What Is Euglycemic DKA and Why Does It Get Missed?

Euglycemic diabetic ketoacidosis is a form of DKA in which the body builds up dangerous levels of acid and ketones while blood sugar stays below 250 mg/dL, sometimes even in the normal range. That near-normal glucose reading is precisely what makes the condition so treacherous: patients, families, and even clinicians may not suspect DKA when the glucose meter does not show the sky-high numbers they associate with a diabetic crisis. The condition has become more common in recent years, largely because of a widely prescribed class of diabetes and heart-failure medications, and it can also strike people who do not have diabetes at all.

What Makes It Different From Typical DKA

In textbook DKA, blood sugar is usually well above 250 mg/dL and often over 500 mg/dL. A study comparing 44 euglycemic DKA patients against hyperglycemic DKA patients found average glucose levels of about 195 mg/dL versus 561 mg/dL in the conventional group.¹ The acid buildup and ketone production, however, are the same underlying emergency. Your blood becomes too acidic, your electrolytes shift, and without treatment, organ failure and death are on the table.

Diagnostic criteria generally call for a blood glucose below 200 mg/dL (some sources use 250 mg/dL as the cutoff), elevated blood ketones, and signs of metabolic acidosis such as a low pH or low bicarbonate level.² It can affect people with type 1 or type 2 diabetes, and the milder glucose numbers frequently delay recognition of the emergency.³

Why the Blood Sugar Stays Low

The underlying mechanism involves a mismatch between insulin activity and the hormones that oppose it, combined with a shortfall in available carbohydrates. In regular DKA, the liver dumps glucose into the bloodstream at the same time that insulin is absent, so sugar soars. In euglycemic DKA, something keeps glucose from climbing: the kidneys may be flushing it out (as happens with certain medications), the person may not be eating enough carbohydrates, or both. Meanwhile, the ratio of glucagon to insulin tilts far enough to shift the body into aggressive fat-burning, producing ketone acids faster than the blood can buffer them.⁴

Think of it this way: the ketoacidosis part of DKA runs on fat breakdown and insulin deficiency, not on high blood sugar. High blood sugar just happens to tag along in the classic version. Strip away the glucose spike and you still have the same dangerous acid storm.

SGLT2 Inhibitors as the Leading Modern Trigger

The single biggest reason euglycemic DKA is on clinicians’ radar today is a class of drugs called SGLT2 inhibitors. Brand names you may recognize include canagliflozin, dapagliflozin, and empagliflozin (marketed under names like Invokana, Farxiga, and Jardiance). These drugs work by forcing the kidneys to excrete excess glucose into the urine, which lowers blood sugar effectively. The side effect is that the very mechanism keeping glucose low also masks the warning sign that would otherwise flag DKA. At the same time, the loss of glucose in urine shifts the body’s fuel economy toward fat, increasing ketone production.⁵

An early case series from practices across the United States identified 13 episodes of SGLT2 inhibitor-associated euglycemic DKA or ketosis in nine people. The absence of high glucose delayed both patients and providers from recognizing the severity of what was happening.⁶ Since then, hundreds of cases have been reported worldwide, and the pattern is consistent: a patient on an SGLT2 inhibitor encounters a metabolic stressor, ketones surge, but the glucose reading looks reassuring enough to delay alarm.

The Perioperative Danger Zone

Surgery is one of the highest-risk settings for euglycemic DKA in people taking SGLT2 inhibitors. The combination of fasting before a procedure, the physical stress of surgery, and the lingering effects of the drug creates a perfect storm. A case series of cardiac surgery patients found that even stopping the SGLT2 inhibitor one to two days before the operation was not always enough. On the first day after surgery, patients developed nausea, vomiting, and rapid breathing alongside an unexpectedly low glucose level and acidosis. Ketone testing confirmed euglycemic DKA.⁷

The timing of when you stop the drug matters. Evidence from a larger inpatient series suggests that euglycemic DKA was rare in patients who stopped their SGLT2 inhibitor at least three days before a planned procedure, but it was more likely in emergency surgeries when the drug could not be stopped in advance.⁸ Most surgical guidelines now recommend holding the medication three to four days before any elective surgery. If you take one of these drugs and have an upcoming procedure, flagging it for your surgical team is worth doing even if they do not ask.

Beyond Medications: Other Triggers

SGLT2 inhibitors get the most attention, but euglycemic DKA existed long before those drugs came to market. It occurs in settings where carbohydrate intake drops dramatically or the body’s ability to produce glucose is impaired. Common scenarios include:

Starvation or fasting: Prolonged fasting, severe illness that prevents eating, or intentional calorie restriction can deplete glycogen stores and push fat metabolism into overdrive.
Alcohol misuse: Heavy drinking impairs the liver’s ability to make new glucose, and the metabolic byproducts of alcohol metabolism further tip the balance toward ketone production.
Pregnancy: The metabolic demands of pregnancy accelerate fat breakdown, and nausea or vomiting that limits food intake can trigger ketoacidosis at lower glucose thresholds than usual.
Chronic liver disease: A damaged liver cannot maintain glucose production, making ketoacidosis more likely during any metabolic stress.
Infections: Acute illness increases stress hormones that oppose insulin, while simultaneously reducing appetite and oral intake.

These triggers can overlap with SGLT2 inhibitor use. Precipitating factors in drug-associated cases frequently include insulin reduction or omission, surgery, alcohol use, intense exercise, and low-carbohydrate diets.⁹ Even outside diabetes entirely, euglycemic ketoacidosis can develop in pregnancy, with glycogen storage diseases, or with cocaine use.¹⁰

The Ketogenic Diet Connection

Ketogenic and very-low-carbohydrate diets have become enormously popular for weight loss and blood sugar management, including among people with diabetes. The irony is that these diets intentionally push the body into a state of ketosis, which is metabolically adjacent to ketoacidosis. For most healthy people, the body regulates ketone levels and keeps them in a safe range. But in someone with diabetes, especially someone also taking an SGLT2 inhibitor or who reduces their insulin dose to match lower carb intake, that regulatory buffer can fail.

Case reports describe patients with new-onset type 1 diabetes developing euglycemic DKA after following a ketogenic diet, with severe carbohydrate restriction identified as the driving factor.¹¹ The combination of an SGLT2 inhibitor and a low-carb diet is particularly risky, since both independently lower blood glucose and promote ketone production. If you have diabetes and want to follow a very-low-carb eating plan, discussing it with your prescribing clinician beforehand is not optional, it is a safety issue.

Non-Diabetic Patients Are Not Immune

SGLT2 inhibitors are now widely prescribed for heart failure and chronic kidney disease in people who do not have diabetes. The assumption has been that non-diabetic patients maintain enough insulin secretion to prevent ketoacidosis. Large clinical trials generally supported that view, with no ketoacidosis reported in the heart-failure arms. But post-marketing reports tell a different story. A narrative review identified six cases of euglycemic ketoacidosis in non-diabetic patients taking SGLT2 inhibitors for heart failure with reduced pumping ability. In five of the six cases, the common thread was reduced food intake from acute illness, fasting, or a perioperative state.¹²

One case from the EMPA-KIDNEY study involved a non-diabetic patient on empagliflozin who developed ketoacidosis, though details were not published. Outside of clinical trials, a handful of additional cases have surfaced, suggesting that SGLT2 inhibitors may occasionally trigger ketoacidosis in non-diabetic patients, particularly when food intake drops.¹³ The incidence is likely to rise as SGLT2 inhibitors are prescribed more broadly for cardiac and renal indications beyond diabetes.¹⁴

Why It Gets Missed

The diagnostic trap is straightforward: nearly every clinician, and every patient who has been educated about DKA, associates the condition with extremely high blood sugar. When someone shows up with nausea, vomiting, abdominal pain, and rapid breathing but their glucose is 180 or even 130, DKA is not the first thing that comes to mind. Those symptoms overlap with gastroenteritis, post-surgical complications, or a dozen other problems.

There is also a differential diagnosis challenge with alcoholic ketoacidosis, which can look almost identical on lab work. Most patients with alcoholic ketoacidosis present with normal or low glucose, and in diabetic patients who also drink heavily, the two conditions can coexist or be easily confused.¹⁵ The treatment approaches differ enough that getting the diagnosis right matters. The key to catching euglycemic DKA is checking ketones and blood gas values in any diabetic patient (or any patient on an SGLT2 inhibitor) who has symptoms of acidosis, regardless of what the glucose reading says. In pediatric and adolescent patients, the same principle applies, and delayed diagnosis can lead to worse outcomes.¹⁶

How Treatment Differs From Standard DKA Protocols

Treating regular DKA follows a well-rehearsed protocol: intravenous insulin to bring down glucose, aggressive fluid replacement, and potassium monitoring. The glucose level itself serves as one of the guideposts for titrating the insulin drip. In euglycemic DKA, that guidepost is unreliable or even misleading, because glucose is already low enough that giving standard insulin doses risks pushing it into dangerous hypoglycemia.

The workaround involves giving intravenous insulin at a fixed rate while simultaneously infusing dextrose-containing fluids to keep glucose from dropping too far. The insulin is not there to lower sugar; it is there to shut off ketone production and allow the body to clear the acid. Some hospitals have developed specific protocols for this, using a fixed insulin infusion alongside titrated dextrose.¹⁷ Without a standardized approach, the risk of hypoglycemia during treatment is real. In the comparative study of 44 euglycemic DKA patients, roughly 18% experienced blood sugar drops below 70 mg/dL during insulin infusion, compared to about 5% of patients with conventional high-glucose DKA.¹⁸

One reassuring finding from the same study: euglycemic DKA patients had milder acidosis on arrival and spent less time on insulin infusions (about 13.5 hours versus 19.4 hours for hyperglycemic DKA).¹⁹ That shorter treatment window may reflect the milder starting point, but it does not mean the condition is less dangerous. The danger lies in the delay before treatment begins, not in the severity once treatment is underway.

What You Can Do If You Are at Risk

If you take an SGLT2 inhibitor, whether for diabetes, heart failure, or kidney disease, the single most useful thing you can do is learn the symptoms of ketoacidosis that do not depend on a glucose reading. Nausea, vomiting, abdominal pain, fatigue, and breathing that feels unusually deep or fast are the red flags. Some patients describe a fruity or acetone-like odor on their breath. If you own a home ketone meter (blood ketone meters are more reliable than urine strips), checking ketones when you feel unwell can catch the problem hours before it becomes an emergency.

Specific situations call for extra vigilance. Any period of reduced food intake, whether from an illness, a planned fast, a strict low-carb diet, or pre-surgical fasting, increases the risk. Heavy drinking is another trigger. If you are cutting insulin doses because your blood sugar is running low on a new diet, that combination of less insulin and less carbohydrate is exactly the setup for euglycemic DKA.²⁰ Before any surgery, make sure the surgical and anesthesia teams know you are on the medication, and confirm the plan for when to stop it preoperatively.

Severity Grading and When to Go to the Emergency Room

Euglycemic DKA can be graded as mild, moderate, or severe based on how acidic the blood has become and how low bicarbonate has dropped. Mild cases have a pH between about 7.25 and 7.30, moderate cases between 7.00 and 7.24, and severe cases fall below 7.00.²¹ These numbers mean nothing to you at home, of course, because you cannot measure your own blood pH. The practical takeaway is that any combination of unexplained vomiting, abdominal pain, and labored breathing in someone on an SGLT2 inhibitor warrants a trip to the emergency department, even if your glucose is 120. Tell the triage team you are on an SGLT2 inhibitor and ask them to check ketones and a blood gas. That sentence alone can shave hours off the diagnostic delay that makes this condition dangerous.

Emergency physicians increasingly recognize the pattern, but it is still not universally on the radar. The most commonly missed population may be non-diabetic heart-failure patients on these drugs, because neither the patient nor the care team is thinking about ketoacidosis as a possibility in someone who does not have diabetes. As SGLT2 inhibitor prescriptions expand into broader cardiac and kidney disease populations, the clinical community is still catching up.