Prognostic Implications of Diabetic Ketoacidosis on Long-term Mortality and Diabetes-related Complications

Abstract

ObjectivesDiabetic ketoacidosis (DKA) occurring after diabetes diagnosis is often associated with risk factors for other diabetes-related complications. In this study we aimed to determine the prognostic implications of DKA on all-cause mortality and complications in type 1 diabetes (T1D). MethodsPreviously collected data from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study were obtained through the the National Institute of Diabetes and Digestive and Kidney Diseases Central Repository. Using Cox proportional hazards models with time-dependent covariates, we examined age- and sex-adjusted, glycated hemoglobin–adjusted, and fully adjusted associations of DKA with all-cause mortality, cardiovascular disease, microvascular, and acute complications over 34 years. ResultsOf the 1,441 study participants, 297 had 488 DKA events. Prior DKA was associated with a higher risk of age- and sex-adjusted all-cause mortality (hazard ratio [HR] 8.28, 95% confidence interval [CI] 3.74 to 18.32, p<0.001), major adverse cardiovascular events (MACEs) (HR 2.05, 95% CI 1.34 to 3.13, p<0.001), and all advanced microvascular and acute complications compared with no prior DKA. Most associations except retinopathy were significant even after adjustment for covariates. In our fully adjusted analysis, prior DKA was associated with a significantly higher risk of subsequent all-cause mortality (HR 9.13, 95% CI 3.87 to 21.50, p<0.001), MACEs (HR 1.66, 95% CI 1.07 to 2.59, p=0.03), advanced kidney disease (HR 2.10, 95% CI 1.00 to 4.22, p=0.049), advanced neuropathy (HR 1.49, 95% CI 1.05 to 2.13, p=0.03), severe hypoglycemia (HR 1.53, 95% CI 1.28 to 1.81, p<0.001), and recurrent DKA (HR 3.24, 95% CI 2.41 to 4.36, p<0.001) compared with person-time without DKA. ConclusionsDKA is a prognostic marker for diabetes complications, including excess all-cause mortality. Intensified clinical interventions, such as cardiovascular prevention strategies, may be warranted after diagnosis of DKA.