MKSAP quiz: Poor glycemic control despite intensification
This month's quiz asks readers to evaluate a 47-year-old woman who was diagnosed with type 2 diabetes mellitus 14 months ago. Despite progressive intensification of diabetes therapy, her plasma glucose levels remain poorly controlled.
A 47-year-old woman is evaluated for hyperglycemia. She was diagnosed with type 2 diabetes mellitus 14 months ago after presenting with fatigue, headaches, polyuria, and polydipsia. Despite progressively intensifying diabetes therapy, her plasma glucose levels remain poorly controlled. She adheres to her medication regimen and a diabetic diet. She has intentionally lost 4.5 kg (10 lb) since her diagnosis. In addition to type 2 diabetes, medical history is significant for hypothyroidism. Medications are levothyroxine, metformin, empagliflozin, and semaglutide.
On physical examination, vital signs are normal. BMI is 27. The remainder of the physical examination is normal.
Hemoglobin A1c is 8.9%. Thyroid function test results and electrolyte, creatinine, and albumin levels are normal. Glutamic acid decarboxylase autoantibody results are positive. Point-of-care capillary glucose levels show a rapid rise in glucose after meals.
Which of the following is the most likely diagnosis?
A. Cushing syndrome
B. Dietary nonadherence
C. Glucagonoma
D. Latent autoimmune diabetes in adults
MKSAP Answer and Critique
The correct answer is D. Latent autoimmune diabetes in adults. This item is available to MKSAP subscribers as item 1 in Extension Set 4 of the Endocrinology and Metabolism section. More information about MKSAP is online.
The most likely diagnosis is latent autoimmune diabetes mellitus in adults (LADA) (Option D). Type 1 diabetes presents at an average age of 13 years, but about one third of new patients are older than age 30 years. When type 1 diabetes presents in adults, it is called LADA or adult-onset type 1 diabetes. It is characterized by autoantibody development leading to β-cell destruction and, ultimately, to insulin deficiency. Persons with LADA are often not initially dependent on insulin; the progression to insulin therapy for LADA is usually slower than that seen in the typical teenage-onset type 1 diabetes but is faster than that of type 2 diabetes. Frequently, patients with LADA are initially misclassified as having type 2 diabetes, especially because autoantibody testing of adults with newly diagnosed type 2 diabetes is not routinely recommended. Therefore, a high index of suspicion is required to make the diagnosis. Clues to presentation include more rapid progression to multiple medication requirements, a progressive rise in glucose values after eating, the presence of other autoimmune disorders, and a lack of obesity (although LADA is also found in persons with obesity). Glutamic acid decarboxylase (GAD) autoantibodies can assist in differentiating between type 2 diabetes and LADA. Despite a relatively short duration of diabetes, this patient has required multiple medications and still has poor glycemic control. She also has a fairly rapid rise in glucose following meals, which is a clue for insulin deficiency. The presence of another autoimmune disorder (hypothyroidism) as well as GAD autoantibody positivity also suggest LADA.
Patients with Cushing syndrome may present with weight gain, diabetes, hypertension, proximal muscle weakness, easy bruising, abdominal striae, a dorsocervical fat pad, supraclavicular fat pads, and ecchymoses. Apart from diabetes, this patient has no findings to suggest Cushing syndrome (Option A).
Dietary nonadherence and medication nonadherence should always be considered in patients with diabetes who have poor glycemic control (Option B). However, dietary nonadherence causing a hemoglobin A1c of 8.9% is usually accompanied by weight gain.
Glucagonoma is a rare neuroendocrine tumor that presents with necrolytic migratory erythema (present in most patients), weight loss, diarrhea, hypoalbuminemia, and hyperglycemia (Option C). Apart from hyperglycemia, this patient does not have other findings suggestive of glucagonoma.
Key Point
- Latent autoimmune diabetes in adults is characterized by autoantibody development leading to β-cell destruction and, ultimately, to insulin deficiency.