Glucose Intolerance with TPN in the Absence of Sepsis
(d) Chromium deficiency is the correct answer—glucose intolerance developing during total parenteral nutrition without sepsis is a classic manifestation of chromium deficiency.
Clinical Evidence for Chromium Deficiency
Chromium deficiency has been definitively documented in patients receiving long-term TPN without chromium supplementation, presenting with glucose intolerance, weight loss, elevated plasma free fatty acids, and neuropathy—all reversed by chromium supplementation 1.
Classic Presentation
The hallmark clinical features of chromium deficiency in TPN patients include:
- Glucose intolerance with insulin resistance despite adequate or elevated insulin levels 2, 3
- Hyperglycemia requiring increasing insulin doses that fails to adequately control blood glucose 4
- Inability to utilize glucose for energy (low respiratory quotient despite high glucose infusion) 2
- Peripheral neuropathy (though not always present) 2, 5
- Weight loss despite adequate caloric provision 2
Pathophysiology
Chromium potentiates insulin action and is essential for normal glucose metabolism 6, 3. During acute illness (burns, trauma, infection), chromium levels drop and may contribute to altered glucose metabolism, but the question specifically excludes sepsis 1. In the absence of infection or metabolic stress, unexplained glucose intolerance in a TPN patient should raise immediate suspicion for chromium deficiency 4.
Why Not the Other Options?
Copper Deficiency
Copper deficiency typically presents with hematologic abnormalities (anemia, neutropenia) and neurologic manifestations (myelopathy, peripheral neuropathy), not primarily glucose intolerance. While copper is affected by prolonged renal replacement therapy, it is not classically associated with glucose metabolism 1.
Zinc Deficiency
Zinc deficiency manifests with dermatitis, alopecia, diarrhea, and impaired wound healing—not glucose intolerance as a primary feature.
Magnesium Deficiency
Magnesium deficiency causes neuromuscular irritability, cardiac arrhythmias, and tetany. While magnesium plays a role in insulin secretion, it is not the classic trace element deficiency associated with glucose intolerance in TPN patients.
Clinical Management
When glucose intolerance develops in TPN patients without sepsis, chromium supplementation (200-250 mcg/day for 2 weeks) should be initiated 2, 4, 5. Response is typically dramatic:
- Glucose tolerance normalizes within 2 weeks 2, 4
- Insulin requirements decrease or can be discontinued 2, 4
- Neuropathy (if present) improves within days to weeks 2, 5
Important Caveats
Serum chromium levels may be unreliable—they can be elevated despite tissue deficiency, and low levels don't always correlate with total body stores 4, 5. The diagnosis is primarily clinical, based on:
- Unexplained glucose intolerance in a TPN patient
- Absence of sepsis or other causes
- Dramatic response to chromium supplementation
Current parenteral chromium recommendations are 10-15 mcg/day for maintenance, though contamination from dextrose solutions may provide additional chromium 1. However, patients with chronic intestinal failure on long-term TPN without adequate chromium supplementation remain at risk for deficiency 1.