Abstract
Adiponectin plays an important role in the development of immune-mediated diseases. Currently published data regarding the relationship between serum/plasma levels of adiponectin and immune-mediated diseases are inconsistent. We therefore conducted this meta-analysis to explore the association of serum/plasma adiponectin levels with immune-mediated diseases in humans. Systematic literature search was conducted to identify all relevant studies. The study quality was assessed by the Newcastle-Ottawa scale. Pooled standard mean difference (SMD) with 95% confidence interval (CI) was calculated by random-effect model analysis. A total of 47 studies were included in our meta-analysis, including 27 studies of type 1 diabetes mellitus (T1DM), 9 studies of rheumatoid arthritis (RA), 7 studies of systemic lupus erythematosus (SLE), and 4 studies of ankylosing spondylitis (AS). The results revealed significant differences in serum/plasma levels of adiponectin between immune-mediated diseases and normal controls (SMD = 1.262, 95% CI 0.766–1.758, p < 0.001). In the subgroup analysis stratified by disease type, the serum/plasma levels of adiponectin in T1DM, RA and SLE patients were higher than those in normal control, but not in AS patients. Moreover, in the subgroup analysis stratified by gender, in both men and women group, the serum/plasma levels of adiponectin in patients with immune-mediated diseases were higher than that in the control group. Furthermore, subgroup analyses also showed that immune-mediated diseases from Asian population, Caucasian population, mean age >40 years, and BMI ≥24 kg/m2 had higher serum/plasma adiponectin levels when compared with normal controls. Collectively, this meta-analysis demonstrates that serum/plasma levels of adiponectin in T1DM, RA and SLE patients were higher than those in normal controls, but not in AS patients.
Similar content being viewed by others
References
Abi Khalil C, Mohammedi K, Aubert R, Abou Jaoude E, Travert F, Hadjadj S, Fumeron F, Roussel R, Marre M (2011) Hyperadiponectinemia is independent of kidney function, diabetes duration, and control in type 1 diabetic patients without microangiopathy. J Clin Endocrinol Metab 96:E485–E487
Aguilera E, Serra-Planas E, Granada ML, Pellitero S, Reverter JL, Alonso N, Soldevila B, Mauricio D, Puig-Domingo M (2015) Relationship of YKL-40 and adiponectin and subclinical atherosclerosis in asymptomatic patients with type 1 diabetes mellitus from a European Mediterranean population. Cardiovasc Diabetol 14:121
Alkady EA, Ahmed HM, Tag L, Abdou MA (2011) Serum and synovial adiponectin, resistin, and visfatin levels in rheumatoid arthritis patients. Relation to disease activity. Z Rheumatol 70:602–608
Al M, Ng L, Tyrrell P, Bargman J, Bradley T, Silverman E (2009) Adipokines as novel biomarkers in paediatric systemic lupus erythematosus. Rheumatology 48:497–501
Al Saeed M, Al Nashar N, Al Nefaie SM, Mohamed HA, Ahmed M, Al Margushi N (2014) Adipokines in Type 1 Diabetes Mellitus. Egypt J Hosp Med 54:88–93
Barbosa Vde S, Francescantônio PL, Silva NA (2015) Leptin and adiponectina in patients with systemic lupus erythematosus: clinical and laboratory correlations. Rev Bras Reumatol 55:140–145
Calderon RM, Diaz S, Szeto A, Llinas JA, Hughes TA, Mendez AJ, Goldberg RB (2015) Elevated lipoprotein lipase activity does not account for the association between adiponectin and HDL in Type 1 Diabetes. J Clin Endocrinol Metab 100:2581–2588
Cho JH, Gregersen PK (2011) Genomics and the multifactorial nature of human autoimmune disease. N Engl J Med 365:1612–1623
Chung CP, Long AG, Solus JF, Rho YH, Oeser A, Raggi P et al (2009) Adipocytokines in systemic lupus erythematosus: relationship to inflammation, insulin resistance and coronary atherosclerosis. Lupus 18:799–806
De Sanctis JB, Zabaleta M, Bianco NE, Garmendia JV, Rivas L (2009) Serum adipokine levels in patients with systemic lupus erythematosus. Autoimmunity 42:272–274
Derdemezis CS, Filippatos TD, Voulgari PV, Tselepis AD, Drosos AA, Kiortsis DN (2010) Leptin and adiponectin levels in patients with ankylosing spondylitis. The effect of infliximab treatment. Clin Exp Rheumatol 28:880–883
Ebina K, Fukuhara A, Ando W, Hirao M, Koga T, Oshima K, Matsuda M, Maeda K, Nakamura T, Ochi T, Shimomura I, Yoshikawa H, Hashimoto J (2009) Serum adiponectin concentrations correlate with severity of rheumatoid arthritis evaluated by extent of joint destruction. Clin Rheumatol 28:445–451
Eleuterio NM, Palei AC, Rangel Machado JS, Tanus-Santos JE, Cavalli RC, Sandrim VC (2014) Correlations between circulating levels of adipokines and anti-angiogenic factors in women with BMI <30 and a late-onset preeclampsia. Hypertens Pregnancy 33:72–80
El-Hini SH, Mohamed FI, Hassan AA, Ali F, Mahmoud A, Ibraheem HM (2013) Visfatin and adiponectin as novel markers for evaluation of metabolic disturbance in recently diagnosed rheumatoid arthritis patients. Rheumatol Int 33:2283–2289
Geyikli I, Keskin M, Kör Y, Akan M (2013) Increased resistin serum concentrations in patients with type 1 diabetes mellitus. J Clin Res Pediatr Endocrinol 5:189–193
Gökşen D, Levent E, Kar S, Ozen S, Darcan S (2013) Serum adiponectin and hsCRP levels and non-invasive radiological methods in the early diagnosis of cardiovascular system complications in children and adolescents with type 1 diabetes mellitus. J Clin Res Pediatr Endocrinol 5:174–181
Gokulakrishnan K, Aravindhan V, Amutha A, Abhijit S, Ranjani H, Anjana RM et al (2013) Serum adiponectin helps to differentiate type 1 and type 2 diabetes among young Asian Indians. Diabetes Technol Ther 15:696–702
Hatziagelaki E, Lambadiari V, Tsiavou A, Gogas H, Bretzel RG, Dimitriadis G (2013) The role of adiponectin as a compensatory mediator for the primary secretory defect in latent autoimmune diabetes in adults. Clin Ther 35:1016–1024
Hotta K, Funahashi T, Arita Y, Takahashi M, Matsuda M, Okamoto Y et al (2000) Plasma concentrations of a novel adipose-specific protein, adiponectin, in type 2 diabetic patients. Arterioscler Thromb Vasc Biol 20:1595–1599
Hughes TA, Calderon RM, Diaz S, Mendez AJ, Goldberg RB (2016) Lipoprotein composition in patients with type 1 diabetes mellitus: impact of lipases and adipokines. J Diabetes Complicat 30:657–668
Iñiguez G, Torrealba IM, Avila A, Cassorla F, Codner E (2008) Adiponectin serum levels and their relationships to androgen concentrations and ovarian volume during puberty in girls with type 1 diabetes mellitus. Horm Res 70:112–117
Iwabuchi A, Kamoda T, Saito M, Nozue H, Izumi I, Hirano T, Sumazaki R (2013) Serum dipeptidyl peptidase 4 activity in children with type 1 diabetes mellitus. J Pediatr Endocrinol Metab 26:1093–1097
Karamifar H, Habibian N, Amirhakimi G, Karamizadeh Z, Alipour A (2013) Adiponectin is a good marker for metabolic state among Type 1 diabetes mellitus patients. Iran J Pediatr 23:295–301
Kobayashi H, Ouchi N, Kihara S, Walsh K, Kumada M, Abe Y, Funahashi T, Matsuzawa Y (2004) Selective suppression of endothelial cell apoptosis by the high molecular weight form of adiponectin. Circ Res 94:e27–e31
Laurberg TB, Frystyk J, Ellingsen T, Hansen IT, Jørgensen A, Tarp U, Hetland ML, Hørslev-Petersen K, Hornung N, Poulsen JH, Flyvbjerg A, Stengaard-Pedersen K (2009) Plasma adiponectin in patients with active, early, and chronic rheumatoid arthritis who are steroid-and disease-modifying antirheumatic drug-naive compared with patients with osteoarthritis and controls. J Rheumatol 36:1885–1891
Lindström T, Frystyk J, Hedman CA, Flyvbjerg A, Arnqvist HJ (2006) Elevated circulating adiponectin in type 1 diabetes is associated with long diabetes duration. Clin Endocrinol (Oxf) 65:776–782
Maahs DM, Ogden LG, Snell-Bergeon JK, Kinney GL, Wadwa RP, Hokanson JE, Dabelea D, Kretowski A, Eckel RH (2007) Determinants of serum adiponectin in persons with and without type 1 diabetes. Am J Epidemiol 166:731–740
Majewska KA, Majewski D, Skowrońska B, Stankiewicz W, Fichna P (2016) Serum leptin and adiponectin levels in children with type 1 diabetes mellitus-relation to body fat mass and disease course. Adv Med Sci 61:117–122
Martos-Moreno GA, Barrios V, Soriano-Guillén L, Argente J (2006) Relationship between adiponectin levels, acylated ghrelin levels, and short-term body mass index changes in children with diabetes mellitus type 1 at diagnosis and after insulin therapy. Eur J Endocrinol 155:757–761
McMahon M, Skaggs BJ, Sahakian L, Grossman J, FitzGerald J, Ragavendra N, Charles-Schoeman C, Chernishof M, Gorn A, Witztum JL, Wong WK, Weisman M, Wallace DJ, La Cava A, Hahn BH (2011) High plasma leptin levels confer increased risk of atherosclerosis in women with systemic lupus erythematosus, and are associated with inflammatory oxidised lipids. Ann Rheum Dis 70:1619–1624
Meral C, Tascilar E, Karademir F, Tanju IA, Cekmez F, Ipcioglu OM, Ercin CN, Gocmen I, Dogru T (2010) Elevated plasma levels of apelin in children with type 1 diabetes mellitus. J Pediatr Endocrinol Metab 23:497–502
Nelson SM, Coan PM, Burton GJ, Lindsay RS (2009) Placental structure in type 1 diabetes: relation to fetal insulin, leptin, and IGF-I. Diabetes 58:2634–2641
Nelson SM, Freeman DJ, Sattar N, Lindsay RS (2009) Erythrocytosis in offspring of mothers with Type 1 diabetes-are factors other than insulin critical determinants? Diabet Med 26:887–892
Neumeier M, Weigert J, Schäffler A, Wehrwein G, Müller-Ladner U, Schölmerich J, Wrede C, Buechler C (2006) Different effects of adiponectin isoforms in human monocytic cells. J Leukoc Biol 79:803–808
Nishizawa H, Shimomura I, Kishida K, Maeda N, Kuriyama H, Nagaretani H et al (2002) Androgens decrease plasma adiponectin, an insulin-sensitizing adipocyte-derived protein. Diabetes 51:2734–2741
Ohashi K, Ouchi N, Matsuzawa Y (2012) Anti-inflammatory and anti-atherogenic properties of adiponectin. Biochimie 94:2137–2142
Okamoto Y, Kihara S, Funnahashi T, Matsuzawa Y, Libby P (2006) Adiponectin: a key adipocytokine in metabolic syndrome. Clin Sci 110:267–278
Otero M, Lago R, Gomez R, Lago F, Dieguez C, Gómez-Reino JJ, Gualillo O (2006) Changes in plasma levels of fat-derived hormones adiponectin, leptin, resistin and visfatin in patients with rheumatoid arthritis. Ann Rheum Dis 65:1198–1201
Ouedraogo R, Gong Y, Berzins B, Wu X, Mahadev K, Hough K, Chan L, Goldstein BJ, Scalia R (2007) Adiponectin deficiency increases leukocyte-endothelium interactions via upregulation of endothelial cell adhesion molecules in vivo. J Clin Investig 117:1718–1726
Ozgen M, Koca SS, Dagli N, Balin M, Ustundag B, Isik A (2010) Serum adiponectin and vaspin levels in rheumatoid arthritis. Arch Med Res 41:457–463
Perseghin G, Lattuada G, De Cobelli F, Esposito A, Costantino F, Canu T, Scifo P, De Taddeo F, Maffi P, Secchi A, Del Maschio A, Luzi L (2005) Reduced intrahepatic fat content is associated with increased whole-body lipid oxidation in patients with type 1 diabetes. Diabetologia 48:2615–2621
Rajala MW, Scherer PE (2003) Minireview: the adipocyte—at the crossroads of energy homeostasis, inflammation, and atherosclerosis. Endocrinology 144:3765–3773
Reynolds HR, Buyon J, Kim M, Rivera TL, Izmirly P, Tunick P, Clancy RM (2010) Association of plasma soluble E-selectin and adiponectin with carotid plaque in patients with systemic lupus erythematosus. Atherosclerosis 210:569–574
Sada KE, Yamasaki Y, Maruyama M, Sugiyama H, Yamamura M, Maeshima Y, Makino H (2006) Altered levels of adipocytokines in association with insulin resistance in patients with systemic lupus erythematosus. J Rheumatol 33:1545–1552
Saijo S, Nagata K, Nakano Y, Tobe T, Kobayashi Y (2005) Inhibition by adiponectin of IL-8 production by human macrophages upon coculturing with late apoptotic cells. Biochem Biophys Res Commun 334:1180–1183
Schäffler A, Herfarth H, Paul G, Ehling A, Müller-Ladner U, Schölmerich J, Zietz B (2004) Identification of influencing variables on adiponectin serum levels in diabetes mellitus type 1 and type 2. Exp Clin Endocrinol Diabetes 112:383–389
Scherer PE, Williams S, Fogliano M, Baldini G, Lodish HF (1995) A novel serum protein similar to C1q, produced exclusively in adipocytes. J Biol Chem 270:26746–26749
Song H, Chan J, Rovin BH (2009) Induction of chemokine expression by adiponectin in vitro is isoform dependent. Transl Res 154:18–26
Syrbe U, Callhoff J, Conrad K, Poddubnyy D, Haibel H, Junker S, Frommer KW, Müller-Ladner U, Neumann E, Sieper J (2015) Serum adipokine levels in patients with ankylosing spondylitis and their relationship to clinical parameters and radiographic spinal progression. Arthritis Rheumatol 67:678–685
Takahashi M, Arita Y, Yamagata K, Matsukawa Y, Okutomi K, Horie M, Shimomura I, Hotta K, Kuriyama H, Kihara S, Nakamura T, Yamashita S, Funahashi T, Matsuzawa Y (2000) Genomic structure and mutations in adipose-specific gene, adiponectin. Int J Obes Relat Metab Disord 24:861–868
Tan BK, Pua S, Syed F, Lewandowski KC, O’Hare JP, Randeva HS (2008) Decreased plasma omentin-1 levels in Type 1 diabetes mellitus. Diabet Med 25:1254–1255
Toussirot E, Grandclément E, Gaugler B, Michel F, Wendling D, Saas P, Dumoulin G (2013) Serum adipokines and adipose tissue distribution in rheumatoid arthritis and ankylosing spondylitis. A comparative study. Front Immunol 4:453
Toussirot E, Streit G, Nguyen NU, Dumoulin G, Le Huédé G, Saas P, Wendling D (2007) Adipose tissue, serum adipokines, and ghrelin in patients with ankylosing spondylitis. Metabolism 56:1383–1389
Versini M, Jeandel PY, Rosenthal E, Shoenfeld Y (2014) Obesity in autoimmune diseases: not a passive bystander. Autoimmun Rev 13:981–1000
Vyse TJ, Todd JA (1996) Genetic analysis of autoimmune disease. Cell 85:311–318
Wells GA, Shea B, O’Connell D, Robertson J, Peterson J, Welch V, Losos M, Tugwell P (2016). http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp. Accessed 20 Aug 2016
Yazıcı D, Yavuz D, Öğünç AV, Sirikçi Ö, Toprak A, Deyneli O, Akalın S (2012) Serum adipokine levels in type 1 diabetic patients: association with carotid intima media thickness. Metab Syndr Relat Disord 10:26–31
Yuan T, Zhao WG, Sun Q, Fu Y, Dong YY, Dong YX, Yang GH, Wang H (2010) Association between four adipokines and insulin sensitivity in patients with obesity, type 1 or type 2 diabetes mellitus, and in the general Chinese population. Chin Med J (Engl) 123:2018–2022
Acknowledgements
This work was supported by Grants from the National Natural Science Foundation of China (81473058).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Rights and permissions
About this article
Cite this article
Zhang, MY., Dini, A.A., Yang, XK. et al. Association between serum/plasma adiponectin levels and immune-mediated diseases: a meta-analysis. Arch Dermatol Res 309, 625–635 (2017). https://doi.org/10.1007/s00403-017-1755-y
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00403-017-1755-y