Diabetes Is a Major Risk Factor for Mortality After Lung Transplantation

Abstract

Survival following lung transplant (LTx) remains significantly lower than after other solid organ transplants. Diabetes mellitus (DM) is a mortality risk factor not comprehensively studied in LTx recipients. Notably, neither the relation of time of DM onset to survival nor the actual causes of DM-associated excess mortality have been described. We determined DM status, DM diagnosis date and all-cause mortality in 386 consecutive adults who underwent LTx at our institution from January 1, 2001 to July 31, 2010. The relationship of DM to survival both as a categorical and time-dependent variable was studied. Fifty-three percent of patients had DM. Overall median survival was 5.2 (95% CI 3.8-6.6) years. At study end, 52% of patients had died, of whom 64% had DM. Estimated median survival was 10 years in patients without DM,) years in patients with DM pre-and post-LTx and 4.3 (3.1-5.5) years in patients with new onset DM. As a timedependent covariate, DM was the strongest risk factor for mortality, hazard ratio 3.96 (2.85-5.51). Bronchiolitis obliterans syndrome was the main cause of death in all patients surviving >90 days, but its incidence was not increased in patients with DM. Further studies are warranted to determine whether improved glycemic control could improve outcomes in LTx recipients.

Prevalence and Predictors of Diabetes After Lung Transplantation: A Prospective, Longitudinal Study

“…The increased mortality in patients with DM in our study is consistent with several retrospective studies (5,8,28) and with data from the ISHLT (2). However, a mechanism has not yet been demonstrated.…”

“…Chronic renal failure is another risk factor for post-Tx mortality, and pre-Tx DM increased chronic renal failure risk by 53% in LTRs (29). We have previously shown that bronchiolitis obliterans syndrome is the main cause of death after LTx, irrespective of DM status (8). DM may directly impair lung function in LTRs, as it does in the general population (30,31), and in patients with CF (32,33).…”

“…Similarly, cumulative incidence of new-onset DM after transplant (NODAT) ranges from 6 to 43% at 1 year (4,5) to 21-60% at 3-5 years (3,(5)(6)(7)(8). The lower figures are from earlier studies when cyclosporin, rather than the more diabetogenic tacrolimus, was the predominant calcineurin inhibitor.…”

“…DM is associated with increased mortality in LTR (2), irrespective of whether it is diagnosed pre-or postLTx (8). LTR survival is relatively poor compared with renal, liver and heart recipients: median survival after LTx is 5.6 years, and less than one-third survive 10 years (2).…”

“…There are many factors contributing to the increased mortality, primarily the high rates of acute rejection and bronchiolitis obliterans syndrome. We have recently demonstrated that DM confers a fourfold increased mortality risk in LTR (8). Data from the International Society for Heart & Lung Transplantation (ISHLT) are more conservative, with DM conferring a hazard ratio of 1.14 for 5-year mortality (2), but patients in this database were not actively screened for DM pre-or post-LTx.…”