Diabetes inHFEHemochromatosis

Abstract

Diabetes in whites of European descent with hemochromatosis was first attributed to pancreatic siderosis. Later observations revealed that the pathogenesis of diabetes in HFE hemochromatosis is multifactorial and its clinical manifestations are heterogeneous. Increased type 2 diabetes risk in HFE hemochromatosis is associated with one or more factors, including abnormal iron homeostasis and iron overload, decreased insulin secretion, cirrhosis, diabetes in first-degree relatives, increased body mass index, insulin resistance, and metabolic syndrome. In p.C282Y homozygotes, serum ferritin, usually elevated at hemochromatosis diagnosis, largely reflects body iron stores but not diabetes risk. In persons with diabetes type 2 without hemochromatosis diagnoses, serum ferritin levels are higher than those of persons without diabetes, but most values are within the reference range. Phlebotomy therapy to achieve iron depletion does not improve diabetes control in all persons with HFE hemochromatosis. The prevalence of type 2 diabetes diagnosed today in whites of European descent with and without HFE hemochromatosis is similar. Routine iron phenotyping or HFE genotyping of patients with type 2 diabetes is not recommended. Herein, we review diabetes in HFE hemochromatosis and the role of iron in diabetes pathogenesis in whites of European descent with and without HFE hemochromatosis.

Diabetes of the exocrine pancreas

“…9,44 The prevalence of diabetes associated with hemochromatosis is falling due to proactive secondary screening of family members; this results in earlier age of diagnosis and an opportunity for improved management to prevent complications. 45 However, as only 60-80% of those with a genetic risk develop biochemical penetrence and there is not always a family history, clinicians need to consider a diagnosis in individuals with diabetes and abnormal liver function tests, arthritis, or other endocrinopathies. 23 Screening for glucose intolerance and diabetes should be routine for all patients with thalassemia major.…”

“…Higher doses may be needed in well-nourished patients with hemochromatosis and insulin resistance due to hepatic involvement. 45,58 Cystic fibrosis patients with diabetes, particularly women, are at risk of poor nutrition, weight loss, deteriorating lung function, and reduced survival. 24 The life expectancy of people with CF has increased and insulin therapy for CFRD may have contributed to improved outcomes.…”

Biochemical assessment of iron profile in type 2 diabetes patients.

“…29 Various reports around the globe demonstrated iron overload in the patients suffering from type 2 diabetes. [30][31][32] Via Haber-Weiss and Fenton reactions, the free iron radicals initiate oxidation of biomolecules leading to generation of hydroxyl radical (OH*). These radicals damage cellular membrane protein and nucleic acid.…”

Homeostatic Model Assessment of Insulin Activity and Iron Profile among Regular Blood Donors at a Tertiary Health Centre, South-West Nigeria

“…This may over time lead to increased IR or reduced insulin sensitivity, manifesting clinically as impaired glucose tolerance or DM. [ 10 ]…”

“…[ 14 ] The exact mechanism of iron overload-induced diabetes is not fully cleared yet, and the suggested mechanism includes: (1) insulin deficiency, (2) IR, and (3) hepatic dysfunction. [ 10 ]…”