Iron Overload Combined with Islet Autoimmunity Causes ‘Ferro-immune’ Hybrid Diabetes: A Case Series
Published: December 1, 2023 | DOI: https://doi.org/10.7860/JCDR/2023/66615.18795
Joanna Y Gong, John M Wentworth, Christopher J Yates, Qi Yang Damien Qi, Spiros Fourlanos
1. Endocrinology Advanced Trainee, Department of Diabetes and Endocrinology, The Royal Melbourne Hospital and Western Health, Melbourne, Victoria, Australia.
2. Head of Research (RMH), Department of Diabetes and Endocrinology, The Royal Melbourne Hospital and The Walter and Eliza Hall Institute of Medical Research (WEHI), Melbourne, Victoria, Australia.
3. Head of Bone and Mineral Medicine (RMH) and Head of Bone Densitometry Unit (RMH), The Royal Melbourne Hospital, and Co-head of Research, Department of Diabetes and Endocrinology, Western Health Melbourne, Victoria, Australia.
4. Endocrinology Advanced Trainee, Department of Diabetes and Endocrinology, The Royal Melbourne Hospital, Melbourne, Victoria, Australia.
5. Director, Department of Diabetes and Endocrinology, The Royal Melbourne Hospital, Melbourne, Victoria, Australia.
Correspondence
Spiros Fourlanos,
Director, Department of Diabetes and Endocrinology, Level 4 West, The Royal Melbourne Hospital, 300 Grattan Street, Parkville, Melbourne, Victoria, Australia.
E-mail: Spiros.Fourlanos@mh.org.au
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 adult-onset 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.
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