Adiponectin level in diabetic kidney disease the relationship with glycemic control and microvascular complications; a mystery unresolved

  • Authors

    • Effat A. E. Tony assuit university faculty of medicine
    • Mohamed H.Mostafa assuit university faculty of medicine
    • Refaat F. Abdelaal assuit university faculty of medicine
    • Abeer A. Tony assuit university faculty of medicine
    • Tahra El- Shereif
    • Madleen Adel A. Abdou
    2018-12-23
    https://doi.org/10.14419/ijm.v6i1.14353
  • T2DM, ADPN, Adiponectin, DKD Diabetic Kidney Disease, ESRD, End Stage Renal Disease.
  • Abstract

    Background: Defining new predictive biomarkers in diabetic kidney disease (DKD) would provide a window of opportunity for preventive and/or therapeutic interventions to prevent or delay the onset of irreversible long-term micro and or macro vascular complications. Adiponectin (ADPN) has been variously associated with diabetic microvascular complications; however, no comprehensive clinical data exist examining the association between adipocytokines and the presence of these complications.

    Aim of study: we aimed to measure the plasma levels of adiponectin in patients with type 2 diabetes mellitus, to assess whether these levels vary with the different stages of DKD according to their e GFR and to evaluate its relation to their microvascular complications and glycemic control.

    Methods: This is a prospective observational study including 100 T2DM classified into two groups according to their albuminuria levels and estimated GFR. Participants subjected to thorough history taking and clinical examination. Serum level of ADPN was assessed in all patients.

    Results: Serum ADPN levels were significantly lower in T2DM patients with nephropathy (P = 0.001), while their levels were non-significantly higher in patients with non-proliferative retinopathy or neuropathy. Their levels were lowered with more advanced stages of DKD with nephropathy and the decrement was dependent on their severity (P<0.001). Levels of ADPN with cutoff value of < 22600 (μg/mL) had ability to diagnose microvascular complications in our diabetic patients with sensitivity (81%) and specificity (27%). Multivariate logistic regression analysis showed that the odds ratio for the presence of nephropathy in the lowest tertile of ADPN was 1.09 (95% CI; 11.45- 13.08, P= 0.06), therefore, ADPN was not an independent risk factor for diabetic nephropathy. However, its higher level was independently associated with increased odds for the presence of neuropathy in particular. Conclusions: ADPN plays a role in the pathogenesis of microvasculopathy in diabetic patients and help to identify high-risk patients and modulate the therapeutic potential in the prevention of DKD.

     

     
  • References

    1. [1] Xue R, Gui D, Zheng L, Zhai R, Wang F, Wang N. Mechanistic insight and management of diabetic nephropathy: recent progress and future perspective. Journal of diabetes research. 2017 2017 7.

      [2] Lim AK, Tesch GH. Inflammation in diabetic nephropathy. Mediators of inflammation. 2012;2012.

      [3] Tonelli M, Sacks F, Pfeffer M, Jhangri GS, Curhan G. Biomarkers of inflammation and progression of chronickidney disease. Kidney international. 2005;68(1):237-45. https://doi.org/10.1111/j.1523-1755.2005.00398.x.

      [4] Sharma K, Ziyadeh FN. Hyperglycemia and diabetic kidney disease: the case for transforming growth factor–β as a key mediator. Diabetes. 1995;44(10):1139-46. https://doi.org/10.2337/diab.44.10.1139.

      [5] Zhang W, Liu H, Al-Shabrawey M, Caldwell RW, Caldwell RB. Inflammation and diabetic retinal microvascular complications. Elsevier; 2011.

      [6] Jung CH, Kim BY, Mok JO, Kang SK, Kim CH. Association between serum adipocytokine levels and microangiopathies in patients with type 2 diabetes mellitus. Journal of diabetes investigation. 2014;5(3):333-9. https://doi.org/10.1111/jdi.12144.

      [7] Ouchi N, Walsh K. Adiponectin as an anti-inflammatory factor. Clinica chimica acta. 2007;380(1-2):24-30. https://doi.org/10.1016/j.cca.2007.01.026.

      [8] Cnop M, Havel P, Utzschneider K, Carr D, Sinha M, Boyko E, et al. Relationship of adiponectin to body fat distribution, insulin sensitivity and plasma lipoproteins: evidence for independent roles of age and sex. Diabetologia. 2003;46(4):459-69. https://doi.org/10.1007/s00125-003-1074-z.

      [9] Ding Y, Li S, Ma R-L, Guo H, Zhang J, and Zhang M, et al. Association of homeostasis model assessment of insulin resistance, adiponectin, and low-grade inflammation with the course of the metabolic syndrome. Clinical biochemistry. 2015 48(7-8):503-7 https://doi.org/10.1016/j.clinbiochem.2015.02.005.

      [10] Wellen KE, Hotamisligil GS. Inflammation, stress, and diabetes. The Journal of clinical investigation. 2005;115(5):1111-9. https://doi.org/10.1172/JCI25102.

      [11] Erlinger TP, Tarver-Carr ME, Powe NR, Appel LJ, Coresh J, Eberhardt MS, et al. Leukocytosis, hypoalbuminemia, and the risk for chronic kidney disease in US adults. American journal of kidney diseases. 2003;42(2):256-63 https://doi.org/10.1016/S0272-6386(03)00650-4.

      [12] Rodríguez AJ, dos Santos Nunes V, Mastronardi CA, Neeman T, Paz-Filho GJ. Association between circulating adipocytokine concentrations and microvascular complications in patients with type 2 diabetes mellitus: A systematic review and meta-analysis of controlled cross-sectional studies. Journal of diabetes and its complications. 2016;30(2):357-67 https://doi.org/10.1016/j.jdiacomp.2015.11.004.

      [13] Baghel M, Modala S, Kumar P. Correlation of creatinine clearance and urine microalbumin in type 2 diabetes mellitus. Int J Basic Appl Med Sci. 2014;4(2):182-6.

      [14] Kramer HJ, Nguyen QD, Curhan G, Hsu C-y. Renal insufficiency in the absence of albuminuria and retinopathy among adults with type 2 diabetes mellitus. Jama. 2003;289(24):3273-7. https://doi.org/10.1001/jama.289.24.3273.

      [15] Caramori ML, Fioretto P, Mauer M. Low glomerular filtration rate in normoalbuminuric type 1 diabetic patients: an indicator of more advanced glomerular lesions. Diabetes. 2003;52(4):1036-40. https://doi.org/10.2337/diabetes.52.4.1036.

      [16] Ninomiya T, Perkovic V, de Galan BE, Zoungas S, Pillai A, Jardine M, et al. Albuminuria and kidney function independently predict cardiovascular and renal outcomes in diabetes. Journal of the American Society of Nephrology. 2009;20(8):1813-21. https://doi.org/10.1681/ASN.2008121270.

      [17] MacIsaac RJ, Panagiotopoulos S, McNeil KJ, Smith TJ, Tsalamandris C, Hao H, et al. Is nonalbuminuric renal insufficiency in type 2 diabetes related to an increase in intrarenal vascular disease? Diabetes care. 2006;29(7):1560-6. https://doi.org/10.2337/dc05-1788.

      [18] Nevelsteen I, Van den Bergh A, Van der Mieren G, Vanderper A, Mubagwa K, Bult H, et al. NO-dependent endothelial dysfunction in type II diabetes is aggravated by dyslipidemia and hypertension, but can be restored by angiotensin-converting enzyme inhibition and weight loss. Journal of vascular research. 2013;50(6):486-97. https://doi.org/10.1159/000355221.

      [19] Kato K, Osawa H, Ochi M, Kusunoki Y, Ebisui O, Ohno K, et al. Serum total and high molecular weight adiponectin levels are correlated with the severity of diabetic retinopathy and nephropathy. Clinical endocrinology. 2008;68(3):442-9.

      [20] Papadopoulou-Marketou N, Kanaka-Gantenbein C, Marketos N, Chrousos GP, Papassotiriou I. Biomarkers of diabetic nephropathy: A 2017 update. Crit Rev Clin Lab Sci. 201.

      [21] Yilmaz MI, Saglam M, Qureshi AR, Carrero JJ, Caglar K, Eyileten T, et al. Endothelial dysfunction in type-2 diabetics with early diabetic nephropathy is associated with low circulating adiponectin. Nephrology Dialysis Transplantation. 2008;23(5):1621-7. https://doi.org/10.1093/ndt/gfm828.

      [22] Sharma K, RamachandraRao S, Qiu G, Usui HK, Zhu Y, Dunn SR, et al. Adiponectin regulates albuminuria and podocyte function in mice. The Journal of clinical investigation. 2008;118(5):1645-56. https://doi.org/10.1172/JCI32691.

      [23] Doumatey A, 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. International journal of nephrology. 2012;2012.

      [24] Ljubic S, Jazbec A, Tomic M, Piljac A, Jurisic Erzen D, Novak B, et al. Inverse levels of adiponectin in type 1 and type 2 diabetes are in accordance with the state of albuminuria. International journal of endocrinology. 2015;2015.

      [25] GaloviÄová A, Lazúrová I, Petrášová D. An association between adiponectin and renal dysfunction in patients with type 2 diabetes mellitus. Vnitrni lekarstvi. 2012;58(11):825-9.

      [26] Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF, Feldman HI, et al. A new equation to estimate glomerular filtration rate. Annals of internal medicine. 2009;150(9):604-12. https://doi.org/10.7326/0003-4819-150-9-200905050-00006.

      [27] Wang G, Gao S, Su N, Xu J, Fu D. Plasma adiponectin levels inversely correlate to clinical parameters in type 2 diabetes mellitus patients with macrovascular diseases. Annals of Clinical & Laboratory Science. 2015;45(3):287-91.

      [28] Yazıcı D, Yavuz D, Öğünç AV, Şirikçi Ö, Toprak A, Deyneli O, et al. Serum adipokine levels in type 1 diabetic patients: association with carotid intima media thickness. Metabolic syndrome and related disorders. 2012;10(1):26-31. https://doi.org/10.1089/met.2011.0052.

      [29] Altinova AE, Toruner F, Bukan N, Yasar DG, Akturk M, Cakir N, et al. Decreased plasma adiponectin is associated with insulin resistance and HDL cholesterol in overweight subjects. Endocrine journal. 2007;54(2):221-6. https://doi.org/10.1507/endocrj.K06-021.

      [30] Izadi V, Farabad E, Azadbakht L. Epidemiologic evidence on serum adiponectin level and lipid profile. International journal of preventive medicine. 2013;4(2):133.

      [31] Looker HC, Krakoff J, Funahashi T, Matsuzawa Y, Tanaka S, Nelson RG, et al. Adiponectin concentrations are influenced by renal function and diabetes duration in Pima Indians with type 2 diabetes. The Journal of Clinical Endocrinology & Metabolism. 2004;89(8):4010-7 https://doi.org/10.1210/jc.2003-031916.

      [32] Isobe T, Saitoh S, Takagi S, Takeuchi H, Chiba Y, Katoh N, et al. Influence of gender, age and renal function on plasma adiponectin level: the Tanno and Sobetsu.

      [33] Kadowaki T, Yamauchi T. Adiponectin and adiponectin receptors. Endocrine reviews. 2005; 26(3):439-51. https://doi.org/10.1210/er.2005-0005.

      [34] Maruyama C, Ishibashi R, Araki R, Koike S, Hirose H, Maruyama T. HMW-adiponectin associates with triglyceride concentrations in type 1 diabetic patients Journal of atherosclerosis and thrombosis. 2009 16(3):207-16. https://doi.org/10.5551/jat.E067.

      [35] Ding EL, Song Y, Malik VS, Liu S. Sex differences of endogenous sex hormones and risk of type 2 diabetes: a systematic review and meta-analysis. Jama. 2006 295(11):1288-99. https://doi.org/10.1001/jama.295.11.1288.

      [36] Rao M, Li L, Tighiouart H, Jaber BL, Pereira BJ, Balakrishnan VS, et al. Plasma adiponectin levels and clinical outcomes among haemodialysis patients. Nephrology Dialysis Transplantation. 2008 23(8):2619-28. https://doi.org/10.1093/ndt/gfn070.

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    A. E. Tony, E., H.Mostafa, M., F. Abdelaal, R., A. Tony, A., El- Shereif, T., & Adel A. Abdou, M. (2018). Adiponectin level in diabetic kidney disease the relationship with glycemic control and microvascular complications; a mystery unresolved. International Journal of Medicine, 6(2), 18-24. https://doi.org/10.14419/ijm.v6i1.14353

    Received date: 2018-06-19

    Accepted date: 2018-07-17

    Published date: 2018-12-23