Diabetes mellitus in lung transplant recipients - prevalence, risk factors and effect on survival

Lung transplantation (LTx) is the only curative treatment option for many patients with end stage lung disease. Organ supply is scarce but even those who undergo the procedure have high rates of morbidity and mortality. Five-year survival is 53% and less than one third are alive 10 years after transplant. Diabetes mellitus (DM) is associated with increased rates of graft failure and mortality following solid organ transplantation, but it has not been comprehensively studied in LTx. Large lung transplant registry studies have shown that DM is a risk factor for 5- and 10-year mortality, but smaller studies have shown conflicting results. International data show that diabetes is common in lung transplant recipients but its prevalence in patients awaiting LTx and the incidence of new onset diabetes after transplant (NODAT) is unclear, as no studies have evaluated patients’ diabetes status both before and after lung transplantation using the ‘gold standard’ biochemical screening test, the oral glucose tolerance test (OGTT). The prevalence of diabetes and the strength of its association with mortality after lung transplantation remains to be determined. As diabetes can be detected and treated relatively easily and cost-effectively, its effect on outcome following lung transplantation warrants further investigation. Three studies were conducted for this thesis: (1) a retrospective study of a 10-year patient cohort, which determined the prevalence of DM and its effect on mortality in adult lung transplant recipients, as well as the causes of death in patients with and without DM; (2) a prospective study in which all patients awaiting LTx were screened for DM to determine the incidence of dysglycaemia, the risk factors for newly diagnosed DM and pre-diabetes, and the sensitivity of HbA1c as a screening test for DM and (3) a prospective study which determined the prevalence of DM and incidence of NODAT after LTx, the risk factors for NODAT and mechanisms of its pathogenesis, and the effect of DM on survival. The retrospective study showed that DM was the major risk factor for mortality following LTx and that death was predominantly caused by bronchiolitis obliterans syndrome, a form of chronic rejection of the transplanted lungs. The prospective studies demonstrated a high prevalence of DM both pre- and post-LTx and a high incidence of NODAT, which affected almost 1 in 3 patients at risk. No factors predicted dysglycaemia in the pre-LTx cohort, and only 1- and 2-hour glucose levels on pre-Tx OGTT correlated with the development of NODAT. Dysglycaemia prior to LTx was mediated by insulin resistance whereas, post-Tx, NODAT appeared to be caused by both insulin resistance and reduced insulin secretion. In accordance with the findings of the retrospective study, DM was associated with significantly reduced survival in the prospective study. In summary, DM was a common comorbidity in patients awaiting LTx and NODAT was a frequent complication following LTx. Furthermore, DM was the strongest risk factor for mortality following LTx, suggesting that early detection and management of the condition may result in significant improvements in patient survival.