Body Iron Stores Are Associated With Serum Insulin and Blood Glucose Concentrations: Population study in 1,013 eastern Finnish men

Tuomainen, Tomi‐Pekka; Nyyssönen, Kristiina; Salonen, Riitita; Tervahauta, Arja; Korpela, H; Lakka, Timo A.; Kaplan, George A.; Salonen, Jukka T.

doi:10.2337/diacare.20.3.426

Cited by 290 publications

(216 citation statements)

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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%

“…The association of insulin resistance with iron overload is largely based on studies of subjects with beta thalassaemia, transfusion iron overload, coexistent liver disease or idiopathic hyperferritinaemia [11,12,40,45,46]. The different distributions of iron in these conditions compared with haemochromatosis (reticuloendothelial vs hepatocellular) [1,47] may explain the differing phenotypes.…”

Section: Discussionmentioning

confidence: 99%

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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%

Section: Discussionmentioning

confidence: 99%

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

et al. 2006

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“…Furthermore, there is an indication that higher iron stores resulting from frequent meat intake might impair insulin sensitivity [52]. This hypothesis is supported by cross-sectional [53] and cohort studies [54], where higher iron stores were associated with higher blood glucose concentrations and higher risk of diabetes. Furthermore, animal studies suggest that iron depletion enhances glucose disposal [55,56].…”

Section: Resultsmentioning

confidence: 90%

Processed meat intake and incidence of Type 2 diabetes in younger and middle-aged women

Schulze¹,

et al. 2003

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Aim/hypothesis. The aim of this study was to investigate the association between processed and other meat intake and incidence of Type 2 diabetes in a large cohort of women. Methods. Incident cases of Type 2 diabetes were identified during 8 years of follow-up in a prospective cohort study of 91246 U.S. women aged 26 to 46 years and being free of diabetes and other major chronic diseases at baseline in 1991. Results. We identified 741 incident cases of confirmed Type 2 diabetes during 716276 person-years of follow-up. The relative risk adjusted for potential nondietary confounders was 1.91 (95% CI: 1.42-2.57) in women consuming processed meat five times or more a week compared with those consuming processed meat less than once a week (p<0.001 for trend). Further adjustment for intakes of magnesium, cereal fibre, glycaemic index, and caffeine or for a Western dietary pattern did not appreciably change the results and associations remained strong after further adjustment for fatty acid and cholesterol intake. Frequent consumption of bacon, hot dogs, and sausage was each associated with an increased risk of diabetes. While total red meat (beef or lamb as main dish, pork as main dish, hamburger, beef, pork or lamb as sandwich or mixed dish) intake was associated with an increased risk of diabetes, this association was attenuated after adjustment for magnesium, cereal fiber, glycaemic index, and caffeine (relative risk: 1.44; 95% CI: 0.92-2.24).

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“…4 4] ng/ml). There was no evidence of a statistical interaction between ferritin levels and sex (p=0.51), and analyses were performed in men and women combined.…”

Section: Resultsmentioning

confidence: 99%

“…These two prospective studies reduce doubt about the temporal sequence which had affected previous cross-sectional or case-control studies [3][4][5][6][7], but several questions still remain unanswered.…”

Section: Introductionmentioning

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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Body Iron Stores Are Associated With Serum Insulin and Blood Glucose Concentrations: Population study in 1,013 eastern Finnish men

Abstract: Mildly elevated body iron stores are associated with statistically significant elevations in glucose homeostasis indexes.

Cited by 290 publications

References 0 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

Processed meat intake and incidence of Type 2 diabetes in younger and middle-aged women

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

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