Title: Role of Adiponectin in Development and Progression of Diabetic Complications
Authors: Soher A. Mohammed Ismail, Ahmed Osman, Mustafa Abd El-Aziz M, Shaimaa Mohammed kamel, Iman A. Fahmy, Mohamed El Hefni, Safyea Mohamed Hussien
DOI: http://dx.doi.org/10.18535/jmscr/v3i12.50
This study aimed to elucidate the role of adiponectin in evolution of microvascular complication of type 2 diabetes mellitus, in particular retinopathy and nephropathy. In addition, we attempted to find a correlation between the serum levels of adiponectin and different parameters such as duration of diabetes, age, sex, glycemic state, insulin resistance, lipid profile and albumin-creatinine ratio in type 2 diabetic patients with retinopathy and nephropathy in order to understand more about these risk factors . This study involved sixty diabetic patients with type 2 diabetes mellitus with or without micro vascular complications involving either retinal or renal vasculatures or both. These patients were recruited from the outpatient clinic (A written consent was obtained from each case included in the study according to the Ethical Committee Approval of the Research Institute of Ophthalmology (RIO), Giza, Egypt. In addition to fifteen healthy subjects were involved and served as reference group. In addition to serum levels of adiponectin, routine diabetic diagnostic markers such as blood glucose levels, glycosylated Hb, insulin resistance, lipid profile, and kidney function tests were performed to all individuals included in the study. Full ophthalmological assessment including Fundus Fluorescein Angiography and clinical examinations (blood pressure, search for lower limb oedema, pallor, renal mass, etc.) have done for each subject. Data of this study revealed that the levels of serum adiponectin were decreased in patients with diabetic retinopathy while they were increased in patients with either diabetic nephropathy alone and to a lesser extent, in diabetic patients with nephropathy and retinopathy. Serum adiponectin levels were found to be correlated with some parameters of lipid profile in patients with mixed conditions, a notion that highlight the role of adiponectin in the pathogenesis of microvascular complications of diabetes. Moreover, these results suggest that increased total serum adiponectin may predict coexistence of vascular endothelial dysfunction in diabetic nephropathy patients. Therefore, we recommended that adiponectin can be used as a prognostic marker for diabetic complications which will initiate a new era for the management of diabetes. 1. Hug C, Wang J, Ahmad NS, Bogan JS, Tsao TS, Lodish HF, 2004 .T-cadherin is a receptor for hexameric and high-molecular-weight forms of Acrp30/adiponectin. ProcNatlAcadSci USA 101: 10308-10313. 2. Trujillo ME, Scherer PE., 2005. Adiponectin journey from an adipocyte secretory protein to biomarker of the metabolic syndrome. J Intern Med; 257:167–175 3. Goldstein BJ, Scalia R. 2004.Adiponectin: a novel adipokine linking adipocytes and vascular function. J Clin Endocrinal Metab; 89:2563–2568 4. K. Rabe, M. Lehrke, K. G. Parhofer, and U. C. Broedl, 2008.“Adipokines and insulin resistance,”MolecularMedicine, vol. 14, no. 11-12, pp. 741–751. 5. Thomas, A.C., G. Armando and Z. Bernard, 2003. Diabetic retinopathy and diabetic macular edema. Diabetes Care, 26: 2653-2664 6. Donald, S.F., L. Aiello, T.W. Gardner, L.K. George, B. George, J.D. Cavallerano, F.L. Ferris and R. Klein, 2004. Retinopathy in diabetes. Diabetes Care, 27: S84-S87. 7. Yilmaz, M.I., A. Sonmez, C. Acikel, T. Celik, N. Bingol, M. Pinar, Z. Bayraklar and M. Ozata, 2004. Adiponectin may play a part in the pathogenesis of diabetic retinopathy. Euro. J. Endocrinol., 151: 135-140. 8. Giunti, S., Barit, D., and Cooper, M. E. (2006). Diabetic nephropathy: from mechanisms to rational therapies. Minerva medica, 97(3), 241-262. 9. Viberti, G. C., Jarrett, R. J., Mahmud, U., Hill, R. D., Argyropoulos, A., and Keen, H. (1982). Microalbuminuria as a predictor of clinical nephropathy in insulin-dependent diabetes mellitus. The Lancet, 319(8287), 1430-1432. 10. Gnudi, L., Thomas, S. M., and Viberti, G. (2007). Mechanical forces in diabetic kidney disease: a trigger for impaired glucose metabolism. Journal of the American Society of Nephrology, 18(8), 2226-2232. 11. Schalkwijk CG, Chaturvedi N, SchramMTet al. and the EURODIAB Prospective Complications Study Group, 2006. Adiponectin is inversely associated with renal function in type 1 diabetic patients. J Clin Endocrinol Metab; 91: 129–135 12. Saraheimo M, Forsblom C, Fagerudd J et al. on behalf of the FinnDiane Study Group ,2005. Serum adiponectin is increased in type 1 diabetic patients with nephropathy. Diabetes Care; 28: 1410–1414 13. Lin J, Hu FB, Curhan G 2007. Serum adiponectin and renal dysfunction in men with type 2 diabetes. Diabetes Care; 30: 239–244 14. Winzer C1, Wagner O, Festa A, Schneider B, Roden M, Bancher-Todesca D, Pacini G, Funahashi T, Kautzky-Willer A.2004.Plasmaadiponectin, insulinsensitivity, and subclinicalinflammation in women with priorgestationaldiabetesmellitus.DiabetesCare.; 27(7):1721-7. 15. Snehalatha C1, Mukesh B, Simon M, Viswanathan V, Haffner SM, Ramachandran A.2003.Plasma adiponectin is an independent predictor of type 2 diabetes in Asian indians. DiabetesCare.; 26(12):3226-9. 16. Yilmaz MI1, Sonmez A, Acikel C, Celik T, Bingol N, Pinar M, Bayraktar Z, Ozata M.2004 .Adiponectin may play a part in the pathogenesis of diabetic retinopathy.Eur J Endocrinol ;151(1):135-40. 17. Ran J1, Xiong X, Liu W, Guo S, Li Q, Zhang R, Lao G. 2010. Increased plasma adiponectin closely associates with vascular endothelial dysfunction in type 2 diabetic patients with diabetic nephropathy.Diabetes Res Clin Pract. ; 88(2):177-83. 18. Sameha Abu EL-Yazid, Nagwa Abd EL-Ghaffar Mohammad, Manal Abd El-Latif, 1 2 1 KhaledYounes, Amanykamal and Mohamed Nabil EL-Nahas, 2008. The Role of Serum Adiponectin Concentration in Diabetic Patients with Diabetic Retinopathy. Australian Journal of Basic and Applied Sciences, 2(3): 535-539. 19. Akiko Higuchi, Koji Ohashi, Shinji Kihara, Kenneth Walsh, Noriyuki Ouchi. 2009. Adiponectin Suppresses Pathological Microvessel Formation in Retina Through Modulation of Tumor Necrosis Factor-_ Expression. Circ Res;104:00-00. 20. Lin J1, Hu FB, Curhan G. 2007. Serum adiponectin and renal dysfunction in men with type 2 diabetes.Diabetes Care.; 30(2):239-44. 21. Ran J1, Xiong X, Liu W, Guo S, Li Q, Zhang R, Lao G. 2010. Increased plasma adiponectin closely associates with vascular endothelial dysfunction in type 2 diabetic patients with diabetic nephropathy.Diabetes Res Clin Pract.;88(2):177-83. 22. M.I. Yilmaz, M. Saglam, A.R. Qureshi, J.J. Carrero, K. Caglar, T. Eyileten, et al., (2008).Endothelial dysfunction in type-2 diabetics with early diabetic nephropathy is associated with low circulating adiponectin, Nephrol. Dial. Transplant. 23:1621–1627. 23. Ford, E. S. (1999). Body mass index, diabetes, and C-reactive protein among US adults.Diabetes care, 22(12), 1971-1977. 24. Ross, R. (1999). Atherosclerosis—an inflammatory disease.New England journal of medicine, 340(2), 115-126. 25. Ross, R. (1999). Atherosclerosis—an inflammatory disease.New England journal of medicine, 340(2), 115-126. 26. Petersen, H. H., Nielsen, J. P., and Heegaard, P. M. H. (2004). Application of acute phase protein measurements in veterinary clinical chemistry.Veterinary research, 35(2), 163-187. 27. Pickup, J. C. (2004). Inflammation and activated innate immunity in the pathogenesis of type 2 diabetes. Diabetes care, 27(3), 813-823. 28. Pasceri, V., Willerson, J. T., and Yeh, E. T. (2000). Direct proinflammatory effect of C-reactive protein on human endothelial cells. Circulation, 102(18), 2165-2168. 29. Pasceri, V., Chang, J., Willerson, J. T., and Yeh, E. T. (2001). Modulation of C-reactive protein–mediated monocyte chemoattractant protein-1 induction in human endothelial cells by anti-atherosclerosis drugs. Circulation, 103(21), 2531-2534. 30. Zwaka, T. P., Hombach, V., and Torzewski, J. (2001). C-reactive protein–mediated low density lipoprotein uptake by macrophages: Implications for atherosclerosis. Circulation, 103(9), 1194-1197. 31. Lagrand, W. K., Niessen, H. W., Wolbink, G. J., Jaspars, L. H., Visser, C. A., Verheugt, F. W., Meijer, C. J., and Hack, C. E. (1997). Creactive protein colocalizes with complement in human hearts during acute myocardial infarction. Circulation, 95(1), 97-103. 32. Griselli, M., Herbert, J., Hutchinson, W. L., Taylor, K. M., Sohail, M., Krausz, T., and Pepys, M. B. (1999). C-reactive protein and complement are important mediators of tissue damage in acute myocardial infarction. The Journal of experimental medicine, 190(12), 1733-1740. 33. Libby, P., Ridker, P. M., and Maseri, A. (2002). Inflammation and atherosclerosis. Circulation, 105(9), 1135-1143. 34. Ola, M. S., Nawaz, M. I., Siddiquei, M. M., Al-Amro, S., and Abu El-Asrar, A. M. (2012). Recent advances in understanding the biochemical and molecular mechanism of diabetic retinopathy. Journal of Diabetes and its Complications, 26, 56-64. 35. Brownlee, M. (2005). The pathobiology of diabetic complications a unifying mechanism. Diabetes, 54(6), 1615-1625. 36. Huebschmann, A. G., Regensteiner, J. G., Vlassara, H., and Reusch, J. E. (2006). Diabetes and advanced glycoxidation end products. Diabetes Care, 29(6), 1420-1432. 37. Ahmed, N., and Thornalley, P. J. (2007). Advanced glycation endproducts: what is their relevance to diabetic complications?. Diabetes, Obesity and Metabolism, 9(3), 233-245. 38. Yan, S. F., Ramasamy, R., and Schmidt, A. M. (2008). Mechanisms of disease: advanced glycation end-products and their receptor in inflammation and diabetes complications. Nature Reviews Endocrinology, 4(5), 285-293. 39. El-Wakf, A. M., Abbas, M., El-Baz, A., and Mohammed, A. (2011). Role of Hypertension and Metabolic Abnormalities in the Development of Diabetic Nephropathy among Egyptian Patients with Type2 Diabetes. Nature and Science, 9(7), 220-228. 40. John, W. G. (1997). Glycated haemoglobin analysis.Annals of clinical biochemistry, 34, 17-31. 41. Diabetes Control and Complication Trial Research Group. (1993). Diabetes Control and Complications Trial (DCCT): the effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin dependent diabetes mellitus. New England Journal of Medicine, 329(14), 977-986. 42. Stratton, I. M., Adler, A. I., Neil, H. A. W., Matthews, D. R., Manley, S. E., Cull, C. A., Hadden, D., Turner, R. C., and Holman, R. R. (2000). Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. British medical journal, 321(7258), 405-412. 43. Nelson, R. G., Knowler, W. C., Pettitt, D. J., Hanson, R. L., and Bennett, P. H. (1995). Incidence and determinants of elevated urinary albumin excretion in Pima Indians with NIDDM. Diabetes Care, 18(2), 182-187. 44. Tapp, R. J., Shaw, J. E., Zimmet, P. Z., Balkau, B., Chadban, S. J., Tonkin, A. M., Welborn, T. A., and Atkins, R. C. (2004). Albuminuria is evident in the early stages of diabetes onset: results from the Australian Diabetes, Obesity, and Lifestyle Study (AusDiab). American journal of kidney diseases: the official journal of the National Kidney Foundation, 44(5), 792-798. 45. Nikzamir, A., Esteghamati, A., Feghhi, M., Nakhjavani, M., Rashidi, A., and Reza, J. Z. (2009). The insertion/deletion polymorphism of the angiotensin-converting enzyme gene is associated with progression, but not development, of albuminuria in Iranian patients with type 2 diabetes. Journal of Renin-Angiotensin-Aldosterone System, 10(2), 109-114. 46. Sato, K. K., Hayashi, T., Harita, N., Yoneda, T., Nakamura, Y., Endo, G., and Kambe, H. (2009). Combined measurement of fasting plasma glucose and A1C is effective for the prediction of type 2 diabetes the Kansai Healthcare Study. Diabetes Care, 32(4), 644-646. 47. Gillett, M. J. (2009). International Expert Committee Report on the Role of the A1C Assay in the Diagnosis of Diabetes: Diabetes Care 2009; 32 (7): 1327–1334. The Clinical Biochemist Reviews, 30(4), 197-200. 48. Fruebis J, Tsao TS, Javorschi S, et al. Proteolytic cleavage product of 30-kDa adipocyte complement-related protein increases fatty acid oxidation in muscle and causes weight loss in mice. ProcNatlAcadSci USA 2001; 98: 2005-2010. 49. Tomas E, Tsao TS, Saha AK, et al. Enhanced muscle fat oxidation and glucose transport by ACRP30 globular domain: acetyl-CoA carboxylase inhibition and AMP-activated protein kinase activation. ProcNatlAcadSci USA 2002; 99: 16309-16313. 50. Yamauchi T, Kamon J, Waki H, et al. The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nat Med 2001; 7: 941-946. 51. Yamauchi T, Kamon J, Ito Y, et al. Cloning of adiponectin receptors that mediate antidiabetic metabolic effects. Nature 2003; 423: 762-769. 52. Tugwood JD, Issemann I, Anderson RG, Bundell KR, McPheat WL, Green S. The mouse peroxisome proliferator activated receptor recognizes a response element in the 5. flanking sequence of the rat acyl CoA oxidase gene. EMBO J 1992; 11: 433-439. 53. Schoonjans K, Staels B, Auwerx J. The peroxisome proliferator activated receptors (PPARs) and their effects on lipid metabolism and adipocyte differentiation. BiochimBiophys Acta 1996; 1302: 93-109. 54. Yamauchi T, Kamon J, Minokoshi Y, et al. Adiponectin stimulates glucose utilization and fattyacid oxidation by activating AMP-activated protein kinase. Nat Med 2002; 8: 1288-1295. 55. Kahn BB, Alquier T, Carling D, Hardie DG. AMP-activated protein kinase: ancient energy gauge provides clues to modern understanding of metabolism. Cell Metab 2005; 1: 15-25. 56. Roepstorff C, Halberg N, Hillig T, et al. Malonyl-CoA and carnitine in regulation of fat oxidation in human skeletal muscle during exercise. Am J Physiol Endocrinol Metab 2005; 288: E133-E142. 57. Sasso, F. C., De Nicola, L., Carbonara, O., Nasti, R., Minutolo, R., Salvatore, T., Conte, G., and Torella, R. (2006). Cardiovascular risk factors and disease management in type 2 diabetic patients with diabetic nephropathy. Diabetes Care, 29(3), 498-503. 58. Klein, R., Klein, B. E., and Moss, S. E. (1992). Epidemiology of proliferative diabetic retinopathy.Diabetes care, 15(12), 1875-1891. 59. Adler, A. I., Stevens, R. J., Manley, S. E., Bilous, R. W., Cull, C. A., and Holman, R. R. (2003). Development and progression of nephropathy in type 2 diabetes: the United Kingdom Prospective Diabetes Study (UKPDS 64). Kidney international, 63(1), 225-232. 60. Festa, A., D'agostino, R., Howard, G., Mykkänen, L., Tracy, R. P., and Haffner, S. M. (2000). Inflammation and microalbuminuria in nondiabetic and type 2 diabetic subjects: The Insulin Resistance Atherosclerosis Study. Kidney international, 58(4), 1703-1710. 61. Viberti, G. C., Jarrett, R. J., Mahmud, U., Hill, R. D., Argyropoulos, A., and Keen, H. (1982). Microalbuminuria as a predictor of clinical nephropathy in insulin-dependent diabetes mellitus. The Lancet, 319(8287), 1430-1432. 62. Mogensen, C. E., and Christensen, C. K. (1984). Predicting diabetic nephropathy in insulin-dependent patients.The New England journal of medicine, 311(2), 89-93. 63. Jarrett, R. J., Viberti, G. C., Argyropoulos, A., Hill, R. D., Mahmud, U., and Murrells, T. J. (1984). Microalbuminuria Predicts Mortality in Noninsulin‐dependent Diabetes. Diabetic Medicine, 1(1), 17- 19. 64. Mattock, M. B., Morrish, N. J., Viberti, G., Keen, H., Fitzgerald, A. P., and Jackson, G. (1992). Prospective study of microalbuminuria as predictor of mortality in NIDDM. Diabetes, 41(6), 735-741. 65. Damsgaard, E. M., Froland, A., Jorgensen, O. D., and Mogensen, C. E. (1992). Eight to nine year mortality in known non-insulin dependent diabetics and controls. Kidney International, 41(4), 731-735. 66. Gall, M. A., Borch-Johnsen, K., Hougaard, P., Nielsen, F. S., and Parving, H. H. (1995). Albuminuria and poor glycemic control predict mortality in NIDDM. Diabetes, 44(11), 1303-1309. 67. MacLeod, J. M., Lutale, J., and Marshall, S. M. (1995). Albumin excretion and vascular deaths in NIDDM.Diabetologia, 38(5), 610-616. 68. Stehouwer, C. D., Zeldenrust, G. C., den Ottolander, G. J., Hackeng, W. H. L., Donker, A. J. M., and Nauta, J. J. P. (1992). Urinary albumin excretion, cardiovascular disease, and endothelial dysfunction in non-insulin-dependent diabetes mellitus. The Lancet, 340(8815), 319-323. 69. Keane, W. F., Brenner, B. M., De Zeeuw, D., Grunfeld, J. P., Mcgill, J., Mitch, W. E., Ribeiro, A. B., Shahinfar, S., Simpson, R. L., Snapinn, S. M., and Toto, R. (2003). The risk of developing end-stage renal disease in patients with type 2 diabetes and nephropathy: the RENAAL study. Kidney international, 63(4), 1499-1507. 70. Stehouwer, C. D., Henry, R. M., Dekker, J. M., Nijpels, G.,Heine, R. J., and Bouter, L. M. (2004). Microalbuminuria is associatedwith impaired brachial artery, flow-mediated vasodilation in elderlyindividuals without and with diabetes: Further evidence for a link between microalbuminuria and endothelial dysfunction—The Hoorn Study. Kidney International, 66(supplement 92), S42-S44. 71. Ritz, E. (2003). Minor renal dysfunction: an emerging independentcardiovascular risk factor. Heart, 89(9), 963-964. 72. Batlle-Gualda, E., Martínez, A. C., Guerra, R. A., and Pascual,E. (1997). Urinary albumin excretion in patients with systemic lupuserythematosus without renal disease.Annals of the rheumatic diseases,56(6), 386-389. 73. Mahmud, N., O'Connell, M. A., Stinson, J., Goggins, M. G.,Weir, D. G., and Kelleher, D. (1995). Tumour necrosis factor-alpha andmicroalbuminuria in patients with inflammatory bowel disease.Europeanjournal of gastroenterology and hepatology, 7(3), 215-219.Abstract
References