1454-P: Major Adverse Cardiovascular Events, Advanced Foot Complications, and Subsequent Risk of Diabetic Ketoacidosis in Type 1 Diabetes

Introduction & Objective: People with type 1 diabetes and diabetes-related complications, including cardiovascular disease, are at increased risk of morbidity and mortality. We aimed to determine if major adverse cardiovascular events (MACE) and microvascular complications independently predict the risk of subsequent diabetic ketoacidosis (DKA).

Methods: We accessed previously-collected data from the DCCT/EDIC Study through the NIDDK Central Repository. We used Multivariable Cox Proportional Hazard models with time-varying exposures and co-variates to examine associations of MACE and microvascular complications (early- and late-stages of neuropathy, nephropathy, and retinopathy) as the exposure, with the subsequent occurrence of DKA as the outcome.

Results: Of 1441 participants, 297 individuals experienced 488 DKA events over 34 years of follow-up. MACE [hazard ratio (HR) 3.11, 95% confidence interval (CI) 1.56-6.17, p=0.001] and late-stage neuropathy, which comprised of foot ulcer or amputation, (HR 1.61, 95% CI 1.06-2.45 p=0.026) were independently associated with higher risk of DKA. Higher DKA risk was also associated with insulin pump use (HR 3.01, 95% CI 2.28-3.98, p<0.001), higher insulin dose (HR for 1 unit/kg/day 2.39, 95% CI 1.72-3.33, p<0.001), female sex (HR 2.01, 95% CI 1.58-2.56, p<0.001), and higher time-updated HbA1c (HR for 1 percent 1.41, 95% CI 1.32-1.51, p<0.001).

Conclusion: In those with type 1 diabetes, a major cardiovascular event, foot ulcer or amputation confers the greatest risk of future DKA independent of previously-recognized risk factors. These findings imply a need to target patients with these events for DKA prevention interventions such as self-management skills for metabolic control, management of depression, and education around DKA.