NODAT: New onset diabetes after transplant

Andric Christopher Prez Ortz !!

Universidad Panamericana Escuela de Medicina Mxico DF

Massachusetts General Hospital Transplant Unit Boston, MA

MentorsNahel Elias, MD PhD

Amundsen Beth, MD

Bloom Jordan, MD

Stapleton Sahael, MD

NODAT

Serious complication with a high reported incidence.

Major independent risk factor for cardiovascular disease.

Potentially asymptomatic and difficult to diagnose.

Curr Opin Organ Transplant 14:375379Circulation 2002; 105:2231

DefinitionNew-onset diabetes after transplantation: 2003 International Consensus Guidelines. Transplantation 2003; 75:S3.

FPG: 126

HbA1C 6.0

Tx w/glucose-lowering drugs

Lack of consensus: 74% vs 56%

FPG 100 125 mg/dl OGTT: ADA

6m after transplantation

Adapted from: Nat Clin Prac Nephrol 2008 4:600 601.

10 % DM

9 % IGT

DM - Diabetes mellitus IGT - Impaired glucose tolerance IFG - Impaired fasting glucose OGTT - Oral glucose tolerance tests

18 % IFG

14 % IGT

(A) Cumulative incidence of new onset diabetes after transplantation according to Kaplan-Meier Analysis. (B) Cumulative incidence of glucose metabolism abnormalities (NODAT

impaired glucose tolerance) according to Kaplan-Meier analysis.

Transplantation 2011;91: 757764)

NODAT incidence at 1 year

Transplantation 2013;96: 58Y64

OGTT FPGOR 0.03 (p=0.0002)

Normal vs DMOR 0.03; (p=0.0001)

Normal vs DM

S 93.4% S 21.6%

NPV 97.6% NPV 89.1%

E 71.9% E 97.6%

PPV 47.2% PPV 61.5%Adapted from: Nephrol Dialysis Transplant 2008

Normal v NODAT POD 5 n: 359 pt

OR - Odds ratio S -Sensitivity NPV - Negative predictive value E - Specificity PPV - Positive predictive valeu

Risk factors (i)Cumulative incidence of NODAT according to:

Transplantation 2011;91: 757764)

Risk factors (ii)Cumulative incidence of NODAT according to:

Transplantation 2011;91: 757764)

Risk factors (iii)

Transplantation Proceedings, 43, 568571 (2011)

Risk Factors for Posttransplant Diabetes Mellitus: Multivariate Analysis

Risk factors (iv)Cumulative incidence of NODAT/NODAT+IGT according to the number of known pretransplant risk factors

Transplantation 2011;91: 757764)

Other factors

NOT significant:

HD: 1.96 (0.735.22)

Pretransplant hypertension/hyperlipidemia: RR 1.523 (0.78-2.97), 1.72 (0.38-3.05)

HLA A30 B8 B27 B4: RR1.364 (0.722.58)

Tacrolimus vs CyclosporineIncidence of diabetes before and after transplant by type of calcineurin inhibitor.

American Journal of Transplantation 2003; 3: 590598

Tacrolimus !Cyclosporine

Drugs

Genetics

Polymorphisms

Zinc (Diabetes 2008; 57:1043).

TCF7L2 (Diabetes Care 2008; 31:63).

Fok1 vitamin D receptor (Transplantation Proceedings 2013, 45, 194196).

Graft risk

Factors Predicting PTDM According to Multivariate Analysis

Transplantation Proceedings, 45, 2892e2898 (2013)

Graft outcome (i)Short-Term Clinical Outcomes in PostRenal Transplant Patients with Previous DM, non-DM, and PTDM

Transplantation Proceedings, 35, 29162918 (2003)

Cardiovascular risk (i)

20% cumulative incidence NODAT v normal (Kidney Int 2006; 69:588)

HR 3.27; 95% (CI 1.22 8.80; p=0.0190)

Independent risk factor for atherosclerotic events (Transplantation 2005; 79:438).

RR 1.34; 95% CI 1.042.18

Recipient survival rate

Survival

0

20

40

60

80

Non diabetic NODAT DM

Adapted from: Transplantation 2005; 79:438.

Conclusion

Decreased patient and graft survival.

Important modifiable non-immunological risk factor.

Targeted intervention: diagnose before transplantation, identify high-risk individuals.

Acknowledgments

Elias Nahel, MD

Beth Amundsen, MD

Jordan Bloom, MD

Sahael Stapleton, MD

Transplant unit team B6

References

Available upon request.