Haemochromatosis Does Not Directly Cause Hypoglycaemic Episodes
Hereditary haemochromatosis causes diabetes and hyperglycaemia, not hypoglycaemia. The disease is associated with abnormal glucose metabolism that manifests as impaired glucose tolerance and type 2 diabetes mellitus, not hypoglycaemic episodes 1.
The Glucose Metabolism Problem in Haemochromatosis
The iron overload in haemochromatosis damages pancreatic beta cells, leading to decreased insulin secretion 2, 3. This pathophysiology results in:
- Diabetes mellitus (prevalence of 23-26% in affected patients) 2
- Impaired glucose tolerance (prevalence of 30%) 2
- Hyperglycaemia, not hypoglycaemia
The 2022 EASL guidelines explicitly list diabetes as a common complication of untreated haemochromatosis, alongside cirrhosis, hepatocellular carcinoma, and arthropathy 1. There is no mention of hypoglycaemia as a manifestation.
Mechanism of Glucose Abnormalities
The primary defect is impaired insulin secretory capacity due to iron deposition in pancreatic beta cells 2, 3, 4. Early in the disease:
- Patients have decreased acute insulin response to glucose (AIRg reduced by 68% in those with IGT) 2
- Compensatory increase in insulin sensitivity may occur initially 2, 4
- As disease progresses, insulin resistance develops, particularly with concomitant obesity or cirrhosis 2, 3
After phlebotomy treatment normalizes iron stores, insulin secretory capacity improves (1.8 to 2.2-fold increase), but paradoxically insulin sensitivity decreases by 70% 4. This demonstrates that the disease process drives patients toward hyperglycaemia, not hypoglycaemia.
Important Clinical Caveat
If a patient with haemochromatosis experiences hypoglycaemic episodes, look for alternative causes:
- Diabetes treatment with insulin or sulfonylureas (iatrogenic hypoglycaemia)
- Concurrent liver cirrhosis with impaired gluconeogenesis
- Other unrelated endocrine disorders (adrenal insufficiency can occur in severe HH) 5
- Separate pathology unrelated to the haemochromatosis itself
The natural history of untreated haemochromatosis moves patients along the spectrum from normal glucose tolerance → impaired glucose tolerance → diabetes mellitus 6, 2, 3. Hypoglycaemia is not part of this disease trajectory.