Plasma level of ATPase inhibitory factor 1 (IF1) is associated with type 2 diabetes risk in humans: A prospective cohort study.

Autor: Pires Da Silva J; Institut des Maladies Métaboliques et Cardiovasculaires, I2MC, Université de Toulouse, Inserm, Université Toulouse III - Paul Sabatier (UPS), UMR1297, Toulouse, France., Wargny M; Nantes Université, CHU Nantes, CNRS, INSERM, l'institut du Thorax, 44000 Nantes, France; Nantes Université, CHU Nantes, Pôle Hospitalo-Universitaire 11 : Santé Publique, Clinique des données, INSERM, CIC 1413, F-44000 Nantes, France., Raffin J; Institut du Vieillissement, Gérontopôle de Toulouse, Centre Hospitalo-Universitaire de Toulouse, Toulouse, France., Croyal M; Nantes Université, CHU Nantes, CNRS, INSERM, l'institut du Thorax, 44000 Nantes, France; Nantes Université, CHU Nantes, CNRS, Inserm, BioCore, US16, SFR Bonamy, F-44000 Nantes, France; CRNH-Ouest Mass Spectrometry Core Facility, 44000 Nantes, France., Duparc T; Institut des Maladies Métaboliques et Cardiovasculaires, I2MC, Université de Toulouse, Inserm, Université Toulouse III - Paul Sabatier (UPS), UMR1297, Toulouse, France., Combes G; Institut des Maladies Métaboliques et Cardiovasculaires, I2MC, Université de Toulouse, Inserm, Université Toulouse III - Paul Sabatier (UPS), UMR1297, Toulouse, France., Genoux A; Institut des Maladies Métaboliques et Cardiovasculaires, I2MC, Université de Toulouse, Inserm, Université Toulouse III - Paul Sabatier (UPS), UMR1297, Toulouse, France; Service de Biochimie, Pôle de biologie, Hôpital de Purpan, CHU de Toulouse, Toulouse, France., Perret B; Institut des Maladies Métaboliques et Cardiovasculaires, I2MC, Université de Toulouse, Inserm, Université Toulouse III - Paul Sabatier (UPS), UMR1297, Toulouse, France; Service de Biochimie, Pôle de biologie, Hôpital de Purpan, CHU de Toulouse, Toulouse, France., Vellas B; Institut du Vieillissement, Gérontopôle de Toulouse, Centre Hospitalo-Universitaire de Toulouse, Toulouse, France; CERPOP UMR 1295, University of Toulouse III, INSERM, UPS, Toulouse, France., Guyonnet S; Institut du Vieillissement, Gérontopôle de Toulouse, Centre Hospitalo-Universitaire de Toulouse, Toulouse, France; CERPOP UMR 1295, University of Toulouse III, INSERM, UPS, Toulouse, France., Thalamas C; Institut des Maladies Métaboliques et Cardiovasculaires, I2MC, Université de Toulouse, Inserm, Université Toulouse III - Paul Sabatier (UPS), UMR1297, Toulouse, France; Clinical Investigation Center, Université de Toulouse, INSERM, Université Toulouse III-Paul Sabatier, Toulouse University Hospitals, CIC1436, F-CRIN/FORCE Network, Toulouse, France., Langin D; Institut des Maladies Métaboliques et Cardiovasculaires, I2MC, Université de Toulouse, Inserm, Université Toulouse III - Paul Sabatier (UPS), UMR1297, Toulouse, France; Service de Biochimie, Pôle de biologie, Hôpital de Purpan, CHU de Toulouse, Toulouse, France; Institut Universitaire de France (IUF), Paris, France., Moro C; Institut des Maladies Métaboliques et Cardiovasculaires, I2MC, Université de Toulouse, Inserm, Université Toulouse III - Paul Sabatier (UPS), UMR1297, Toulouse, France., Viguerie N; Institut des Maladies Métaboliques et Cardiovasculaires, I2MC, Université de Toulouse, Inserm, Université Toulouse III - Paul Sabatier (UPS), UMR1297, Toulouse, France., Rolland Y; Institut du Vieillissement, Gérontopôle de Toulouse, Centre Hospitalo-Universitaire de Toulouse, Toulouse, France; CERPOP UMR 1295, University of Toulouse III, INSERM, UPS, Toulouse, France., Barreto PS; Institut du Vieillissement, Gérontopôle de Toulouse, Centre Hospitalo-Universitaire de Toulouse, Toulouse, France; CERPOP UMR 1295, University of Toulouse III, INSERM, UPS, Toulouse, France., Cariou B; Nantes Université, CHU Nantes, CNRS, INSERM, l'institut du Thorax, 44000 Nantes, France., Martinez LO; Institut des Maladies Métaboliques et Cardiovasculaires, I2MC, Université de Toulouse, Inserm, Université Toulouse III - Paul Sabatier (UPS), UMR1297, Toulouse, France. Electronic address: Laurent.Martinez@inserm.fr.
Jazyk: angličtina
Zdroj: Diabetes & metabolism [Diabetes Metab] 2023 Jan; Vol. 49 (1), pp. 101391. Date of Electronic Publication: 2022 Sep 26.
DOI: 10.1016/j.diabet.2022.101391
Abstrakt: Aim: Mitochondrial dysfunction is associated with the development of type 2 diabetes mellitus (T2DM). It is thus of clinical relevance to identify plasma biomarkers of mitochondrial dysfunction associated with the risk of T2DM. ATPase inhibitory factor 1 (IF1) endogenously inhibits mitochondrial ATP synthase activity. Here, we analyzed association of the plasma IF1 level with markers of glucose homeostasis and with the conversion to new-onset diabetes (NOD) in individuals with prediabetes.
Methods: In the IT-DIAB prospective study, the baseline plasma level of IF1 was measured in 307 participants with prediabetes. The primary outcome was the incidence of NOD within five years of follow-up. Cross-sectional analysis of the IF1 level was also done in two independent interventional studies. Correlations between plasma IF1 and metabolic parameters at baseline were assessed by Spearman's correlation coefficients, and the association with the risk of NOD was determined using Cox proportional-hazards models.
Results: In IT-DIAB, the mean IF1 plasma level was lower in participants who developed NOD than in those who did not (537 ± 248 versus 621 ± 313 ng/mL, P   = 0.01). The plasma IF1 level negatively correlated with clinical variables associated with obesity and insulin resistance, including the body mass index (r = -0.20, P  = 0.0005) and homeostasis model assessment of insulin resistance (HOMA-IR). (r = -0.37, P < 0.0001). Conversely, IF1 was positively associated with plasma markers of cardiometabolic health, such as HDL-C (r = 0.63, P  <  0.0001) and apoA-I (r = 0.33, P  <  0.0001). These correlations were confirmed in cross-sectional analyses. In IT-DIAB, the IF1 level was significantly associated with a lower risk of T2DM after adjustment for age, sex, and fasting plasma glucose (HR [95% CI] per 1 SD = 0.76 [0.62; 0.94], P   = 0.012).
Conclusion: We identified for the first time the mitochondrial-related biomarker IF1 as being associated with the risk of T2DM.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)
Databáze: MEDLINE
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