MKSAP quiz: Fasting hypoglycemia
This month's quiz asks readers to evaluate a 42-year-old man recently diagnosed with diabetes two weeks after a hospitalization for diabetic ketoacidosis.
A 42-year-old man is evaluated 2 weeks after a hospitalization for diabetic ketoacidosis and newly diagnosed diabetes mellitus. His hemoglobin A1c level at the time was 12%. A glutamic acid decarboxylase antibody test result was negative. He was discharged with insulin glargine. He reports frequent fasting hypoglycemia early in the morning, typically with a glucose level of 55 to 65 mg/dL (3.1-3.6 mmol/L). His mother was diagnosed with type 2 diabetes at age 50 years.
Physical examination findings, including vital signs, are normal.
Which of the following is the most appropriate diagnostic test to perform next?
A. Hemoglobin A1c
B. Morning serum cortisol
C. Plasma C-peptide
D. Random plasma glucose
MKSAP Answer and Critique
The correct answer is C. Plasma C-peptide. This content is available to ACP MKSAP subscribers in the Endocrinology & Metabolism section. More information about ACP MKSAP is available online.
Plasma C-peptide measurement (Option C) is the most appropriate diagnostic test to perform next. This patient likely has ketosis-prone diabetes mellitus (KPD) and should be evaluated for preserved β-cell function to determine the best treatment regimen. The term KPD incorporates several glycemic syndromes previously known as ketosis-prone type 2 diabetes, type 1B diabetes, or atypical diabetes. KPD presents with episodic diabetic ketoacidosis (DKA) resulting from insulin deficiency but has varying periods of insulin dependence and independence. Initially, insulin therapy is required until DKA has resolved and the β cells are no longer impaired by glucose toxicity. Afterward, β cells may be able to produce enough insulin to suppress lipolysis. Patients with preserved β-cell function are often able to discontinue insulin, but treatment with metformin or injectable agents is often required. Plasma C-peptide is a marker for endogenous insulin production and residual β-cell function. A detectable C-peptide level would suggest that the patient's pancreas is still producing insulin, making him a candidate for noninsulin medications, such as metformin. Notably, significant hyperglycemia can induce glucose toxicity and impair the release of insulin and C-peptide; therefore, C-peptide levels are most useful when the glucose level remains below 225 mg/dL (12.5 mmol/L).
Hemoglobin A1c (Option A) is a valuable tool for assessing long-term glycemic control, but it does not provide information about the underlying mechanism of diabetes. In KPD, hemoglobin A1c measurement would not reveal the presence of residual insulin production and would not guide medication selection (i.e., insulin versus noninsulin medications). Additionally, this patient's hemoglobin A1c was measured very recently, and repeat measurement at this time is unlikely to be helpful.
Patients with type 1 diabetes have an increased risk for other autoimmune disorders, including autoimmune primary adrenal insufficiency. In a patient with type 1 diabetes and frequent hypoglycemia, morning serum cortisol measurement (Option B) might be an appropriate option. However, this patient's glutamic acid decarboxylase antibody test result was negative, pointing away from a diagnosis of type 1 diabetes. Furthermore, he does not have other symptoms suggestive of adrenal insufficiency. Measuring his morning serum cortisol level would not provide specific insights into the management of his KPD.
Random plasma glucose measurement (Option D) can help assess immediate glycemic control but does not provide diagnostic information about the type of diabetes or the potential for insulin production.
Key Points
- Ketosis-prone diabetes mellitus presents with episodic diabetic ketoacidosis resulting from insulin deficiency but has varying periods of insulin dependence and independence.
- Plasma C-peptide is a marker for endogenous insulin production and residual β-cell function and can be used to determine whether patients with ketosis-prone diabetes require insulin therapy.