Capillary Blood Ketone Level and the Prediction of Future Diabetic Ketoacidosis Risk in Type 1 Diabetes

Identification of those at risk of diabetic ketoacidosis (DKA) in T1D is challenging. Rather than during illness while DKA is developing, we aimed to determine if levels of routine point-of-care capillary blood ketones could predict DKA months prior to the event. In exploratory analysis, we examined 484 participants randomly assigned to placebo in an adjunct-to-insulin medication trial program (NCT02414958 and NCT02580591). Participants provided morning fasted capillary blood ketone levels twice per week via electronic logbook, and we calculated the maximum and mean level for each individual during a 2-month baseline period. Outcome was the 6 to 12-month occurrence of trial-adjudicated DKA. Area under the Curve (AUC) for the Receiver Operator Characteristic curves were generated. In sensitivity analysis we applied supervised machine learning methods (gradient-boosted trees). Participants had median age 43 [IQR 33, 54], mean HbA1c 8.2±0.6 percent, and provided 2 [1, 4] ketone measurements per week. Twelve DKA events occurred at median 105 [43, 199] days. Maximum and mean ketone levels were higher at baseline for the 12 cases compared to controls (for example, maximum ketone level 0.8 [0.6, 1.2] compared to 0.3 [0.2, 0.7] mmol/L, p=0.002). Maximum ketone level had AUC of 0.769 (95% CI 0.655-0.883). Maximum ketone ≥0.8 mmol/L had sensitivity 64%, specificity 78%, and likelihood ratios positive and negative of 2.9 and 0.5. Machine learning methods outperformed the single-metric analyses. Results provide proof-of-concept that routine capillary ketone surveillance can identify individuals at high-risk of future DKA. Simple or complex machine learning algorithms could be implemented in ketone meters or in future continuous ketone measurement technology. Disclosure C.Song: None. D.Cherney: Other Relationship; Boehringer Ingelheim-Lilly, Merck, AstraZeneca, Sanofi, Mitsubishi-Tanabe, Abbvie, Janssen, Bayer, Prometic, BMS, Maze, Gilead, CSL-Behring, Otsuka, Novartis, Youngene, Lexicon and Novo-Nordisk, Research Support; Boehringer Ingelheim-Lilly, Merck, Janssen, Sanofi, AstraZeneca, CSL-Behring and Novo-Nordisk. D.Mumford: None. G.Tomlinson: None. L.Lovblom: None. B.A.Perkins: Advisory Panel; Dexcom, Inc., Insulet Corporation, Novo Nordisk, Sanofi, Vertex Pharmaceuticals Incorporated, Other Relationship; Abbott, Medtronic, Sanofi, Research Support; Novo Nordisk, Bank of Montreal (BMO). S.Dhaliwal: None. P.Bapat: None. A.M.K.Bakhsh: None. D.R.Budhram: None. D.Scarr: None. A.Weisman: None. M.Fralick: None. N.Ivers: Consultant; Novo Nordisk Canada Inc., IQVIA Inc. Funding Diabetes Canada (OG-3-21-5572-BP)