Severe diabetic ketoacidosis (DKA) is a critical medical condition that often necessitates emergency treatment and hospitalization. Although DKA primarily impacts individuals with type 1 diabetes (T1D), its annual incidence among adults with T1D ranges from 4% to 8% following diagnosis. Continuous glucose monitoring (CGM) has become a standard tool for managing T1D and type 2 diabetes (T2D) in patients using insulin or aiming to improve self-management. However, advances in continuous dual glucose-ketone monitoring (DGK) technology offer new possibilities for clinical research and patient care. This article explores the potential applications of DGK in clinical research, with a focus on T1D, while also considering its broader relevance for T2D and other patient populations.
GosmanovAR, GosmanovaEO, KitabchiAE. Hyperglycemic crises: Diabetic ketoacidosis and hyperglycemic hyperosmolar state. [Updated 2021 May 9]. In: FeingoldKR, AhmedSF, AnawaltB, et al., editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000. Available from: https://www.ncbi.nlm.nih.gov/books/NBK279052/ [Last accessed: March 18, 2025].
2.
UmpierrezGE, DavisGM, ElSayedNA, et al.Hyperglycaemic crises in adults with diabetes: A consensus report. Diabetologia, 2024; 67(8):1455–1479; doi: 10.1007/s00125-024-06183-8
Kanikarla-MarieP, JainSK. Hyperketonemia and ketosis increase the risk of complications in type 1 diabetes. Free Radic Biol Med, 2016; 95:268–277; doi: 10.1016/j.freeradbiomed.2016.03.020
5.
BaoYK, MaJ, GanesanVC, McGillJB. Mistaken identity: Missed diagnosis of type 1 diabetes in an older adult. Med Res Arch, 2019; 7(8):1962.
6.
DandonaP, MathieuC, PhillipM, et al.; DEPICT-1 Investigators. Efficacy and safety of dapagliflozin in patients with inadequately controlled type 1 diabetes: The DEPICT-1 52-week study. Diabetes Care, 2018; 41(12):2552–2559.
7.
RosenstockJ, MarquardJ, LaffelLM, et al.Empagliflozin as adjunctive to insulin therapy in type 1 diabetes: The EASE Trials. Diabetes Care, 2018; 41(12):2560–2569.
8.
BuseJB, GargSK, RosenstockJ, et al.Fifty-two-week efficacy and safety of sotagliflozin, a dual SGLT and SGLT2 inhibitor, as adjunct therapy to insulin in adults with type 1 diabetes (inTandem1). Diabetes Care, 2018; 67(Supplement_1); doi: 10.2337/db18-212-OR
9.
LiK, XuG. Safety and efficacy of sodium glucose co-transporter 2 inhibitors combined with insulin in adults with type 1 diabetes: A meta-analysis of randomized controlled trials. J Diabetes, 2019; 11(8):645–655; doi: 10.1111/1753-0407.12890
10.
DanneT, GargS, PetersAL, et al.International consensus on risk management of diabetic ketoacidosis in patients with type 1 diabetes treated with Sodium–Glucose Cotransporter (SGLT) inhibitors. Diabetes Care, 2019; 42(6):1147–1154.
11.
ResnickO, BrilF, BeauchampG. Glucagon-like peptide-1 receptor agonists and type 1 diabetes: A potential game changer? Front Endocrinol (Lausanne), 2024; 15:1520313; doi: 10.3389/fendo.2024.1520313
12.
KhuntiK, CerielloA, CosX, De BlockC. Achievement of guideline targets for blood pressure, lipid, and glycaemic control in type 2 diabetes: A meta-analysis. Diabetes Res Clin Pract, 2018; 137:137–148; doi: 10.1016/j.diabres.2017.12.004
13.
PriggeR, McKnightJA, WildSH, et al.International comparison of glycaemic control in people with type 1 diabetes: An update and extension. Diabet Med, 2022; 39(5):e14766; doi: 10.1111/dme.14766
14.
Bin RakhisSASr, AlDuwayhisNM, AleidN, et al.Glycemic control for type 2 diabetes mellitus patients: A systematic review. Cureus, 2022; 14(6):e26180; doi: 10.7759/cureus.26180
15.
SchnellO, BattelinoT, BergenstalRM, et al.CVOT summit 2022 report: New cardiovascular, kidney, and glycemic outcomes. Cardiovasc Diabetol, 2023; 22(1):59; doi: 10.1186/s12933-023-01788-6
16.
MarxN, RydenL, BrosiusF, et al.Towards living guidelines on cardiorenal outcomes in diabetes: A pilot project of the Taskforce of the Guideline Workshop 2020. Diabetes Res Clin Pract, 2021; 177:108870; doi: 10.1016/j.diabres.2021.108870
17.
CollinsL, CostelloRA. Glucagon-Like Peptide-1 Receptor Agonists. [Updated 2023 Jan 13]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023. Available from: https://www.ncbi.nlm.nih.gov/books/NBK551568/ [Last accessed: August 26, 2023].
18.
NauckMA, QuastDR, WefersJ, MeierJJ. GLP-1 receptor agonists in the treatment of type 2 diabetes - state-of-the-art. Mol Metab, 2021; 46:101102; doi: 10.1016/j.molmet.2020.101102
19.
JastreboffAM, AronneLJ, AhmadNN, et al.; SURMOUNT-1 Investigators. Tirzepatide once weekly for the treatment of obesity. N Engl J Med, 2022; 387(3):205–216; doi: 10.1056/NEJMoa2206038
20.
FríasJP, DaviesMJ, RosenstockJ, et al.; SURPASS-2 Investigators. Tirzepatide versus Semaglutide once weekly in patients with type 2 diabetes. N Engl J Med, 2021; 385(6):503–515; doi: 10.1056/NEJMoa2107519
21.
ChavdaVP, AjabiyaJ, TeliD, et al.Tirzepatide, a new era of dual-targeted treatment for diabetes and obesity: A mini-review. Molecules, 2022; 27(13):4315; doi: 10.3390/molecules27134315
22.
DahlD, OnishiY, NorwoodP, et al.Effect of subcutaneous Tirzepatide vs placebo added to titrated insulin glargine on glycemic control in patients with type 2 diabetes: The SURPASS-5 randomized clinical trial. JAMA, 2022; 327(6):534–545; doi: 10.1001/jama.2022.0078
23.
AgarwalR, FilippatosG, PittB, et al.; FIDELIO-DKD and FIGARO-DKD investigators. Cardiovascular and kidney outcomes with finerenone in patients with type 2 diabetes and chronic kidney disease: The FIDELITY pooled analysis. Eur Heart J, 2022; 43(6):474–484; doi: 10.1093/eurheartj/ehab777
24.
AnsonM, ZhaoSS, AustinP, et al.SGLT2i and GLP-1 RA therapy in type 1 diabetes and reno-vascular outcomes: A real-world study. Diabetologia, 2023; 66(10):1869–1881; doi: 10.1007/s00125-023-05975-8
25.
FarsaniSF, BrodoviczK, SoleymanlouN, et al.Incidence and prevalence of diabetic ketoacidosis (DKA) among adults with type 1 diabetes mellitus (T1D): A systematic literature review. BMJ Open, 2017; 7(7):e016587; doi: 10.1136/bmjopen-2017-016587
26.
NealB, PerkovicV, MahaffeyKW, et al.; CANVAS Program Collaborative Group. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med, 2017; 377(7):644–657; doi: 10.1056/NEJMoa1611925
27.
WiviottSD, RazI, BonacaMP, et al.; DECLARE–TIMI 58 Investigators. Dapagliflozin and cardiovascular outcomes in type 2 diabetes. N Engl J Med, 2019; 380(4):347–357; doi: 10.1056/NEJMoa1812389
28.
InzucchiSE, ZinmanB, WannerC, et al.SGLT-2 inhibitors and cardiovascular risk: Proposed pathways and review of ongoing outcome trials. Diab Vasc Dis Res, 2015; 12(2):90–100; doi: 10.1177/1479164114559852
29.
NganJ, KongYW, GoadJ, et al.Rationale and design of a randomised phase II multicentre crossover trial investigating a sodium-glucose co-transporter 2 inhibitor, dapagliflozin, combined with a novel continuous ketone monitor in adults with type 1 diabetes to reduce the risk of diabetic ketoacidosis: The PARTNER study. BMJ Open, 2025; 15(5):e098457; doi: 10.1136/bmjopen-2024-098457
30.
YangM, YueH, XuQ, et al.Pioglitazone reduces serum ketone bodies in sodium-glucose cotransporter-2 inhibitor-treated non-obese type 2 diabetes: A single-centre, randomized, crossover trial. Diabetes Obes Metab, 2024; 26(8):3137–3146; doi: 10.1111/dom.15641
31.
PietschnerR, KolwelterJ, BoschA, et al.Effect of empagliflozin on ketone bodies in patients with stable chronic heart failure. Cardiovasc Diabetol, 2021; 20(1):219; doi: 10.1186/s12933-021-01410-7
32.
ScarrD, LovblomE, YeH, et al.Ketone production and excretion even during mild hyperglycemia and the impact of sodium-glucose co-transporter inhibition in type 1 diabetes. Diabetes Res Clin Pract, 2024; 207:111031; doi: 10.1016/j.diabres.2023.111031
33.
Canadian Kidney Foundation. The Sodium Glucose Co-Transport-2 Inhibition Diabetes and Kidney Function Loss in Type 1 Diabetes (SUGARNSALT) research project. Available from: https://kidney.ca/Research/Supported-Research/SUGARNSALT-Project# [Last accessed: May7, 2025].
34.
GoldenbergRM, GilbertJD, HramiakIM, et al.Sodium-glucose co-transporter inhibitors, their role in type 1 diabetes treatment and a risk mitigation strategy for preventing diabetic ketoacidosis: The STOP DKA Protocol. Diabetes Obes Metab, 2019; 21(10):2192–2202; doi: 10.1111/dom.13811
35.
GargSK, PetersAL, BuseJB, et al.Strategy for mitigating DKA risk in patients with type 1 diabetes on adjunctive treatment with SGLT inhibitors: A STICH protocol. Diabetes Technol Ther, 2018; 20(9):571–575; doi: 10.1089/dia.2018.0246
36.
SongC, DhaliwalS, BapatP, et al.Point-of-Care capillary blood ketone measurements and the prediction of future ketoacidosis risk in type 1 diabetes. Diabetes Care, 2023; 46(11):1973–1977; doi: 10.2337/dc23-0840
37.
BapatP, BudhramDR, BakhshA, et al.Longitudinal determination of diabetes complications and other clinical variables as risk factors for diabetic ketoacidosis in type 1 diabetes. Diabetes Care, 2025 Apr 1;48(4):614–622; doi: 10.2337/dc24-2385
38.
AlshamiA, PurewalT, DouediS, et al.Effect of insulin pump use on diabetic ketoacidosis in type 1 diabetes mellitus: A matched cohort study. J Clin Med, 2021; 10(5):1–8.
39.
BudhramDR, BapatP, BakhshA, et al.Insulin pump use and diabetic ketoacidosis risk in type 1 diabetes: Secular trends over four decades. Diabetes Technol Ther, 2025; 27(2):139–143; doi: 10.1089/dia.2024.0272
40.
Kanikarla-MarieP, JainSK. Hyperketonemia (acetoacetate) upregulates NADPH oxidase 4 and elevates oxidative stress, ICAM-1, and monocyte adhesivity in endothelial cells. Cell Physiol Biochem, 2015; 35(1):364–373; doi: 10.1159/000369702
41.
PeacockS, FrizelleI, HussainS. A systematic review of commercial hybrid closed-loop automated insulin delivery systems. Diabetes Ther, 2023; 14(5):839–855; doi: 10.1007/s13300-023-01394-5
42.
BeckRW, KanapkaLG, BretonMD, et al.A meta-analysis of randomized trial outcomes for the t:Slim X2 insulin pump with Control-IQ technology in youth and adults from age 2 to 72. Diabetes Technol Ther, 2023; 25(5):329–342; doi: 10.1089/dia.2022.0558
43.
KudvaYC, RaghinaruD, LumJW, et al.; 2IQP Study Group. A randomized trial of automated insulin delivery in type 2 diabetes. N Engl J Med, 2025; 392(18):1801–1812; doi: 10.1056/NEJMoa2415948
44.
LevyCJ, RaghinaruD, KudvaYC, et al.Beneficial effects of control-IQ automated insulin delivery in basal-bolus and basal-only insulin users with type 2 Diabetes. Clin Diabetes, 2024; 42(1):116–124.
45.
MetzgerBE, RavnikarV, VileisisRA, FreinkelN. “Accelerated starvation” and the skipped breakfast in late normal pregnancy. Lancet, 1982; 1(8272):588–592; doi: 10.1016/s0140-6736(82)91750-0
46.
BattelinoT, AlexanderCM, AmielSA, et al.Continuous glucose monitoring and metrics for clinical trials: an international consensus statement. Lancet Diabetes Endocrinol, 2023; 11(1):42–57; doi: 10.1016/S2213-8587(22)00319-9
47.
KolnesKJ, NilsenETF, BrufladtS, et al.Effects of seven days’ fasting on physical performance and metabolic adaptation during exercise in humans. Nat Commun, 2025; 16(1):122; doi: 10.1038/s41467-024-55418-0
