Potential Role of Increased Iron Stores in Diabetes

Wilson, James G.; Lindquist, Jennifer H.; Grambow, Steven C.; Crook, Errol D.; Maher, Joseph F.

doi:10.1097/00000441-200306000-00004

Cited by 156 publications

(106 citation statements)

References 56 publications

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“…The study of mouse models of haemochromatosis also suggests that iron overload and not the HFE mutations per se are responsible for the glucose homeostasis phenotype [15], and the heterozygous controls in this study did not have elevated serum ferritin concentrations. Further support for the primary role of iron in the pathogenesis of haemochromatosis-associated diabetes is found in reports that even in the absence of HFE mutations individuals with diabetes have higher than average iron indices [38][39][40].…”

Section: Discussionmentioning

confidence: 85%

High prevalence of abnormal glucose homeostasis secondary to decreased insulin secretion in individuals with hereditary haemochromatosis

et al. 2006

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Aims/hypothesis: The prevalence and mechanisms of diabetes in hereditary haemochromatosis are not known. We therefore measured glucose tolerance, insulin secretory capacity and insulin sensitivity in adults with haemochromatosis.Subjects and methods: Subjects recruited from referrals to a haemochromatosis clinic underwent OGTT and frequently sampled IVGTT. A chart review of former clinic patients was also performed. Results: The prevalence of diabetes (23%) and IGT (30%) was increased in haemochromatosis compared with matched control subjects (0% diabetes and 14% IGT). Subjects with haemochromatosis and diabetes were overweight (14%) or obese (86%). The prevalence of diabetes, as determined by chart review of fasting glucose values, in subjects who had haemochromatosis and were in the 40-79 years age range was 26%. Overall, patients with haemochromatosis and control subjects had similar values for acute insulin response to glucose and insulin sensitivity. However, patients with haemochromatosis and IGT had a 68% decrease in acute insulin response to glucose (p<0.02) compared with those with NGT. They were not insulin-resistant, exhibiting instead a 62% increase in insulin sensitivity (NS). Haemochromatosis subjects with diabetes exhibited further declines in acute insulin response to glucose, insulin resistance, or both.Conclusions/interpretation: Diabetes and IGT are common in haemochromatosis, justifying screening for diabetes and therapeutic phlebotomy. The major abnormality associated with IGT is decreased insulin secretory capacity. Diabetes is usually associated with obesity and concomitant insulin resistance.

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Section: Discussionmentioning

confidence: 85%

High prevalence of abnormal glucose homeostasis secondary to decreased insulin secretion in individuals with hereditary haemochromatosis

et al. 2006

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“…Oxidative stress can also lead to hyperglycaemia through disturbed glucose metabolism [24]. In addition, iron accumulation in hepatocytes may interfere with the insulin-extracting capacity of the liver [25], and affect insulin synthesis and secretion in the pancreas [26]. Iron excess probably contributes initially to insulin resistance and subsequently to decreased insulin secretion [26].…”

Section: Discussionmentioning

confidence: 99%

Elevated serum ferritin levels predict new-onset type 2 diabetes: results from the EPIC-Norfolk prospective study

et al. 2007

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Aims/hypothesis The aim of this study was to examine the association between baseline body iron stores and new-onset diabetes. Subjects and methods We studied the association between baseline serum ferritin concentration and type 2 diabetes in 360 clinically incident diabetes cases and 758 controls nested within the EPIC (European Prospective Investigation of Cancer)-Norfolk Cohort Study. Serum ferritin levels were categorised into five groups: sex-specific quartiles of the normal range of ferritin and a group with clinically raised ferritin below levels indicative of haemochromatosis. Results Baseline serum ferritin was higher among cases than control participants (geometric mean: men 96.6 vs 67.8 ng/ml, respectively, p<0.001; women 45.9 vs 34.8 ng/ ml, respectively, p=0.005). In analyses adjusted for known risk factors (age, BMI, sex, family history, physical activity, smoking habit) and dietary factors measured by 7-day food diary, the risk of diabetes was markedly elevated in participants with clinically raised ferritin compared with the lowest quartile (odds ratio [OR] 7.4, 95% CI 3.5-15.4). Further adjustment for potential confounding by inflammation (C-reactive protein, IL-6 and fibrinogen) had no material impact on the observed association, while adjustment for hepatic enzymes (alanine aminotransferase and γ glutamyl transferase) and adiponectin attenuated the magnitude of association, but it remained statistically significant (OR 3.2 [1.3-7.6]). Conclusions/interpretation Serum ferritin is an important and independent predictor of the development of diabetes. This finding may have important implications for understanding the aetiology of diabetes.

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“…La insulina provoca una estimulación rápida de la absorción de Fe en adipocitos y hepatocitos 41 y el Fe interfiere con la acción de la insulina en el hígado, contribuyendo a la RI a través de mecanismos relacionados tanto con la capacidad de sensibilización como la secreción de insulina 42 . Además, la insulina posiblemente activa el factor inducible por hipoxia 1α (HIF-1α), que potenciaría los efectos inflamatorios del tejido adiposo 43 .…”

Section: Obesidad Y Hepcidinaunclassified

Anemia de las enfermedades crónicas asociada a obesidad: papel de la hepcidina como mediador central

2013

Rev. méd. Chile

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Recent evidence suggests that obesity-related inflammation may play a central role in hepcidin regulation. Hepcidin is a key regulator of iron homeostasis and has now been suggested as a central mediator of iron metabolism disorders involved in the pathogenesis of anemia of chronic disease. In this review, we focus on subclinical inflammation in obesity and its effect on hepcidin levels, as the most plausible explanation for the relationship between anemia of chronic disease and obesity.( Rev Med Chile 2013; 141: 887-894).

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Potential Role of Increased Iron Stores in Diabetes

Cited by 156 publications

References 56 publications

High prevalence of abnormal glucose homeostasis secondary to decreased insulin secretion in individuals with hereditary haemochromatosis

High prevalence of abnormal glucose homeostasis secondary to decreased insulin secretion in individuals with hereditary haemochromatosis

Elevated serum ferritin levels predict new-onset type 2 diabetes: results from the EPIC-Norfolk prospective study

Anemia de las enfermedades crónicas asociada a obesidad: papel de la hepcidina como mediador central

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