A 20-year-old woman is evaluated during a follow-up visit for diabetes mellitus. She was hospitalized for diabetic ketoacidosis (DKA) 6 weeks ago but had been previously well. No inciting cause of the DKA was determined. She was discharged on basal-bolus insulin. Since discharge, she has implemented dietary and lifestyle interventions and has lost 4.0 kg (8.8 lb), and her insulin dose has been steadily reduced. Average fasting blood glucose is now 98 mg/dL (5.4 mmol/L) and remaining daytime blood glucose values have been less than 115 mg/dL (6.4 mmol/L). Her family history is significant for type 2 diabetes in her mother, maternal aunts, and grandmother.
On physical examination, vital signs are normal. BMI is 30. Central adiposity and acanthosis nigricans are noted. The remainder of the physical examination is normal.
Laboratory studies show a hemoglobin A1c of 5.9%, fasting C-peptide of 3.2 ng/mL (1.1 nmol/L) (normal range, 0.8-3.1 ng/mL [0.3-1.0 nmol/L]), fasting glucose of 107 mg/dL (5.9 mmol/L), and testing for glutamic acid decarboxylase antibodies is negative.
At this visit, the decision was made to discontinue the insulin.
Which of the following is the most appropriate treatment?
D. No additional treatment
MKSAP Answer and Critique
The correct answer is C. Metformin. This item is available to MKSAP 19 subscribers as item 47 in the Endocrinology and Metabolism section. More information about MKSAP is online.
This patient has ketosis-prone diabetes mellitus and should be transitioned from insulin to metformin (Option C). The term “ketosis-prone diabetes” incorporates several glycemic syndromes and is also known as ketosis-prone type 2 diabetes mellitus, “Flatbush diabetes,” idiopathic type 1 diabetes, type 1B diabetes, and atypical diabetes. These syndromes present with episodic diabetic ketoacidosis (DKA) resulting from insulin deficiency but have variable periods of insulin dependence and independence. For individuals with ketosis-prone diabetes, insulin therapy for DKA is required until DKA has resolved and the β cells are no longer impaired by glucose toxicity and can produce sufficient amounts of insulin to suppress lipolysis. Assessment of β-cell reserve with a fasting C-peptide level should be performed weeks to months after the episode of DKA; β-cell function is indicated by a C-peptide concentration of at least 1 ng/mL (0.33 nmol/L). Patients should also be evaluated for type 1 diabetes with fasting C-peptide measurement or a glutamic acid decarboxylase antibodies test. This patient has the clinical characteristics of type 2 diabetes (insulin production, obesity, strong family history), intact β-cell function, negative antibodies, and is on relatively low doses of insulin for her body weight. The insulin may be discontinued, and she can start metformin.
No clinical evidence supports that sodium-glucose cotransporter 2 inhibitors such as empagliflozin (Option A) are effective treatment in ketosis-prone diabetes. Moreover, this class of medications carries a higher risk for euglycemic DKA and thus would not be the best option in a patient with ketosis-prone diabetes.
Glimepiride (Option B) is a sulfonylurea and is associated with weight gain. It is not the best option for this patient with obesity, who would benefit more from an insulin sensitizer like metformin.
The American Diabetes Association recommends that all patients with type 2 diabetes should be treated with metformin as an initial agent, along with aggressive lifestyle modifications. Given the previous episode of DKA, lifestyle changes alone with no additional treatment (Option D) are insufficient to manage diabetes in this patient.
- Ketosis-prone diabetes mellitus presents with episodic diabetic ketoacidosis resulting from insulin deficiency but has variable periods of insulin dependence and independence.
- For individuals with ketosis-prone diabetes mellitus, insulin therapy for the treatment of diabetic ketoacidosis (DKA) is required until DKA has resolved and the β cells are no longer impaired by glucose toxicity.