If you’re preparing for the United States Medical Licensing Examination® (USMLE®) Step 1 exam, you might want to know which questions are most often missed by test-prep takers. Check out this example from Kaplan Medical, and read an expert explanation of the answer. Also check out all posts in this series.
This month’s stumper
A 7-year-old girl is brought to the physician by her parents because of increased thirst and bed-wetting. She has lost 2.3 kg (5 pounds) in the past month despite an increased appetite. Her temperature is 37.0°C (98.6°F), pulse is 74 a minute, respirations are 14 a minute, and blood pressure is 116/70 mm Hg. Physical examination is unremarkable. A urinary dipstick test shows that glucose is present in the urine.
Which of the following laboratory findings in serum is most likely?
A. Decreased concentration of beta-hydroxybutyrate.
B. Decreased concentration of hemoglobin A1c.
C. Decreased osmolality.
D. Increased antibodies against glutamic acid decarboxylase.
E. Increased concentration of C-peptide.
The correct answer is D.
Kaplan Medical explains why
A child with glucosuria, polyuria, polydipsia, and weight loss despite increased appetite is likely to have type 1 diabetes mellitus. This form of diabetes has an important autoimmune component to its etiology; as many as 85 percent of patients have islet cell autoantibodies in their blood in the first few weeks after onset of the disease. Most of these antibodies are directed against glutamic acid decarboxylase (GAD65), an enzyme that is present in beta cells. GAD65 is the largest component tested in the islet cell antibody test. A positive test is useful to distinguish between type 1 and type 2 diabetes.
Even if you are not familiar with glutamic acid decarboxylase with respect to diabetes, the other options can be eliminated.
Why the other answers are wrong
Choice A: The insulin deficiency associated with autoimmune destruction of the beta cells leads to increased breakdown of triglycerides with a consequently increased rate of formation of ketone bodies. The primary ketone body produced is beta-hydroxybutyrate, the blood level of which is increased (not decreased) in type 1 diabetes. If untreated, type 1 diabetes can rapidly progress to ketoacidosis and coma.
Choice B: Insulin deficiency leads to decreased glucose uptake and hyperglycemia. The increase in blood glucose results in increased glycosylation of hemoglobin in red blood cells. Hence, the hemoglobin A1c (HBA1c) concentration will be increased (not decreased), reflecting long-standing hyperglycemia. Clinically, HbA1c reflects average glycemic control in the past three to six months since red cells have a life span of up to 120 days. HbA1C levels less than 6-7 percent is preferred to minimize microvascular damage.
Choice C: Another consequence of the increased blood glucose is increased serum osmolality (not decreased). If the osmolality exceeds 330 mOsmol/kg H2O, consciousness begins to be impaired.
Choice E: beta-cell destruction in type 1 diabetes leads to decreased secretion of insulin. Since insulin and C-peptide are released on a 1:1 ratio by the beta cells, the secretion of C-peptide is also decreased (not increased. Insulin is first synthesized as preproinsulin, with an initial leader sequence of hydrophobic amino acids that allows the developing protein to be extruded from the ribosomes into the rough endoplasmic reticulum. The "pre" segment is then cleaved off, leaving proinsulin. Proinsulin is packaged into secretory granules within the Golgi, and as the granules bud off, enzymes cleave the precursor into insulin and C-peptide. In contrast, C-peptide would not be present in synthetic insulin.
Tips to remember
- Type 1 diabetes mellitus usually presents in children with glucosuria, polyuria, polydipsia, and weight loss.
- The condition is often related to autoimmune destruction of the pancreatic islet beta cells and, in many patients, an autoantibody is directed against glutamic acid decarboxylase.
- Other features of type 1 diabetes mellitus include insulin deficiency, hyperglycemia, increased hemoglobin A1c, increased serum osmolality, and decreased C-peptide.
For more prep questions on USMLE Steps 1, 2 and 3, view
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