We appreciate the comments of Hjelmesæth et al. (1) in this issue of Diabetes Care, who have made important contributions to the field of post-transplantation diabetes (PTD) and thank them for their interest in our work. We echo their remarks about the uncertainty surrounding the true incidence of PTD and agree that prospective studies conducted using sound methods are the best source of reliable estimates of the incidence of PTD. Their work on the impact of glucocorticoids on PTD concurs with the results of our metaregression (2) suggesting that the incidence of PTD varies with the choice of immunosuppression.

The lack of a uniform definition for PTD furthers the uncertainty about the estimates of true incidence of PTD. The American Diabetes Association (ADA) Expert Committee criteria for diagnosis of diabetes take advantage of the glycemic threshold above which the risk for microvascular complications, namely retinopathy, increases rapidly (3). In the post-transplantation period, researchers have failed to identify a similar glycemic threshold (if one exists) for macrovascular complications and infections, the main adverse outcomes of PTD. Furthermore, the relentless deterioration of β-cell function of type 2 diabetes may not occur in PTD (4). Thus, the ADA diagnostic criteria fail to appropriately characterize the prognosis and natural history of PTD. Alternatively, randomized trials of antihyperglycemic strategies after transplantation could identify a glycemic threshold above which it becomes optimally safe and cost-effective to intervene.

Family history of diabetes is an important risk factor in other forms of diabetes and may well be an important risk factor for PTD, as Hjelmesæth et al. argue. However, family history of diabetes is a very difficult variable to measure. Sackett (5) notes that family information bias—when “the flow of family information about exposure and illness is stimulated by, and directed to, a new case in its midst” leading to different family histories of illness obtained from affected and unaffected siblings—may overestimate its impact. Until researchers systematically collect family history data using the same protocol in all participants before transplantation (and report doing so like Hjelmesæth et al. [4]), we will remain uncertain as to the true importance of this risk factor.

Also, we concur with Hjelmesæth and colleagues that the issues of efficacy (e.g., prevention of adverse outcomes of PTD and improved quality of life), safety (e.g., hypoglycemia and interaction with immunosuppressive agents), and cost-effectiveness will be determining factors in the design of antihyperglycemic regimens for transplant recipients.

1.
Hjelmesæth J, Trond J, Egeland T, Hagen M, Hartmann A: Response to Montori (Letter).
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2.
Montori VM, Basu A, Erwin PJ, Velosa JA, Gabriel SE, Kudva YC: Posttransplantation diabetes: a systematic review of the literature (Review Article).
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The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus: Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus.
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4.
Hjelmesæth J, Hartmann A, Kofstad J, Stenstrom J, Leivestad T, Egeland T, Fauchald P: Glucose intolerance after renal transplantation depends upon prednisolone dose and recipient age.
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Sackett DL: Bias in analytic research.
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Address correspondence to Dr. Yogish C. Kudva, Mayo Clinic, 200 First St. SW, Rochester, MN 55905. E-mail: kudva.yogish@mayo.edu.