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Liver transplant: risk factors for diabetes mellitus

A study on risk factors of new-onset diabetes 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 new-onset diabetes mellitus. Since all of these factors can be detected prior to undergoing a transplant, treatment should be tailored to the patient's risk.

The development of new-onset diabetes mellitus 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 new-onset diabetes mellitus. However, the exact incidence of new-onset diabetes mellitus 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, of the Hopital 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 new-onset diabetes mellitus, the date of diagnosis was noted, along with the immunosuppressive treatment and diabetes management they had received.

The results showed an incidence of new-onset diabetes mellitus 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 new-onset diabetes mellitus 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 new-onset diabetes mellitus. The authors note that since abnormal glucose regulation prior to transplantation has been implicated as a possible risk factor of new-onset diabetes mellitus 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 new-onset diabetes mellitus.

" Our study suggests that it may eventually be possible to derive a composite risk factor equation for the development of new-onset diabetes mellitus 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, Paul J. Thuluvath, of the Johns Hopkins University School of Medicine in Baltimore notes that the study confirms that a significant number of patients develop new-onset diabetes mellitus 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 new-onset diabetes mellitus 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 new-onset diabetes mellitus will have an impact on long-term survival, and therefore it is important to continue to study the impact of new-onset diabetes mellitus 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."

Source: Liver Transplantation, 2007