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Three Part Question

In [adults with diabetic ketoacidosis presenting to the emergency department], what is the [significance and etiology] of [euglycemia (serum blood glucose less than 200)]?

Clinical Scenario

A 28 year old patient with a past medical history of type II diabetes and irritable bowel syndrome currently taking a SGLT-2 inhibitor for his diabetes presents to the Emergency Department with the chief complaint of nausea and vomiting with associated fatigue. The patient is evaluated and treated for their nausea and vomiting. The patient continues to have intractable vomiting despite conventional therapy. On laboratory evaluation they are found to have a blood sugar of 162, pH of 7.2, elevated betahydroxybutyrate and large ketones in the urine.

Search Strategy

Medline 1966-08/17 using OVID interface, Cochrane Library (2017), and Embase
[(exp Ketoacidosis) AND (exp euglycemia OR euglycaemia OR euglycemic)]

Search Outcome

98 studies were identified; the majority of publications were single case reports or reviews. Two case series addressed the three part question

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Munro JF, Campbell IW, McCuish AC, Duncan LJP June 1973 Scotland	Diabetics admitted to the diabetic ward	Retrospective case series analysis of patients admitted to the diabetic ward with diabetic metabolic decompensation	Patients presenting in DKA with blood glucose levels less than 300	211 total episodes of DKA - 37 episodes presented with blood sugars less than 300	Low number of total episodes analyzed; no comparison of sample patient groups (hyperglycemic > 300) vs euglycemic (<300)
Peters AL, Buschur EO, Buse JB, Cohan P, Diner JC, Hirsch IB May 2015 United States	Patients with Type 1 or Type 2 Diabetes that are on SGLT-2 Inhibitors that presented to the hospital in DKA	Case Series of patients presenting with euglycemic DKA (Blood Glucose < 300) that are on SGLT-2 Inhibitors	Association between use of a SGLT-2 inhibitor and presentation to the hospital in euglycemic DKA	13 cases from across the United States presented with euglycemic DKA all of which had a delay in recognition of diagnosis and approriate therapy	It is a case series, only 13 cases from various centers around United States. No comparison group.

Comment(s)

Diabetic ketoacidosis (DKA) is characterized by a triad of hyperglycemia (>250mg/dL), anion gap acidosis, and increased plasma ketones. Rarely these patients can present with blood glucose levels of less than 200 mg/dl, which is defined as euglycemic DKA. Euglycemic DKA is classically considered rare but this is perhaps a result of underrecognition and underreporting. It occurs in patients with type 1 diabetes, but can possibly occur in type 2 diabetes as well. The best evidence to address our clinical question consisted of two case series. In the hierarchy of evidence, this represents level IV evidence. This is due to lack of control subjects, making case series prone to bias. However, while the exact mechanism of euglycemic DKA is unknown these two studies suggest several possible etiologies for euglycemic DKA, including decreased caloric intake, heavy alcohol consumption, pregnancy, chronic liver disease, glycogen storage disorders, and use of newer antihyperglycemic medications (sodium glucose cotransporter 2 inhibitors) ofthen in the setting of continued insulin use. Awareness that DKA can occur in the setting of relative euglycemia is critical to recognize this life-threatening complication of diabetes.

Clinical Bottom Line

All 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, should be promptly evaluated for urine and/or serum ketones, even if glucose levels are nearly normal to avoid the missed diagnosis of DKA.

References

1. Munro JF, Campbell IW, McCuish AC, Duncan LJP Euglycemic Diabetic Ketoacidosis BMJ Br Med J 1973;2:578
2. Peters AL, Buschur EO, Buse JB, Cohan P, Diner JC, Hirsch IB Euglycemic Diabetic Ketoacidosis: A Potential Complication of Treatment With Sodium-Glucose Cotransporter 2 Inhibition Diabetes Care 2015 Sep;38(9):1687-93