A new study on risk factors of new-onset diabetes mellitus (NODM) following liver transplant found that a history of obesity, impaired fasting glucose and hepatitis C infection (HCV) paired with the use of a particular immunosuppressant are associated with an increased risk of NODM. Since all of these factors can be detected prior to undergoing a transplant, treatment should be tailored to the patient's risk.
The results of this study appear in the January 2007 issue of Liver Transplantation, the official journal of the American Association for the Study of Liver Diseases (AASLD) and the International Liver Transplantation Society (ILTS). The journal is published on behalf of the societies by John Wiley & Sons, Inc. and is available online via Wiley InterScience at http://www.
The development of NODM after a liver transplant is associated with increased cardiovascular disease and death, a higher incidence of rejection, more infections and reduced quality of life. It is therefore likely that the survival rate following liver transplant could be improved by reducing the incidence of NODM. However, the exact incidence of NODM is not clear because existing studies have used varying criteria. In addition, no definitive risk factors have been clearly established. Immunosuppressive drugs are known to contribute to diabetes, although this effect varies depending on the drug; calcineurine inhibitors are less likely to cause diabetes than steroids.
Led by Faouzi Saliba, M.D. of the Hôpital Paul Brousse in Villejuif, France, the study included 211 patients from 10 transplant centers in France who had undergone a liver transplant between October 2003 and June 2004. Patients' clinical records were reviewed and their fasting blood glucose levels were recorded 3, 6, 12 and 18 months after undergoing the transplant. For those with NODM, the date of diagnosis was noted, along with the immunosuppressive treatment and diabetes management they had received.
The results showed an incidence of NODM of 22.7 percent, with the majority of the cases diagnosed within three months of transplant. In addition, 12.4 percent of the patients with normal glucose levels pre-transplant developed impaired fasting glucose (IFG). The risk factors for developing NODM included HCV infection (especially when combined with the immunosuppressant tacrolimus), IFG prior to the transplant, and a history of clinical obesity. In addition, the presence of at least two cardiovascular risk factors and a history of either gestational diabetes or having given birth to a baby weighing over 4 kilograms also increased the risk of NODM. The authors note that since abnormal glucose regulation prior to transplantation has been implicated as a possible risk factor of NODM and IFG emerged as a strong predictor of the condition in the current study, pre-transplantation glucose screening may be important in helping to predict NODM.
"Our study suggests that it may eventually be possible to derive a composite risk factor equation for the development of NODM following liver transplantation with appropriate weighing for each variable, perhaps similar to the risk assessment instruments developed for the primary prevention of cardiovascular disease," the authors conclude.
In an accompanying editorial in the same issue, Paul J. Thuluvath, M.D., F.R.C.P, of the Johns Hopkins University School of Medicine in Baltimore notes that the study confirms that a significant number of patients develop NODM after liver transplantation, however almost all of them were on steroids and developed the disease within 3 months of transplant. A previous study showed that 24 of 88 patients were found to have diabetes mellitus at the end of the first year post-transplant, but by the end of the second year only 8 of them had the condition. "This may suggest that many patients in the cohort studied by Saliba et al. may not have diabetes with longer follow up especially when steroid is discontinued," the author states. He adds that the increased incidence of NODM in patients with HCV is noteworthy and confirms the trends seen in previous studies, although the mechanisms of how this happens remain unclear. "It is probable that NODM will have an impact on long-term survival, and therefore it is important to continue to study the impact of NODM and its intervention on long-term graft and patient survival in patients with and without HCV," the author concludes. "As we develop newer immunosuppressive drugs, we now have the ability to improve the diabetic control by tailoring and manipulating the medications in liver transplant recipients."
Article: "Risk Factors for New-Onset Diabetes Mellitus Following Liver Transplantation and Impact of Hepatitis C Infection: An Observational Multicenter Study," Faouzi Saliba, Mohamed Lakehal, Georges-Philippe Pageaux, Bruno Roche, Claire Vanlemmens, Christophe Duvoux, Jérome Dumortier, Ephrem Salamé, Yvon Calmus, Didier Maugendre, Liver Transplantation; January 2007 (DOI: 10.1002/lt.21010).
Editorial: "Is There a Link Between Hepatitis C Virus and New Onset of Diabetes Mellitus After Liver Transplantation?" Paul J. Thuluvath, Liver Transplantation; January 2007 (DOI: 10.1002/lt.21024).