Diabetology & Metabolic Syndrome

BioMed Central

Open Access

Review

Post-transplant diabetes mellitus

Marlia B Gomes*1 and Roberta A Cobas2
Address: 1Diabetes and Metabology Unit from Pedro Ernesto University Hospital, Medical Science School, State University of Rio de Janeiro (UERJ
and 2Program in Clinical and Experimental Pathophysiology (PGCLINEX) Diabetes and Metabology Unit, Pedro Ernesto University Hospital,
State University of Rio de Janeiro (UERJ
Email: Marlia B Gomes* - mariliabgomes@uol.com.br; Roberta A Cobas - robertacobas@ig.com.br
* Corresponding author

Published: 5 October 2009

Diabetology & Metabolic Syndrome 2009, 1:14

doi:10.1186/1758-5996-1-14

Received: 26 March 2009

Accepted: 5 October 2009

This article is available from: http://www.dmsjournal.com/content/1/1/14

2009 Gomes and Cobas; licensee BioMed Central Ltd.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0),
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract
In recent decades, Diabetes Mellitus has become a severe and growing global public healthcare
problem due to the increase of its prevalence, morbidity and mortality. Post-transplant diabetes
mellitus (PTDM) is a complication which takes place after a solid organ transplant, and its incidence
is widely variable, ranging from 2 to 53%. Some factors increase the risk of PTDM, such as age,
ethnicity, cadaver-donor kidney presence of the hepatitis C virus and cytomegalovirus, overweight
and obesity and the Immunosuppression scheme established in the immediate post-transplant
period. High doses of tacrolimus and corticosteroid represent the highest risk for developing
PTDM.
Considering that the development of PTDM is associated with a higher risk of complications, such
as infections and cardiovascular disease - thus representing a higher life threatening risk and a
higher cost for the Health System - the relevance of identifying the risk factors and of the early
diagnosis combined with appropriate therapy will be high for the follow up, and eventually resulting
in the success of the procedure as far as patient survival and transplantation durability.

Introduction
In recent decades, Diabetes Mellitus has become a severe
and growing global public health problem in developed
and developing countries due to the increase of its prevalence, morbidity and mortality. Recent estimates by the
World Health Organization (WHO) forecast a significant
increase in the number of individuals suffering from diabetes until the year 2030. Then, the number of estimated
diabetes-suffering individuals constitutes a universe of
nearly 366 million people [1]. Approximately 90% of
them will develop type 2 Diabetes Mellitus (T2DM), in
the age range of 45-64 years-old, in developing countries,
where it is known that the access conditions to specialized
medical centers are not always satisfactory [1].

Post-transplant diabetes (PTDM) is a complication that

occurs after a solid organ transplant, being also considered as a secondary type of diabetes mellitus [2]. The very
first cases were described in 1964 after a liver transplant by
Thomas Starzl. The latest estimates about its incidence
report a wide variability, of 2-53%, of which 4-25%
occurred after a kidney transplant and 2.5-25% after a
liver transplant. Such variability of post-transplant diabetes is reportedly related to the difficulty in defining, diagnosing and identifying the potential risk factors associated
with this entity [3]. As for post kidney transplant diabetes,
estimating that the number of chronic kidney disease
patients under dialysis treatment in the world is around
1.5 million, we may infer that the number of post kidney
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Diabetology & Metabolic Syndrome 2009, 1:14

transplant diabetes cases will increase significantly in the

next few decades [4]. The same assumption may also
apply to other solid organ transplants.
Considering that the development of post-transplant diabetes is associated with a higher risk of complications,
such as infections and cardiovascular disease - thus representing a higher life-threatening risk and a higher cost for
the Healthcare System - the relevance of identifying risk
factors and of the early diagnosis combined with appropriate therapy will be high for the 4 follow-up, and eventually resulting in the success of the procedure as far as
patient survival and transplant long-term durability [3,510].
This review aims at discussing and establishing some procedures to facilitate the approach to those patients in the
daily clinical practice.
1. Identifying Risk Factors
Some of the factors that increase the risk of developing
post-transplant diabetes have already been identified.
Instructively, such factors could be assorted in non-modifiable, potentially modifiable and modifiable risk factors
(table 1). Here will be only considered the potentially
modifiable and the modifiable risk factors. In the potentially modifiable group, cytomegalovirus infection (both
asymptomatic and symptomatic) is the most prevalent
(which may alter the secretion of insulin [6] and the hepatitis C virus (HCV) infection which is more widely associated with insulin resistance, though it may cause a
cytopathic effect on beta cells [11,12]. The treatment
using interferon in the pre-transplant period for HCV
patients significantly reduced the incidence of post-transplant diabetes [2]. The presence of IGT in the pre-transplant period is already a condition requiring lifestyle
changes [5,6].

The modifiable risk factors include corticosteroid therapy

that increases the resistance to peripheral and hepatic
insulin and calcineurin inhibitors (cyclosporine e tac-

http://www.dmsjournal.com/content/1/1/14

rolimus), that cause further reduction of insulin secretion

by a direct toxic effect on beta cell [13-18]. Despite differences in doses of PTDM doses and definition criteria, the
use of tracolimus is generally associated with a risk of
developing PTDM 30% higher than cyclosporine, that
presents an 18% risk [19-22], mainly in HCV patients
[20]. Some studies recommend that the maximum plasma
concentration of tracolimus in the immediate post-transplant period be 15 ng/mL[2]. For patients taking tracolimus and cyclosporine, the incidence peak of IGT and/or
diabetes was 60 days after the transplant; however, at 6
and 12 months, the renal PTDM incidence was still higher
in the group treated with tracolimus, as compared to the
group treated with cyclosporine [14]. The ideal dose of
corticoid so as not to induce a dramatic increase in PTDM
is still under discussion. In a study conducted in our environment, the prednisone dose >1.3 mg/kg/day was associated with a higher risk of renal PTDM. The use of low
prednisolone doses, 5 mg/day, seems to be the most indicated [3].
Regarding the presence of obesity and other SM components, the most appropriate action would be the early lifestyle change (diet + physical exercises) still in the pretransplant period, according to the patient's clinical condition and control over other risk factors, such as hypertension and dyslipidemia [5].
2. Diagnosis of glucose intolerance and diabetes
According to the latest International Consensus about
PTDM, every patient in the pre-transplant period must be
examined for glucose intolerance and diabetes. The anamnesis and clinical history of the patient will also be important for the identification of risk factors and comorbidities.

The criteria for diagnosing glucose intolerance and posttransplant diabetes follow the standards established by
the American Diabetes Association (ADA) [23] and Brazilian Society of Diabetes Association (SBD) [24] as
described below:

Table 1: Risk factors for post-transplant diabetes development

Non-modifiable

Potentially modifiable

Modifiable

Ethnicity (non-Caucasian)
Age >40 years-old
Recipient's gender (M)
Donor's gender (M)
Family history of DM
HLA
HLA (mismatches)
Cadaver-donor
History of acute rejection

Infections
HCV
CMV
IGT (pre-transplantation)

Immunosuppressive Therapy
Tacrolimus
Cyclosporine
Corticosteroid
Sirolimus
Obesity
MS components

IGT, Impaired glucose tolerance; MS, Metabolic Syndrome

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Diabetology & Metabolic Syndrome 2009, 1:14

2.1 Diabetes
Diabetes symptoms with randomized plasma blood glucose 200 mg/dL (11.1 mmol/L) or

Fasting plasma glucose (FPG) (at least 8 hours fast) 126

mg/dL (7.0 mmol/L)
2.2 Fasting intolerance
FPG 110 mg/dL (6.1 mmol/L) and < 126 mg/dL (7.0
mmol/L)

2.3 Oral test for glucose intolerance (glucose load at 75 g

of anhydrous glucose dissolved in water) 2-hour plasma
glucose 140 mg/dL (7.8 mmol/L) and < 200 mg/dL
(11.1 mmol/L)
The diagnosis of any glucose intolerance must be confirmed by a test on the following day.
3. Clinical management of patients with PTDM
The clinical managing of patients with PTDM is generally
the same as recommended for T2DM and as established
by ADA, Brazilian Society of Diabetes (SBD) and other
guidelines [23-27].
3.1 Glucose and risk factors control
Desired Glucose level: HbA1c <6.5%

LDL-cholesterol <100 mg/dL(<2.59 mmol/L)

HDL-cholesterol >50 mg/dL (1.3 mmol/L) for women
and >40 mg/dL (1.0 mmol/L) for men

http://www.dmsjournal.com/content/1/1/14

3. Glitazones: for acting on the insulin resistance, they

could be indicated for these patients, but the side
effects must be assessed (weight gain, edema, anemia,
pulmonary edema and heart failure). The risk of fractures must be considered, mainly in patients that
make chronic use of corticosteroid.
4. GLP-1 analog and DPP-IV inhibitors: there is no
information around the use of these drugs for PTDM.
Both GLP-1 and GIP incretins are eliminated through
the kidneys.
5. Immunosuppression individualization: to assess
the replacement of tracolimus for cyclosporine and
the use of low corticosteroid doses
Regarding dyslipidemia, it is considered that the treatment using statin must be established if the proper LDL
level is not reached. The blood pressure treatment must be
thorough and the renal function must be monitored.
Drug interactions must be carefully assessed. Drugs
metabolized by cytochrome P-450 isoenzyme CYP 3 A4
must be monitored. Inducers (rifampicin, carbamazepine,
phenytoin) and inhibitors (cyclosporine, gemfibrozil) of
that system may modify the kinetics of some oral agents
such as repaglinide, increasing its half-life and resulting in
hypoglycemia.
4. Follow-up for PTDM patients
Recommendations: quarterly HbA1c determination, lipid
profile twice or thrice a year, microalbuminuria screening,
yearly ophthalmologic analysis, feet examination on
every follow-up visit.

Triglycerides <200 mg/dL (2.6 mmol/L)

Conclusion
Systolic blood pressure <130 mm Hg and diastolic blood
pressure <80 mm Hg
Body weight control
3.2 Therapeutical approach
In case diet and physical exercise are not enough to reach
the desired glucose and lipid levels, diabetes treatment
must include oral drugs, combined oral therapy and also
insulin and even insulin monotherapy (it will be required
for 25% of the patients). Regarding oral agent therapy, the
following items should be observed:

Patients diagnosed with PTDM have higher risk of cardiovascular disease and infections than the general population and such problems may compromise the survival
period and the transplant durability [6,7]. PTDM is considered a significant cause of morbidity e mortality in
transplant patients. The early identification of such condition in addition to a thorough treatment of diabetes and
its co-morbidities will definitely determine its progression.

Competing interests
The authors declare that they have no competing interests.

1. Metformin: assess kidney function for the risk of lactic acidosis

Authors' contributions

2. Sulfonylurea: drugs metabolized and eliminated

through the kidney may cause hypoglycemia mainly
in elderly patients. Glinide would not have such
effects.

RAC: has revised the literature

MBG: has written the manuscript

All authors read and approved the final manuscript.

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Diabetology & Metabolic Syndrome 2009, 1:14

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