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NODAT

Almost one 3rd of non-diabetic kidney transplant recipients may develop persistent impairment of glucose metabolism within 6 months’ post-transplant

New onset diabetes after transplant (NODAT) in renal transplant recipients


 

Almost one 3rd of non-diabetic kidney transplant recipients (KTRs) may develop persistent impairment of glucose metabolism within 6 months’ post-transplant. New Onset Diabetes After Transplantation (NODAT) has a negative impact on patient and allograft outcome. NODAT may be developed any timing post-transplant with a symptomatized patient in addition to a random blood glucose 200 mg/dl (11.1 mmol/l), fasting blood glucose 126 mg/dL (7.0 mmol/L) or a 2-h plasma glucose ≥ 200 mg /dL L (11.1 mmol/L) via an oral glucose tolerance testing.

Pre-diabetic hyperglycemia can be diagnosed via a FBG (fasting blood glucose) value of 100-125 mg/dL (5.6-6.9 mmol/L) or a 2-h. blood glucose value of 140-199 mg/dL (7.8-11.0 mmol/L) via an oral glucose tolerance testing (ADA guide-lines). Glucocorticoids, CNI (calcineurin inhibitors) and sirolimus that usually included in the post-transplant immunosuppressive protocol can increase the risk of NODAT development. As compared to CyA (cyclosporine) tacrolimus is more diabeto-genic to the kidney transplant recipient (KTRs). On the other hand, MMF (mycophenolate mofetil) and Azathioprine are almost non-diabetogenic.

Screening work-up for the risk factors for NODAT, in addition to the history of gestational diabetes should be assessed in the pre-transplant preparation. Furthermore, fasting blood glucose, metabolic syndrome-related markers and other cardiovascular-related risk factors. Patients’ counseling in regard to the risk of NODAT evolution and the related necessary modifications to limit this risk.  

Dietitians should have their role in competing NODAT evolution with timely referral of the high risk patients. ALL KTRs should have regular testing for fasting plasma glucose on a weekly basis within the 1st 4 weeks after transplantation, then 3-6 monthly basis post-transplantation, and then every year forwards. In addition, HBA1c (hemoglobin A1c) can be revised after 3 months’ post-operative, particularly if obtaining a fasting blood-glucose level was impractical.

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MANAGEMENT OF NODAT

The attempt to manage and improve glucose tolerance is currently endangered by an increased risk of graft rejection. Considering this caution, the following approach has been suggested:

1]    In patients with NODAT, glucocorticoid doses should be lowered early and as soon as possible. Complete holding of glucocorticoids is not recommended.

2]    NO switch of tacrolimus to CyA is recommended unless other tacrolimus-induced adverse effects was present. Tacrolimus dosage can be reduced whenever possible.

3]    KTRs with uncontrolled diabetes despite reducing tacrolimus dose, switching to CyA can be considered.

4]    A stepwise strategy has been advised for NODAT control, as follows:

1)    Non-pharmacological approach,

2)    Oral single therapy (monotherapy),

3)    Combined oral therapy, and finally,

4)    Insulin therapy providing decompensated metabolic balance was not present.

5]    Commencing oral therapy has been advised with glipizide at a dose of 2.5-5 mg/day and then increment to 10 mg twice/day as required to keep the HbA1c at <7 %.

6]     On the other hand meglitinides e.g., repaglinide (Prandin) have been advised by some experts before sulfonylureas can be utilized, as sulfonylureas may induce potential renal toxicity. In regard to thiazolinediones they must be discarded among KTRs due to their adverse untoward effects.

7]    Insulin therapy is generally advised with:

1)    The presence of metabolic decompensation,

2)    The presence of adverse untoward effects with oral medications, or

3)     HbA1c values that are currently exceeding 7 %.

8]    Multiple medications and/or multiple-dosage, intensive insulin dosages or insulin-pump technique may be all considered. KTRs requiring insulin therapy are better referred early to a specialized endocrinologist.


N.B. This Blogger is created to declare the development of diabetes mellitus after transplantation (NODAT).


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