Incidence and Risk Factors for the Development of New-Onset Diabetes after Kidney Transplantation

Abstract

Objective New-onset diabetes mellitus after transplantation (NODAT), also known as posttransplant diabetes mellitus, is a common complication after kidney transplantation. It is associated with an increased risk of graft failure and death. Therefore, minimizing the risk of NODAT is a priority after kidney transplantation. This study aimed to determine the incidence of NODAT, the risk factors for its development, and the therapeutic drugs used for its management.

Patients and Methods This is an observational, retrospective study on kidney recipients who were followed up in our center in 2021. After excluding known diabetic patients, second transplant patients, and those with follow-up periods less than 6 months, 308 recipients were included in the study. Demographic, clinical, and laboratory data were collected from the patient records. The patients were categorized as diabetic or nondiabetic.

Results All patients' mean age was 35.9±11.6 years (standard deviation). The male-to-female ratio was 2.13:1. The overall incidence of NODAT was 38.3%. The median time to NODAT diagnosis was 6 months. Patients older than 40 were more likely to develop NODAT (61.1%; p = 0.000). The prevalence of pretransplant body mass index (BMI) more than 25 was significantly higher (67.6%) in diabetic than among nondiabetic patients (p = 0.000). NODAT patients were more likely to have had a rejection episode (65 vs. 35% in nondiabetic patients; p = 0.011). A high trough level of calcineurin inhibitors carried a significant risk of NODAT development. Tacrolimus trough level more than or equal to 10 ng/mL had an odds ratio of 57.9 (95% confidence interval [CI] 7.689–1262.2; p = 0.0007) for the development of NODAT. Likewise, a cyclosporine-A trough level more than or equal to 150 ng/mL had an odds ratio of 100.7 (95% CI: 7.31–4293.5; p = 0.0028).

Conclusion NODAT incidence was high in this study. Older age, high BMI, prior rejection episode, steroid dose, and high calcineurin inhibitors trough levels were significant risk factors for developing NODAT.

Keywords

new-onset diabetes after transplantation - tacrolimus - cyclosporine-A - kidney transplant - calcineurin inhibitors

Introduction

Kidney transplantation is the only currently available cure for end-stage renal disease .[1] Renal transplant recipients' survival time has gradually increased because of the improved survival rate during the perioperative period and enhancements in treatment with antirejection drugs.[2] Hence, long-term complications and the quality of life of transplant recipients have received more attention. Among these, new-onset diabetes after transplant (NODAT) is a serious and frequent metabolic complication after renal transplantation and is considered a risk for patients undergoing renal transplantation.[3] NODAT may severely impact both short- and long-term outcomes of renal transplant recipients in terms of graft and patient survival.[4] It has been shown that NODAT significantly increases acute rejection, kidney graft loss, mortality, and healthcare costs.[5] [6] However, it too often goes undiagnosed, underestimated, or poorly managed. There is a wide variation in the incidence of NODAT, ranging from 2 to 53%.[7] [8] This wide range of reported incidence may be due in part to the lack of a standard definition of the condition, differences in the duration of follow-up, and the presence of both modifiable and nonmodifiable risk factors.[9] Another possible reason is the lack of screening for hyperglycemia in the posttransplant setting since some patients have transient hyperglycemia after the transplant, whereas others develop persistent diabetes.[7] Several risk factors for NODAT have been identified. These include older age,[5] obesity,[10] metabolic syndrome,[11] family history of diabetes,[3] and history of glucose intolerance.[12] Furthermore, cytomegalovirus infection,[13] hepatitis C infection,[14] and the use of certain medications such as calcineurin inhibitors (CNIs)[15] and corticosteroids are other risk factors.[16] [17] It has been recognized that autosomal dominant polycystic kidney disease is a risk factor for developing NODAT.[18] NODAT shares features of type 1 diabetes (caused by β-cell destruction leading to insulin deficiency) and type 2 diabetes mellitus (T2DM, characterized by varying degrees of insulin resistance). However, NODAT tends to have more of the criteria of T2DM and is regarded as a form of T2DM.[19] Although hyperglycemia consistent with a diagnosis of diabetes is observed in more than 90% of renal transplant recipients within the first weeks after transplantation, only a fraction of the patients subsequently develop either impaired glucose tolerance or NODAT.[20] This bidirectional nature of glucose metabolism in the setting of solid organ transplantation is unique and clinically well demonstrated.[21] CNIs (i.e., cyclosporine-A [CsA] and tacrolimus) are also associated with an increased risk of NODAT.[6] [15] CsA and tacrolimus have direct inhibitory effects on pancreatic β-cells. Tacrolimus exhibits a stronger dose-dependent suppressive effect on insulin secretion; both drugs have also demonstrated adverse effects on insulin sensitivity.[22] An increased risk of NODAT has also been reported with immunosuppressive regimens comprising the mammalian target of rapamycin inhibitors, sirolimus, or everolimus. The latter appears to worsen insulin secretion and insulin resistance, particularly when combined with CNIs (especially with tacrolimus).[23] We aimed to determine the incidence of NODAT in Libyan kidney transplant recipients and study the risk factors associated with its development and the therapeutic options used in its management.

Patients and Methods

Patient Characteristics

This retrospective study was carried out in 2022 on all adult kidney allograft recipients at the Libyan National General Authority for Organ, Tissue, and Cell Transplantation in Tripoli, Libya, who were followed up in the outpatient clinic during 2021. Exclusion criteria were known history of diabetes, age under 18 years at the time of transplantation, multiorgan transplantation, follow-up period less than 6 months, and patients who had undergone two or more renal transplants. The demographic characteristics such as age, gender, body mass index (BMI), etiology of primary renal disease, history of dialysis, pharmacologic therapy (maintenance therapy), family history of diabetes, and follow-up period were recorded.

Definitions

The diagnosis of NODAT was based on the diagnostic criteria for diabetes proposed at the International Consensus Meeting on Post-Transplantation Diabetes Mellitus in 2013, which recommends delaying the screening and diagnosis of NODAT until at least 45 days after transplantation to allow stabilization of the immunosuppression levels.[24] These include polyuria, polydipsia, or unexplained weight loss plus random blood glucose more than or equal to 200 mg/dL, or the presence of fasting plasma glucose (FPG) of more than or equal to 126 mg/dL, or second-hour plasma glucose more than or equal to 200 mg/dL during an oral glucose tolerance test.[24] In addition, NODAT is considered to have developed when the patient is using glucose-lowering medications (insulin and oral hypoglycemic agents for > 1 month) prescribed by a nephrologist or endocrinologist at the time of the study. The diagnosis should be confirmed by measuring FBG and hemoglobin A1c (HbA1c), but our study was a retrospective analysis. Therefore, patients with transient hyperglycemia were not considered as having NODAT and were included in the non-NODAT group. In other words, only the patients who still had diabetes and were treated with antidiabetic agents on the day of the study were included in the NODAT group. HbA1c was not a diagnostic criterion in the first 3 months after transplantation. After that, it was used as a diagnostic criterion in combination with elevated FBG levels.

The NODAT group was divided into four subgroups according to the time interval between renal transplantation and diagnosis of NODAT: less than 3 months, 3 to 6 months, 6 to 12 months, and more than 12 months. The clinical and laboratory findings of the NODAT and non-NODAT groups were compared to identify the risk factors associated with NODAT.

Immunosuppressive Medications

Induction therapy was given to all the patients. According to induction therapy, immunosuppression comprises rabbit antithymocyte globulin or interleukin-2 receptor monoclonal antibody (basiliximab). Methylprednisolone (1,000 mg) is given intraoperatively, followed by tapering oral prednisolone 30 mg for 1 week, 10 mg for 1 month, and 5 mg on the 12th week posttransplantation. Mycophenolate-mofetil (MMF) or mycophenolate sodium (MMY) at 1,000 mg or 720 mg twice daily, given postoperatively, with dose adjustment to avoid side effects. CsA was started at 8 mg/kg/day, tacrolimus at 0.2 mg/kg/day, and then adjusted according to trough blood levels. Target CsA levels at 3 months were 150 to 250 ng/mL and then tapered to 100 to 150 ng/mL by 1 year. Target tacrolimus levels were 7 to 10 ng/mL in the first 3 months and then tapered to 4 to 7 ng/mL. The standard immunosuppressive protocol (maintenance therapy) consisted mainly of triple therapy composed of steroids, a CNI (CsA or tacrolimus), and MMF/MMY in most recipients.

Statistical Analysis

Data were analyzed with SPSS software version 25. All continuous data are expressed as mean ± standard deviation (SD) and were analyzed by unpaired t-test. Categorical data are expressed as numbers and percentages and analyzed by the Χ2 test. Binary logistic regression analysis was done to evaluate the odds ratios of various parameters associated with the increased risk of NODAT. p-Value less than 0.05 was considered statistically significant.

Results

Characteristics of the Study Population

The study was done on 308 kidney transplant patients who fulfilled the inclusion and exclusion criteria. The mean age (SD) of the recipients was 35.9±11.6 years. Male recipients were predominant (68% males and 32% females), with a sex ratio of 2.13:1. The mean duration (SD) of hemodialysis before transplantation was 17.6 ± 22.8 months (SD). The graft was from living-related donors in 76.9% of the cases, and 4.2% were from cadaveric donors (done abroad). A family history of diabetes was documented as either positive or negative in 141 patients in the study, of which 49 (15.9%) cases have a positive family history of diabetes. Almost half of the transplants (45%) were performed in Tripoli ([Table 1]). The original kidney disease was not established in 61.0% of the cases. It was glomerulonephritis in 15.3%, hypertension in 10.7%, and autosomal dominant polycystic kidney disease in 4.2% of the patients. There was a significant association between the original kidney disease and the development of diabetes (p = 0.005; [Table 2]).

Table 1 Epidemiologic characters of the study group

Variable	All patients	DM group	Non-DM group	p-Value
Follow-up period (mean ± SD, years)	6.46 (±3.32)	6.47 (±3.25)	6.45 (±3.38)
Recipients
Age (mean ± SD) years	35.9 ±11.6	40.5 ±11.4	32.9 ±10.7
Age category (years)
≤ 40	213 (69.2%)	60 (28.2%)	153 (71.8%)	0.000
˃ 40	95 (30.8%)	58 (61.1%)	37 (38.9%)
Sex
Male	209 (68%)	83 (39.7%)	126 (60.3%)	0.531
Female	99 (32%)	35 (35.4%)	64 (64.6%)
Body mass index
Mean (±SD)	23.4±3.8	24.1±4.0	22.9±3.6
≤ 25	82 (26.6%)	23 (28.0%)	59 (72.0%)	0.000
˃ 25	34 (11.0%)	23 (67.6%)	11 (32.4%)
Donors
Age (mean ± SD)	22.2±18.4	20.1±17.6	23.6±18.7
≤ 40	146 (75%)	61 (41.8%)	85 (58.2%)	0.028
˃ 40	50 (25%)	12 (24.0%)	38 (76.0%)
Sex
Male	164 (68%)	62 (37.8%)	102 (62.2%)	0.272
Female	77 (32%)	28 (36.4%)	49 (63.6%)
Consanguinity
Live related	237 (76.9%)	89 (37.6%)	148 (62.4%)	0.866
Live unrelated	58 (18.8%)	24 (41.4%)	34 (58.6%)
Cadaveric	13 (4.2%)	5 (38.5%)	8 (61.5%)
HLA-DR
Zero mismatch	30 (20.0%)	12 (40%)	18 (60%)	0.814
≤ 3 mismatch	96 (64.4%)	35 (36.5%)	61 (63.5%)
˃ 3 mismatch	23 (14.4%)	9 (39.1%)	14 (60.9%)
Family history of DM
Negative	92 (29.9%)	35 (38%)	57 (62.0%)	0.474
Positive	49 (15.9%)	22 (44.9%)	27 (55.1%)
Hemodialysis duration
Mean ± SD (months)	17.6±22.8	16.9±23.0	18.1±22.8	0.683
Place of transplant
Tripoli	139 (45.1%)	53 (38.1%)	86 (61.9%)	0.52
Abroad	169 (54.9%)	65 (38.5%)	104 (61.5%)
Prior rejection
Yes	20 (6.5%)	13 (65%)	7 (35%)	0.011
No	288 (93.5%)	105 (36.5%)	183 (63.5%)

Abbreviations: DM, diabetes mellitus; HLA-DR, ---; SD, standard deviation.

Table 2 Original kidney disease

Disease	All patients	DM group	Non-DM group	p-Value
GN	47 (15.3%)	12 (25.5%)	35 (74.5%)	0.005
Autosomal dominant polycystic kidney disease	13 (4.2%)	7 (53.8%)	6 (46.2%)
Hypertension	33 (10.7%)	21 (63.6%)	12 (36.4%)
Congenital (VUR, PUV, horseshoe kidney)	10 (3.2%)	3 (30.0%)	7 (70.0%)
Renal stone	7 (2.3%)	4 (57.1%)	3 (42.9%)
Hyperoxalosis	2 (0.6%)	0	2 (100%)
Systemic lupus erythematosus, rheumatoid arthritis, Wegener's granulomatosis	3 (1.0%)	3 (100%)	0
Pre-eclampsia	4 (1.3%)	1 (25%)	3 (75%)
Drugs (contrast)	1 (0.3%)	1 (100%)	0
Undetermined	188 (61.0%)	66 (35.1%)	122 (64.9%)

Abbreviations: GN, glomerulonephritis; PUV, posterior urethral valve; VUR, vesicoureteric reflux.

NODAT Frequency and Timing

The NODAT occurred in 38.3% of the cohort. The mean time between the transplant and the onset of NODAT was 12±14.7 months, and the median time was 6 months. NODAT was diagnosed in 41.3, 32.1, and 26.6% of the patients within 3 months, 3 to 12 months, and beyond 12 months, respectively ([Fig. 1]). The mean fasting blood sugar at the diagnosis was 181.37 mg/dL ± 55.57 (SD). Of the patients who developed NODAT, 58.5% required oral agents for treatment, 9.3% required insulin therapy, and 16.9% required more than one drug ([Table 3]).

Fig. 1 Time interval between transplantation and onset of NODAT.

Table 3 Blood glucose control parameters and used antidiabetic medications

Parameter	At diagnosis	On last visit
Fasting blood sugar (mg/dL)
• Mean ± SD	181 ± 56	120±33
• Median	163	116
HgbA1c (%)
• Mean ± SD	6.2±3.1	6.3 ± 0.8
• Median	6.9	6.2
Antidiabetic medications	Number (%)
• Diet only	18 (15.3%)
• Metformin	11 (9.3%)
• Insulin	11 (9.3%)
• Sulfonylurea (Gliclazide)	58 (49.2%)
• Dual combination	20 (16.9%)
• All	118(100%)

Abbreviation: SD, standard deviation.

NODAT Risk Factors

When comparing those who developed NODAT with those who did not, we found that the recipient's age more than 40 years was significantly associated with NODAT (61.1% in NODAT vs. 38.9% in nondiabetic, p = 0.000). The recipient's BMI more than 25 before the transplant was also significantly associated with NODAT (67.6% in NODAT vs. 32.4% in nondiabetic, p = 0.000).

Prior transplant rejection also had a significant impact on the development of NODAT: 65% of those who had experienced rejection developed NODAT versus 35% for those who did not develop diabetes (p = 0.011). Moreover, donor age and the original kidney disease were also significantly associated with developing NODAT (p = 0.028 and 0.005, respectively). Other factors, such as the recipient's sex, family history of diabetes mellitus, duration of hemodialysis before transplant, and the number of HLA mismatches, were not associated with the development of NODAT (p > 0.05; [Tables 1] and [2]). The associations of immunosuppressive drugs with NODAT are presented in [Table 4]. There was no significant association between the drug regime and the development of NODAT (p = 0.688). However, the drug trough levels were significantly associated with the development of NODAT. Tacrolimus trough level more than or equal to 10 ng/mL was a significant risk factor for NODAT compared to a level less than 10 ng/mL (p = 0.000). Those with a CsA trough level more than or equal to 150 ng/mL were more likely to develop NODAT than those with lower levels (p = 0.000). Furthermore, prednisolone more than 5 mg per day was significantly associated with the development of NODAT compared to lower levels (p = 0.001; [Table 4]). We identified five factors associated with an increased risk of NODAT in kidney recipients. These factors and the fold increase in the risk were as follows: age more than 40 years (x 2.3), BMI more than 25 (x1.35), prior graft rejection (x 5.5), tacrolimus level more than or equal to 10 ng/mL (x57.9), and CsA level more than or equal to 150 ng/mL (x100; [Tables 5] and [6]).

Table 4 Association of immunosuppressive drugs with development of NODAT

Drugs (% within the level)	All patients	NODAT group	Non-DM	p-Value
Prednisolone dose				0.001
Mean ± SD total dose	7.2 ± 5.3	8.8 ± 6.7	6.2±4.0
Prednisolone dose
≤ 5 mg	91 (35%)	22 (24.2%)	69 (75.8%)
˃ 5 mg	171 (65%)	79 (46.2%)	92 (53.8%)
Steroid use				0.838
Yes	262 (85.1%)	101 (85.8%)	161 (84.7%)
No	46 (14.9%)	17 (14.4%)	29 (15.3%)
Tacrolimus tough level (ng/ml)				0.000
Mean ± SD	5.0 ± 4.9	6.7±6.1	4.0±3.7
< 10	157 (80%)	48 (30.6%)	109 (69.4%)
≥ 10	38 (20%)	30 (78.9%)	8 (21.1%)
CsA level (ng/ml)				0.000
Mean ± SD	42.2±79.1	57.2 ± 99.8	32.7 ± 61.2
< 150	52 (62%)	12 (23.1%)	40 (76.9%)
≥ 150	32 (38%)	23 (71.9%)	9 (28.1%)
Drug regime				0.688
Tacrolimus+ MMF + prednisolone	206 (66.9%)	79 (38.3%)	127 (61.7%)
CsA + MMF + prednisolone	96 (31.2%)	37 (38.5%)	59 (61.5%)
Rapamine + MMF + prednisolone	4 (1.3%)	2 (50%)	2 (50%)
Cellcept + prednisolone	2 (0.6%)	0	2 (100%)

Abbreviations: CsA, cyclosporine A; DM, diabetes mellitus; MMF, mycophenolate-mofetil; NODAT, New-onset diabetes mellitus after transplantation; SD, standard deviation.

Table 5 Odds ratio for NODAT risk factors

	Odds ratio exp(B)	95% CI	p-Value (>|z|)
Intercept	0.065	0.0033–0.40	0.015
Recipient's age ˃ 40 years	2.362	1.013–5.54	0.046
Occurrence of prior rejection	5.534	1.115–32.53	0.041
CsA level ≥ 150 ng/mL	100.7	7.309–4293.42	0.003
Tacrolimus level ≥ 10 ng/ml	57.93	7.69–1262.18	0.0007
BMI ˃ 25	1.347	0.423–4.262	0.008

Abbreviations: BMI, body mass index; CI, confidence interval; CsA, cyclosporine A; NODAT, new-onset diabetes mellitus after transplantation.

Table 6 Binary logistic regression of NODAT risk factors

	Estimate	SE	z value	Pr(>|z|)
Intercept	–2.7304	1.1186	–2.441	0.014653
Recipient's age (>40 vs. ≤ 40) years	0.8594	0.4308	1.995	0.046029
Prior rejection (yes vs. no)	1.7109	0.8363	2.046	0.040766
CsA level (≥ 150 vs. ˂ 150) ng/mL	4.6125	1.5471	2.981	0.002870
Tacrolimus level (≥ 10 vs. < 10) ng/mL	4.0593	1.2015	3.379	0.000729
BMI (> 25 vs. ≤ 25)	–0.7763	0.4396	–1.766	0.0077395

Abbreviations: BMI, body mass index; CsA, cyclosporine-A; NODAT, new-onset diabetes mellitus after transplantation; SE, standard error.

Discussion

The prevalence of diabetes mellitus is rapidly rising worldwide due to a sedentary lifestyle and consumption of high-calorie diets. The global diabetes prevalence was estimated to be 463 million people in 2019 and was expected to rise to 578 million by 2030.[25] Kidney transplantation may increase the risk of diabetes in those receiving transplants. This study found that the incidence of NODAT among kidney recipients was 38.3%, which is similar to that reported from Bahrain (33.5%),[26] and India (33.85%).[27] Nevertheless, it is more often higher than in other Arab countries,[28] [29] [30] Japan,[31] France,[32] the United States,[5] Russia,[33] Singapore,[34] and Canada.[35] The rates in these countries ranged between 7 and 24.2%. The differences in the prevalence rates may be attributed to variable numbers of patients, racial differences, differences in the protocols of immunosuppressive agents, and different follow-up periods.

In this study, the median time to development of NODAT was 6 months. Nearly half of the patients developed NODAT in the first 6 months posttransplantation (47.5%), which resembles previous reports.[6] [19] [29] [30] This result is also concurring with other studies reporting a higher incidence of NODAT in the initial posttransplant period, which could be attributed to the use of immunosuppressive medication in the early posttransplant period, especially high-dose steroids.

This study revealed that the recipient's age has an impact on the development of NODAT. The mean age of the NODAT group was significantly higher than the nondiabetic group (40.5 ± 11.4 vs. 32.9 ± 10.7 years, p = 0.001). Furthermore, 61% of the kidney recipients with NODAT were older than 40 versus 38.9% in the nondiabetic group (p = 0.000). Recipients aged more than or equal to 40 years were 2.3 times more likely to develop diabetes than those below less than 40 years. This results confirm other studies.[7] [29] [30] On the other hand, the mean age of the patients in other studies was higher than in this study, for example, in Bahrain (51 vs. 41 years) and Japan (46.8 vs. 41 years).[26] [31] High BMI at the time of transplantation was associated with the development of NODAT in this study: 67.6% of NODAT recipients had BMI more than 25 vs. 32.4% in the nondiabetic group (p = 0.000). This is consistent with most studies confirming this association.[3] [5] [10] [16] [28] [29] [30] [31] However, Montori et al found no association between the development of NODAT and obesity in transplant recipients.[36]

This study did not demonstrate a significant association between a family history of diabetes and the development of NODAT (p = 0.474), which is at odds with many studies reporting a significant association.[26] [29] [30] This might be due to underdiagnoses of DM in our society in the absence of a sound primary healthcare system, and it is conceivable that our patients did not accurately report their family history of DM.[37]

Although the drug regime had no significant impact on the risk of diabetes in our study, there was a significant association between NODAT development and the prednisolone dose. Of those taking more than 5 mg/day prednisolone, 46.2% developed NODAT, whereas only 24.2% of those receiving lower doses developed the condition (p = 0.001). Moreover, the risk of developing diabetes increased 2.7 times in those with prednisolone doses more than 5 mg/day (p-value = 0.000). These results are compatible with other studies that establish the effect of cumulative dosages and duration of therapy on the development of NODAT.[3] [26] Our physicians may include steroids in the drug regime of the patients, especially those who had been transplanted abroad, for whom full information about their transplantation is unavailable. Also, steroids are used to treat rejection episodes, which were significantly associated with the development of diabetes in this study. Patients who had previous graft rejection were 5.5 times more likely to develop diabetes than those who had no such episodes in this study.

Many studies recognized CNIs as a risk factor for developing NODAT because they decrease insulin secretion, increase insulin resistance, and have a direct toxic effect on the pancreatic β-cells.[17] [38] This study is in line with these reports, as we found that the development of diabetes was significantly linked to a high trough level of the drug. With tacrolimus trough levels more than 10 ng/mL, the likelihood of diabetes increased, as reported elsewhere.[28] [30] High CsA trough level was also associated with an increased risk of diabetes, as reported elsewhere.[39]

As for the management of NODAT, this study showed that most (58.5%) of the patients responded to oral hypoglycemic agents (metformin, gliclazide) and diet and lifestyle modifications. Only 9.3% were managed with insulin, and 16.9% needed a combination of drugs, but 15.3% were treated solely with diet control and lifestyle modification. Almost all the patients were within the target of an HbA1c of less than 7%, as reported in other studies.[8] [40]

Conclusion

There was a high incidence of NODAT in the transplant recipients in the studied setting. Older age, obesity, previous rejection episode, high CNIs trough level, and high steroid dose were risk factors for developing NODAT. Predicting the patients at the highest risk of NODAT based on the tests done before transplantation is of paramount importance, especially in addressing immunosuppressive drug levels according to a patient's immunological status, to decrease the diabetogenic risk of these drugs.

Conflict of Interest

None declared.

Acknowledgments

The author would like to thank Dr. Munir Abudher and my colleagues in the outpatients transplant clinic for their encouragement and support.

Author Contributions

Single authorship.

Compliance with Ethical Principles

Verbal consent was taken from the scientific committee of the transplant center and all data were collected and analyzed nameless. No formal ethical approval was sought.

• References

• 1 Aktaş A. Transplanted kidney function evaluation. Semin Nucl Med 2014; 44 (02) 129-145
• 2 Del Carro U, Fiorina P, Amadio S. et al. Evaluation of polyneuropathy markers in type 1 diabetic kidney transplant patients and effects of islet transplantation: neurophysiological and skin biopsy longitudinal analysis. Diabetes Care 2007; 30 (12) 3063-3069
• 3 Davidson J, Wilkinson A, Dantal J. et al. New-onset diabetes after transplantation: 2003 international consensus guidelines1. Transplantation 2003; 75 (10) SS3-SS24
• 4 Sheu A, Depczynski B, O'Sullivan AJ, Luxton G, Mangos G. The effect of different glycaemic states on renal transplant outcomes. J Diabetes Res 2016;2016
• 5 Kasiske BL, Snyder JJ, Gilbertson D, Matas AJ. Diabetes mellitus after kidney transplantation in the United States. Am J Transplant 2003; 3 (02) 178-185
• 6 Woodward RS, Schnitzler MA, Baty J. et al. Incidence and cost of new onset diabetes mellitus among U.S. wait-listed and transplanted renal allograft recipients. Am J Transplant 2003; 3 (05) 590-598
• 7 Reisaeter AV, Hartmann A. Risk factors and incidence of posttransplant diabetes mellitus. Transplant Proc. 2001; Aug;33(5A Suppl): 8S-18S
• 8 Choudhury PS, Mukhopadhyay P, Roychowdhary A, Chowdhury S, Ghosh S. Prevalence and Predictors of “New-onset Diabetes after Transplantation” (NODAT) in renal transplant recipients: an observational study. Indian J Endocrinol Metab 2019; 23 (03) 273-277
• 9 Pham P-TT, Pham P-MT, Pham SV, Pham P-AT, Pham P-CT. New onset diabetes after transplantation (NODAT): an overview. Diabetes Metab Syndr Obes 2011; 4: 175-186
• 10 Bonato V, Barni R, Cataldo D. et al. Analysis of posttransplant diabetes mellitus prevalence in a population of kidney transplant recipients. Transplant Proc. 2008; Jul-Aug; 40 (06) 1888-1890
• 11 Bayer ND, Cochetti PT, Anil Kumar MS, Teal V, Huan Y, Doria C. Association of metabolic syndrome with development of new-onset diabetes after transplantation. Transplantation 2010; 90 (08) 861-866
• 12 Hjelmesaeth J, Hartmann A, Kofstad J. et al. Glucose intolerance after renal transplantation depends upon prednisolone dose and recipient age. Transplantation 1997; 64 (07) 979-983
• 13 Hjelmesaeth J, Müller F, Jenssen T, Rollag H, Sagedal S, Hartmann A. Is there a link between cytomegalovirus infection and new-onset posttransplantation diabetes mellitus? Potential mechanisms of virus induced β-cell damage. Nephrol Dial Transplant 2005; 20 (11) 2311-2315
• 14 Bloom RD, Rao V, Weng F, Grossman RA, Cohen D, Mange KC. Association of hepatitis C with posttransplant diabetes in renal transplant patients on tacrolimus. J Am Soc Nephrol 2002; 13 (05) 1374-1380
• 15 Vincenti F, Friman S, Scheuermann E. et al; DIRECT (Diabetes Incidence after Renal Transplantation: Neoral C Monitoring Versus Tacrolimus) Investigators. Results of an international, randomized trial comparing glucose metabolism disorders and outcome with cyclosporine versus tacrolimus. Am J Transplant 2007; 7 (06) 1506-1514
• 16 Luan FL, Steffick DE, Ojo AO. New-onset diabetes mellitus in kidney transplant recipients discharged on steroid-free immunosuppression. Transplantation 2011; 91 (03) 334-341
• 17 Yates CJ, Fourlanos S, Hjelmesaeth J, Colman PG, Cohney SJ. New-onset diabetes after kidney transplantation-changes and challenges. Am J Transplant 2012; 12 (04) 820-828
• 18 Hamer RA, Chow CL, Ong ACM, McKane WS. Polycystic kidney disease is a risk factor for new-onset diabetes after transplantation. Transplantation 2007; 83 (01) 36-40
• 19 Cosio FG, Pesavento TE, Osei K, Henry ML, Ferguson RM. Post-transplant diabetes mellitus: increasing incidence in renal allograft recipients transplanted in recent years. Kidney Int 2001; 59 (02) 732-737
• 20 Chakkera HA, Weil EJ, Castro J. et al. Hyperglycemia during the immediate period after kidney transplantation. Clin J Am Soc Nephrol 2009; 4 (04) 853-859
• 21 Gebhardt S, Jara M, Malinowski M. et al. Risk factors of metabolic disorders after liver transplantation: an analysis of data from fasted patients. Transplantation 2015; 99 (06) 1243-1249
• 22 Chakkera HA, Kudva Y, Kaplan B. Calcineurin inhibitors: pharmacologic mechanisms impacting both insulin resistance and insulin secretion leading to glucose dysregulation and diabetes mellitus. Clin Pharmacol Ther 2017; 101 (01) 114-120
• 23 Vergès B. mTOR and cardiovascular diseases: diabetes mellitus. Transplantation 2018; 102 (2S, Suppl (Suppl. 01) S47-S49
• 24 Sharif A, Hecking M, de Vries APJ, Porrini E, Hornum M, Rasoul-Rockenschaub S. Proceedings from an international consensus meeting on posttransplantation diabetes mellitus: recommendations and future directions. Am J Transplant 2014; 14 (09) 1992-2000
• 25 Saeedi P, Petersohn I, Salpea P, Malanda B, Karuranga S, Unwin N. IDF Diabetes Atlas Committee. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas, 9^th edition. Diabetes Res Clin Pract 2019; 157: 107843
• 26 Al-Ghareeb SM, El-Agroudy AE, Al Arrayed SM, Al Arrayed A, Alhellow HA. Risk factors and outcomes of new-onset diabetes after transplant: single-centre experience. Exp Clin Transplant 2012; 10 (05) 458-465
• 27 Patel DD, Modi KP, Patel AK, Chaudhary V. New onset of diabetes mellitus in Indian renal transplant recipient–a retrospective study. Int J Pharm Pharm Sci 2015; 7 (11) 228-232
• 28 Zbiti N, Souly K, Errami Z. et al. Post-transplantation diabetes mellitus. Saudi J Kidney Dis Transpl 2012; 23 (05) 1104-1108
• 29 Nagib AM, Refaie AF, Akl AI. et al. New onset diabetes mellitus after living donor renal transplantation: a unique pattern in the Egyptian population. J Diabetes Metab 2015; 6 (04) 1-5
• 30 Aleid H, Alhuraiji A, Alqaraawi A. et al. New-onset diabetes after kidney transplantation: incidence, risk factors, and outcomes. Saudi J Kidney Dis Transpl 2016; 27 (06) 1155-1161
• 31 Okumi M, Unagami K, Hirai T, Shimizu T, Ishida H, Tanabe K. Japan Academic Consortium of Kidney Transplantation (JACK). Diabetes mellitus after kidney transplantation in Japanese patients: The Japan Academic Consortium of Kidney Transplantation study. Int J Urol 2017; 24 (03) 197-204
• 32 Kamar N, Mariat C, Delahousse M. et al; Diapason Study Group. Diabetes mellitus after kidney transplantation: a French multicentre observational study. Nephrol Dial Transplant 2007; 22 (07) 1986-1993
• 33 Novikova MS, Allazova SS, Kotenko ON. EMS. Post-transplant diabetes mellitus in patients with kidney allotransplantation. Clinical Nephrology 2018; 4: 20-24
• 34 Bee YM, Tan HC, Tay TL, Kee TYS, Goh S-Y, Kek PC. Incidence and risk factors for development of new-onset diabetes after kidney transplantation. Ann Acad Med Singap 2011; 40 (04) 160-167
• 35 Gourishankar S, Jhangri GS, Tonelli M, Wales LH, Cockfield SM. Development of diabetes mellitus following kidney transplantation: a Canadian experience. Am J Transplant 2004; 4 (11) 1876-1882
• 36 Montori VM, Basu A, Erwin PJ, Velosa JA, Gabriel SE, Kudva YC. Posttransplantation diabetes: a systematic review of the literature. Diabetes Care 2002; 25 (03) 583-592
• 37 El Oakley RM, Ghrew MH, Aboutwerat AA. et al; National Health Systems Conference. Consultation on the Libyan health systems: towards patient-centred services. Libyan J Med 2013; 8 (01) 20233 DOI: 10.3402/ljm.v8i0.20233.
• 38 Hernández-Fisac I, Pizarro-Delgado J, Calle C. et al. Tacrolimus-induced diabetes in rats courses with suppressed insulin gene expression in pancreatic islets. Am J Transplant 2007; 7 (11) 2455-2462
• 39 Nanayakkara LSH, Sheriffdeen AH. Post–kidney transplantation diabetes mellitus in Sri Lanka. Transplant Proc. 2002; 345 (02) 10010
• 40 Undre NA, Van Hooff J, Christiaans M. et al. Low systemic exposure to tacrolimus correlates with acute rejection. Transplant Proc. 1999; 296-298

Publication History

Article published online:
05 April 2023