The diagnosis of low blood sugar, or hypoglycaemia, plays a vital role in managing both acute episodes and long-term blood glucose disorders. Prompt, accurate diagnosis helps prevent complications, guides treatment, and uncovers underlying causes that may need further medical intervention. The process combines clinical evaluation, blood tests, medical history analysis, and sometimes prolonged monitoring.
Whipple’s Triad: The Gold Standard
The gold standard for diagnosing hypoglycaemia relies on Whipple’s triad, which includes three key components:
- Symptoms consistent with hypoglycaemia (e.g., shaking, confusion, sweating).
- A blood test showing low plasma glucose levels during the symptoms.
- Relief of symptoms once glucose levels rise.
Whipple’s triad confirms that low blood sugar causes the symptoms, not another medical condition. This concept helps in ambiguous cases or when patients experience recurrent episodes without a clear cause.
Step 1: Medical History and Physical Examination
The doctor will start by taking a detailed medical history. They will ask about:
- The frequency, timing, and severity of episodes.
- Any triggers, such as fasting, exercise, alcohol, or medications.
- Whether the person has diabetes or other health conditions.
- Dietary habits, weight loss, and medication use, especially insulin or sulphonylureas.
- Recent illnesses, surgeries, or changes in lifestyle.
During the physical examination, the doctor may observe clinical signs of hypoglycaemia. However, many people’s blood sugar levels may have normalized by the time they visit a doctor. If necessary, the doctor may provoke symptoms under controlled conditions, especially if insulinoma (insulin-producing tumour) or reactive hypoglycaemia is suspected.
Step 2: Blood Glucose Testing
Blood glucose testing serves as the cornerstone for diagnosing low blood sugar. Hypoglycaemia is defined as a blood glucose level below 3.9 mmol/L (70 mg/dL) in adults, though symptoms typically appear when levels drop below 3.0 mmol/L (54 mg/dL). Venous blood samples are preferred over finger-prick tests for accuracy.
In emergency situations, such as confusion, seizures, or loss of consciousness, a point-of-care glucose test (e.g., bedside glucometer) is immediately performed. If the blood sugar is low and no other cause is apparent, doctors will treat the patient with intravenous glucose or glucagon injections before continuing the investigation.
Step 3: Additional Diagnostic Tests
For patients with recurrent, unexplained hypoglycaemia, doctors may conduct additional tests:
- 72-hour fasting test: A hospital-supervised test to diagnose insulinoma or other causes of endogenous hyperinsulinaemia. The patient fasts under observation while doctors monitor glucose, insulin, C-peptide, and proinsulin levels every few hours.
- Mixed Meal Tolerance Test (MMTT): A test to diagnose reactive hypoglycaemia, measuring blood glucose and insulin after consuming a high-carbohydrate meal.
- Continuous Glucose Monitoring (CGM): Ideal for people with fluctuating or nocturnal hypoglycaemia, CGM tracks blood sugar minute by minute, helping to identify patterns, such as drops during sleep or after exercise.
- Laboratory hormonal panels: In cases where adrenal insufficiency or pituitary disorders are suspected, doctors may test for cortisol, ACTH, growth hormone, and thyroid function.
- Liver and kidney function tests: These organs play a key role in glucose regulation. Dysfunction in either can contribute to hypoglycaemia. Enzyme panels, bilirubin levels, and renal markers (e.g., creatinine) are assessed.
Step 4: Exogenous vs Endogenous Causes
Diagnosing whether the cause is exogenous (external) or endogenous (internal) is crucial. For example:
- High insulin with low C-peptide suggests factitious hypoglycaemia, possibly due to improper use of synthetic insulin.
- Elevated insulin and C-peptide together might indicate an insulinoma or sulphonylurea ingestion. If sulphonylurea use is suspected, a drug screen using high-performance liquid chromatography (HPLC) or mass spectrometry can confirm it.
Step 5: Neonatal Hypoglycaemia
For newborns or infants, doctors use different protocols to diagnose hypoglycaemia. They routinely screen at-risk babies, including those born premature, with low birth weight, or to diabetic mothers. If glucose levels are low, doctors may run further tests to identify metabolic or hormonal conditions like glycogen storage diseases or hyperinsulinism.
Step 6: Nocturnal Hypoglycaemia in Diabetes
Nocturnal hypoglycaemia is a concern for people with diabetes. CGM data showing drops in blood sugar at night can help adjust insulin dosing or bedtime snack routines. Patients may report symptoms like morning headaches, vivid dreams, or extreme fatigue, all of which may be related to overnight hypoglycaemia.
Step 7: Rare Causes in Non-Diabetic Individuals
For people without diabetes, doctors should not overlook rare causes of hypoglycaemia. One such cause is autoimmune hypoglycaemia, where the body produces antibodies against insulin or its receptors. It can occur alongside other autoimmune conditions or medications, and it requires specialized antibody testing.
Step 8: Timing is Crucial
Diagnosing hypoglycaemia can be tricky since many people feel unwell but have normal glucose levels when tested later. To capture these fluctuations, doctors often recommend that patients:
- Use home glucometers or CGM devices.
- Keep a symptom diary tracking food intake, stress, and activity levels.
This data helps doctors identify patterns and confirm whether symptoms align with hypoglycaemia.
Conclusion
The diagnosis of low blood sugar involves more than identifying a low glucose level. It requires a comprehensive approach that combines symptom tracking, blood tests, and sometimes advanced diagnostic procedures. Confirming hypoglycaemia and understanding its causes — from medication errors to rare metabolic disorders — is essential for managing the condition and preventing future episodes.
