Review of post transplant diabetes or new onset diabetes after transplantation

2. Learning objectives
• What is post transplant diabetes ?
• How is it different from other types of diabetes ?
• What are the challenges in prevention,diagnosis and management ?
• Effect of transplant on glucose metabolism/diabetes
• Effect of diabetes on transplant

3. Terminology – no longer NODAT
• 2003 – first international consensus guidelines on NODAT
• 2013 – consensus guidelines revised
1. NODAT to PTDM
2. Timing – PTDM to be diagnosed only after discharge, on stable
immunosuppression,without acute illness,rejection or infection
3. HbA1c >6.5 % can be used to diagnose, but should not be used to screen for
PTDM , especially in the first year after transplantion

5. Incidence
Shivaswamy, Vijay; Boerner, Brian; Larsen, Jennifer (2015): Post-transplant diabetes mellitus: Causes,
treatment, and impact on outcomes. In Endocrine reviews, pp. er20151084.

6. Prevalence
• 10 to 15% in literature *
• 50 to 60% in JIPMER
Jenssen, Trond; Hartmann, Anders (2015): Emerging treatments for post-transplantation diabetes mellitus. In Nature
reviews. Nephrology 11 (8), pp. 465–477.

7. Risk factors
Sharif, Adnan; Cohney, Solomon (2015): Post-transplantation diabetes—state of the art. In The Lancet Diabetes &
Endocrinology.

8. Risk factors
Shivaswamy, Vijay; Boerner, Brian; Larsen, Jennifer (2015): Post-transplant diabetes mellitus: Causes, treatment,
and impact on outcomes. In Endocrine reviews, pp. er20151084.

9. Pathophysiology

10. Immunosuppression and CV profile

11. Role of stress/ inflammation
• Ongoing graft vs host response
• Acute vs chronic rejection
• Reduced renal function
• Greater incidence of chronic infections
• HCV - ? Through hepatic inflammation
• CMV
• Leucocyte mediated damage to β cells
• Proinflammatory cytokines
• Prophylaxis does not prevent PTDM

12. Others
• Vitamin D deficiency
• RCT on vitamin D supplementation going on
• Statins
• Class effect vs drug effect – atorvastatin > fluvastatin

13. Diagnosis
• Commonly used – FPG – poor sensitivity
• HbA1c – reliability issues in the first year
• OGTT – cumbersome, timing of OGTT
• Gold standard
• Reproducibility issues
• Reversal – upto 20% over 5 years
• Novel approaches
• Afternoon or late evening blood glucose
• OGTT for those with HbA1c between 5.7 to 6.4 %

14. How is it different?

15. Effect of diabetes on transplant
• Heart transplant – does not affect survival, increases hypertension,
renal failure, rejection and infection
• Liver transplation – increases HCV infection and fibrosis, affects short
term survival but minimal effect on long term survival
• Renal – decreases survival and increases rejection
• PTDM better than pre existing DM

16. Effect of diabetes on transplant

17. Management
• Goals not clearly established
• Prevention
• Treatment

18. Risk factors
Sharif, Adnan; Cohney, Solomon (2015): Post-transplantation diabetes—state of the art. In The Lancet Diabetes &
Endocrinology.

19. In patient treatment considerations

20. Renal impairment and diabetes drugs

22. OHAs – potential considerations

23. CV risk mitigation
• BP control
• KDOQI - <140/80 mm Hg
• KDIGO - <130 / 80 mm Hg
• ACE inhibitor / ARB – first line, prefer ARB in hyperkalemia
• Diuretics are second line
• CCBs – drug interaction with immunosuppressants
• Dyslipidemia management
• Statins – weaker evidence base
• Sirolimus and everolimus – severe hypertriglyceridemia
• Statins + fibrates / niacin – rhabdomyolisis / liver injury in patients taking CNI

24. Others
• Eye care and feet care same as routine diabetes
• Annual influenza vaccine
• 5 yearly Pneumococcal vaccine
• Tacrolimus /sirolimus induced oligospermia / hypogonadism
• Contraception / prepregnancy counseling

25. Summary
• PTDM prevalence depends on definition – substantial burden
• Pitfalls in diagnosis – wait till at least 3 months after transplant
• Preventive advice important, risk prediction algorithms not well
developed yet
• ?tackle non traditional risk factors
• Metformin, Linagliptin and insulin
• Drug interactions – increase toxicity / decrease efficacy of
immunosuppressive agents
• Team work