Plasma calprotectin and new-onset type 2 diabetes in the general population: a prospective cohort study

Arno R Bourgonje; Martin F Bourgonje; Sara Sokooti; Sacha la Bastide-van Gemert; Tom Nilsen; Clara Hidden; Ron T Gansevoort; Douwe J Mulder; Jan-Luuk Hillebrands; Stephan J L Bakker; André van Beek; Robin P F Dullaart; Harry van Goor; Amaal E Abdulle

doi:10.1210/clinem/dgae130

Plasma calprotectin and new-onset type 2 diabetes in the general population: a prospective cohort study

J Clin Endocrinol Metab. 2024 Mar 4:dgae130. doi: 10.1210/clinem/dgae130. Online ahead of print.

Authors

Affiliations

¹ Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
² The Henry D. Janowitz Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, United States of America.
³ Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
⁴ Department of Internal Medicine, Division of Endocrinology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
⁵ Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
⁶ Gentian AS, Moss, Norway.
⁷ Department of Internal Medicine, Division of Nephrology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
⁸ Department of Internal Medicine, Division of Vascular Medicine, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.

PMID: 38436468
DOI: 10.1210/clinem/dgae130

Abstract

Background: Systemic inflammation plays a pivotal role in the development of type 2 diabetes (T2D). Here we hypothesized that circulating levels of calprotectin, a myeloid cell-derived biomarker of inflammation, is associated with the development of new-onset T2D in the general population.

Methods: A total of 4,815 initially non-diabetic participants of the Prevention of Renal and Vascular ENd-stage Disease (PREVEND), a prospective population-based cohort study, were assessed for plasma levels of calprotectin at baseline. Circulating levels of calprotectin were investigated for potential associations with the risk of new-onset T2D, defined as a fasting plasma glucose level ≥7.0 mmol/l, a random plasma glucose level ≥11.1 mmol/l, a self-reported physician-based diagnosis of T2D, the use of glucose-lowering drugs, or any combinations thereof.

Results: Median plasma calprotectin levels were 0.49 [0.35-0.69] mg/l. Plasma calprotectin levels were significantly associated with the risk of new-onset T2D (hazard ratio [HR] per doubling 1.42 [95% confidence interval: 1.22-1.66], P<0.001). The association remained independent of adjustment for age and sex (HR 1.34 [95%CI: 1.14-1.57], P<0.001), but not after further adjustment for potentially confounding factors (HR 1.11 [95% CI: 0.90-1.37], P=0.326), with adjustment for hyperlipidemia and high-sensitivity C-reactive protein explaining the loss of significance. Stratified analyses showed significant effect modification by hypertension, history of cardiovascular disease and HOMA-IR (Pinteraction≤0.001 for each), with higher HRs in individuals without hypertension, without history of cardiovascular disease and with below-median HOMA-IR.

Conclusions: Elevated plasma levels of calprotectin are associated with a higher risk of developing T2D in the general population and may represent a moveable inflammatory biomarker. This association, however, does not represent a direct effect, and seems dependent on hyperlipidemia and systemic inflammation.

Keywords: biomarker; calprotectin; epidemiology; type 2 diabetes.