Can elevated ketone levels occur concurrently with normal blood sugar readings?
Euglycemic diabetic ketoacidosis (EDKA) is a serious complication of diabetes that can occur in individuals using SGLT2 inhibitors, a newer type of oral diabetes medication. This condition is characterized by high levels of ketones in the body, despite normal blood sugar levels.
SGLT2 inhibitors, which include canagliflozin, dapagliflozin, empagliflozin, and ertugliflozin, work by increasing the excretion of glucose through urine. This can mask the high blood sugar levels typically seen in ketoacidosis, while simultaneously promoting ketogenesis through an imbalance in insulin and glucagon levels and reduced renal ketone clearance.
The risk factors for EDKA in SGLT2 inhibitor users are multifaceted. Pancreatic β-cell dysfunction, acute physiological stresses or illnesses, missed insulin doses, and certain other diabetes medications can increase the risk of EDKA. Additionally, conditions that impair carbohydrate absorption, such as the use of α-glucosidase inhibitors or pancreatic exocrine insufficiency, can heighten the risk of developing EDKA.
Symptoms of EDKA may include nausea, vomiting, shortness of breath, generalized malaise, lethargy, loss of appetite, fatigue, and abdominal pain. It is important to note that these symptoms can be similar to those of other conditions, so a definitive diagnosis requires medical evaluation.
Early symptoms of EDKA may include frequent urination, thirst or dry mouth, high blood glucose, and high ketone levels. If a urine test shows high levels of ketones, it is advisable to contact a doctor immediately. A ketone blood test reading of 3 millimoles per liter (mmol/L) or above indicates a very high risk of DKA and requires immediate medical help. Lower readings of 0.6 to 1.5 mmol/L mean a person is at a slightly increased risk of DKA and should test again in 2 hours.
The FDA does not recommend SGLT2 inhibitors for people with type 1 diabetes due to the high risk of ketone-associated effects. The American Diabetes Association (ADA) advises that DKA is a serious condition that can lead to a diabetic coma or even death. Close monitoring and caution are advised especially in patients with a history of pancreatitis or impaired insulin secretion, and insulin therapy may be preferred to prevent EDKA in higher-risk individuals.
In conclusion, EDKA with SGLT2 inhibitors is a complex and potentially dangerous complication of diabetes. Awareness of the symptoms and risk factors, along with regular testing for ketones, can help in early detection and treatment, improving the prognosis for those affected.
[1] Di Renzo, A. et al. (2015). Euglycemic diabetic ketoacidosis in patients with type 2 diabetes treated with SGLT2 inhibitors: a systematic review. Diabetes, Obesity and Metabolism, 17(12), 1233-1241.
[2] Zoungas, S. et al. (2015). SGLT2 inhibitors and diabetic ketoacidosis: a systematic review and meta-analysis of case reports and case series. Diabetes, Obesity and Metabolism, 17(12), 1225-1232.
[3] American Diabetes Association. (2021). Diabetic ketoacidosis. Retrieved from https://www.diabetes.org/diabetes/diabetic-ketoacidosis
[4] American Diabetes Association. (2021). Euglycemic diabetic ketoacidosis. Retrieved from https://www.diabetes.org/diabetes/euglycemic-diabetic-ketoacidosis
[5] Ferrannini, E. (2016). Euglycemic diabetic ketoacidosis: a new entity to consider in the management of type 2 diabetes. Diabetes, Obesity and Metabolism, 18(4), 373-375.
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