Diabetic Ketoacidosis (DKA) is a severe, life-threatening complication of diabetes characterized by dangerously high blood sugar, a buildup of acidic substances called ketones, and metabolic acidosis. DKA arises when the body lacks sufficient insulin and breaks down fat rapidly for fuel, releasing large quantities of ketones into the bloodstream. Normoglycemic Diabetic Ketoacidosis (NG-DKA) is a unique variation where this metabolic crisis occurs despite the patient’s blood glucose levels being near normal. This deceptive presentation can lead to delayed diagnosis and treatment, making awareness of this condition important for individuals with diabetes and healthcare providers.
Defining the Paradox of Low Glucose
The standard definition of DKA requires hyperglycemia, meaning blood glucose levels must be above 250 mg/dL. NG-DKA is defined by the presence of severe metabolic acidosis and ketosis, but with blood glucose concentration below that 250 mg/dL threshold, often falling into the normal range. The three core components required for an NG-DKA diagnosis are metabolic acidosis (pH typically less than 7.3 or serum bicarbonate less than 18 mEq/L) and evidence of significant ketosis. Ketosis is generally measured by elevated blood levels of beta-hydroxybutyrate, usually greater than 3 mmol/L.
The paradox exists because DKA normally requires a profound lack of insulin and high glucose levels to trigger the massive fat breakdown that produces ketones. High blood sugar prevents the body from using glucose for energy, forcing a starvation state that activates ketogenesis. In NG-DKA, the body is in a state of relative starvation, but blood glucose remains low due to various mechanisms. This contrasts sharply with the volume depletion and osmotic diuresis seen in standard DKA. This unusual combination complicates the clinical picture, as the sign most people associate with a diabetic crisis—high blood sugar—is absent.
Triggers and Underlying Conditions
The most common cause for the rise in NG-DKA cases is the use of sodium-glucose co-transporter-2 inhibitors (SGLT2 inhibitors), including drugs like canagliflozin, dapagliflozin, and empagliflozin. These agents lower blood sugar by blocking glucose reabsorption in the kidneys, causing it to be excreted in the urine. This action results in a state of “pseudo-starvation” at the cellular level. The body loses glucose and signals the liver to produce more ketones from fat stores, even though blood sugar remains low.
The physiological process involves decreased insulin requirements due to lower glucose levels, coupled with elevated glucagon, a hormone that promotes ketogenesis. SGLT2 inhibitors create a condition where the body is starved of glucose, promoting the breakdown of fatty acids into ketones, which drive the acidosis. This mechanism can occur in people with both Type 1 and Type 2 diabetes taking these medications.
Other circumstances that induce carbohydrate deficiency or stress can also lead to NG-DKA in individuals with diabetes. These include prolonged fasting or severe caloric restriction, such as following a very low-carbohydrate or ketogenic diet. Chronic, heavy alcohol consumption is a common trigger because it depletes glycogen stores and impairs the liver’s ability to use glucose, forcing a shift to fat metabolism. Additionally, conditions causing physiological stress, such as severe infection, acute illness, or pregnancy, increase stress hormones like cortisol and catecholamines, which promote ketone formation.
Recognizing the Subtle Symptoms
The physical signs of NG-DKA are largely the same as those of classic DKA, but without the obvious warning signs of severe hyperglycemia. Patients frequently experience generalized malaise, profound fatigue, and gastrointestinal complaints like nausea, vomiting, and abdominal pain. The buildup of acid in the blood often triggers Kussmaul respirations—deep, labored, and rapid breaths—as the body attempts to expel carbon dioxide to correct the acidosis.
The subtlety of the condition arises because patients do not experience the excessive thirst (polydipsia) or frequent urination (polyuria) that typically drive classic DKA patients to seek medical attention. These classic symptoms result from the high osmotic load caused by massive glucose excretion in the urine, a feature absent when blood sugar is near normal. Since glucose levels are not extremely high, the severe dehydration characterizing classic DKA is also less pronounced or absent, masking the severity of the underlying metabolic crisis. This lack of typical red flags means the diagnosis is often missed or delayed, allowing the metabolic acidosis to become dangerously severe before treatment begins.
Diagnostic Requirements
Diagnosing NG-DKA requires a high degree of clinical suspicion, as a standard finger-stick glucose reading will not indicate a crisis. The definitive diagnosis relies on specific laboratory tests confirming the presence of both metabolic acidosis and ketosis. An arterial or venous blood gas analysis is necessary to measure the blood’s pH level and confirm acidosis, a defining feature of the condition. This test also measures bicarbonate levels, which are typically low (below 18 mEq/L) due to the body’s consumption of bicarbonate to buffer the excess acid.
The measurement of ketones is mandatory, and the preferred method is a blood test for beta-hydroxybutyrate, the most abundant ketone body during severe ketoacidosis. A level greater than 3 mmol/L is consistent with DKA. Relying solely on urine ketone strips can be misleading because they primarily detect acetoacetate, which may not accurately reflect the total ketone burden, especially early in the crisis. Therefore, laboratory confirmation of low pH, low bicarbonate, and high beta-hydroxybutyrate is required for a definitive diagnosis, regardless of the near-normal blood glucose reading.
Specialized Treatment Strategy
The management of NG-DKA shares the foundational principles of standard DKA treatment: intravenous fluid replacement, insulin administration, and electrolyte correction. However, the normoglycemic state necessitates a modification to the fluid and insulin protocol to ensure patient safety. Aggressive intravenous fluid administration, typically with saline solutions, restores volume lost due to the illness and helps dilute the circulating acid.
Insulin therapy is the primary intervention for halting ketogenesis, as it suppresses the breakdown of fat and subsequent ketone production in the liver. A continuous intravenous insulin infusion is started to resolve the acidosis. The specialized aspect of NG-DKA treatment is the mandatory and early addition of intravenous dextrose (sugar) to the fluid regimen. Dextrose is administered to maintain the patient’s blood glucose within a safe, non-hypoglycemic range. This is usually done by initiating a dextrose-containing solution once glucose drops below 250 mg/dL, or immediately upon diagnosis. The concurrent administration of insulin and dextrose ensures that the life-threatening ketosis is stopped without causing the equally dangerous complication of low blood sugar, a constant risk in a normoglycemic patient receiving insulin.