Post-transplant hyperglycaemia: a study of risk factors

Abstract

Background: Post-transplant diabetes mellitus (PTDM) has several identifiable pre- and post-transplant risk factors. The link to nutritional status pre-transplant has not been explored previously. This study was conducted to identify risk factors for the development of PTDM, with emphasis on pre-transplant nutritional status and glucose tolerance.

Methods: Non-diabetic adult end-stage renal failure patients awaiting renal transplantation were studied prospectively. Their nutritional status was assessed as body mass index (BMI), serum albumin, and the evolution of these parameters over time prior to transplantation. An oral glucose tolerance test (OGTT) was performed pre- and serially post-transplant until 6 months. Pre- and post-transplant risk factors such as age, nutritional status, glucose tolerance parameters and immunosuppression were related to the development of PTDM or impaired glucose tolerance (IGT) post-transplant.

Results: The mean age of 174 patients studied over a 2-year period was 32.9 +/- 9.7 years. The mean post-transplant follow-up was 25.6 +/- 12.8 months. The mean BMI at recruitment was 18.3 +/- 2.4 kg/m(2). The rate of increase in BMI pre-transplant showed an inverse correlation with the baseline BMI (r = -0.34, P = 0.000) and formed an independent marker of nutritional status. PTDM developed in 21.4% patients and 24.1% had IGT. On univariate and multivariate analyses, the factors significantly associated with the development of PTDM were greater age, more rapid increase in dry weight after starting haemodialysis (HD), elevated pre-transplant OGTT responses and cyclosporin (CsA) and prednisolone doses early post-transplant. Additionally, on multivariate analysis, higher CsA trough level > 300 ng/ml at 3 months increased the risk for the development of PTDM. Of patients who developed PTDM, 57% had impairment of glucose tolerance pre-transplant (> 140 mg/dl at 2 h). Patients with a 1-h glucose value greater than the 50th percentile on pre-transplant OGTT had a 3.9-fold greater risk for the development of PTDM (P = 0.05, 95% CI = 1.03-11.1). In those patients with higher 1-h glucose (> 50th percentile) who also gained in dry weight rapidly pre-transplant, the risk increased to 5.3 (P = 0.02). Of 76 patients with abnormal OGTT early post-transplant, only 68% continued to have PTDM or IGT post-transplant, the remainder reverting to normal glucose tolerance.

Conclusions: Persistent abnormal glucose tolerance after transplantation was seen in 45% of the patients. Pre-transplant factors including greater age, abnormal glucose tolerance parameters, and rapid gain in dry weight on HD, along with higher prednisolone and CsA doses early post-transplant were the important factors associated with the development of PTDM. Identification of patients with pre-transplant risks might allow modification of post-transplant immunosuppression with non-diabetogenic agents.