• Lidija Petkovska University Clinic for Toxicology ,Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, North Macedonia
  • Natasha Simonovska University Clinic for Toxicology ,Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, North Macedonia
  • Aleksandra Babulovska University Clinic for Toxicology ,Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, North Macedonia
  • Afrodita Berat Huseini University Clinic for Toxicology ,Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, North Macedonia
  • Julijana Brezovska Kavrakova Institute of Medical and Experimental Biochemistry, Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, North Macedonia
  • Zvezdana Petronijevik University Clinic for Nephrology, Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, North Macedonia
  • Beti Zafirova Ivanovska 3Institute of Epidemiology, Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, North Macedonia


Posttransplantation disturbances in glucose metabolism and increased insulin resistance  are major factors affecting overall cardiovascular morbidity, reduced graft function, and survival after renal transplantation. We analyzed the prevalence of increased insulin resistance simultaneously with the prevalence of pre-diabetes in kidney transplant patients receiving a Cyclosporine-A based immunosuppression, and analyzed the risk factors for its occurrence, as well as the consequences on graft function. Fifty-nine  recipients of a living donor kidney, without previously diagnosed diabetes, were included in this cross-sectional and prospective study. All patients were on the same triple calcineurin inhibitor based immunosuppressive therapy at maintenance doses. In all of them, OGTT was performed at least 6 months after transplantation in order to determine the prevalence of glucose disorders, as well as to determine the indices for insulin resistance and insulin secretion. We also analyzed potential risk factors for their occurrence. According to the OGTT results, patients were divided into two groups: a group with dysglycemia and a group of normoglycemic patients. Graft function was also monitored after a certain follow-up period in both groups. The overall prevalence of glucose disturbances and insulin resistance was 33.9% (20/59) and 86.44% (51/59), respectively. In the group with dysglycemia, the prevalence of insulin resistance was 95% (19/20), while the beta -function index was decreased in 40% (8/20). The mean value of the insulin resistance index in the dysglycemic group was significantly higher (3.139 ± 1.11) compared to the normoglycemic group (2.264±1.00),p ˂0.01. The most significant risk factors for increased insulin resistance in the group with dysglycemia were: shorter transplant period, higher doses of Cyclosporine-A, post-load insulin and the the insulin secretion index. In this group of patients, a significant decrease in e-GFR was observed after an average of 18 months of follow-up. The prevalence of IR after renal transplantation is high in all patients, and especially in patients with disorders of glucose metabolism. The routine application of OGTT as a diagnostic tool for occult diabetes and pre-diabetes and the determination of insulin resistance can contribute to reducing their prevalence, since most of the risk factors for their occurrence are potentially modifiable.

Keywords: kidney transplantation, pre-diabetes, insulin resistance, immunosuppression


1.Morales JM, Marcén R, del Castillo D, Andres A, Gonzalez-Molina M, Oppenheimer F, et al. Risk factors for graft loss and mortality after renal transplantation according to recipient age: a prospective multicentre study. Nephrol Dial Transplant. 2012; 27(suppl_4): iv39-46.
2.Jardine A. Assesing cardiovascular risk profile of immunosuppressive agents. Transplantation. 2001; 72 (12): SS81-8.
3.Midtvedt K, Hjelmesæth J, Hartmann A, Lund K, Paulsen D, Egeland T, Jenssen T. Insulin resistance after renal transplantation: the effect of steroid dose reduction and withdrawal. J Am Soc Nephrol. 2004; 15(12): 3233-9.
4.Rodriguez -Rodriguez AE, Porrini E, Hornum M, Donate-Correa J, Morales-Febles R. Ramchand SK et al. Post-Transplat Diabetes mellitus and Prediabates in Renal Transplant recipients: An Update. Nephron. 2021; 145: 317-29.
5.Oterdoom LH, de Vries AP, Gansevoort RT, van Son WJ, van der Heide JJ, Ploeg RJ, et al. Determinants of insulin resistance in renal transplant recipients. Transplantation. 2007; 83(1): 29-35.
6.Porrini E, Delgado P, Torres A. Metabolic syndrome, insulin resistance, and chronic allograft dysfunction. Kidney Int. 2010 ; 78: S42-6.
7.Meyer C, Pimenta W, Woerle HJ, Van Haeften T, Szoke E, Mitrakou A, et al. Different mechanisms for impaired fasting glucose and impaired postprandial glucose tolerance in humans. Diabetes care. 2006; 29(8): 1909-14.
8.Montori VM, Basu A, Erwin PJ, Velosa A, Gabriel SE, Kudva YC. Posttransplantation diabetes: a systematic review of the literature. Diabetes Care. 2002; 25(3): 583-92.
9.Porrini EL, Diaz JM, Moreso F, Delgado Mallen PI, SilvaTores I, Ibernon M, et al. Clinical evolution of post-transplant diabetes mellitus. Nephrol Dial Transplant. 2016; 31(3): 495-505.
10.Bergrem HA, Valderhaug TG, Hartmann A, Hjelmesaeth J, Leivestad T, Bergrem H, et al. Undiagnosed diabetes in kidney transplant candidates: a case – finding strategy. Clin J Am Soc Nephrol. 2010; 5(4): 616-22.
11.Chakkera HA, Weil EJ, Castro J, Heilman RL, Reddy KS, Mazur MJ, et al. Hyperglycemia during the immediate period after kidney transplantation. Clin J Am Soc Nephrol. 2009; 4(4):853-9.
12.Shivaswamy V, Boerner B, Larsen J. Post-transplant diabetes mellitus: causes, treatment, and impact on outcomes. Endocr Rev. 2016; 37(1): 37-61.
13.Fishbane S, Spinowitz B. Update on anemia in ESRD and earlier stage of CKD: core curriculum 2018. Am J Kideny Dis. 2018; 71(3): 423-35.
14.EL Okle AZ, El-Arbagy AR, Yassein YS, Khodir SZ, El Sayed Kasem H. Effect od erythropoietin treatment on hemoglobin A1c levels in diabetic patients with chronic kidney disease. J Egypt Soc Nephrol Transplant. 2019; 19: 86-94.
15.Freeman AM, Pennings N. Insulin resistance. In StatPearls [Internet] 2022 Jul 4. StatPearls Publishing.
16.Rabasa-Lhoret R, Bastard JP, Jan V, Ducluzeau PH, Andreelli F, Guebre F, et al. Modified quantitative insulin sensitivity check index is better correlated to hyperinsulinemic glucose clamp than other fasting-based index of insulin sensitivity in different insulin-resistant states. J Clinl Endocrino Metab. 2003; 88(10): 4917-23.
17. Muniyappa R, Madan R, Varghese RT. Assessing insulin sensitivity and resistance in humans. Endotext [Internet]. 2021 Aug 9.
18. De Lucena DD, de Sá JR, Medina-Pestana JO, Rangel ÉB. Modifiable variables are major risk factors for posttransplant diabetes mellitus in a time-dependent manner in kidney transplant: an observational cohort study. J. Diabetes Res. 2020 Mar 18; 2020. https://doi.org/10.1155/2020/1938703
19.Axelrod DA, Cheungpasitporn W, Bunnapradist S, Schnitzler MA, Xiao H, McAdams-DeMarco M, et al. Posttransplant Diabetes Mellitus and Immunosuppression Selection in Older and Obese Kidney Recipients). Kidney med. 2022; 4(1): 100377.
20.Chan HW, Cheung CY, Liu YL, Chan YH, Wong HS, Chak WL, Choi KS, Chau KF, Li CS. Prevalence of abnormal glucose metabolism in Chinese renal transplant recipients: a single centre study. Nephrol Dial Transplant. 2008; 23(10): 3337-42.
21.Şaşak G, Sezer S, Colak T, Acar FN, Haberal M. Factors associated with insulin resistance after long-term renal transplantation. Transplant proc. 2011; 43(2): 575-7. Elsevier.
22.Petkovska L, Ivanovski N, Dimitrovski C, Serafimovski V. Clinical importance of insulin resistance after renal transplantation in patients on triple immunosuppressive therapy with cyclosporine, corticosteroids and mycofenolat mofetil. Contributions, Sec.Biol. Med. Sci., MASA. 2008; (29):129-39.
23.Trovati M, Ponziani MC, Massucco P, Anfossi G, Mularoni EM, Burzacca S, et al. Blood glucose pre‐prandial baseline decreases from morning to evening in type 2 diabetes: role of fasting blood glucose and influence on post‐prandial excursions. Eur J Clin Invest. 2002; 32(3): 179-86.
24.Cole EH, Prasad GV, Cardella CJ, Kim JS, Tinckam KJ, Cattran DC, Schiff JR, Landsberg DN, Zaltzman JS, Gill JS. A pilot study of reduced dose cyclosporine and corticosteroids to reduce new onset diabetes mellitus and acute rejection in kidney transplant recipients. Transplantation research. 2013; 2(1): 1-7.
25.Shah T, Kasravi A, Huang E, Hayashi R, Young B, Cho YW, Bunnapradist S. Risk factors for development of new- onset diabetes mellitus after kidney transplantation. Transplantation. 2006; 82(12): 1673-6.
26.Bang JB, Oh CK, Kim YS, Kim SH, Yu HC, Kim CD, et al. Insulin secretion and insulin resistance trajectories over 1 year after kidney transplantation: a multicenter prospective cohort study. Endocrinol Metab. 2020; 35(4): 820-9.
27.Kurella M, Lo J, Chertow G. Metabolic syndrome and the risk for chronic kidney disease among nondiabetic adults. J Am Soc Nephrol. 2005; 16: 2134-40.
28.Tomaszewski M, Charchar FJ, Maric C, McClure J, Crawford L, Grzeszczak W, et al. Glomerular hyperfiltration: a new marker of metabolic risk. Kidney Int. 2007; 71(8): 816-21.
29.Bosma RJ, Kwakernaak AJ, Homan Van Der Heide JJ, De Jong PE, Navis GJ. Body mass index and glomerular hyperfiltration in renal transplant recipients: cross‐sectional analysis and long‐term impact. Am J Transplant. 2007; 7(3): 645-52.
30.Guthoff M, Wagner R, Weichbrodt K, Nadalin S, Königsrainer A, Häring HU, et al. Dynamics of glucose metabolism after kidney transplantation. Kidney Blood Press Res. 2017; 42(3): 598-607.
How to Cite
PETKOVSKA, Lidija et al. А PREVALENCE AND RISK FACTORS FOR INSULIN RESISTANCE AND DYSGLYCEMIA AFTER KIDNEY TRANSPLANTATION IN PATIENTS ON CYCLOSPORINE-A BASED IMMUNOSUPPRESSION. Journal of Morphological Sciences, [S.l.], v. 5, n. 3, p. 35-44, dec. 2022. ISSN 2545-4706. Available at: <https://jms.mk/jms/article/view/vol5no3-7>. Date accessed: 09 feb. 2023.