This document discusses new-onset diabetes after transplantation (NODAT), which occurs in some patients after receiving a solid organ transplant. It defines NODAT and reviews its epidemiology and risk factors. The document outlines the pathogenesis and risk of NODAT associated with different immunosuppressive drugs. It also discusses the diagnosis, screening, and management of NODAT, including monitoring patients, treating hyperglycemia, and controlling cardiovascular risk factors. The document notes ongoing areas of uncertainty around preventing NODAT and determining the long-term impacts of improved glycemic control.

1. Dr.Robin Maskey,MD,Internal Medicine
Fellow, Endocrinology
Sir Gangaram Hospital

2.  Introduction
 Epidemiology
 Defination and Diagnosis of NODAT
 Pathogenesis of NODAT
 Risk Factors for NODAT
 Sequelae of NODAT
 Management
 Controversies and Areas of Uncertainty

3. 
Posttransplant diabetes, or new-onset diabetes after
transplantation(NODAT),
is
observed
after
transplantation of kidney, liver, lung, heart, and other
solid organs, as well as bone marrow and hematopoietic
stem cells.

Also as Secondary type of diabetes mellitus

Among renal transplant patients, the risk of NODAT peaks
within the first year, with incidence rates as high as
15%;thereafter, the annual incidence rate falls to6%.
(J Clin Endocrinol Metab 96: 3289–3297, 2011 )

4. •
The incidence of NODAT ranges from
approximately 4% to 25% of renal allograft,2.5
to 25% of liver transplant,4 to 40% of heart
transplant and 30 to 35% of lung transplant
recipients.
•
The variation is due to lack of standard
defination, duration of follow up, presence of
of risk factors and type of organ transplant.
Diabetes,Metabolic Syndrome and Obesity:Targets and Therapy,2011:4 175-186

5. •
The true incremental incidence of diabetes occurs mainly during the first
6 months posttransplantation, when patients are treated with high doses
of immunosuppression.

Approximately 50% of people diagnosed with NODAT experience
improvement in glucose tolerance after the immunosuppressive agents
have been decreased or tapered to maintenance doses.
•
The most accurate incidence of NODAT under calcineurin inhibitor (CNI)
therapy is provided by the prospective study of Vincenti et al. reporting
an incidence of NODAT reaching 20.5% within the first 6 months
postrenal transplantation
(J Clin Endocrinol Metab 96: 3289–3297, 2011 )

6. DIABETES CARE,VOLUME 36,MAY 2013

8. WHO AND 2003 updated ADA criteria :
 Symptoms of diabetes mellitus + casual PG
≥200mg/dl(11.1 mM) or
 FPG ≥ 126 mg/dl (7.0 mM) or
 2-hr PPG ≥200mg/dl(11.1 mM) during OGTT

The use of glycosylated hemoglobin (HbA1c) for
diagnosis of diabetes or prediabetes during the
peritransplant period is not recommended.
Diabetes,Metabolic Syndrome and Obesity:Targets and Therapy,2011:4 175-186

9. DIABETES CARE,VOLUME 36,MAY 2013

11. Immunosuppressive
agents
Pathogenic mechanisms
Comments
Corticosteriods
• Decrease Peripheral insulin
sensitivity
•Inhibit pancreatic production &
secretion
•Increase Hepatic gluconeogenesis
•lipolysis
Cyclosporine
•Decreased insulin
secretion(CsA>Tac)
•Decreased insulin synthesis
•Decreased β cell density
•Dose dependant
•Impact of complete
withdrawl of ch low dose
steriods unclear
•Potenital NODAT risk
decreased in steroid free
regimens
•Dose dependant
•Diabetogenic effect
increased with increase
steroid dose
Tacrolimus
•Decreased insulin secretion
Same as cyclosporine
Sirolimus
•Impair pancreatic β cell response
•increased Diabetogenic
effect with CNIs

12. 

In addition to the risk of developing the well-known
long term complications of diabetes, NODAT also
identifies patients at high risk for adverse clinical
outcomes:
loss of the renal allograft, infections, cardiovascular events, and
increased mortality among renal transplant patients

Among liver transplant recipients, NODAT is associated with increased
cardiovascular morbidity and mortality, more fatal infections more
neuropsychiatric complications, higher rejection rates, and poorer graft
survival

Among lung transplant recipients, cytomegalovirus (CMV) infection and
acute rejection episodes
(J Clin Endocrinol Metab 96: 3289–3297, 2011 )

13. Pretransplant period
 Document baseline blood glucose status
 Assess diabetes risk factors
 Identify high-risk subjects
 Initiate lifestyle intervention
 Dietary counseling
 Exercise counseling
J Clin Endocrinol Metab, November 2011, 96(11):3289–3297

14. Insulin infusion can be used, as appropriate, to
manage perioperative stress hyperglycemia.
 Once patients begin to eat after surgery, the
regimen can be changed to sc insulin (basal or basalbolus, as appropriate).
 With a decline in postoperative stress and reduction
of steroid doses, many patients can be weaned off
insulin before discharge.

J Clin Endocrinol Metab, November 2011, 96(11):3289–3297

15. Posttransplant period
 Immunosuppressive regimen
Minimize steroid dose
Minimize calcineurin inhibitor exposure
 Treat hyperglycemia beginning in the
peritransplant period
 Close follow-up of all patients, especially those
with prediabetes
J Clin Endocrinol Metab, November 2011, 96(11):3289–3297

16.  Patients discharged without hyperglycemia
should have FPG testing at least weekly
during the first month, then every 3 months
for 1 yr, and annually thereafter.
 Once a blood glucose-based diagnosis of
NODAT has been established in a patient
who is more than 3 months posttransplant,
the HbA1c can be used to monitor glycemic
control .

17. Posttransplant period





For those who develop NODAT
Diabetes education
Appropriate medical therapy based on severity of
hyperglycemia
Surveillance for microvascular complications
Optimize insulin therapy during episodes of high-dose
steroid exposure
Evaluate and control comorbid conditions
Hypertension
Dyslipidemia
Hyperuricemia
Other





J Clin Endocrinol Metab, November 2011, 96(11):3289–3297

18.  Depending on the organ transplanted and
the state of kidney, liver, and cardiac
function, some oral antidiabetes drugs may
be absolutely or relatively contraindicated. In
such instances, insulin often becomes an
early option.
 Careful attention must be paid to the toxicity
profiles of antidiabetes agents in the
transplant population

19. 
The pancreatic b-cell is exposed to several stressors
immediately after kidney transplant surgery, including the
surgical procedure itself, high-dose corticosteroids, and
initiation of CNIs.

Thus, resting the b-cell with basal insulin and optimizing bcell protection with tighter control to near-normoglycemic
treatment goals could further reduce the number of patients
with future impaired glucose tolerance and NODAT.

The standard regimens (basal insulin, split-mix, basal-bolus)
are all applicable in the management of NODAT.

20. 
Steroid-sparing or steroid- free regimens appear to be
associated with decreased risk of NODAT

Tacrolimus, a potent inhibitor of insulin secretion, has been
associated with a greater risk of NODAT compared with
cyclosporine

Belatacept, a selective inhibitor of T-cell activation, is a
parenteral immunosuppressant that replaces CNIs. Studies
suggest that transplant recipients who receive belatacept
have a better metabolic profile and a lower incidence of
NODAT compared with those who receive CNIs .

21. The calcineurin inhibitors cyclosporine and
tacrolimus are known to increase cholesterol levels,
so patients may require adjustment of statin dose
after transplant.
 Pravastatin and fluvastatin, which are not
metabolized by CYP3A4, tend to be used
preferentially in transplant patients with
dyslipidemia.
 Sirolimus and glucocorticoids are associated with
hypertriglyceridemia that may require treatment
with fibrates.


22. The National Kidney Foundation recommends that
blood pressure control be maintained at below
130/80 mm Hg in renal transplant recipients
 The beta- blockers and calcium channel blockers
appear to be well tolerated and effective .
 Microalbuminuria is a predictor of renal allograft
loss and increased mortality
 Besides the risk of gout, hyperuricemia is associated
with cardiovascular disease, inflammation, insulin
resistance, and decreased renal graft survival


23.  Primary prevention of NODAT
 Optimal immunosuppressive regimen
 Optimal glycemic management
J Clin Endocrinol Metab, November 2011, 96(11):3289–3297

24.  The current recommendation is to identify high-
risk patients during the pretransplant period.
 Once identified, such highrisk subjects can
empirically be offered lifestyle intervention to
decrease obesity and increase physical ctivity, as
appropriate.
 The use of medications to prevent type 2
diabetes has been well documented in the
general population,but not yet in transplant
recipients

25. 




Type 2 diabetes mellitus and NODAT share similar risk
factors, especially obesity.
Obesity prevention may also benefit patients who already
have received a transplant because there is an observed
weight gain of 10% during the first year after transplant .
Earlier studies documented a survival benefit associated with
higher BMI in dialysis patients .
Recent studies suggest that it is higher muscle mass, rather
than higher fat mass, that predicts longer survival in dialysis
patients.
Thus, a lifestyle intervention aimed at lowering fat mass may
be appropriate for the prevention of NODAT.

26.  Toxicities from antirejection
immunosuppressive medications constitute
the strongest trigger for NODAT
 Aiming for the lowest effective dose of
corticosteroids in the posttransplant patient
minimizes the risk of dysglycemia.
 Also, there are limited data showing benefit
of substituting cyclosporine for tacrolimus in
immunosuppressive regimens

27.  NODAThas been identified as a risk factor for
graft rejection, long-term graft failure, and
decreased patient survival, the mechanisms
linking hyperglycemia to these adverse
outcomes remain to be determined.
 Improved glycemic control decreases
infections in liver transplant recipients

28.  NODAT is a common complication after solid
organ transplant and has variably adverse
impact on patient and allograft outcomes.
 The most important risk factor predisposing
to the development of NODAT is the
immunosuppressive drugs.
 Risk stratification and intervention to
minimize risk should be integral part of the
management of NODAT patients.

29.  Thank you