Effects of Late Conversion from Twice-Daily to Once-Daily Slow Release Tacrolimus on the Insulin Resistance Indexes in Kidney Transplant Patients
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Design
2.2. Clinical and Laboratory Parameter Analysis
- -
- McAuley (McA) = exp [2.63 − 0.28 ln (insulin in mU/L) − 0.31 ln (triglycerides in mmol/L)]
- -
- HOMA = fasting Glucose(mg/dl) × fasting Insulin(µU/mL) / 405.
2.3. Statistical Analysis
3. Results
3.1. Patient Characteristics
3.2. Effects of the Conversion from TacBID to TacOD
4. Discussion
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Langsford, D.; Dwyer, K.M. Dysglycemia after renal transplantation: Definition, pathogenesis, outcomes and implications for management. World J. Diabetes 2015, 6, 1132–1151. [Google Scholar] [CrossRef] [PubMed]
- Gourishankar, S.; Jhangri, G.S.; Tonelli, M.; Wales, L.H.; Cockfield, S.M. Development of diabetes mellitus following kidney transplantation: A Canadian experience. Am. J. Transplant. 2004, 4, 1876–1882. [Google Scholar] [CrossRef] [PubMed]
- Rodrigo, E.; Santos, L.; Piñera, C.; Millán, J.C.R.S.; Quintela, M.E.; Toyos, C.; Allende, N.; Gómez-Alamillo, C.; Arias, M. Prediction at first year of incident new-onset diabetes after kidney transplantation by risk prediction models. Diabetes Care 2012, 35, 471–473. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ekstrand, A.V.; Eriksson, J.G.; Grönhagen-Riska, C.; Ahonen, P.J.; Groop, L. Insulin resistance and insulin deficiency in the pathogenesis of posttransplantation diabetes in man. Transplantation 1992, 53, 563–569. [Google Scholar] [CrossRef]
- Nam, J.H.; Mun, J.I.; Kim, S.I.; Kang, S.W.; Choi, K.H.; Park, K.; Ahn, C.W.; Cha, B.S.; Song, Y.D.; Lim, S.K.; et al. Beta-cell dysfunction rather than insulin resistance is the main contributing factor for development of postrenal transplantation diabetes mellitus. Transplantation 2001, 71, 1417–1423. [Google Scholar] [CrossRef]
- Pham, P.-T.T. New onset diabetes after transplantation (NODAT): An overview. Diabetes Metab. Syndr. Obes. 2011, 4, 175–186. [Google Scholar] [CrossRef] [Green Version]
- Kasiske, B.L.; Snyder, J.J.; Gilbertson, D.; Matas, A.J. Diabetes mellitus after kidney transplantation in the United States. Am. J. Transplant. 2003, 3, 178–185. [Google Scholar] [CrossRef]
- Weir, M.R.; Fink, J.C. Risk for posttransplant diabetes mellitus with current immunosuppressive medications. Am. J. Kidney Dis. 1999, 34, 1–13. [Google Scholar] [CrossRef]
- Kuo, T.; McQueen, A.; Chen, T.C.; Wang, J.C. Regulation of glucose homeostasis by glucocorticoids. Adv. Exp. Med. Biol. 2015, 872, 99–126. [Google Scholar]
- Heisel, O.; Heisel, R.; Balshaw, R.; Keown, P. New onset diabetes mellitus in patients receiving calcineurin inhibitors: A systematic review and meta-analysis. Am. J. Transplant. 2004, 4, 583–595. [Google Scholar] [CrossRef]
- Knoll, G.A.; Bell, R.C. Tacrolimus versus cyclosporin for immunosuppression in renal transplantation: Meta-analysis of randomised trials. BMJ 1999, 318, 1104–1107. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Vincenti, F.; Friman, S.; Scheuermann, E.; Rostaing, L.; Jenssen, T.; Campistol, J.M.; Uchida, K.; Pescovitz, M.D.; Marchetti, P.; Tuncer, M.; et al. Results of an international, randomized trial comparing glucose metabolism disorders and outcome with cyclosporine versus tacrolimus. Am. J. Transplant. 2007, 7, 1506–1514. [Google Scholar] [CrossRef] [PubMed]
- Van Duijnhoven, E.M.; Boots, J.M.; Christiaans, M.H.; Wolffenbuttel, B.H.; Van Hooff, J.P. Influence of Tacrolimus on glucose metabolism before and after renal transplantation: A prospective study. J. Am. Soc. Nephrol. 2001, 12, 583–588. [Google Scholar]
- Marks, W.H.; Harding, M.W.; Handschumacher, R.; Marks, C.; Lorber, M.I. The immunochemical distribution of cyclophilin in normal mammalian tissues. Transplantation 1991, 52, 340–345. [Google Scholar] [CrossRef] [PubMed]
- Tamura, K.; Fujimura, T.; Tsutsumi, T.; Nakamura, K.; Ogawa, T.; Atumaru, C.; Hirano, Y.; Ohara, K.; Ohtsuka, K.; Shimomura, K. Transcriptional inhibition of insulin by FK506 and possible involvement of FK506 binding protein-12 in pancreatic beta-cell. Transplantation 1995, 59, 1606–1613. [Google Scholar]
- Boots, J.M.M.; Van Duijnhoven, E.M.; Christiaans, M.H.L.; Wolffenbuttel, B.H.R.; Van Hooff, J.P. Glucose metabolism in renal transplant recipients on tacrolimus: The effect of steroid withdrawal and tacrolimus trough level reduction. J. Am. Soc. Nephrol. 2002, 13, 221–227. [Google Scholar]
- Delling, U.; Tureckova, J.; Lim, H.W.; De Windt, L.J.; Rotwein, P.; Molkentin, J.D. A calcineurin-NFATc3-dependent pathway regulates skeletal muscle differentiation and slow myosin heavy-chain expression. Mol. Cell Biol. 2000, 20, 6660. [Google Scholar] [CrossRef] [PubMed]
- Graef, I.A.; Chen, F.; Chen, L.; Kuo, A.; Crabtree, G.R. Signals transduced by Ca(2+)/calcineurin and NFATc3/c4 pattern the developing vasculature. Cell 2001, 105, 863. [Google Scholar] [CrossRef] [Green Version]
- Lin, J.; Wu, H.; Tarr, P.T.; Zhang, C.Y.; Wu, Z.; Boss, O.; Michael, L.F.; Puigserver, P.; Isotani, E.; Olson, E.N.; et al. Transcriptional co-activator PGC-1α drives the formation of slow-twitch muscle fibres. Nature 2002, 418, 797. [Google Scholar] [CrossRef]
- McKinsey, T.A.; Zhang, C.-L.; Lu, J.; Olson, E.N. Signal-dependent nuclear export of a histone deacetylase regulates muscle differentiation. Nature 2000, 408, 106–111. [Google Scholar] [CrossRef]
- Chakkera, H.A.; Mandarino, L.J. Calcineurin inhibition and new-onset diabetes mellitus after transplantation. Transplantation 2013, 95, 647–652. [Google Scholar] [CrossRef] [PubMed]
- Song, Y.; Manson, J.E.; Tinker, L.; Howard, B.V.; Kuller, L.H.; Nathan, L.; Rifai, N.; Liu, S. Insulin sensitivity and insulin secretion determined by homeostasis model assessment and risk of diabetes in a multiethnic cohort of women: The women’s health initiative observational study. Diabetes Care 2007, 30, 1747–1752. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- McAuley, K.A.; Williams, S.M.; Mann, J.I.; Walker, R.J.; Lewis-Barned, N.J.; Temple, L.A.; Duncan, A.W. Diagnosing insulin resistance in the general population. Diabetes Care 2001, 24, 460–464. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Levey, A.S.; Stevens, L.A.; Schmid, C.H.; Zhang, Y.L.; Castro, A.F., 3rd; Feldman, H.I.; Kusek, J.W.; Eggers, P.; Van Lente, F.; Greene, T.; et al. A new equation to estimate glomerular filtration rate. Ann. Intern. Med. 2009, 150, 604–612. [Google Scholar] [CrossRef] [PubMed]
- Vanhove, T.; Vermeulen, T.; Annaert, P.; Lerut, E.; Kuypers, D. High intrapatient variability of tacrolimus concentrations predicts accelerated progression of chronic histologic lesions in renal recipients. Am. J. Transplant. 2016, 16, 2954–2963. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Midtvedt, K.; Jenssen, T.; Hartmann, A.; Vethe, N.T.; Bergan, S.; Havnes, K.; Åsberg, A. No change in insulin sensitivity in renal transplant recipients converted from standard to once-daily prolonged release tacrolimus. Nephrol. Dial. Transplant. 2011, 26, 3767–3772. [Google Scholar] [CrossRef] [Green Version]
- Ruangkanchanasetr, P.; Sanohdontree, N.; Supaporn, T.; Sathavarodom, N.; Satirapoj, B. Beta cell function and insulin resistance after conversion from tacrolimus twice-daily to extended-release tacrolimus once-daily in stable renal transplant recipients. Ann. Transplant. 2016, 21, 765–774. [Google Scholar] [CrossRef]
- Jones, A.; Hattersley, A.T. The clinical utility of C-peptide measurement in the care of patients with diabetes. Diabet. Med. 2013, 30, 803–817. [Google Scholar] [CrossRef] [Green Version]
- Banu, S.; Jabir, N.R.; Manjunath, C.N.; Shakil, S.; Kamal, M.A. C-peptide and its correlation to parameters of insulin resistance in the metabolic syndrome. CNS Neurol. Disord. Drug Targets 2010, 10, 921–927. [Google Scholar] [CrossRef]
- El-Agroudy, A.E.; Wafa, E.W.; Gheith, O.E.; Shehab el-Dein, A.B.; Ghoneim, M.A. Weight gain after renal transplantation is a risk factor for patient and graft outcome. Transplantation 2004, 77, 1381–1385. [Google Scholar] [CrossRef]
- Jezior, D.; Krajewska, M.; Madziarska, K.; Kurc-Darak, B.; Janczak, D.; Patrzałek, D.; Borysławski, K.; Klinger, M. Posttransplant overweight and obesity: Myth or reality? Transplant. Proc. 2007, 39, 2772–2775. [Google Scholar] [CrossRef] [PubMed]
- Pirsch, J.D. Weight gain after kidney transplantation: Weigh too much! Transplantation 2008, 85, 1387–1388. [Google Scholar] [CrossRef] [PubMed]
- Chang, S.H.; McDonald, S.P. Post-kidney transplant weight change as marker of poor survival outcomes. Transplantation 2008, 85, 1443–1448. [Google Scholar] [CrossRef] [PubMed]
- Turolo, S.; Tirelli, A.S.; Ferraresso, M.; Ghio, L.; Belingheri, M.; Groppali, E.; Torresani, E.; Edefonti, A. Frequencies and roles of CYP3A5, CYP3A4 and ABCB1 single nucleotide polymorphisms in Italian teenagers after kidney transplantation. Pharmacol. Rep. 2010, 62, 1159–1169. [Google Scholar] [CrossRef]
- Glowacki, F.; Lionet, A.; Hammelin, J.-P.; Labalette, M.; Provot, F.; Hazzan, M.; Broly, F.; Noël, C.; Cauffiez, C.; Cauffiez, C. Influence of cytochrome P450 3A5 (CYP3A5) genetic polymorphism on the pharmacokinetics of the prolonged-release, once-daily formulation of tacrolimus in stable renal transplant recipients. Clin. Pharmacokinet. 2011, 50, 451–459. [Google Scholar] [CrossRef]
Total Population | |
---|---|
N | 20 |
Gender (M/F) | 8/12 |
Age (years—IQR) | 52 (26–79) |
BMI (kg/m2) | 23.6 ± 3.6 |
Time from transplantation (years) * | 3.2 ± 1.4 |
Living donor transplantation, n (%) | 3 (15%) |
Primary cause of ESRD, n (%) | |
- HTN/vascular | 7 (35) |
- GLN | 8 (40) |
- Hereditary | 3 (15) |
Other/UN | 2 (10) |
N = 20 | TacBID | TacOD |
---|---|---|
Systolic blood pressure (mmHg) | 132 ± 12 | 130 ± 12 |
Diastolic blood pressure (mmHg) | 78 ± 6 | 76 ± 5 |
BMI (kg/m2) | 23.6 ± 3.6 | 24.9 ± 3.4 |
eGFR (ml/min./1.73 m2) | 80 ± 1.2 | 80 ± 1.3 |
Serum creatinine (mg/dL) | 1.2 ± 0.31 | 1.2 ± 0.39 |
Total cholesterol (mg/dL) | 200 ± 28 | 201 ± 30 |
HDL cholesterol (mg/dL) | 55 ± 0.4 | 56 ± 0.3 |
LDL cholesterol (mg/dL) | 94 ± 0.5 | 95 ± 0.6 |
TG (mg/dL) | 137 ± 48 | 113 ± 52 |
N = 20 | TacBID | TacOD | p-Values |
---|---|---|---|
Tac trough levels (ng/mL) | 8.5 ± 2 | 6.1 ± 1.9 | <0.001 |
HOMA-index | 1.42 ± 0.4 | 1.8 ± 0.7 | 0.07 |
McAuley-index | 7.12 ± 1 | 7.58 ± 1.4 | 0.27 |
Glucose (mg/dL) | 93.4 ± 19 | 93.7 ± 17 | 0.6 |
Insulin (mU/L) | 7.6 ± 2.69 | 8.8 ± 3.8 | 0.28 |
C-peptide | 3.02 ± 1.13 | 2.5 ± 0.8 | <0.01 |
HbA1c (%) | 5.64 ± 0.6 | 5.61 ± 0.5 | 0.48 |
Uric Acid (mg/dL) | 5.36 ± 1.17 | 5.45 ± 1.22 | 0.7 |
Tac trough Levels N = 20 | Correlation Coefficient | p-Values |
---|---|---|
Glucose | 0.12 | 0.2 |
Insulin | 0.03 | 0.8 |
C-peptide | 0.2 | 0.06 |
HbA1c | 0.16 | 0.1 |
Uric Acid | −0.2 | 0.4 |
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Share and Cite
Cademartori, V.; Massarino, F.; Parodi, E.L.; Paoletti, E.; Russo, R.; Sofia, A.; Fontana, I.; Viazzi, F.; Esposito, P.; Garibotto, G. Effects of Late Conversion from Twice-Daily to Once-Daily Slow Release Tacrolimus on the Insulin Resistance Indexes in Kidney Transplant Patients. Transplantology 2021, 2, 49-56. https://doi.org/10.3390/transplantology2010005
Cademartori V, Massarino F, Parodi EL, Paoletti E, Russo R, Sofia A, Fontana I, Viazzi F, Esposito P, Garibotto G. Effects of Late Conversion from Twice-Daily to Once-Daily Slow Release Tacrolimus on the Insulin Resistance Indexes in Kidney Transplant Patients. Transplantology. 2021; 2(1):49-56. https://doi.org/10.3390/transplantology2010005
Chicago/Turabian StyleCademartori, Valeria, Fabio Massarino, Emanuele L. Parodi, Ernesto Paoletti, Rodolfo Russo, Antonella Sofia, Iris Fontana, Francesca Viazzi, Pasquale Esposito, and Giacomo Garibotto. 2021. "Effects of Late Conversion from Twice-Daily to Once-Daily Slow Release Tacrolimus on the Insulin Resistance Indexes in Kidney Transplant Patients" Transplantology 2, no. 1: 49-56. https://doi.org/10.3390/transplantology2010005