Euglycemic diabetic ketoacidosis (DKA) is a medical concern, especially for individuals taking SGLT2 inhibitors. DKA is a serious complication of diabetes, but euglycemic DKA is a form where blood sugar levels remain normal, making its identification more challenging. SGLT2 inhibitors, while beneficial, have been linked to this serious condition.
Understanding Euglycemic Diabetic Ketoacidosis
Diabetic Ketoacidosis (DKA) is a serious complication resulting from insufficient insulin, causing the body to break down fat for energy. This process produces acidic ketones, dangerously increasing blood acidity. In typical DKA, blood glucose levels are elevated, often exceeding 250 mg/dL.
Euglycemic DKA (EDKA) is a distinct form of DKA where blood glucose levels are normal, typically below 250 mg/dL, despite high ketone levels and metabolic acidosis. This normal blood sugar makes EDKA difficult to diagnose, as the usual high glucose indicator is absent. The underlying metabolic state involves cellular glucose starvation or depletion of glycogen stores, prompting fat breakdown for fuel even with some glucose present.
SGLT2 Inhibitors A Closer Look
SGLT2 inhibitors are a class of prescription medications, including canagliflozin, dapagliflozin, empagliflozin, and ertugliflozin. They are primarily used to manage type 2 diabetes by improving blood sugar control. Beyond diabetes, some SGLT2 inhibitors are also approved for use in heart failure and chronic kidney disease, highlighting their broader benefits.
SGLT2 inhibitors target a specific protein in the kidneys. They block the sodium-glucose co-transporter 2 (SGLT2) protein, which is responsible for reabsorbing about 90% of the filtered glucose back into the bloodstream from the kidney tubules. By inhibiting this protein, SGLT2 inhibitors cause more glucose to be excreted in the urine, a process called glucosuria, lowering blood sugar levels. This mechanism works independently of the pancreas’s insulin production or the body’s insulin sensitivity.
The Connection SGLT2 Inhibitors and Euglycemic DKA
SGLT2 inhibitors contribute to EDKA by altering metabolic signals. By increasing glucose excretion in the urine, these medications can lead the body to perceive a state of glucose deficit or starvation, even when blood sugar levels are normal. This perceived starvation can trigger the release of counter-regulatory hormones, such as glucagon, while simultaneously reducing insulin secretion.
The resulting imbalance, characterized by a higher glucagon-to-insulin ratio, promotes the breakdown of fats (lipolysis) and the production of ketones in the liver (ketogenesis). This increased ketone production, coupled with the continued urinary glucose excretion that keeps blood sugar levels normal, creates the conditions for EDKA. The kidney’s reabsorption of ketones may also be increased when SGLT2 inhibitors are used, further contributing to ketone accumulation.
Several factors can increase the risk of developing EDKA in individuals taking SGLT2 inhibitors. These include prolonged fasting, acute illness, surgical procedures, reduced food intake, or adherence to very low-carbohydrate or ketogenic diets. Alcohol consumption, dehydration, and any condition leading to insulin deficiency or reduced insulin dosages can also heighten this risk. While EDKA is a rare side effect, it is a serious concern with SGLT2 inhibitor use.
Recognizing and Managing Euglycemic DKA
Recognizing EDKA is particularly challenging because it presents without the typical high blood sugar levels seen in classic DKA. Individuals on SGLT2 inhibitors should be aware of symptoms similar to traditional DKA but occurring with normal glucose, such as nausea, vomiting, abdominal pain, fatigue, excessive thirst, frequent urination, a fruity odor on the breath, malaise, weakness, dyspnea, drowsiness, or altered mental status.
If these symptoms appear, especially in someone taking an SGLT2 inhibitor, immediate medical attention is advised. Diagnosis of EDKA involves blood tests to check for elevated ketone levels and low blood pH (indicating acidosis), alongside blood glucose levels below 250 mg/dL. A blood bicarbonate level below 18 mEq/L is also characteristic.
Treatment for EDKA involves several principles. Fluid and electrolyte replacement are initiated to correct dehydration and imbalances. Insulin administration is an essential part of treatment, even with normal blood glucose levels, to stop ketone production and reverse acidosis. Dextrose-containing fluids may be given with insulin to prevent hypoglycemia while addressing the acidosis. Addressing any underlying cause is also important.
Reducing the Risk of Euglycemic DKA
Reducing the risk of SGLT2 inhibitor-induced EDKA involves proactive measures. Patient education is important, emphasizing awareness of EDKA symptoms and the importance of seeking prompt medical help. Patients should be counseled on the signs of ketoacidosis despite normal blood glucose concentrations.
Medication management during periods of increased risk is also important. Patients taking SGLT2 inhibitors are advised to temporarily stop their medication before planned surgeries or during acute illnesses, such as gastroenteritis, or if they are fasting. These are often referred to as “sick day rules.” Patients should always consult their doctor before making any changes to their medication regimen, as the SGLT2 inhibitor should not be restarted until they are well and eating and drinking normally.
Regular monitoring for ketones, during periods of increased risk, can help with early detection. This can involve using urine ketone strips or a blood ketone meter as advised by a healthcare professional. Dietary considerations are also relevant; very low-carbohydrate or ketogenic diets may increase the risk and should be discussed with a doctor. Open communication with healthcare providers about all medications, lifestyle changes, and any concerning symptoms is important.