Dataset Information

Association of Multiple Biomarkers of Iron Metabolism and Type 2 Diabetes: The EPIC-InterAct Study.

ABSTRACT: OBJECTIVE:Observational studies show an association between ferritin and type 2 diabetes (T2D), suggesting a role of high iron stores in T2D development. However, ferritin is influenced by factors other than iron stores, which is less the case for other biomarkers of iron metabolism. We investigated associations of ferritin, transferrin saturation (TSAT), serum iron, and transferrin with T2D incidence to clarify the role of iron in the pathogenesis of T2D. RESEARCH DESIGN AND METHODS:The European Prospective Investigation into Cancer and Nutrition-InterAct study includes 12,403 incident T2D cases and a representative subcohort of 16,154 individuals from a European cohort with 3.99 million person-years of follow-up. We studied the prospective association of ferritin, TSAT, serum iron, and transferrin with incident T2D in 11,052 cases and a random subcohort of 15,182 individuals and assessed whether these associations differed by subgroups of the population. RESULTS:Higher levels of ferritin and transferrin were associated with a higher risk of T2D (hazard ratio [HR] [95% CI] in men and women, respectively: 1.07 [1.01-1.12] and 1.12 [1.05-1.19] per 100 ?g/L higher ferritin level; 1.11 [1.00-1.24] and 1.22 [1.12-1.33] per 0.5 g/L higher transferrin level) after adjustment for age, center, BMI, physical activity, smoking status, education, hs-CRP, alanine aminotransferase, and ?-glutamyl transferase. Elevated TSAT (?45% vs. <45%) was associated with a lower risk of T2D in women (0.68 [0.54-0.86]) but was not statistically significantly associated in men (0.90 [0.75-1.08]). Serum iron was not associated with T2D. The association of ferritin with T2D was stronger among leaner individuals (Pinteraction < 0.01). CONCLUSIONS:The pattern of association of TSAT and transferrin with T2D suggests that the underlying relationship between iron stores and T2D is more complex than the simple link suggested by the association of ferritin with T2D.

SUBMITTER: Podmore C

PROVIDER: S-EPMC5058436 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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Association of Multiple Biomarkers of Iron Metabolism and Type 2 Diabetes: The EPIC-InterAct Study.

Podmore Clara C Meidtner Karina K Schulze Matthias B MB Scott Robert A RA Ramond Anna A Butterworth Adam S AS Di Angelantonio Emanuele E Danesh John J Arriola Larraitz L Barricarte Aurelio A Boeing Heiner H Clavel-Chapelon Françoise F Cross Amanda J AJ Dahm Christina C CC Fagherazzi Guy G Franks Paul W PW Gavrila Diana D Grioni Sara S Gunter Marc J MJ Gusto Gaelle G Jakszyn Paula P Katzke Verena V Key Timothy J TJ Kühn Tilman T Mattiello Amalia A Nilsson Peter M PM Olsen Anja A Overvad Kim K Palli Domenico D Quirós J Ramón JR Rolandsson Olov O Sacerdote Carlotta C Sánchez-Cantalejo Emilio E Slimani Nadia N Sluijs Ivonne I Spijkerman Annemieke M W AM Tjonneland Anne A Tumino Rosario R van der A Daphne L DL van der Schouw Yvonne T YT Feskens Edith J M EJ Forouhi Nita G NG Sharp Stephen J SJ Riboli Elio E Langenberg Claudia C Wareham Nicholas J NJ

Diabetes care 20160209 4

<h4>Objective</h4>Observational studies show an association between ferritin and type 2 diabetes (T2D), suggesting a role of high iron stores in T2D development. However, ferritin is influenced by factors other than iron stores, which is less the case for other biomarkers of iron metabolism. We investigated associations of ferritin, transferrin saturation (TSAT), serum iron, and transferrin with T2D incidence to clarify the role of iron in the pathogenesis of T2D.<h4>Research design and methods< ...[more]

PMID: 26861925

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Project description:ObjectiveTo investigate the association of plasma vitamin C and carotenoids, as indicators of fruit and vegetable intake, with the risk of type 2 diabetes.DesignProspective case-cohort study.SettingPopulations from eight European countries.Participants9754 participants with incident type 2 diabetes, and a subcohort of 13 662 individuals from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort of 340 234 participants: EPIC-InterAct case-cohort study.Main outcome measureIncident type 2 diabetes.ResultsIn a multivariable adjusted model, higher plasma vitamin C was associated with a lower risk of developing type 2 diabetes (hazard ratio per standard deviation 0.82, 95% confidence interval 0.76 to 0.89). A similar inverse association was shown for total carotenoids (hazard ratio per standard deviation 0.75, 0.68 to 0.82). A composite biomarker score (split into five equal groups), comprising vitamin C and individual carotenoids, was inversely associated with type 2 diabetes with hazard ratios 0.77, 0.66, 0.59, and 0.50 for groups 2-5 compared with group 1 (the lowest group). Self-reported median fruit and vegetable intake was 274 g/day, 396 g/day, and 508 g/day for participants in categories defined by groups 1, 3, and 5 of the composite biomarker score, respectively. One standard deviation difference in the composite biomarker score, equivalent to a 66 (95% confidence interval 61 to 71) g/day difference in total fruit and vegetable intake, was associated with a hazard ratio of 0.75 (0.67 to 0.83). This would be equivalent to an absolute risk reduction of 0.95 per 1000 person years of follow up if achieved across an entire population with the characteristics of the eight European countries included in this analysis.ConclusionsThese findings indicate an inverse association between plasma vitamin C, carotenoids, and their composite biomarker score, and incident type 2 diabetes in different European countries. These biomarkers are objective indicators of fruit and vegetable consumption, and suggest that diets rich in even modestly higher fruit and vegetable consumption could help to prevent development of type 2 diabetes.

Project description:BackgroundUnderstanding of the genetic basis of type 2 diabetes (T2D) has progressed rapidly, but the interactions between common genetic variants and lifestyle risk factors have not been systematically investigated in studies with adequate statistical power. Therefore, we aimed to quantify the combined effects of genetic and lifestyle factors on risk of T2D in order to inform strategies for prevention.Methods and findingsThe InterAct study includes 12,403 incident T2D cases and a representative sub-cohort of 16,154 individuals from a cohort of 340,234 European participants with 3.99 million person-years of follow-up. We studied the combined effects of an additive genetic T2D risk score and modifiable and non-modifiable risk factors using Prentice-weighted Cox regression and random effects meta-analysis methods. The effect of the genetic score was significantly greater in younger individuals (p for interaction ?=?1.20×10-4). Relative genetic risk (per standard deviation [4.4 risk alleles]) was also larger in participants who were leaner, both in terms of body mass index (p for interaction ?=?1.50×10-3) and waist circumference (p for interaction ?=?7.49×10-9). Examination of absolute risks by strata showed the importance of obesity for T2D risk. The 10-y cumulative incidence of T2D rose from 0.25% to 0.89% across extreme quartiles of the genetic score in normal weight individuals, compared to 4.22% to 7.99% in obese individuals. We detected no significant interactions between the genetic score and sex, diabetes family history, physical activity, or dietary habits assessed by a Mediterranean diet score.ConclusionsThe relative effect of a T2D genetic risk score is greater in younger and leaner participants. However, this sub-group is at low absolute risk and would not be a logical target for preventive interventions. The high absolute risk associated with obesity at any level of genetic risk highlights the importance of universal rather than targeted approaches to lifestyle intervention.

Dataset Information

Association of Multiple Biomarkers of Iron Metabolism and Type 2 Diabetes: The EPIC-InterAct Study.

Publications

Association of Multiple Biomarkers of Iron Metabolism and Type 2 Diabetes: The EPIC-InterAct Study.

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