PMID- 36174852
OWN - NLM
STAT- MEDLINE
DCOM- 20230127
LR  - 20230322
IS  - 1878-1780 (Electronic)
IS  - 1262-3636 (Linking)
VI  - 49
IP  - 1
DP  - 2023 Jan
TI  - Plasma level of ATPase inhibitory factor 1 (IF1) is associated with type 2 
      diabetes risk in humans: A prospective cohort study.
PG  - 101391
LID - S1262-3636(22)00073-8 [pii]
LID - 10.1016/j.diabet.2022.101391 [doi]
AB  - 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.
CI  - Copyright (c) 2022 The Authors. Published by Elsevier Masson SAS.. All rights 
      reserved.
FAU - Pires Da Silva, Julie
AU  - Pires Da Silva J
AD  - Institut des Maladies Metaboliques et Cardiovasculaires, I2MC, Universite de 
      Toulouse, Inserm, Universite Toulouse III - Paul Sabatier (UPS), UMR1297, 
      Toulouse, France.
FAU - Wargny, Matthieu
AU  - Wargny M
AD  - Nantes Universite, CHU Nantes, CNRS, INSERM, l'institut du Thorax, 44000 Nantes, 
      France; Nantes Universite, CHU Nantes, Pole Hospitalo-Universitaire 11 : Sante 
      Publique, Clinique des donnees, INSERM, CIC 1413, F-44000 Nantes, France.
FAU - Raffin, Jeremy
AU  - Raffin J
AD  - Institut du Vieillissement, Gerontopole de Toulouse, Centre 
      Hospitalo-Universitaire de Toulouse, Toulouse, France.
FAU - Croyal, Mikael
AU  - Croyal M
AD  - Nantes Universite, CHU Nantes, CNRS, INSERM, l'institut du Thorax, 44000 Nantes, 
      France; Nantes Universite, CHU Nantes, CNRS, Inserm, BioCore, US16, SFR Bonamy, 
      F-44000 Nantes, France; CRNH-Ouest Mass Spectrometry Core Facility, 44000 Nantes, 
      France.
FAU - Duparc, Thibaut
AU  - Duparc T
AD  - Institut des Maladies Metaboliques et Cardiovasculaires, I2MC, Universite de 
      Toulouse, Inserm, Universite Toulouse III - Paul Sabatier (UPS), UMR1297, 
      Toulouse, France.
FAU - Combes, Guillaume
AU  - Combes G
AD  - Institut des Maladies Metaboliques et Cardiovasculaires, I2MC, Universite de 
      Toulouse, Inserm, Universite Toulouse III - Paul Sabatier (UPS), UMR1297, 
      Toulouse, France.
FAU - Genoux, Annelise
AU  - Genoux A
AD  - Institut des Maladies Metaboliques et Cardiovasculaires, I2MC, Universite de 
      Toulouse, Inserm, Universite Toulouse III - Paul Sabatier (UPS), UMR1297, 
      Toulouse, France; Service de Biochimie, Pole de biologie, Hopital de Purpan, CHU 
      de Toulouse, Toulouse, France.
FAU - Perret, Bertrand
AU  - Perret B
AD  - Institut des Maladies Metaboliques et Cardiovasculaires, I2MC, Universite de 
      Toulouse, Inserm, Universite Toulouse III - Paul Sabatier (UPS), UMR1297, 
      Toulouse, France; Service de Biochimie, Pole de biologie, Hopital de Purpan, CHU 
      de Toulouse, Toulouse, France.
FAU - Vellas, Bruno
AU  - Vellas B
AD  - Institut du Vieillissement, Gerontopole de Toulouse, Centre 
      Hospitalo-Universitaire de Toulouse, Toulouse, France; CERPOP UMR 1295, 
      University of Toulouse III, INSERM, UPS, Toulouse, France.
FAU - Guyonnet, Sophie
AU  - Guyonnet S
AD  - Institut du Vieillissement, Gerontopole de Toulouse, Centre 
      Hospitalo-Universitaire de Toulouse, Toulouse, France; CERPOP UMR 1295, 
      University of Toulouse III, INSERM, UPS, Toulouse, France.
FAU - Thalamas, Claire
AU  - Thalamas C
AD  - Institut des Maladies Metaboliques et Cardiovasculaires, I2MC, Universite de 
      Toulouse, Inserm, Universite Toulouse III - Paul Sabatier (UPS), UMR1297, 
      Toulouse, France; Clinical Investigation Center, Universite de Toulouse, INSERM, 
      Universite Toulouse III-Paul Sabatier, Toulouse University Hospitals, CIC1436, 
      F-CRIN/FORCE Network, Toulouse, France.
FAU - Langin, Dominique
AU  - Langin D
AD  - Institut des Maladies Metaboliques et Cardiovasculaires, I2MC, Universite de 
      Toulouse, Inserm, Universite Toulouse III - Paul Sabatier (UPS), UMR1297, 
      Toulouse, France; Service de Biochimie, Pole de biologie, Hopital de Purpan, CHU 
      de Toulouse, Toulouse, France; Institut Universitaire de France (IUF), Paris, 
      France.
FAU - Moro, Cedric
AU  - Moro C
AD  - Institut des Maladies Metaboliques et Cardiovasculaires, I2MC, Universite de 
      Toulouse, Inserm, Universite Toulouse III - Paul Sabatier (UPS), UMR1297, 
      Toulouse, France.
FAU - Viguerie, Nathalie
AU  - Viguerie N
AD  - Institut des Maladies Metaboliques et Cardiovasculaires, I2MC, Universite de 
      Toulouse, Inserm, Universite Toulouse III - Paul Sabatier (UPS), UMR1297, 
      Toulouse, France.
FAU - Rolland, Yves
AU  - Rolland Y
AD  - Institut du Vieillissement, Gerontopole de Toulouse, Centre 
      Hospitalo-Universitaire de Toulouse, Toulouse, France; CERPOP UMR 1295, 
      University of Toulouse III, INSERM, UPS, Toulouse, France.
FAU - Barreto, Philipe de Souto
AU  - Barreto PS
AD  - Institut du Vieillissement, Gerontopole de Toulouse, Centre 
      Hospitalo-Universitaire de Toulouse, Toulouse, France; CERPOP UMR 1295, 
      University of Toulouse III, INSERM, UPS, Toulouse, France.
FAU - Cariou, Bertrand
AU  - Cariou B
AD  - Nantes Universite, CHU Nantes, CNRS, INSERM, l'institut du Thorax, 44000 Nantes, 
      France.
FAU - Martinez, Laurent O
AU  - Martinez LO
AD  - Institut des Maladies Metaboliques et Cardiovasculaires, I2MC, Universite de 
      Toulouse, Inserm, Universite Toulouse III - Paul Sabatier (UPS), UMR1297, 
      Toulouse, France. Electronic address: Laurent.Martinez@inserm.fr.
CN  - MAPT/DSA Group
AD  - Members are listed in the acknowledgements.
LA  - eng
PT  - Journal Article
DEP - 20220926
PL  - France
TA  - Diabetes Metab
JT  - Diabetes & metabolism
JID - 9607599
RN  - 0 (Biomarkers)
RN  - EC 3.6.1.- (Adenosine Triphosphatases)
SB  - IM
MH  - Humans
MH  - *Diabetes Mellitus, Type 2
MH  - Prospective Studies
MH  - *Prediabetic State/metabolism
MH  - *Insulin Resistance
MH  - Cross-Sectional Studies
MH  - Biomarkers
MH  - Adenosine Triphosphatases
OTO - NOTNLM
OT  - ATP synthase
OT  - High-density lipoprotein
OT  - IF1
OT  - Mitochondria
OT  - New-onset diabetes
OT  - Type 2 diabetes
COIS- 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.
EDAT- 2022/09/30 06:00
MHDA- 2023/01/28 06:00
CRDT- 2022/09/29 19:36
PHST- 2022/07/25 00:00 [received]
PHST- 2022/09/15 00:00 [revised]
PHST- 2022/09/22 00:00 [accepted]
PHST- 2022/09/30 06:00 [pubmed]
PHST- 2023/01/28 06:00 [medline]
PHST- 2022/09/29 19:36 [entrez]
AID - S1262-3636(22)00073-8 [pii]
AID - 10.1016/j.diabet.2022.101391 [doi]
PST - ppublish
SO  - Diabetes Metab. 2023 Jan;49(1):101391. doi: 10.1016/j.diabet.2022.101391. Epub 
      2022 Sep 26.