Effect of acute iron infusion on insulin secretion: A randomized, double-blind, placebo-controlled trial

Evrim Jaccard; Kévin Seyssel; Alexandre Gouveia; Catherine Vergely; Laila Baratali; Cédric Gubelmann; Marc Froissart; Bernard Favrat; Pedro Marques-Vidal; Luc Tappy; Gérard Waeber

doi:10.1016/j.eclinm.2022.101434

Effect of acute iron infusion on insulin secretion: A randomized, double-blind, placebo-controlled trial

EClinicalMedicine. 2022 May 6:48:101434. doi: 10.1016/j.eclinm.2022.101434. eCollection 2022 Jun.

Affiliations

¹ Department of Medicine, Lausanne University Hospital (CHUV) and University of Lausanne, rue du Bugnon 46, Lausanne 1011, Switzerland.
² Department of Biomedical Sciences, Faculty of Biology and Medicine, University of Lausanne, rue du Bugnon 7a, Lausanne 1005, Switzerland.
³ Center for Primary Care and Public Health, University of Lausanne, rue du Bugnon 44, Lausanne, Switzerland.
⁴ Pathophysiology and Epidemiology of Cerebro-Cardiovascular Diseases (PEC2, EA7460),UFR des Sciences de Santé, University of Bourgogne Franche-Comté, 7 boulevard Jeanne d' Arc, Dijon 21079, France.
⁵ Clinical Research Center, CHUV, University of Lausanne, Switzerland.

Abstract

Background: Chronic exposure to high iron levels increases diabetes risk partly by inducing oxidative stress, but the consequences of acute iron administration on beta cells are unknown. We tested whether the acute administration of iron for the correction of iron deficiency influenced insulin secretion and the production of reactive oxygen species.

Methods: Single-center, double-blinded, randomized controlled trial conducted between June 2017 and March 2020. 32 women aged 18 to 47 years, displaying symptomatic iron deficiency without anaemia, were recruited from a community setting and randomly allocated (1:1) to a single infusion of 1000 mg intravenous ferric carboxymaltose (iron) or saline (placebo). The primary outcome was the between group mean difference from baseline to day 28 in first and second phase insulin secretion, assessed by a two-step hyperglycaemic clamp. All analyses were performed by intention to treat. This trial was registered in ClinicalTrials.gov NCT03191201.

Findings: Iron infusion did not affect first and second phase insulin release. For first phase, the between group mean difference from baseline to day 28 was 0 μU × 10 min/mL [95% CI, -22 to 22, P = 0.99]. For second phase, it was -5 μUx10min/mL [95% CI, -161 to 151; P = 0.95] at the first plateau of the clamp and -249 μUx10min/mL [95% CI, -635 to 137; P = 0.20] at the second plateau. Iron infusion increased serum ascorbyl/ascorbate ratio, a marker of plasma oxidative stress, at day 14, with restoration of normal ratio at day 28 relative to placebo. Finally, high-sensitive C-reactive protein levels remained similar among groups.

Interpretation: In iron deficient women without anaemia, intravenous administration of 1000 mg of iron in a single sitting did not impair glucose-induced insulin secretion despite a transient increase in the levels of circulating reactive oxygen species.

Funding: The Swiss National Science Foundation, University of Lausanne and Leenaards, Raymond-Berger and Placide Nicod Foundations.

Keywords: Inflammation; Insulin secretion; Insulin sensitivity; Iron deficiency; Iron sufficiency; Type 2 diabetes.

Associated data

ClinicalTrials.gov/NCT03191201