Immunosuppression-induced diabetes mellitus

Iain A. M. MacPhee, Susan Snowden and Rene W. S. Chang

Department of Renal Medicine and Transplantation, St George's Hospital, London, UK Email: imacphee{at}sghms.ac.uk

Sir,

We are concerned that recent reassurances on the low rate of immunosuppression-induced diabetes mellitus (DM) with calcineurin inhibitor-based regimens are founded on absence of evidence rather than evidence of absence. Recently, Margreiter [1] published the results of a large multi-centre study comparing tacrolimus with cyclosporin microemulsion in renal transplantation. They concluded that the incidence of DM was no higher in the tacrolimus-treated group. A serious flaw in this analysis was that DM was defined as the requirement for treatment with insulin for more than 30 days. No data were shown for patients treated with oral hypoglycaemic agents. From our experience, this classification would underestimate the incidence of immunosuppression-induced DM by 50%.

We have reviewed our data for 129 consecutive renal transplants done at St George's Hospital since 1995, with 1-year follow-up, treated with tacrolimus and prednisolone with the addition of azathioprine or mycophenolate mofetil in some cases. Our standard steroid dosing regimen is 500 mg methylprednisolone at the time of surgery, then 20 mg prednisolone per day, reducing by 5 mg every 2 weeks to a maintenance dose of 5 mg daily. Target tacrolimus whole blood 12 h post-dose (trough) concentrations were 15–20 ng/ml for the first week, 10–15 ng/ml for the first 3 months, then 8–10 ng/ml until the end of the first year. Twenty patients who were diabetic at the time of transplantation were excluded from the analysis. Table 1Go shows the numbers of patients who required treatment for DM according to race, a well-defined risk-factor [2]. Our rate of insulin requirement at any time in Caucasian patients of 6.7% agrees well with the figure of 4.5% reported for a largely Caucasian population [1] and 8.7% reported in the European multi-centre study [3]. Our overall figure for requirement of insulin treatment of 11% is lower than the rate of 19.9% reported by Pirsch et al. [4]. Unfortunately, none of these papers indicates clearly the number of patients requiring oral hypoglycaemic drug treatment at 1 year.


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Table 1.  Hypoglycaemic treatments

 
Our results are in agreement with those of First et al. [5], who found that 5.7% of tacrolimus-treated patients required insulin treatment and 6.2% required oral hypoglycaemic drug treatment, in a population with similar demographics to our own. Their description of requirement for oral hypoglycaemic treatment as hyperglycaemia rather than DM, is an intriguing semantic distinction.

Our observations suggest that the true incidence of immunosuppression-induced DM has been underestimated by the reported large multicentre trials of tacrolimus, because of the disregarding of oral hypoglycaemic-treated type II DM. Given that the prognostic implications relate to the diabetic state rather than the treatment, it is important that immunosuppression-induced type II DM is taken into account in the analysis of future studies.

References

  1. Margreiter R. Efficacy and safety of tacrolimus compared with cyclosporin microemulsion in renal transplantation: a randomised multicentre study. Lancet2002; 359: 741–746[ISI][Medline]
  2. Neylan JF. Racial differences in renal transplantation after immunosuppression with tacrolimus versus cyclosporine. Transplantation1998; 65: 512–523
  3. Mayer DA, Dmitrewski J, Squifflet J-P et al. Multicenter randomised trial comparing tacrolimus (FK506) and cyclosporine in the prevention of renal allograft rejection. Transplantation1997; 64: 436–443[ISI][Medline]
  4. Pirsch JD, Miller J, Deierhoi MH et al. A comparison of tacrolimus (FK506) and cyclosporine for immunosuppression after cadaveric renal transplantation. Transplantation1997; 63: 977–983[ISI][Medline]
  5. First RM, Gerber DA, Hariharan S et al. Posttransplant diabetes mellitus in kidney allograft recipients: incidence, risk factors and management. Transplantation2002; 73: 379–386[ISI][Medline]




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