Diagnosing PTDM.

Abstract

Roy M. First and colleagues (1) evaluated the incidence, risk factors, and management of posttransplant diabetes mellitus (PTDM) in a retrospective study of 369 renal transplant recipients. Patients treated with insulin were categorized to have PTDM, whereas recipients receiving oral hypoglycemic agents (OHA) were classified as “hyperglycemic.” The authors introduced previously unpublished diagnostic criteria for posttransplant glucose intolerance including “hyperglycemia,” defined as fasting blood glucose between 160 and 250 mg/dL (8.9–13.9 mmol/L), and PTDM, defined as fasting blood glucose above 250 mg/dL (13.9 mmol/L). We argue that the suggested criteria should not be used to diagnose PTDM. First, diabetes mellitus is a heterogeneous group of disorders that have hyperglycemia in common. Experts in the United States (American Diabetes Association) and World Health Organization have agreed upon a classification based on etiology, including four main categories: (I) type 1 diabetes, (II) type 2 diabetes, (III) other specific types of diabetes, and (IV) gestational diabetes (2,3). Because immunosuppressive therapy is the major pathogenetic factor for the development of PTDM (1,4), it seems appropriate to include PTDM in group III, more specifically in the subgroup of drug- or chemical-induced diabetes (IIIE). However, PTDM also shares features with type 2 diabetes (group II), and both insulin resistance and relative insulin deficiency are involved in the pathogenesis (4). Second, the Expert Committee has also established common diagnostic criteria for the first three main groups of diabetes (2). Diabetes mellitus is diagnosed if fasting plasma glucose is greater than or equal to 126 mg/dL (7.0 mmol/L) or 2 hour plasma glucose greater than or equal to 200 mg/dL (11.1 mmol/L), confirmed by repeat testing on a different day (2). These glucose values represent cutpoints corresponding to a significant increase in the prevalence of microvascular (retinopathy and nephropathy) and cardiovascular complications documented in several studies (2). To our knowledge, no prospective or longitudinal study has specifically addressed the incidence of and risk factors for microvascular complications of PTDM. However, the evidence from the general population is strong and consistent, and there is no reason to believe that transplant recipients can tolerate higher blood glucose levels than otherwise healthy individuals can without developing the complications of diabetes. Actually the opposite may well be true. Finally, because recipients with PTDM are insulin resistant, treatment should include lifestyle intervention, weight reduction if indicated, and increased physical activity. In addition, treatment with OHA or insulin may be necessary to reach the therapeutic targets. It is also important to take into account the danger of hypoglycemia (sulfonylureas) and lactic acidosis (metformin) in recipients with impaired renal function. However, glipizide is less likely to cause hypoglycemia and has been shown not to interfere with cyclosporine pharmacokinetics (5). We agree that the thiazolidinediones are promising OHAs, but we do not recommend using them as first line therapy until the safety in renal transplant recipients has been documented. In conclusion, PTDM should be diagnosed according to internationally accepted diagnostic criteria for diabetes (2–4). The suggested criteria by First and colleagues (1), have too low of sensitivity and will underestimate the incidence of this serious posttransplant complication. Jøran Hjelmesæth Trond Jenssen Anders Hartmann