Euglycemic KetoacidosisEdit

Euglycemic ketoacidosis (EKA) is a form of ketoacidosis in which a metabolic acidosis with ketosis occurs even when blood glucose levels are normal or only mildly elevated. It is most often discussed in the context of diabetes mellitus, but it can arise in other settings as well. Because the glucose level can appear deceptively reassuring, clinicians must rely on the full metabolic picture—anion gap, ketones, acid–base balance, and the clinical trigger—rather than glucose alone. EKA has drawn particular attention as newer therapies and dietary patterns interact with glucose control, sometimes creating diagnostic gray areas that require careful assessment of physiology and risk factors. See diabetic ketoacidosis for related concepts, and SGLT2 inhibitors for a medication class frequently associated with this condition.

EKA sits at the intersection of metabolism, endocrinology, and clinical medicine. It illustrates how insulin activity, glucagon, and ketone production can diverge from glucose readings under stress, illness, or pharmacologic influence. The condition is implementable within a broader framework of metabolic acidosis and ketogenesis, topics central to understanding how the body shifts fuel sources in times of relative insulin deficiency or increased counter-regulatory hormones. See beta-hydroxybutyrate and ketogenesis for biochemical context, and metabolic acidosis for the acid–base background.

Pathophysiology

Euglycemic ketoacidosis results from a relative or absolute deficiency of insulin and/or an excess of counter-regulatory hormones (such as glucagon, cortisol, catecholamines, and growth hormone). This hormonal milieu promotes lipolysis, releasing free fatty acids that the liver converts into ketone bodies (most notably beta-hydroxybutyrate and acetoacetate). Because glucose production and utilization are influenced by several factors, blood glucose can remain normal or only mildly elevated even as ketogenesis proceeds. Some triggers, notably the use of certain medications or restricted caloric intake, can blunt glucose levels further by increasing renal glucose loss or shifting metabolism toward ketone production.

Key mechanisms include: - Insulin deficiency or resistance leading to unchecked lipolysis and ketogenesis. See insulin and glucagon for hormonal regulation. - Hemodynamic and metabolic stress that raises counter-regulatory hormones, further promoting ketone formation. - In certain contexts, interventions or conditions (such as SGLT2 inhibitors) that lower plasma glucose through non-insulin means while still permitting or promoting ketogenesis. - Variations in liver and peripheral tissue metabolism that maintain normal glucose levels while driving acidosis via ketones.

See also beta-hydroxybutyrate and acetone for the specific ketone bodies involved, and anion gap for the typical laboratory signature.

Causes and risk factors

EKA can arise in diverse clinical scenarios. While the classic teaching centers on people with diabetes, recognition of non-diabetic and drug-related causes broadens the diagnostic lens.

Diabetes mellitus with factors that elevate ketogenesis without marked hyperglycemia: inadequate insulin administration, illness, dehydration, or physiologic stress that increases counter-regulatory hormones. See diabetic ketoacidosis for the broader spectrum.
Pregnancy: pregnancy induces metabolic changes that heighten insulin resistance and ketone production, which can contribute to euglycemic presentations. See pregnancy for physiological context.
Prolonged fasting or caloric restriction, especially with concurrent illnesses or dehydration, which can shift metabolism toward ketone use and away from glucose accumulation.
Low-carbohydrate or ketogenic diets: deliberate restriction of carbohydrate intake can lower blood glucose and raise ketone production, potentially precipitating EKA in susceptible individuals.
Alcohol-related ketoacidosis: heavy or binge drinking with poor nutritional intake can produce a similar ketogenic picture, sometimes with relatively normal glucose early on.
SGLT2 inhibitors: these drugs promote glycosuria and can lower glucose levels while permitting ongoing ketogenesis, creating a milieu favorable to euglycemic ketoacidosis. See SGLT2 inhibitors for the pharmacologic class and clinical considerations.
Illness, dehydration, and acute stressors that reduce insulin action or increase glucagon and cortisol levels, even in people without longstanding diabetes.

Cross-referenced topics: SGLT2 inhibitors, low-carbohydrate diet, alcoholic ketoacidosis, and pregnancy.

Clinical presentation and diagnosis

EKA often presents with nonspecific symptoms that overlap with other acute conditions, making awareness and suspicion important, especially when glucose readings are normal.

Symptoms: nausea, vomiting, abdominal pain, thirst, polyuria, weakness, or malaise. Respiratory compensation (Kussmaul breathing) may occur in the setting of metabolic acidosis.
Vital signs and exam: tachypnea, signs of dehydration, or hemodynamic instability depending on fluid status and underlying trigger.
Laboratory pattern: high anion gap metabolic acidosis with elevated serum ketones. Blood glucose is normal or only mildly elevated (often < 250 mg/dL, though thresholds vary). Serum bicarbonate is reduced, and the anion gap is typically widened.
Key laboratory markers: presence of ketones in serum or urine, elevated beta-hydroxybutyrate relative to acetoacetate, and electrolyte abnormalities (notably potassium shifts as insulin and acidosis interact).
Differential diagnosis: alcoholic ketoacidosis, fasting ketoacidosis, lactic acidosis, non-ketotic hyperglycemia, and other causes of high anion gap acidosis. Diagnostic workups emphasize acid–base status, ketone measurement, and clinical context; distinguishing features include glucose level, history of fasting or alcohol use, and medication exposure.
Cross-links: diabetic ketoacidosis for comparative presentation, and metabolic acidosis for context.

Management

Treating EKA requires addressing both the metabolic derangements and the precipitating cause, with care to avoid delays that can worsen acidosis or electrolyte disturbances.

Fluid resuscitation: start with isotonic saline to correct volume depletion and support perfusion; adjust as clinically indicated.
Insulin therapy: administer insulin to suppress ketogenesis and correct acidosis when needed, while closely monitoring glucose. If glucose drops toward hypoglycemia, switch to dextrose-containing fluids to keep treatment ongoing.
Glucose management: when glucose is sufficiently lowered or to maintain safe levels, continue insulin to halt ketone production; provide dextrose to prevent hypoglycemia during ongoing insulin.
Electrolyte management: monitor and correct potassium carefully, as insulin therapy and acidosis correction can cause rapid shifts. K+ replacement is common to maintain a safe serum potassium range.
Ketone and acid–base correction: bicarbonate therapy is reserved for severe acidosis (e.g., pH < 6.9); most cases improve with insulin and fluids.
Treat underlying cause: if an SGLT2 inhibitor is involved, hold the medication and reassess therapy; address infection, dehydration, pregnancy-related factors, fasting state, or dietary contributors as appropriate.
Monitoring: frequent blood glucose checks, serial electrolytes, acid–base status, and clinical reassessment to guide ongoing therapy and to determine when ketosis resolves.
See related discussions on diabetic ketoacidosis and the role of SGLT2 inhibitors in precipitating this condition.

Prognosis and prevention

With prompt recognition and appropriate management, outcomes in EKA are generally favorable. Delays in diagnosis can lead to progression of acidosis and electrolyte disturbances, so awareness among clinicians and patients is important, particularly for those on medications like SGLT2 inhibitors or on very low-carbohydrate regimens.

Prevention strategies focus on risk-factor modification and early recognition: - Careful use of SGLT2 inhibitors in patients with risk factors for ketosis, with patient education about signs of acidosis and when to seek care. - Hydration and electrolyte management during illnesses, fasting, or dehydration, especially for individuals on ketogenic or very-low-carbohydrate diets. - Pregnant individuals with diabetes or metabolic risk factors should be monitored for ketosis and managed per obstetric and endocrinology guidelines. - Clinicians should maintain a high index of suspicion for EKA in the right clinical context, even when glucose readings are not markedly elevated.