Interpreting a Glucose Tolerance Curve
A 52-year-old man with a BMI of 31 attends a clinic after reporting fatigue and frequent urination. He fasted for 10 hours. A 75 g oral glucose drink was given at time 0, and plasma glucose was measured at intervals. Results (mmol/L): fasting 6.4; 30 min 10.9; 60 min 12.8; 90 min 11.1; 120 min 9.6. A healthy reference person of the same age, tested under identical conditions, peaked at 7.8 mmol/L at 45 min and returned to 5.1 mmol/L by 120 min. The man had eaten a large carbohydrate meal the night before and slept poorly. He takes no medication. His fasting insulin is elevated, and his C-peptide is also elevated.
1. Using the two curves, explain which features of the patient's response indicate impaired glucose regulation rather than simply a high-carbohydrate meal the night before.
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The key comparison is the shape and the return to baseline, not just the peak.
- Fasting value: 6.4 mmol/L is above the healthy reference (which returned to 5.1). A single high meal the night before could raise fasting glucose slightly, but the combination of a raised fasting value and a slow decline is more consistent with impaired regulation.
- Peak height and timing: the patient peaks later (60 min, 12.8 mmol/L) than the reference (45 min, 7.8 mmol/L). A delayed, higher peak suggests glucose is entering the blood faster than it is being cleared.
- Failure to return: at 120 min the patient is still 9.6 mmol/L, whereas the reference has returned to near fasting. This is the strongest single indicator - clearance is impaired.
- Hormone evidence: elevated fasting insulin with elevated C-peptide indicates the pancreas is secreting large amounts of insulin (C-peptide is co-secreted with insulin), yet glucose remains high. That points to insulin resistance rather than insulin deficiency.
A high-carbohydrate meal and poor sleep can shift values modestly, but they do not explain a sustained 120-minute value nearly 4.5 mmol/L above the reference. The judgement is that the curve reflects resistance plus impaired clearance, not a one-off dietary effect.
2. The patient asks whether his elevated insulin means his pancreas is 'working well'. Construct a response that distinguishes insulin resistance from insulin deficiency, using the C-peptide result.
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His pancreas is currently secreting plenty of insulin - the high C-peptide confirms this, because C-peptide is released in equimolar amounts with insulin and is not cleared as quickly, so it is a good marker of the body's own output. So in one sense the beta cells are 'working'.
But the reason output is high is that the tissues are resistant to insulin's signal. The pancreas is compensating by producing more. This is different from insulin deficiency, where output falls and C-peptide would be low.
The clinical implication matters: in resistance, the problem is at the target tissues, so the strategy targets sensitivity (weight reduction, activity, and if needed medication that improves sensitivity). In deficiency, the strategy is replacement. Telling him 'your pancreas works well' is misleading - it is working hard to overcome a problem elsewhere, and over years a compensating pancreas can fatigue. The honest answer is that his insulin level is high because it is being ignored, not because everything is fine.