: Adiponectin and development of type 2 diabetes in the Pima Indian population. Lancet 2002, 360:57-58.
• [23]Mather KJ, Funahashi T, Matsuzawa Y, Edelstein S, Bray GA, Kahn SE, Crandall J, Marcovina S, Goldstein B, Goldberg R: Adiponectin, change in adiponectin, and progression to diabetes in the diabetes prevention program. Diabetes 2008, 57:980-986.
• [24]Thorand B, Zierer A, Baumert J, Meisinger C, Herder C, Koenig W: Associations between leptin and the leptin/adiponectin ratio and incident type 2 diabetes in middle-aged men and women: results from the MONICA/KORA Augsburg Study 1984–2002. Diabetic Med 2010, 27:1004-1011.
• [25]Lindberg S, Jensen JS, Bjerre M, Pedersen SH, Frystyk J, Flyvbjerg A, Galatius S, Jeppesen J, Mogelvang R: Adiponectin, type 2 diabetes and cardiovascular risk. Eur J Preventive Cardiol 2013. published online 21 November
• [26]Otero M, Lago R, Lago F, Casanueva FF, Dieguez C, Gomez-Reino JJ, Gualillo O: Leptin, from fat to inflammation: Old questions and new insights. FEBS Lett 2005, 579:295-301.
• [27]Farooqi IS, O’Rahilly S: Leptin: a pivotal regulator of human energy homeostasis. Am J Clin Nutr 2009, 89:980S-984S.
• [28]Myers MG, Cowley MA, Munzberg H: Mechanisms of leptin action and leptin resistance. Ann Rev Physiol 2008, 70:537-556.
• [29]Martin SS, Qasim A, Reilly MP: Leptin resistance: a possible interface of inflammation and metabolism in obesity-related cardiovascular disease. J Am Coll Cardiol 2008, 52:1201-1210.
• [30]Schmidt MI, Duncan BB, Vigo A, Pankow JS, Couper D, Ballantyne CM, Hoogeveen RC, Heiss G: Leptin and incident type 2 diabetes: risk or protection? Diabetologia 2006, 49:2086-2096.
• [31]Abdelgadir M, Elbagir M, Eltom M, Berne C, Ahrén B: Reduced leptin concentrations in subjects with type 2 diabetes mellitus in Sudan. Metabolism 2002, 51:304-306.
• [32]Bahceci M, Gokalp D, Bahceci S, Tuzcu A, Atmaca S, Arikan S: The correlation between adiposity and adiponectin, tumor necrosis factor alpha, interleukin-6 and high-sensitivity c-reactive protein levels. Is adipocyte size associated with inflammation in adults? J Endocrinol Invest 2007, 30:210-214.
• [33]Lilja M, Rolandsson O, Norberg M, Soderberg S: The impact of leptin and adiponectin on incident type 2 diabetes is modified by sex and insulin resistance. Metab Syndr Relat Disord 2012, 10:143-151.
• [34]Putz DM, Goldner WS, Bar RS, Haynes WG, Sivitz WI: Adiponectin and C-reactive protein in obesity, type 2 diabetes, and monodrug therapy. Metabolism 2004, 53(11):1454-1461.
• [35]Yuan G, Zhou L, Tang J, Yang Y, Gu W, Li F, Hong J, Gu Y, Li X, Ning G, Chen M: Serum CRP levels are equally elevated in newly diagnosed type 2 diabetes and impaired glucose tolerance and related to adiponectin levels and insulin sensitivity. Diabetes Res Clin Pract 2006, 72(3):244-250.
• [36]Neuparth MJ, Proença JB, Santos-Silva A, Coimbra S: Adipokines, oxidized low- density lipoprotein, and C-reactive protein levels in lean, overweight, and obese Portuguese patients with type 2 diabetes. Obesity 2013. Article ID 142097
• [37]Hansen D, Dendale P, Beelen M, Jonkers RAM, Mullens A, Corluy L, Meeusen R, van Loon LJC: Plasma adipokine and inflammatory marker concentrations are altered in obese, as opposed to non-obese, type 2 diabetes patients. Eur J Appl Physiol 2010, 109:397-404.
• [38]Ryo M, Nakamura T, Kihara S, Kumada M, Shibazaki S, Takahashi M, Nagai M, Matsuzawa Y, Funahashi T: Adiponectin as a biomarker of the metabolic syndrome. Circulation J 2004, 68:975-981.
• [39]Mojiminiyi OA, Abdella NA, Al Arouj M, Ben Nakhi A: Adiponectin, insulin resistance and clinical expression of the metabolic syndrome in patients with type 2 diabetes. Int J Obesity 2007, 31:213-220.
• [40]Lee JM, Kim SR, Yoo SJ, Hong OK, Son HS, Chang SA: The relationship between adipokines, metabolic parameters and insulin resistance in patients with metabolic syndrome and type 2 diabetes. J Int Med Res 2009, 37:1803-1812.
• [41]Krakoff J, Funahashi T, Stehouwer CD, Schalkwijk CG, Tanaka S, Matsuzawa Y, Kobes S, Tataranni PA, Hanson RL, Knowler WC, Lindsay RS: Inflammatory markers, adiponectin, and risk of type 2 diabetes in the pima Indian. Diabetes Care 2003, 26:1745-1751.
• [42]Fasshauer M, Klein J, Neumann S, Eszlinger M, Paschke R: Hormonal regulation of adiponectin gene expression in 3 T3-L1 adipocytes. Biochem Biophys Res Commun 2002, 290:1084-1089.
• [43]Mohlig M, Wegewitz U, Osterhoff M, Isken F, Ristow M, Pfeiffer AF, Spranger J: Insulin decreases human adiponectin plasma levels. Horm Metab Res 2002, 34:655-658.
• [44]Fasshauer M, Kralisch S, Klier M, Lossner U, Bluher M, Klein J, Paschke R: Adiponectin gene expression and secretion is inhibited by interleukin-6 in 3 T3-L1 adipocytes. Biochem Biophys Res Commun 2003, 301:1045-1050.
• [45]Hotta K, Funahashi T, Arita Y, Takahashi M, Matsuda M, Okamoto M, Iwahashi H, Kuriyama H, Ouchi N, Maeda K, Nishida M, Kihara S, Sakai N, Nakajima T, Hasegawa K, Muraguchi M, Ohmoto Y, Nakamura T, Ya-mashita S, Hanafusa T, Matsuzawa Y: Plasma concentrations of a novel, adipose- specific protein, adiponectin, in type 2 diabetic patients. Arterio Thromb Vascul Biol 2000, 20:1595-1599.
• [46]Considine RV, Sinha MK, Heiman ML, Kriauciunas A, Stephens TW, Nyce MR, Ohannesian JP, Marco CC, McKee LJ, Bauer TL, Caro JF: Serum immunoreactive- leptin concentration in normal weight and obese humans. N Engl J Med 1996, 334:292-295.
• [47]Park K-G, Park KS, Kim M-J, Kim H-S, Suh Y-S, Ahn JD, Park K-K, Chang Y-C, Lee I-K: Relationship between serum adiponectin and leptin concentrations and body fat distribution. Diabetes Res Clin Pract 2004, 63(2):135-142.
• [48]Tajtakova M, Petrasova D, Pidanicova A, Gallovicova A, Blanarova C, Petrovicova J: Serum levels of leptin, adiponectin, retinol binding protein 4 and leptin/adiponectin molar ratio as another possible marker of insulin resistance in obese. Bratisl Lek Listy 2010, 111:212-215.
• [49]Satoh N, Naruse M, Usui T, Tagami T, Suganami T, Yamada K, Kuzuya H, Shimatsu A, Ogawa Y: Leptin to adiponectin ratio as a potential atherogenic index in obese type 2 diabetic patients. Diabetes Care 2004, 27:2488-2490.
• [50]Schulze MB, Rimm EB, Shai I, Rifai N, Hu FB: Relationship between adiponectin and glycemic control, blood lipids, and inflammatory markers in men with type 2 diabetes. Diabetes Care 2004, 27:1680-1687.
• [51]Marques-Vidal P, Bastardot F, von Kanel R, Paccaud F, Preisig M, Waeber G, Vollenweider P: Association between circulating cytokine levels, diabetes and insulin resistance in a population-based sample (CoLaus study). Clin Endocrinol 2013, 78:232-241.
• [52]Wang X, Bao W, Liu J, Ouyang YY, Wang D, Rong S, Xiao X, Shan ZL, Zhang Y, Yao P, Liu LG: Inflammatory markers and risk of type 2 diabetes: a systematic review and meta-analysis. Diabetes Care 2013, 36(1):166-175.
• [53]Aronson D, Bartha P, Zinder O, Kerner A, Shitman E, Markiewicz W, Brook GJ, Levy Y: Association between fasting glucose and C-reactive protein in middle-aged subjects. Diabetic Med 2004, 21(1):39-44.
• [54]Choi J, Joseph L, Pilote L: Obesity and C-reactive protein in various populations: a systematic review and meta-analysis. Obesity Rev 2013, 14:232-244.
• [55]Temelkova-Kurktschiev T, Siegert G, Bergmann S, Henkel E, Koehler C, Jaross W, Hanefeld M: Subclinical inflammation is strongly related to insulin resistance but not to impaired insulin secretion in a high risk population for diabetes. Metabolism 2002, 51:743-749.
• [56]Chou HH, Hsu LA, Liu CJ, Teng MS, Wu S, Ko YL: Insulin resistance is associated with C-reactive protein independent of abdominal obesity in nondiabetic Taiwanese. Metabolism 2010, 59(6):824-830.
• [57]Pradhan AD, Cook NR, Buring JE, Manson JE, Ridker PM: C-reactive protein is independently associated with fasting insulin in nondiabetic women. Arterioscler Thromb Vasc Biol 2003, 23:650-655.