New-onset diabetes after transplantation (NODAT): an evaluation of definitions in clinical trials

Transplantation. 2013 Jul 15;96(1):58-64. doi: 10.1097/TP.0b013e318293fcf8.

Abstract

Background: New-onset diabetes after transplantation (NODAT) occurs commonly. Prior NODAT definitions have been inconsistent. Based on the American Diabetic Association criteria, we propose a new approach to defining NODAT.

Methods: Analysis of 1416 at-risk transplant recipients was performed. Data from three de novo Astellas registration transplant studies (two kidney and one liver) evaluated NODAT in 634 at-risk patients receiving tacrolimus, 630 at-risk patients receiving tacrolimus extended release, and 152 at-risk patients receiving cyclosporine. NODAT was defined as a composite endpoint consisting of first occurrence of one of four parameters: (i) two fasting plasma glucose levels ≥ 126 mg/dL (≥ 7.0 mmol/L) ≥ 30 days apart, (ii) oral hypoglycemic agent use for ≥ 30 consecutive days, (iii) insulin therapy for ≥ 30 consecutive days, and (iv) hemoglobin A1c ≥ 6.5%. We evaluated each of the above parameters, as well as the composite endpoint, in an attempt to establish an appropriate clinical approach to the diagnosis of NODAT.

Results: The composite definition results in a 1-year NODAT incidence of 30% to 37% in kidney and 44% to 45% in liver transplant recipients treated with tacrolimus. NODAT incidence was significantly higher with tacrolimus than cyclosporine; there was no difference between the two tacrolimus formulations.

Conclusions: Based on these analyses, the proposed composite definition for NODAT, incorporating broader criteria, is recommended for clinical trials. Appropriate definitions of NODAT allow for a better understanding of the incidence of this complication and may result in earlier initiation of therapy with improved long-term outcomes.

MeSH terms

  • Clinical Trials as Topic
  • Cyclosporine / therapeutic use
  • Diabetes Mellitus, Type 2 / drug therapy
  • Diabetes Mellitus, Type 2 / epidemiology*
  • Female
  • Graft Survival / drug effects
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • Immunosuppressive Agents / therapeutic use
  • Incidence
  • Kidney Transplantation / adverse effects*
  • Kidney Transplantation / statistics & numerical data
  • Liver Transplantation / adverse effects*
  • Liver Transplantation / statistics & numerical data
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Postoperative Complications / drug therapy
  • Postoperative Complications / epidemiology*
  • Prevalence
  • Registries / statistics & numerical data
  • Risk Factors
  • Tacrolimus / therapeutic use
  • Terminology as Topic*

Substances

  • Hypoglycemic Agents
  • Immunosuppressive Agents
  • Cyclosporine
  • Tacrolimus