Montori et al. (1) have performed an extensive and impressive review of the literature addressing the incidence of post-transplantation diabetes (PTD), risk factors for its development, prognostic implications, and optimal management of the disease. We would like to comment on some aspects of their article.

First, prospective cohort studies are generally accepted to have the most appropriate design to assess the incidence of a disease (2). In the present review, seven randomized clinical trials of immunosuppressive drugs, four case-control studies, and only four cohort studies were included to assess the incidence of PTD. Moreover, only one RCT and one CC study met the review’s methodological quality criterion on PTD surveillance. In this perspective, the incidence figures may have been underestimated and should be interpreted with caution.

Second, the authors call for further research to establish criteria for diagnosing PTD on the basis of its prognostic complications. We feel that until such documentation is available, physicians and scientists should rely on the evidence from the general population and implement the diagnostic criteria for diabetes given by the American Diabetes Association (3) and the Expert Committee (4). There is no reason to believe that solid organ transplant recipients are better protected against the harmful effects of chronic hyperglycemia than otherwise healthy individuals.

Moreover, in our opinion, the review underestimates the impact of glucocorticoids on the development of PTD. We addressed this question specifically in a single-center prospective cohort study (5) a few years ago. A total of 173 consecutive previously nondiabetic renal-transplant recipients were observed during a period of 3 months from the day of transplantation (5). All patients received prednisolone, 97% received cyclosporine A (CsA), and 87% received azathioprine. Ten weeks after transplantation, the majority (n = 167) underwent a 75-g oral glucose tolerance test (OGTT). Several potential risk factors for PTD were assessed, including the daily doses of prednisolone and CsA, the total doses of steroids, intravenous methyl prednisolone and oral prednisolone, and the CsA whole blood through levels. The actual daily prednisolone dose was strongly and independently associated with the development of PTD. Ten months later, 91 of the first 103 patients were recruited to a follow-up study including a repeated OGTT (6). The results showed that tapering off prednisolone, but not CsA, significantly improved glucose tolerance during the follow-up period.

In addition, the importance of a family history of diabetes was questioned. Hathaway et al. (7) reported that a family history of diabetes was an independent risk factor for PTD (odds ratio 5.00) in a prospective cohort study including 86 patients followed for at least 18 months post-transplantation. We confirmed this finding in our study (odds ratio 3.93) (5).

Finally, we agree that trials evaluating the safety and efficacy of oral glucose-lowering agents are needed. We have previously documented that glipizide does not interfere with CsA pharmacokinetics (8), and this oral hypoglycemic agent probably is less likely to cause hypoglycemia than other sulfonylureas (9).

1.
Montori VM, Basu A, Erwin PJ, Velosa JA, Gabriel SE, Kudva YC: Posttransplantation diabetes: a systematic review of the literature.
Diabetes Care
25
:
583
–592,
2002
2.
Gordis L:
Epidemiology
. Philadelphia, PA, W.B. Saunders,
2000
3.
American Diabetes Association: Screening for diabetes (Position Statement).
Diabetes Care
25 (Suppl. 1)
:
S21
–S24,
2002
4.
The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus: Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus.
Diabetes Care
25 (Suppl. 1)
:
S5
–S20,
2002
5.
Hjelmesæth J, Hartmann A, Kofstad J, Stenstrøm J, Leivestad T, Egeland T, Fauchald P: Glucose intolerance after renal transplantation depends upon prednisolone dose and recipient age.
Transplantation
64
:
979
–983,
1997
6.
Hjelmesæth J, Hartmann A, Kofstad J, Egeland T, Stenstrøm J, Fauchald P: Tapering off prednisolone and cyclosporin the first year after renal transplantation: the effect on glucose tolerance.
Nephrol Dial Transplant
16
:
829
–835,
2001
7.
Hathaway DK, Tolley EA, Blakeley ML, Winsett RP, Gaber AO: Development of an index to predict posttransplant diabetes mellitus.
Clin Transplant
7
:
330
–338,
1993
8.
Sagedal S, Aasberg A, Hartmann A, Bergen S, Berg KJ: Glipizide treatment of post-transplant diabetes does not interfere with cyclosporine pharmacokinetics in renal allograft recipients.
Clin Transplant
6
:
553
–556,
1998
9.
Harrower AD: Pharmacokinetics of oral antihyperglycemic agents in patients with renal insufficiency.
Clin Pharmacokinet
2
:
111
–119,
1996

Address correspondence to Jøran Hjelmesæth, Medical Department, Vestfold Central Hospital, Boks 2168, 3103 Tønsberg, Norway. E-mail: joran@online.no.