Hypoglycemia and ketone bodies

10 DOH Abu Dhabi (HAAD) lab licensing practice questions on Hypoglycemia and ketone bodies, part of Clinical Chemistry. The first 10 are below; the first 5 with answers and explanations (tap Show answer after you have chosen), the rest in Learn with a free account.

1. Question 1 · Hard

   A 71-year-old man without diabetes, who has a large pleural mass on CT with the biopsy pending, is brought in confused early in the morning. Blood taken during the episode: plasma glucose 2.0 mmol/L (36 mg/dL); insulin below 3 pmol/L (inappropriate if 18 or more); C-peptide below 0.1 nmol/L (inappropriate if 0.2 or more); proinsulin below 5 pmol/L; beta-hydroxybutyrate 0.2 mmol/L (usually above 2.7 mmol/L in fasting hypoglycemia without insulin action); cortisol 610 nmol/L (22 µg/dL); sulfonylurea screen negative. Glucose rose by 2.4 mmol/L (43 mg/dL) within 30 minutes of intravenous glucagon (a rise of 1.4 mmol/L or more is significant). Liver and kidney function are normal. The most likely mechanism of his hypoglycemia is:

   1. ACortisol deficiency from adrenal failure
   2. BCovert ingestion of a sulfonylurea drug
   3. CTumour secretion of incompletely processed IGF-2
   4. DAutonomous insulin secretion by a pancreatic insulinoma

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   Answer: C · Tumour secretion of incompletely processed IGF-2

   Insulin, C-peptide and proinsulin are all suppressed, so neither beta-cell insulin secretion nor a sulfonylurea is driving the hypoglycemia. Yet beta-hydroxybutyrate is suppressed and glucagon still releases glucose, which shows that something with insulin-like action is blocking ketogenesis and keeping glycogen in the liver. Large mesenchymal tumours, such as solitary fibrous tumours of the pleura, can secrete incompletely processed ('big') IGF-2, which activates insulin receptors and suppresses growth hormone and IGF-1. A cortisol of 610 nmol/L during hypoglycemia is an adequate stress response, and adrenal failure would allow ketosis. Measuring IGF-2 and IGF-1 on the sample taken during the episode, with a raised IGF-2 to IGF-1 ratio, supports the diagnosis.

   • A: His cortisol response is adequate, and cortisol deficiency would not suppress ketones.
   • B: Sulfonylureas raise insulin and C-peptide, and the screen is negative.
   • D: An insulinoma gives inappropriately raised insulin, C-peptide and proinsulin.

2. Question 2 · Hard

   A 48-year-old man who drinks heavily presents after 3 days of vomiting and not eating. Results: glucose 4.8 mmol/L (86 mg/dL), pH 7.21, bicarbonate 10 mmol/L, lactate 2.1 mmol/L, no osmolal gap. The urine ketone strip is only trace positive, yet plasma beta-hydroxybutyrate is 7.8 mmol/L (reference below 0.6). Why does the strip underestimate the ketosis?

   1. AThe pad reacts mainly with acetone, which evaporates
   2. BEthanol in the urine blocks the nitroprusside reaction
   3. CLactate in the urine competes for the test pad
   4. DHigh NADH from ethanol shifts acetoacetate to beta-hydroxybutyrate

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   Answer: D · High NADH from ethanol shifts acetoacetate to beta-hydroxybutyrate

   Oxidation of ethanol by alcohol and aldehyde dehydrogenases produces NADH, and the high NADH:NAD+ ratio drives beta-hydroxybutyrate dehydrogenase toward beta-hydroxybutyrate. In alcoholic ketoacidosis, beta-hydroxybutyrate can therefore be many times higher than acetoacetate. The nitroprusside pad reacts mainly with acetoacetate, weakly with acetone and not at all with beta-hydroxybutyrate, so it can badly underestimate the ketosis. A blood beta-hydroxybutyrate test should be used whenever alcoholic ketoacidosis is suspected.

   • A: The pad reacts mainly with acetoacetate; acetone is a minor ketone.
   • B: Ethanol does not inhibit the nitroprusside reaction.
   • C: Lactate does not react with or block the nitroprusside pad.

3. Question 3 · Easy

   In a person with diabetes, the ADA classes a glucose below which value as level 2 (clinically significant) hypoglycemia?

   1. A3.0 mmol/L (54 mg/dL)
   2. B4.4 mmol/L (80 mg/dL)
   3. C2.2 mmol/L (40 mg/dL)
   4. D3.9 mmol/L (70 mg/dL)

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   Answer: A · 3.0 mmol/L (54 mg/dL)

   The ADA grades hypoglycemia in diabetes by severity. Level 1 is a glucose below 3.9 mmol/L (70 mg/dL) but at or above 3.0 mmol/L; level 2 is below 3.0 mmol/L (54 mg/dL), where neuroglycopenic symptoms begin and urgent treatment is needed. Level 3 is a severe event with altered mental or physical state that needs another person's help, whatever the glucose. A low meter reading should not delay treatment, but a laboratory plasma glucose confirms it when the meter may be unreliable.

   • B: 4.4 mmol/L (80 mg/dL) is within the normal fasting range.
   • C: 2.2 mmol/L (40 mg/dL) is below the level 2 cut-off, so it would miss many significant episodes.
   • D: 3.9 mmol/L (70 mg/dL) is the alert value that defines level 1.

4. Question 4 · Medium

   During a supervised fast, a 4-year-old's hypoglycemia comes with low plasma free fatty acids and low beta-hydroxybutyrate. This pattern points most to:

   1. AKetotic hypoglycemia of childhood
   2. BHyperinsulinism
   3. CA fatty acid oxidation defect
   4. DCortisol deficiency

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   Answer: B · Hyperinsulinism

   Insulin blocks lipolysis in fat tissue and ketone production in the liver, so hypoglycemia caused by too much insulin comes with low free fatty acids and low ketones. In fatty acid oxidation defects, lipolysis works and free fatty acids are high, but the liver cannot turn them into ketones. In ketotic hypoglycemia and in cortisol or growth hormone deficiency, both free fatty acids and ketones rise as expected. A critical sample taken at the moment of hypoglycemia (glucose, insulin, C-peptide, beta-hydroxybutyrate, free fatty acids, cortisol, growth hormone) is what makes this distinction possible.

   • A: Ketotic hypoglycemia shows high free fatty acids and high ketones.
   • C: Fatty acid oxidation defects show high free fatty acids with inappropriately low ketones.
   • D: Cortisol deficiency in a child usually gives hypoglycemia with appropriate ketosis.

5. Question 5 · Medium

   Four adults not known to have diabetes have these venous results. Using DKA criteria of glucose 11.1 mmol/L (200 mg/dL) or more, beta-hydroxybutyrate (BHB) 3.0 mmol/L or more, and pH below 7.30 or bicarbonate below 18 mmol/L, which set meets the definition of DKA?

   1. AGlucose 14 mmol/L, BHB 3.4 mmol/L, pH 7.35, HCO3- 21 mmol/L
   2. BGlucose 16 mmol/L, BHB 4.2 mmol/L, pH 7.22, HCO3- 12 mmol/L
   3. CGlucose 48 mmol/L, BHB 0.9 mmol/L, pH 7.34, HCO3- 20 mmol/L
   4. DGlucose 4.6 mmol/L, BHB 2.1 mmol/L, pH 7.36, HCO3- 20 mmol/L

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   Answer: B · Glucose 16 mmol/L, BHB 4.2 mmol/L, pH 7.22, HCO3- 12 mmol/L

   DKA needs all three parts: hyperglycemia (or known diabetes), significant ketonemia and a metabolic acidosis. Only the first set has a glucose above 11.1 mmol/L, a BHB above 3.0 mmol/L and both a low pH and a low bicarbonate. These cut-offs follow the 2024 international consensus on hyperglycemic crises, which prefers blood BHB to urine ketones. A very high glucose with little ketosis points instead to hyperosmolar hyperglycemic state.

   • A: Ketosis with hyperglycemia but normal pH and bicarbonate is ketosis without acidosis.
   • C: Very high glucose with little ketosis and no real acidosis fits hyperosmolar hyperglycemic state.
   • D: Mild ketosis with normal glucose and pH fits starvation ketosis.

6. Question 6 · Hard

   A 45-year-old woman without diabetes has confusion before breakfast. In a supervised fast she has symptoms at 14 hours, when blood shows: glucose 2.3 mmol/L (41 mg/dL), insulin 54 pmol/L, C-peptide 0.5 nmol/L (1.5 ng/mL), proinsulin 22 pmol/L, beta-hydroxybutyrate 0.3 mmol/L. Sulfonylurea screen and insulin antibodies are negative. At this glucose, insulin above 18 pmol/L, C-peptide above 0.2 nmol/L and proinsulin above 5 pmol/L are inappropriate. What is the most likely cause?

   1. AInsulin autoimmune syndrome
   2. BInjection of exogenous insulin
   3. CInsulinoma
   4. DHidden sulfonylurea use

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7. Question 7 · Hard

   A 6-month-old girl in a UAE hospital started weaning foods with fruit purée and juice two weeks ago. Since then she vomits, sweats and becomes drowsy within an hour of these feeds, and her liver is enlarged. During an episode: glucose 2.0 mmol/L (36 mg/dL), phosphate low, ALT raised. Urine is positive for reducing substances by copper reduction but negative for glucose on the dipstick. Which enzyme is most likely deficient?

   1. AFructokinase
   2. BGalactose-1-phosphate uridyltransferase
   3. CGlucose-6-phosphatase
   4. DAldolase B

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8. Question 8 · Medium

   During treatment of diabetic ketoacidosis, which test best tracks the resolution of ketosis?

   1. ASerum acetone
   2. BBlood beta-hydroxybutyrate
   3. CUrine nitroprusside ketones
   4. DPlasma glucose

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9. Question 9 · Hard

   A 14-month-old becomes very drowsy after a day of vomiting with a viral illness; the liver is slightly enlarged. Results: glucose 1.9 mmol/L (34 mg/dL), beta-hydroxybutyrate 0.2 mmol/L (inappropriately low for the glucose), free fatty acids raised, insulin undetectable, ammonia mildly raised. Plasma acylcarnitines show raised octanoylcarnitine (C8). The most likely diagnosis is:

   1. ACongenital hyperinsulinism
   2. BKetotic hypoglycemia
   3. CGlycogen storage disease type I
   4. DMCAD deficiency

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10. Question 10 · Easy

    Ketone bodies are made from acetyl-CoA mainly in the mitochondria of:

    1. AHepatocytes
    2. BSkeletal muscle fibers
    3. CAdipocytes
    4. DRenal tubular cells

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