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

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.

Conflict of interest statement

LT has received speaker's fees from Soremartec Italy srl and from Nestlé AG, Switzerland for lectures unrelated to this study. Other authors have nothing to declare.

© 2022 The Authors.

Figures

Figure 1

CONSORT diagram. Study participation by treatment group. sTf indicated transferrin saturation.

Figure 2

Iron induced change in the levels of antioxidants and circulating ROS. Iron transitorily decreased serum ascorbate levels at day 14 with restoration at day 28 (panel A) with no effect for placebo. There was an increase in serum ascrobyl/ascorbate ratio at day 14 with restoration of normal ratio at day 28 and no effect for placebo (panel B). The serum antioxidant status (ORAC units) remained unchanged throughout the study period (panel C). Serum ascorbate levels, serum ascrobyl/ascorbate ratio and serum antioxidant status were normalized for baseline values. The red line in the boxplot is the median of the estimate. P values are for the effect of the intervention at 14 and 28 days.