Hypoglycemia is a fact of life for most people with diabetes on glucose lowering medication. However, it is an uncommon clinical problem in other patients. There is no plasma glucose level that defines hypoglycemia. Instead, hypoglycemia is confirmed by documentation of Whipple’s Triad: Symptoms of hypoglycemia Low plasma glucose Symptom resolution when glucose administered Hypoglycemic disorders used to be classified as fasting or postprandial. However, a more useful classification is based on whether the patient is seemingly well or Ill. Causes in the ill patient include: drugs alcohol critical illness cortisol deficiency non-islet cell tumours Causes in the seemingly well patient include: insulinoma, functional β-cell disorders autoimmune hypoglycemia accidental, surreptitious or malicious ingestion of glucose lowering medication Always ask about neurogenic/autonomic symptoms such as tremor, palpitations, anxiety, sweating, hunger and tingling, and neuroglycopenic symptoms such as visual change, confusion, unusual behaviour, weakness, seizure, and coma. In the ill patient, ask about: an error with a glucose lowering medication medications with known risk of hypoglycemia alcohol addiction with periods of not eating hepatic, renal or cardiac failure; or sepsis, trauma or burns symptoms of adrenocortical insufficiency or malignancy In the seemingly well patient, ask about: timing and relationship to food frequency, duration episode prevention, treatment weight gain (eating to prevent hypoglycemia) blood glucose during an episode relatives with diabetes or access to antihyperglycemic agents at home or work a family history of multiple endocrine neoplasia type 1 (MEN-1) previous Roux-en-Y surgery In the ill patient: Draw plasma glucose during symptoms of hypoglycemia Review medications Assess hepatic, renal and cardiac function Investigate for adrenocortical insufficiency or nonislet cell tumour if suspected.
In the seemingly well patient, if you are able to observe a spontaneous episode, measure plasma glucose, insulin, C-peptide, pro-insulin and beta-hydroxybutyrate. If you can’t observe a spontaneous episode, recreate the circumstances in which symptomatic hypoglycemia is likely to occur with a fast of up to 72 hours or after a mixed meal. With an insulinoma, most patients will experience hypoglycemia within 24 hours of fasting. Despite having a plasma glucose < 3 mmol/L, plasma insulin, C-peptide, and proinsulin levels will be inappropriately elevated. Insulinomas are rare tumours and most are benign, small and solitary. They should be localized through imaging, and surgically removed. Remember that evaluation and management of hypoglycemia is recommended only when Whipple’s triad is documented.
Choose investigations based on whether the patient appears seemingly well or ill.
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