Interesting presentation of dka
41-year-old female presenting with reported elevated blood sugars in the 200s, 3 days of vomiting and diarrhea. She states that she vomited twice today without any blood. She states that about 2 weeks ago she was started on a new medication called Farxiga. She has no known sick contacts, no travel out of the country and no new antibiotics. She has not consumed non-potable water. No diarrhea today.
Pertinent Exam Findings:
Dry mucous moist membranes
LUQ and tenderness at the epigastric area
BMP: AG 21/ bicarb 7 /glucose 168 K 4.8/ normal renal function
VBG: pH 7.22/ HCO3 5
Beta hydroxybutyrate: 6.7
Patient was given IV insulin bolus and drip. She was given IVF with D5 and supplemental potassium and admitted to the ICU for further medical management.
Diabetic ketoacidosis (DKA) is traditionally defined as hyperglycemia (>250 mg/dL), anion gap acidosis, and plasma ketones. Euglycemic DKA (euDKA), is essentially DKA with a serum glucose <200 mg/dL. Euglycemic DKA is a rare entity that mostly occurs in patients with type 1 diabetes, but can possibly occur in type 2 diabetes as well. The exact mechanism of euDKA is not entirely known, but has been associated with partial treatment of diabetes, carbohydrate food restriction, alcohol intake, and inhibition of gluconeogenesis. euDKA, can also be associated with sodium-glucose cotransporter 2 (SGLT-2) inhibitor medications. These medications first came onto the market in 2013 and are FDA approved for the treatment of type 2 diabetes, however many physicians use them off-label for type I diabetes due to their ability to improve average glucose levels, reduce glycemic variability without increasing hypoglycemia, and finally promote weight loss.
Does euDKA Exist even in Patients not Using SGLT-2 Inhibitors?
The short answer is YES. Munro JF et al  reviewed a case series of 37 episodes of euDKA in a publication from 1973. Although, dated and not robust evidence there are some take home messages:
All but one episode was in insulin dependent diabetics
Vomiting was the most frequent symptom of euDKA in 32% of patients
Management in most cases consisted of: Intravenous fluids and electrolyte replacement.
No deaths occurred in this case series
What are the Names of the SGLT-2 Inhibitors?
Ipragliflozin (Suglat) – Approved in Japan
Dapagliflozin (Farxiga) – 1st SGLT2 Inhibitor Approved; Approved in US
Luseogliflozin (Lusefi) – Approved in Japan
Tofogliflozin (Apleway; Deberza) – Approved in Japan
Canagliflozin (Invokana) – Approved in US & Canada
Empagliflozin (Jardiance) – Approved in US
How do SGLT-2 Inhibitors Cause euDKA?
High Yield Points:
*In patients with diabetes mellitus, on a SGLT-2 inhibitor and/or carbohydrate food restriction, who present with nausea/vomiting, fatigue, or the development of a metabolic acidosis, checking a urine and/or serum ketones is critical to not miss a case of euDKA.
*The treatment of euDKA will be nearly identical to DKA:
IVF: Treat dehydration; In addition to balanced crystalloids, start fluids with dextrose , due to the serum blood glucose already being low (i.e. <200mg/dL),
IV Insulin: Close the anion gap and reverse the metabolic acidosis
Taken from http://rebelem.com/euglycemic-dka-not-myth/
Peters AL et al. Euglycemic Diabetic Ketoacidosis: A Potential Complication of Treatment with Sodium-Glucose Cotransporter 2 Inhibition. Diabetes Care 2015; 38 (9): 1687 – 93. PMID: 26078479
Ogawa W and Sakaguchi K. Euglycemic Diabetic Ketoacidosis Induced by SGLT2 Inhibitors: Possible Mechanism and Contributing Factors. J Diabetes Investig 2016; 7 (2): 135 – 8. PMID: 27042263
Hine J et al. SGLT Inhibition and Euglycemic Diabetic Ketoacidosis. Lancet Diabetes Endocrinal 2015; 3: 503 – 504. PMID: 26025388
Hayami T et al. Case of Ketoacidosis by a Sodium-Glucose Cotransporter 2 Inhibitor in a Diabetic Patient with a Low-Carbohydrate Diet. J Diabetes Investig 2015; 6: 587 – 590. PMCID: PMC4578500
Munro JF et al. Euglycemic Diabetic Ketoacidosis. BMJ 1973; 2 (5866: 578 – 80. PMID: 4197425