Background: High molecular weight (HMW) adiponectin has antiatherogenic, antiinflammatory and antidiabetic properties and these effects have been linked to its effect on high density lipoprotein cholesterol (HDL-c). Single nucleotide polymorphisms (SNPs) in the adiponectin gene influence adiponectin levels. We examined the relationship between HMW-adiponectin levels and cardiometabolic traits in normo- and hyperglycemic mixed ancestry South Africans and correlated these levels to two common polymorphisms.
Methods: HMW-adiponectin was determined in 101 subjects from the Cape Town Bellville South community-based study on a mixed ancestry population. Comparisons were made between individuals with normo- and hyperglycemia. Two common SNPs, ADIPOQ SNPs rs17300539 and rs266729, known to affect adiponectin levels were also tested for. Levels of HMW-adiponectin were then correlated with cardiometabolic traits in all groups.
Results: Levels of HMW-adiponectin were not significantly different in the normo- and hyperglycemic groups (median 11.6 vs. 10.5 μg/mL, p=0.3060) and in men and women (8.44 vs. 11.34 μg/mL, p=0.67). ADIPOQ SNPs rs17300539 and rs266729 did not influence levels of HMW-adiponectin. Robust correlation analyses revealed a significant positive correlation between HMW-adiponectin and HDL-c (r=0.45; 95%CI: 0.27–0.59), similarly in normo- and hyperglycemic participants (p>0.99). This association was substantially attenuated in robust linear regressions adjusted for age, gender and adiposity.
Conclusions: Adiponectin levels in this population were not determined by the commonest SNPs of the adiponectin gene, were unaffected by glycemic status; but were significantly correlated with HDL-c levels. Previous studies have attributed some of the beneficial effects of adiponectin to its effect on HDL-c.
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1. Litvinova L, Atochin D, Vasilenko M, Farrakhov N, Zatolokin P, Vaysbeyn I, Kirienkova E. Role of adiponectin and proinflammatory gene expression in adipose tissue chronic inflammation in women with metabolic syndrome. Diabetol Metab Syndr 2014; 6: 137.
2. Gable DR, Hurel SJ, Humphries SE. Adiponectin and its gene variants as risk factors for insulin resistance, the metabolic syndrome and cardiovascular disease. Atherosclerosis 2006; 188: 231–44.
3. Lee S, Kwak HB. Role of adiponectin in metabolic and cardiovascular disease. J Exerc Rehabil 2014; 10: 54–9.
4. Rabin KR, Kamari Y, Avni I, Grossman E, Sharabi Y. Adiponectin: linking the metabolic syndrome to its cardiovascular consequences. Expert Rev Cardiovasc Ther 2005; 3: 465–71.
5. Balsan GA, da Costa Viera JL, de Oliveira AM, Portal VL. Relationship between adiponectin, obesity and insulin resistance. Rev Assoc Med Bras 2015; 61: 72–80.
6. Yadav A, Kataria MA, Saini V, Yadav A. The role of leptin and adiponectin in insulin resistance. Clin Chim Acta 2013; 417: 80–4.
7. Ryo M, Nakamura T, Kihara S, Kumada M, Shibazaki S, Takahashi M, et al. Adiponectin as a biomarker of the metabolic syndrome. Circ J 2004; 68: 975–81.
8. Suriyaprom K, Phonrat B, Tungtrongchitr R. Association of adiponectin gene −11377C>G polymorphism with adiponectin levels and the metabolic syndrome in Thais. Asia Pac J Clin Nutr 2014; 23: 167–73.
9. Dujić T, Bego T, Mlinar B, Semiz S, Malenica M, Prnjavorac B, Ostanek B, Marc J, Čaušević A. Effects of the PPARG gene polymorphisms on markers of obesity and the metabolic syndrome in bosnian subjects. J Med Biochem 2014; 4: 323–32.
10. Fisman EZ, Tenenbaum A. Adiponectin: a manifold therapeutic target for metabolic syndrome, diabetes, and coronary disease? Cardiovasc Diabetol 2014; 13: 103.
11. Wannamethee SG, Whincup PH, Lennon L, Sattar N. Circulating adiponectin levels and mortality in elderly men with and without cardiovascular disease and heart failure. Arch Intern Med 2007; 167: 1510–7.
12. Lee ES, Park S, Kim E, Yoon YS, Ahn HY, Park CY, et al. Association between adiponectin levels and coronary heart disease and mortality: a systematic review and meta-analysis. Int J Epidemiol 2013; 42: 1029–39.
13. Hascoet S, Elbaz M, Bongard V, Bouisset F, Verdier C, Vindis C, et al. Adiponectin and long-term mortality in coronary artery disease participants and controls. Arterioscler Thromb Vasc Biol 2013; 33: e19–e29.
14. Wu ZJ, Cheng YJ, Gu Wj, Aung LHH. Adiponectin is associated with increased mortality in patients with already established cardiovascular disease: a systematic review and meta-analysis. Metabolism 2014; 63: 1157–66.
15. Alehagen U, Vorkapic E, Ljungberg L, Länne T, Wågsäter D. Gender difference in adiponectin associated with cardiovascular mortality. BMC Medical Genetics 2015; 16: 37.
16. Kizer JR. Adiponectin, cardiovascular disease, and mortality: parsing the dual prognostic implications of a complex adipokine. Metabolism 2014; 63: 1079–83.
17. Choi SH, Ku EJ, Hong ES, Lim S, Kim KW, Moon JH, et al. High serum adiponectin concentration and low body mass index are significantly associated with increased all-cause and cardiovascular mortality in an elderly cohort, »adiponectin paradox«, The Korean Longitudinal Study on Health and Aging (KLoSHA). Int J Cardiol 2015; 183: 91–7.
18. Witberg G, Ayers CR, Turer AT, Lev E, Kornowski R, de Lemos J, Neeland IJ. Relation of adiponectin to all-cause mortality, cardiovascular mortality, and major adverse cardiovascular events (from the Dallas Heart Study). Am J Cardiol 2016; 117: 574–9.
19. Doumatey AP, Zhou J, Huang H, Adeleye J, Balogun W, Fasanmade O, et al. Circulating adiponectin is associated with renal function independent of age and serum lipids in West Africans. Int J Nephrol 2012; 2012: 730920.
20. Ferris WF, Naran NH, Crowther NJ, Rheeder P, van der Merwe L, Chetty N. The relationship between insulin sensitivity and serum adiponectin levels in three population groups. Horm Metab Res 2005; 37: 695–701.
21. Sobngwi E, Effoe V, Boudou P, Niamen D, Gautier JF, Mbanya JC. Waist circumference does not predict circulating adiponectin levels in sub-Saharan women. Cardiovasc Diabetol 2007; 6: 31.
22. Obot AS, Usoro CAO, Nsonwu-Anyanwu AC, Egbe ER, Ekott JU, Usoro AJ. Adiponectin and cardiovascular risk factors in relation with glycemic control in type 2 diabetics. Int J Res Med Sci 2013; 1: 563–70.
23. Vasseur F, Meyre D, Froguel P. Adiponectin, type 2 diabetes and the metabolic syndrome: lessons from human genetic studies. Expert Rev Mol Med 2006; 8: 1–11.
24. Comuzzie AG, Funahashi T, Sonnenberg G, Martin LJ, Jacob HJ, Kwiteck Black AE, et al. The genetic basis of plasma variation in adiponectin, a global endophenotype for obesity and the metabolic syndrome. J Clin Endocrinol Metab 2001; 86: 4321–5.
25. Li P, Jiang R, Li L, Liu C, Yang F, Qiu Y. Correlation of serum adiponectin and adiponectin gene polymorphisms with metabolic syndrome in Chinese adolescents. Eur J Clin Nutr 2015; 69: 62–7.
26. Kocova M, Sukarova-Angelovska E, Tanaskoska M, Palcevska-Kocevska S, Krstevska M. Metabolic setup and risks in obese children. J Med Biochem 2015; 34: 31–7.
27. Han LY, Wu QH, Jiao ML, Hao YH, Liang LB, Gao LG, et al. Associations between single-nucleotide polymorphisms (+45T>G, +276G>T, −11377C>G, −11391G>A) of adiponectin gene and type 2 diabetes mellitus: a systematic review and meta-analysis. Diabetologica 2011; 54: 2303–14.
28. Kaftan AN, Hussain MK. Association of adiponectin gene polymorphism rs266729 with type two diabetes in Iraqi population. A pilot study. Gene 2015; 570: 95–9.
29. Erasmus RT, Soita DJ, Hassan MS, Blanco-Blanco E, Vergotine Z, Kegne AP, Matsha TE. High prevalence of diabetes mellitus and metabolic syndrome in a South African Coloured population: baseline data of a study in Bellville, Cape Town. S Afr Med J 2012; 102: 841–4.
30. Zemlin AE, Matsha TE, Hassan MS, Erasmus RT. HbA1c of 6.5% to diagnose diabetes mellitus – does it work for us? – the Bellville South Africa study. PLoS One 2011; 6: e22558.
31. Matsha TE, Hassan MS, Kidd M, Erasmus RT. The 30-year cardiovascular risk profile of South Africans with diagnosed diabetes, undiagnosed diabetes, pre-diabetes or normoglycaemia: the Bellville, South Africa pilot study. Cardiovasc J Afr 2012; 23: 5–11.
32. Chalmers J, MacMahon S, Mancia G, Whitworth J, Beilin L, Hansson L, et al. World Health Organization–International Society of Hypertension Guidelines for the management of hypertension. Guidelines sub-committee of the World Health Organization. Clin Exp Hypertens 1999; 21: 1009–60.
33. Alberti KG, Zimmet PZ. Definition, diagnosis and classification of diabetes mellitus and its complications. Part I: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabet Med 1998; 15: 539–53.
34. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985; 28: 412–9.
35. Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 1972; 18: 499–502.
36. Ebinuma H, Miyazaki O, Yago H, Hara K, Yamauchi T, Kadowaki T. A novel ELISA system for selective measurement of human adiponectin multimers by using proteases. Clin Chim Acta 2006; 372: 47–53.
37. Li S, Shin HJ, Ding EL, van Dam RM. Adiponectin levels and risk of type 2 diabetes: a systematic review and meta-analysis. JAMA 2009; 302: 179–88.
38. Hivert MF, Sullivan LM, Shrader P, Fox CS, Nathan DM, D’Agostino RB Sr, et al. Insulin resistance influences the association of adiponectin levels with diabetes incidence in two population-based cohorts: the Cooperative Health Research in the Region of Augsburg (KORA) S4/F4 study and the Framingham Offspring Study. Diabetologia 2011; 54: 1019–24.
39. Doumatey AP, Bentley AR, Zhou J, Huang H, Adeyemo A, Rotimi CN. Paradoxical hyperadiponectinemia is associated with the metabolically healthy obese (MHO) phenotype in African Americans. J Endocrin Metab 2012; 2: 51–65.
40. Ding Y, Li S, Ma R, Guo H, Zhang J, Zhang M, et al. Association of homeostasis of insulin resistance, adiponectin, and low-grade inflammation with the course of the metabolic syndrome. Clin Biochem 2015; 48: 503–7.
41. Moriyama K, Negami M, Takahashi E. HDL2-cholesterol/HDL3-cholesterol ratio was associated with insulin resistance, high-molecular-weight adiponectin, and components for metabolic syndrome in Japanese. Diabetes Res Clin Pract 2014; 106: 360–5.
42. Wannamethee SG, Welsh P, Whincup PH, Sawar N, Thomas MC, Gudnarsson V, Sattar N. High adiponectin and increased risk of cardiovascular disease and mortality in asymptomatic older men: does NT-proBNP help to explain this association? Eur J Cardiovasc Prev Rehabil 2011; 18: 65–71.
43. Omar F, Dave JA, King JA, Levitt NS, Pillay TS. High molecular weight (HMW): total adiponectin ratio is low in HIV-infected women receiving protease inhibitors. BMC Clin Pathol 2014; 14: 46.
44. Dessain PH, Woodiwiss AJ, Norton GR, Tsang L, Solomon A. Independent associations of total and high molecular weight adiponectin with cardiometabolic risk and surrogate markers of enhanced early atherogenesis in black and white patients with rheumatoid arthritis: a cross-sectional study. Arthritis Res Ther 2013; 15: R128.
45. Meilleur KG, Doumatey A, Huang H, Charles B, Chen G, Zhou J, et al. Circulating adiponectin is associated with obesity and serum lipids in West Africans. J Clin Endocrinol Metab 2010; 95: 3517–21.
46. Orluwene CG, Kasia BE. Relationship between serum adiponectin and plasma fatty acids composition in offshore (rig) workers in Bayelsa State, Nigeria. IOSR Journal of Pharmacy 2013; 3: 39–46.
47. Ntyintyane L, Panz V, Raal FJ, Gill G. Leptin, adiponectin, and high-sensitivity C-reactive protein in relation to the metabolic syndrome in urban South African Blacks with and without coronary artery disease. Metab Syndr Relat Disord 2009; 7: 243–8.
48. Hara K, Horikoshi M, Yamauchi T, Yago H, Miyazaki O, Ebinuma H, et al. Measurement of the high-molecular weight form of adiponectin in plasma is useful for the prediction of insulin resistance and metabolic syndrome. Diabetes Care 2006; 29: 1357–62.
49. Aso Y, Yamamoto R, Wakabayashi S, Uchida T, Takayangi K, Okuno T, et al. Comparison of serum high-molecular weight (HMW) adiponectin with total adiponectin concentrations in type 2 diabetic patients with coronary artery disease using a novel enzyme-linked immunosorbent assay to detect HMW adiponectin. Diabetes 2006; 55: 1954–60.
50. Nakashima R, Kamei N, Yamane K, Nakanishi S, Nakashima A, Kohno N. Decreased total and high molecular weight adiponectin are independent risk factors for the development of type 2 diabetes in Japanese-Americans. J Clin Endocrinol Metab 2006; 91: 3873–7.
51. Seino Y, Hirose H, Saito I, Itoh H. High molecular weight multimer form of adiponectin as a useful marker to evaluate insulin resistance and metabolic syndrome in Japanese men. Metabolism 2007; 56: 1493–9.
52. Goto M, Goto A, Morita A, Deura K, Sasaki S, Aiba N, et al. Low-molecular-weight adiponectin and high-molecular-weight adiponectin levels in relation to diabetes. Obesity 2014; 22: 401–7.
53. Lin CH, Ho CY, Liu CS, Lin WY, Li CI, Yang CW, et al. Influence of adiponectin gene polymorphisms on adiponectin serum level and insulin resistance index in Taiwanese metabolic syndrome patients. Chin J Physiol 2012; 55: 405–11.
54. Henneman P, Aulchenko YS, Frants RR, Zorkoltseva IV, Zillikens MC, Frolich M, et al. Genetic architecture of plasma adiponectin overlaps with the genetics of metabolic syndrome-related traits. Diabetes Care 2010; 33: 908–13.
55. Gao M, Ding D, Huang J, Qu Y, Wang Y, Huang Q. Association of genetic variants in the adiponectin gene with metabolic syndrome: a case-control study and a systematic meta-analysis in the Chinese population. PLoS One, 2013, 8:e58412.
56. Pischon T, Hu FB, Girman CJ, Rifai N, Manson JE, Rexrode KM, Rimm EB. Plasma total and high molecular weight adiponectin levels and risk of coronary heart disease in women. Atherosclerosis 2011; 219: 322–9.
57. Heideman C, Sun Q, van Dam RM, Meigs JB, Zhang C, Tworoger SS, et al. Total and high-molecular-weight adiponectin and resistin in relation to the risk for type 2 diabetes in women. Ann Intern Med 2008; 149: 307–16.
58. Sattar N, Watt P, Cherry L, Ebrahim S, Davey Smith G, Lawlor DA. High molecular weight adiponectin is not associated with incident coronary heart disease in older women: a nested prospective case-control study. J Clin Endocrinol Metab 2008; 93: 1846–9.
59. Van Linthout S, Foryst-Ludwig A, Spillmann F, Peng J, Feng Y, Meloni M, et al. Impact of HDL on adipose tissue metabolism and adiponectin expression. Atherosclerosis 2010; 210: 438–44.
60. Christou GA, Tellis CC, Elisaf MS, Tselepis AD, Kiortsis DN. High density lipoprotein is positively correlated with the changes in circulating total adiponectin and high molecular weight adiponectin during dietary and fenofibrate treatment. Hormones 2012; 11: 178–88.