This study compared the risk of new onset diabetes after transplantation (NODAT) in kidney transplant recipients receiving either early corticosteroid withdrawal (CSWD) or chronic corticosteroid (CCS) therapy. Over 5 years of follow up: - There was no difference in patient survival or graft loss between the CSWD and CCS groups. - Rates of death and graft loss were also not different for those with or without NODAT. - However, insulin use was significantly higher at 5 years in the CCS group (11.1%) compared to the CSWD group (6.3%). - For the other 8 definitions of NODAT, there were no significant differences

1. D A N I E L L E
J O U R N A L C L U B
J A N U A R Y 2 6 T H , 2 0 1 6
New Onset Diabetes After
Transplantation (NODAT)

2. Introduction about NODAT
 More common in African
American and Hispanic
 Risk factors: elderly
patients, obese patient,
history of infection with
hepatitis C and CMV
 Immunosuppression
such as CNI and
Corticosteroids,
especially tacrolimus
increase the risk of
NODAT

3. Purpose of the Study
 Look deeper into the
frequency , timing of
development and risk
associated with NODAT
 With a double-blinded,
placebo controlled trial
with early corticosteroid
withdrawal
 Eight definitions of
NODAT was used to
analyzed the results as well
as the recent American
Diabetes Associated (ADA)
definition of NODAT

4. Study Design
 The participants of this study was randomized 1:1,
participants who are African American were also
divided evenly between the two groups, as well as
donor types (living or decreased)
 The two groups was the Corticosteroid withdrawal or
the Chronic Corticosteroid group

5. Similarities-Tacrolimus
 Tacrolimus dosing : was
on ABW, dose was 0.15-
0.2 mg/kg/day initiated
within 72 hours post-
transplant
 Target trough was 10-20
ng/mL post-transplant
day 7 to 90, beyond 90
target level were 5-15
ng/mL

6. Similarities- MMF
 All patient received MMF
1 g preoperatively and 2-
3g/day postoperatively
from PTD 3 -14
 After that the dose was
reduce to 2g/day

7. Similarities- Induction Therapy
 The agent that was used
for induction therapy
was chosen by the
preference of the testing
center
 Basiliximab, Daclizumab
or Thymoglobulin

8. How the Groups differ
 All the participants received unblinded
corticosteroids for the first 7 days after transplant
 On PTD 8 patients received the blinded drug
 The CSWD group got placebo
 While the CCS group received a prednisone taper

9. The Taper
 Prednisone dosing in the CCS
group was:
- PTD 8-14 (0.4 mg/kg)
- PTD 15 -29 (0.3mg/kg)
- PTD 30-89 (0.2mg/kg)
- PTD 90-119 (0.15mg/kg)
- PTD 120- 180 (0.1mg/kg)
- PTD > 180 5mg daily

10. HbA1c and Blood Sugar
 HbA1c was obtained at
baseline and months
6,12,24,36,48, 60
 Fasting blood Sugar was
obtained at baseline, daily
for the first 7 days PTD,
and at weeks 2,4,6,8 and at
months 3,6,12,24,36,48,60
 The definition of treatment
of diabetes was the use of
insulin and/or
hypoglycemic agent

11. Statistical Analysis
 Kaplan- Meier time to
event analysis were
measured by log-rank
test
 Life-table analysis was
used to analyzed each of
the 8 definition of
NODAT

12. The Eight Definitions of NODAT
1. ADA criteria, fasting blood glucose (FBG) > or equal to 126 mg/dl two
times or glucose > or equal 200 mg/dL one time, or HbA1c > or equal
to 6.5 % two times, or glucose > 126 mg/dl and HbA1c > or equal to 6.5
% simultaneously one time
2. FBG > or equal to 126 mg/dL on two separate occasions during follow-
up
3. FBG > 126 mg/dL on two separate occasions or treatment with oral
hypoglycemic agents or insulin during follow-up
4. HbA1c > or equal to 6.0% on two separate occasions during follow-up
5. HbA1c > or equal to 6.5% on two separate occasions during follow-up
6. Treatment with oral hypoglycemic agents or insulin during follow-up
7. Teat with insulin during follow-uo
8. Treat with oral hypoglycemic agents during follow-up

13. Results
 Total of 277 non-diabetic transplant patients (CCS
135, CSWD 142)
 No difference were observed at 5 years in patient
survival or in death-censored graft survival
 Rates of death and graft loss in subjects with NODAT
were not in different to those without NODAT in
both groups

14. Results- Drug Levels
 Tacrolimus trough levels stayed within the target
range in the two groups at all times
 MMF dosing was lower in the CSWD group between
4 weeks and 3 years, but not after.

15. Results –Insulin and hypoglycemic agents
 At the 5 year follow up, there was more insulin use in
subjects not diabetic at baseline with CCS than with
CSWD
 There was no significant difference in the use of oral
hypoglycemic agents between the two groups

16. Discussion- Benefits
 This study had a follow up of 5 years which is longer
than most randomized studies only follow
participants for 1 year
 Which allows more of a in depth look at the
participants

17. Conclusions
 Low-dose corticosteroids (5mg/day) with
immunosuppression such as MMF and tacrolimus
had little effect on NODAT risk
 At 5 years, insulin use was significantly higher in the
CCS group (11.1 %) vs. CSWD group (6.3%)
 Besides insulin use none of the other 8 NODAT
definition had significant difference between the two
groups

18. Implications for treatment
 Corticosteroids are a critical component of post-
transplant immunosuppression regimens
 Based on the results of this study corticosteroids
should be prescribed postoperatively, with tapering
to prevent withdrawal

19. The Positive Benefit of the Study
 Doubled blinded, control randomized, 1:1 ratio
 Evenly match groups
 Long duration (5 years)
 Multiple sites
 Multiple Variant analysis
 Clear and specific definitions of NODAT ( 8 total)
 Close follow-up of participants

20. Limitations
 Participants are low-risk of develop diabetes
 This study did not look into patients with high risk of
rejection
 Use ADA definition diabetes might have influence
participants qualification for this study since fasting
glucose results may be transient

21. Questions