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

Terminology – no longer NODAT• 2003 – first international consensus guidelines on NODAT• 2013 – consensus guidelines revised

1. NODAT to PTDM2. Timing – PTDM to be diagnosed only after discharge, on stable

immunosuppression,without acute illness,rejection or infection3. HbA1c >6.5 % can be used to diagnose, but should not be used to screen for

PTDM , especially in the first year after transplantion

Incidence

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

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.

Risk factors

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

Risk factors

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

Pathophysiology

Immunosuppression and CV profile

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

Others• Vitamin D deficiency• RCT on vitamin D supplementation going on

• Statins• Class effect vs drug effect – atorvastatin > fluvastatin

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 %

How is it different?

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

Effect of diabetes on transplant

Management• Goals not clearly established• Prevention • Treatment

Risk factors

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

In patient treatment considerations

Renal impairment and diabetes drugs

OHAs – potential considerations

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

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

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