(CSEMP031) ELEVATED DKA RISK FOLLOWING ULCER OR AMPUTATION IN T1D: 34 YEAR FOLLOW-UP OF DCCT/EDIC

Abstract: BACKGROUND. People with type 1 diabetes and advanced neuropathy complications have augmented risk of adverse outcomes including mortality and cardiovascular disease. We aimed to determine if advanced neuropathy independently increases risk of acute complications such as diabetic ketoacidosis (DKA).
METHODS. We accessed previously-collected data from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Study, an interval and open cohort study, through the NIH Public Repository. For advanced neuropathy as the exposure, occurrence of self-reported and verified ulcer or amputation, as well as first DKA from enrolment as the outcome, were evaluated annually throughout follow-up. Multivariable Cox Proportional Hazard models with time-varying exposure and co-variates collected annually were used.
RESULTS. 1441 people participated in the DCCT, 1375 of whom joined the EDIC phase, representing 95% of the surviving participants. At baseline of the DCCT, mean age was 26.8 (SD 7.1) years, diabetes duration was 5.6 (SD 4.2) years, HbA1c was 8.9 (SD 1.6) %, 47% were female, and 97% were white. There were 527 foot ulcers noted and 202 amputation events among 226 individuals, and 488 DKA events among 297 individuals. Ulcer/amputation was associated with increased risk of DKA (Univariable Hazard Ratio 1.8, 95% confidence interval 1.2 to 2.8, p = 0.004). In multivariable analysis, ulcer/amputation was independently associated with increased risk of DKA (Hazard Ratio 1.7, 95% confidence interval 1.1 to 2.5, p = 0.019). DKA risk was also associated with insulin pump use (HR 3.0, 2.2 to 3.9, p< 0.001), higher insulin dose (HR for 1 unit/kg/day 2.4, 1.7 to 3.3, p< 0.001), female sex (HR 2.0, 1.5 to 2.6, p< 0.001), shorter duration of diabetes (HR for 10 years 1.4, 1.0 to 1.9, p = 0.025), and higher time-updated HbA1c (HR for 1 percent 1.4, 1.3 to 1.5, p< 0.001). In this model, there was no association with age, baseline HbA1c, weight or time-updated retinopathy or nephropathy.
CONCLUSIONS. In addition to previously reported augmented mortality and cardiovascular disease risk, this analysis demonstrates a substantially higher risk of DKA independent of possible confounders and other complications in those with a history of foot ulcer or amputation. This implies a need for greater metabolic control, self-management skills and education in those with advanced neuropathy. The mechanism of such acute complications and the other adverse outcomes requires further study.