Iron Overload Combined with Islet Autoimmunity Causes ‘Ferro-immune’ Hybrid Diabetes: A Case Series

Abstract

Iron’s role in diabetes pathophysiology is underrecognised. Authors describe three cases (two females and one male) with evidence of ‘ferro-immune’ hybrid diabetes, HFE C282Y homozygosity with islet autoimmunity. Case one describes iron overload followed by classical autoimmune diabetes. A 20-year-old female presented with non transfusion-dependent hereditary spherocytosis, contributing to hepatic iron overload. At the age of 26 years, the patient presented with diabetic ketoacidosis and elevated Glutamic Acid Decarboxylase (GAD) (50.5 U/mL) and Islet Antigen 2 (IA-2) (>4,000 U/mL) autoantibodies, and commenced insulin therapy. Two months after her diabetes diagnosis, she began iron chelation therapy. Case two describes haemochromatosis followed by adultonset diabetes. A fit 78-year-old woman was diagnosed with haemochromatosis at the age of 58 years and presumed to have Type 2 Diabetes (T2D) at the age of 66 years. However, subsequent testing revealed GAD autoantibody positivity (24 U/mL) with normal C-peptide levels (0.55 nmol/L). Her diabetes was diet-controlled, and her transferrin saturation normalised while GAD seropositivity resolved spontaneously. Case three describes slowly-progressive autoimmune diabetes preceding haemochromatosis. A lean man was diagnosed with latent autoimmune diabetes in adulthood with elevated GAD autoantibodies (11 U/mL). At the age of 81 years, he was diagnosed with haemochromatosis (transferrin saturation 61%), which was followed by a decline in glycaemic control (HbA1c 8.3% to 9.0%). A paired fasting glucose (10.8 mmol/L) and C-peptide (0.15 nmol/L) indicated insulin deficiency, and he remains dependent on insulin therapy. Reducing iron levels through venesection or iron chelation may help decrease islet inflammation and potentially, autoimmunity. A family history of haemochromatosis or an atypical diabetes presentation should prompt an investigation into iron status. Additionally, a low C-peptide level in the presence of haemochromatosis should prompt an investigation into islet autoantibody status.

Keywords

• autoimmune
• chelation
• genetic
• haemochromatosis
• insulin deficiency