Hypomagnesemia and the risk of new-onset diabetes after liver transplantation

Abstract

New-onset diabetes after transplantation (NODAT) is a frequent complication after liver transplantation and has a negative impact on both patient and graft survival. In analogy with the previous finding of an association between posttransplant hypomagnesemia and NODAT in renal transplant recipients, the relation between both pretransplant and posttransplant hypomagnesemia and NODAT was studied in liver transplant recipients (LTRs). One hundred sixty-nine adult LTRs (>18 years old) without diabetes who underwent transplantation between 2004 and 2009 were studied (mean age ¼ 52.11 6 12.6 years, proportion of LTRs who were male ¼ 67.5%, body mass index ¼ 25.5 6 4.4 kg/m 2 , proportion receiving tacrolimus ¼ 90.0%). NODAT was defined according to the American Diabetes Association criteria. The association of NODAT with both pretransplant and posttransplant serum magnesium (Mg) was examined. Overall, 52 of 169 patients (30.8%) developed NODAT, and 57.7% of these (30 patients) were treated with antidiabetic drugs. Both pretransplant Mg levels and Mg levels in the first month after transplantation were lower in patients developing NODAT (P ¼ 0.008 and P ¼ 0.001, respectively). A multivariate regression model (adjusted for weight, pretransplant glucose levels, hyperglycemia in the first week after transplantation, gender, hepatitis C, and corticosteroid dosing) demonstrated both pretransplant Mg levels (hazard ratio ¼ 0.844 per 0.1 mg/dL increase, 95% confidence interval ¼ 0.764-0.932, P ¼ 0.001) and posttransplant Mg levels (hazard ratio ¼ 0.659, 95% confidence interval ¼ 0.518-0.838, P ¼ 0.001) to be independent predictors of NODAT together with age, biopsy-proven acute rejection, and cytomegalovirus (CMV) infection in the first year after transplantation. In conclusion, pretransplant hypomagnesemia and early posttransplant hypomagnesemia are independent predictors of new-onset diabetes after liver transplantation. New-onset diabetes after transplantation (NODAT) is a frequent complication after liver transplantation and develops in 10% to 30% of all patients according to the majority of studies [1][2][3] ; another 10% to 30% of patients already have diabetes before transplantation. 4 NODAT has a negative impact on both graft and patient survival and is related to chronic rejection and hepatic artery thrombosis. A recent study by our group has demonstrated that posttransplant hypomagnesemia is an independent risk factor for NODAT in the renal transplant population.6 Hypomagnesemia in renal transplant recipients (RTRs) is more common with tacrolimus-based immunosuppressive regimens versus cyclosporine-based ones 7 but overall seems more connected to the use of calcineurin inhibitors (CNIs).8 It is due mainly to

Post-Transplant Diabetes Mellitus: Causes, Treatment, and Impact on Outcomes

“…A smaller retrospective study revealed similar findings (77). A study in liver transplant recipients also suggested that early posttransplant hypomagnesemia was associated with increased PTDM (78). A small clinical trial of magnesium supplementation was conducted to determine the relative impact of hypomagnesemia on PTDM in CNI-treated kidney transplant recipients.…”

“…First-phase, second-phase, and area-under-the-curve insulin secretion were all lower in CMVpositive recipients (133). CMV infection has also been associated with increased risk for PTDM after liver transplant, although in few studies (78,118). To date, CMV infection has not yet been suggested to be a significant contributing factor for PTDM after heart or lung transplant.…”

CMV: Prevention, Diagnosis and Therapy

“…Citations are examples supporting these statements and are not meant to include all references on this topic. Additional references can be found in the comprehensive review by Freeman (5) General indirect effects-elevated risks Bacterial infections (19,134,135) Fungal infection (19,26) Viral infections (summarized in (6)) PTLD (136) Cardiovascular events (137) New-onset diabetes mellitus after transplantation (138,139) Immunosenescence (140) Acute rejection (36,37,134) Mortality (19,134,(141)(142)(143)(144) Transplant-specific indirect effects Chronic allograft nephropathy and/or allograft loss after renal transplant (19,145,146) Accelerated hepatitis C recurrence after liver transplant (147) Hepatic artery thrombosis after liver transplant (144,148,149) Allograft vasculopathy after cardiac transplant (150,151) Bronchiolitis obliterans after lung transplant (37,141,143) hereafter referred to as D+/R−). Preemptive therapy is defined as serial testing done weekly or biweekly for the first few months after transplant or after treatment of rejection, with treatment dose antiviral therapy initiated once a certain defined positive threshold is reached.…”

Hypomagnesemia and the Risk of New-Onset Diabetes Mellitus after Kidney Transplantation

“…The same research group published similar results based on a cohort of 169 liver transplant recipients. 35 The findings of Van Laecke et al…”