Altered insulin sensitivity and immune function in patients with colorectal cancer.
Cancer
Cytokines
Gastrointestinal adenocarcinoma
Inflammasome
Inflammation
Insulin resistance
Journal
Clinical nutrition ESPEN
ISSN: 2405-4577
Titre abrégé: Clin Nutr ESPEN
Pays: England
ID NLM: 101654592
Informations de publication
Date de publication:
Dec 2023
Dec 2023
Historique:
received:
24
08
2023
revised:
01
09
2023
accepted:
19
09
2023
medline:
11
12
2023
pubmed:
7
12
2023
entrez:
6
12
2023
Statut:
ppublish
Résumé
Insulin resistance and chronic inflammation have been reported in patients with cancer. However, many of the underlying mechanisms and associations are yet to be unveiled. We examined both the level of insulin sensitivity and markers of inflammation in patients with colorectal cancer for comparison to controls. Clinical exploratory study of patients with colorectal cancer (n = 20) and matched controls (n = 10). Insulin sensitivity was quantified using the hyperinsulinemic normoglycemic clamp and blood samples were taken for quantification of several key, both intra- and extracellular, inflammatory markers. We analysed the differences in these parameters between the two groups. Patients exhibited both insulin resistance (M-value, patients median (Mdn) 4.57 interquartile range (IQR) 3.49-5.75; controls Mdn 5.79 (IQR 5.20-6.81), p = 0.049), as well as increased plasma levels of the pro-inflammatory cytokines IL-1β (patients Mdn 0.48 (IQR 0.33-0.58); controls Mdn 0.36 (IQR 0.29-0.42), p = 0.02) and IL-6 (patients Mdn 3.21 (IQR 2.31-4.93); controls Mdn 2.16 (IQR 1.50-2.65), p = 0.02). The latter is present despite an almost two to three fold decrease (p < 0.01) in caspase-1 activity, a facilitating enzyme of IL-1β production, within circulating immune cells. Patients with colorectal cancer displayed insulin resistance and higher levels of plasma IL-1β and IL-6, in comparison to matched healthy controls. The finding of a seemingly disconnect between inflammasome (caspase-1) activity and plasma levels of key pro-inflammatory cytokines in cancer patients may suggest that, in parallel to dysregulated immune cells, tumour-driven inflammatory pathways also are in effect.
Sections du résumé
BACKGROUND & AIMS
OBJECTIVE
Insulin resistance and chronic inflammation have been reported in patients with cancer. However, many of the underlying mechanisms and associations are yet to be unveiled. We examined both the level of insulin sensitivity and markers of inflammation in patients with colorectal cancer for comparison to controls.
METHODS
METHODS
Clinical exploratory study of patients with colorectal cancer (n = 20) and matched controls (n = 10). Insulin sensitivity was quantified using the hyperinsulinemic normoglycemic clamp and blood samples were taken for quantification of several key, both intra- and extracellular, inflammatory markers. We analysed the differences in these parameters between the two groups.
RESULTS
RESULTS
Patients exhibited both insulin resistance (M-value, patients median (Mdn) 4.57 interquartile range (IQR) 3.49-5.75; controls Mdn 5.79 (IQR 5.20-6.81), p = 0.049), as well as increased plasma levels of the pro-inflammatory cytokines IL-1β (patients Mdn 0.48 (IQR 0.33-0.58); controls Mdn 0.36 (IQR 0.29-0.42), p = 0.02) and IL-6 (patients Mdn 3.21 (IQR 2.31-4.93); controls Mdn 2.16 (IQR 1.50-2.65), p = 0.02). The latter is present despite an almost two to three fold decrease (p < 0.01) in caspase-1 activity, a facilitating enzyme of IL-1β production, within circulating immune cells.
CONCLUSION
CONCLUSIONS
Patients with colorectal cancer displayed insulin resistance and higher levels of plasma IL-1β and IL-6, in comparison to matched healthy controls. The finding of a seemingly disconnect between inflammasome (caspase-1) activity and plasma levels of key pro-inflammatory cytokines in cancer patients may suggest that, in parallel to dysregulated immune cells, tumour-driven inflammatory pathways also are in effect.
Identifiants
pubmed: 38057005
pii: S2405-4577(23)02147-2
doi: 10.1016/j.clnesp.2023.09.917
pii:
doi:
Substances chimiques
NLR Family, Pyrin Domain-Containing 3 Protein
0
Interleukin-6
0
Cytokines
0
Interleukin-1beta
0
Caspases
EC 3.4.22.-
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
193-200Informations de copyright
Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest Authors declare that they have no competing interests.