Hypoglycaemia Evaluation and Management
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Direct answer
Hypoglycaemia is a plasma glucose below 70 mg/dL in diabetes care, but evaluation in a non-diabetic adult starts with the Whipple triad: typical symptoms, a documented low glucose (usually below 55 mg/dL) and relief after glucose correction. In a non-diabetic adult with fasting hypoglycaemia, the key question is whether insulin, C-peptide and proinsulin are inappropriately high, pointing to endogenous hyperinsulinism such as insulinoma or a sulfonylurea.
What you must remember
- Whipple triad: symptoms, a documented low plasma glucose and resolution of symptoms after glucose correction.
- Thresholds: in diabetes care, below 70 mg/dL is hypoglycaemia and below 54 mg/dL is clinically significant; in non-diabetic evaluation about 55 mg/dL is the usual cut-off.
- Insulinoma pattern: high insulin, high C-peptide and high proinsulin during a supervised fast, with suppressed ketones.
- Exogenous insulin: high insulin with suppressed C-peptide, the key contrast with insulinoma.
- Sulfonylurea: high insulin and high C-peptide, with a positive drug screen.
- Quinine: stimulates insulin release and is an important cause of hypoglycaemia in severe malaria.
- Conscious patient: 15 to 20 g of fast-acting carbohydrate, then recheck glucose in 15 minutes.
A supervised fast in a 38-year-old woman
A 38-year-old woman describes early-morning sweating, confusion and palpitations that settle after eating, and her glucose is 40 mg/dL during one episode. A supervised 72-hour fast is arranged with frequent glucose checks, and at hour 48 she becomes confused with a glucose of 42 mg/dL.
- Insulin and C-peptide: Insulin is inappropriately high, with C-peptide and proinsulin raised and beta-hydroxybutyrate suppressed.
- Drug screen: A sulfonylurea screen is negative, which excludes drug exposure.
- Localise: Endoscopic ultrasound or cross-sectional imaging localises a small pancreatic lesion, and surgical resection is planned.
- Bridge: Diazoxide and frequent feeds control symptoms before surgery.
- Counsel: The patient is counselled about driving and work, because recurrent hypoglycaemia can be dangerous while the diagnosis is being established.
Each branch changes management, which is why the measurements are taken together. A positive screen with high C-peptide would mean sulfonylurea exposure, while low C-peptide with high insulin would instead suggest exogenous insulin.
Where the exam tries to catch you
Four traps recur.
- Trap: using C-peptide alone to separate insulinoma from sulfonylurea use. Correct: both produce high insulin and high C-peptide, so the drug screen is the discriminating test, while exogenous insulin suppresses C-peptide.
- Trap: expecting classic adrenergic warning symptoms in every patient. Correct: beta-blockers blunt them, so neuroglycopenic symptoms may be the only clue.
- Trap: ignoring alcohol. Correct: alcohol impairs gluconeogenesis and can cause hypoglycaemia hours after drinking, particularly in fasting individuals.
- Trap: forgetting non-islet cell tumours and post-bariatric hypoglycaemia. Correct: non-islet cell tumours secrete large IGF-2 forms with low insulin and low ketones, and post-bariatric hypoglycaemia follows gastric bypass.
Frequently asked questions
What is the Whipple triad?
The Whipple triad is the combination of symptoms consistent with hypoglycaemia, a documented low plasma glucose, and relief of symptoms once glucose is restored. It confirms that the symptoms are truly due to low glucose. Examiners expect you to name all three components.
Which laboratory pattern distinguishes exogenous insulin from insulinoma?
Exogenous insulin produces high insulin with suppressed C-peptide, whereas insulinoma produces high insulin with high C-peptide and proinsulin. A raised C-peptide therefore points toward endogenous insulin secretion. A drug screen is needed alongside these tests when sulfonylureas are suspected.
Why is quinine a notable cause of hypoglycaemia in India?
Quinine stimulates insulin release from pancreatic beta cells and can cause severe hypoglycaemia, particularly in patients with severe falciparum malaria. It is therefore a relevant cause in Indian practice. Glucose monitoring is important during quinine treatment.
How is conscious hypoglycaemia treated in an adult?
Conscious hypoglycaemia is treated with 15 to 20 g of fast-acting oral carbohydrate, such as glucose tablets or sugar in water. Glucose is rechecked after 15 minutes and the treatment repeated if it remains low. A longer-acting carbohydrate meal follows once the patient is stable.
Which tests are used when insulinoma is suspected?
A supervised fast with serial glucose, insulin, C-peptide, proinsulin and beta-hydroxybutyrate measurements is the key test for suspected insulinoma. Sulfonylurea screening and exclusion of exogenous insulin are performed at the same time. Localisation uses endoscopic ultrasound or cross-sectional imaging.