What do you mean the sugar is normal?

Here is a post from one of our EM residents, Dr Andew Ho. 
Its about a rare but not impossible scenario which may get more common in the future. See if you can figure out the problem before clicking on the answer button. 

An uncommon diabetic emergency…

You are on a P2 shift. It has been a busy shift so far with many of your existing patients having gastroenteritis. You pick up a new chart which says “vomiting since last night”. This is a 30 year old male with a past history significant only for Type 2 Diabetes Mellitus on follow up with his private General Practitioner (GP). 
He takes pride in having good diabetic control so far. He has been on metformin, and was recently started on empagliflozin (SGLT-2 inhibitor). He also exercises regularly, and under advice of his GP, started on a ketogenic diet (similar to an Atkin’s diet) 4 days prior.
He now complains of non-bloody, non-bilious vomiting - 10 episodes daily for the past 3 days.  He also developed epigastric pain today. There is no complaint of loose stools or fever. Contact and travel history are unremarkable. He is haemodynamically stable and his abdomen is soft and non-tender to palpation

What are your differential diagnoses?

Diabetic ketoacidosis
Infective gastroenteritis
Acute pancreatitis
Intestinal obstruction

The patient reveals that he checked his own blood sugar just before calling the ambulance, and it was 8.3. You decided to administer an antiemetic and send off some bloods.

The renal panel shows: U 6.0, K 4.2, Na 133, Bicarbonate 5, Cr 86. The venous gas shows a profound metabolic acidosis with pH 7.10, and BE -20.6. Blood ketones come back at 5.8

What is going on here an what is the pathophysiology?

This is Euglycemic DKA (EuDKA). EuDKA is an uncommon entity that mostly occurs in Type 1 DM, but can also occur in Type 2 DM. A learning point here is that the EuDKA would be completely missed if we just looked at the blood glucose alone or if the patient’s medication list was not available. A delayed diagnosis would lead to delayed treatment, and complications of a worsening acidemia. 

What do we know about the clinical features of this entity?

There are two case series on this rare entity. The larger series (37 cases in 17 patients) in the literature is published by Munro et al (1973)2. Peters et al published another series in 2015, featuring 13 cases in 9 patients3.

-          32% presented with vomiting, 10% with abdominal pain, 9% with thirst (Munro et al)
-          Mean duration of symptoms <2 days (range 6 hours – 8 days, Munro et al)
-          8/37 cases had concomitant infections (Munro et al)
-          Many cases had a history of carbohydrate restriction (eg missed school lunch, poor appetite, dental pain, Munro et al)

-          17/17 patients were young, range 10-28 years (Munro et al)
-          11/17 patients were female (Munro et al)
-          5/17 patients experienced recurrence during the study period (Munro et al)
-          16/17 patients were insulin-dependent diabetics (Munro et al)
-          1/17 patient was an undiagnosed diabetic! (Munro et al)
-          7/9 patients had type 1 diabetes, 2/9 with type 2 (Peters et al)
-          9/9 patients were on SGLT-2 inhibitors (Peters et al) – as SGLT-2 is being prescribed more since being released in 2013, we may see more EuDKAs!
-          37/37 cases survived to discharge (Munro et al)

Risk factors:
-          SGLT-2 Inhibitors - Ipragliflozin, Dapagliflozin, Luseogliflozin, Tofogliflozin, Canagliflozin, Empagliflozin. Not sure which are approved in Singapore. Our patient is on Empagliflozin.
-          Carbohydrate restriction – ketogenic diet, poor appetite
-          Increased insulin dosage
-          Alcohol abuse

Treatment4–6 (expert opinion level of evidence only)
IV fluids with balanced crystalloids (with 5% dextrose) – You add dextrose to drip sooner than you would in DKA
-          IV insulin (to close the anion gap and reverse the metabolic acidosis)
-          Watch potassium while on insulin
-          Treat any underlying precipitants eg infections.
-          Correct predisposing factors: review diet, anti-diabetic meds
Our patient was started on IV insulin 0.5 unit/h, with a dextrose/saline drip. He was given regular anti-emetics. His ketones was on a decreasing trend, and metabolic acidosis resolved. He was taken off his empagliflozin on discharge and converted to subcutaneous insulin injections with metformin.

Clinical take home point?
Suspect EuDKA in patients with risk factors and clinical suspicion. The importance of history taking to uncover a patient’s pre-existing medication list cannot be over-emphasized. Check a urine or serum ketone, especially if a HAGMA is seen.

1.        Ireland JT, Thomson WS. Euglycemic diabetic ketoacidosis. Br Med J. 1973;3(5871):107.
2.        Munro JF, Campbell IW, McCuish AC, et al. Euglycaemic diabetic ketoacidosis. Br Med J. 1973;2(5866):578-580.
3.        Peters AL, Buschur EO, Buse JB, et al. Euglycemic diabetic ketoacidosis: A potential complication of treatment with sodium-glucose cotransporter 2 inhibition. Diabetes Care. 2015;38(9):1687-1693. doi:10.2337/dc15-0843.
4.        Rezaie S. Euglycemic DKA: It’s not a Myth. http://rebelem.com/euglycemic-dka-not-myth/. Published 2016. Accessed June 28, 2017.
5.        KAILASH P. Euglycemic DKA Secondary to SGLT2 inhibitors. http://www.emdocs.net/euglycemic-dka-secondary-sglt2-inhibitors/. Published 2017. Accessed June 28, 2017.

6.        Cocchio C. Euglycemic DKA from SGLT2 Inhibitors: Don’t Worry, I Can’t Pronounce Them Either. http://empharmd.blogspot.sg/2016/05/euglycemic-dka-from-sglt2-inhibitors.html. Published 2016. Accessed June 28, 2017.

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