Endre søk
RefereraExporteraLink to record
Permanent link

Direct link
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annet format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annet språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
Serum cathepsin S is associated with decreased insulin sensitivity and the development of diabetes type 2 in a community-based cohort of elderly men
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.ORCID-id: 0000-0003-2256-6972
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.ORCID-id: 0000-0003-2247-8454
Vise andre og tillknytning
2013 (engelsk)Inngår i: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 36, nr 1, s. 163-165Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

OBJECTIVE:

To investigate associations between serum cathepsin S, impaired insulin sensitivity, defective insulin secretion, and diabetes risk in a community-based sample of elderly men without diabetes.

RESEARCH DESIGN AND METHODS:

Serum cathepsin S, insulin sensitivity (euglycemic-hyperinsulinemic clamp), and insulin secretion (early insulin response during an oral glucose tolerance test) were measured in 905 participants of the Uppsala Longitudinal Study of Adult Men (mean age, 71 years). Thirty participants developed diabetes during 6 years of follow-up.

RESULTS:

After adjustment for age, anthropometric variables, and inflammatory markers, higher cathepsin S was associated with decreased insulin sensitivity (regression coefficient per SD increase -0.09 [95% CI -0.14 to -0.04], P = 0.001), but no association with early insulin response was found. Moreover, higher cathepsin S was associated with a higher risk for developing diabetes (odds ratio per SD increase 1.48 [1.08-2.01], P = 0.01).

CONCLUSIONS:

Cathepsin S activity appears to be involved in the early dysregulation of glucose and insulin metabolism.

sted, utgiver, år, opplag, sider
2013. Vol. 36, nr 1, s. 163-165
Emneord [en]
Cathepsin S inflammation adipose tissue insulin resistance diabetes
HSV kategori
Identifikatorer
URN: urn:nbn:se:uu:diva-233997DOI: 10.2337/dc12-0494ISI: 000314465700048PubMedID: 22923671OAI: oai:DiVA.org:uu-233997DiVA, id: diva2:755055
Tilgjengelig fra: 2014-10-13 Laget: 2014-10-13 Sist oppdatert: 2018-06-25bibliografisk kontrollert
Inngår i avhandling
1. Cathepsin S as a Biomarker of Low-grade Inflammation, Insulin Resistance, and Cardiometabolic Disease Risk
Åpne denne publikasjonen i ny fane eller vindu >>Cathepsin S as a Biomarker of Low-grade Inflammation, Insulin Resistance, and Cardiometabolic Disease Risk
2014 (engelsk)Doktoravhandling, med artikler (Annet vitenskapelig)
Abstract [en]

Cathepsin S is a protease important in major histocompatibility complex (MHC) class II antigen presentation and also in degrading the extracellular matrix. Studies, most of them experimental, have shown that cathepsin S is involved in different pathological conditions such as obesity, inflammation, atherosclerosis, diabetes, and cancer.

The overall hypothesis of this report is that high levels of circulating cathepsin S, is a biomarker that reflects pathology induced by inflammation and obesity. The overall aim of this report was to investigate possible associations between circulating cathepsin S, inflammation, glucometabolic disturbance, and its associated diseases in the community. As cathepsin S appears to be a novel risk marker for several pathological conditions, we also wanted to examine the effect of dietary intervention on circulating cathepsin S concentrations.

This thesis is based on data from three community-based cohorts, the Uppsala longitudinal study of adult men (ULSAM), the prospective investigation of the vasculature in Uppsala seniors (PIVUS), and a post-hoc study from the randomized controlled NORDIET trial.

In the first study, we identified a cross-sectional positive association between serum cathepsin S and two markers of cytokine-mediated inflammation, CRP and IL-6. These associations were similar in non-obese individuals. In longitudinal analyses, higher cathepsin S at baseline was associated with higher CRP and IL-6 levels after six years of follow-up. In the second study, we identified a cross-sectional association between increased serum levels of cathepsin S and reduced insulin sensitivity. These associations were similar in non-obese individuals. No significant association was observed between cathepsin S and insulin secretion. In longitudinal analysis, higher cathepsin S levels were associated with an increased risk of developing diabetes during the six-year follow-up. In the third study, we found that higher serum levels of cathepsin S were associated with increased mortality risk. Moreover, in the ULSAM cohort, serum cathepsin S was independently associated with cause-specific mortality from cardiovascular disease and cancer. In the fourth study, we identified that adherence to an ad libitum healthy Nordic diet for 6 weeks slightly decreased the levels of plasma cathepsin S in normal or marginally overweight individuals, relative to the control group. Changes in circulating cathepsin S concentrations were correlated with changes in body weight, LDL-C, and total cholesterol.

Conclusion: This thesis shows that circulating cathepsin S is a biomarker that independently reflects inflammation, insulin resistance, the risk of developing diabetes, and mortality risk. Furthermore, a Nordic diet moderately reduced cathepsin S levels in normal-weight and overweight men and women. This effect may be partially mediated by diet-induced weight loss and possibly by reduced LDL-C concentrations.

 

sted, utgiver, år, opplag, sider
Uppsala: Acta Universitatis Upsaliensis, 2014. s. 48
Serie
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1046
Emneord
epidemiology, cathepsin S, inflammation, insulin resistance, diabetes, mortality, cardiovascular mortality, cancer mortality, healthy Nordic diet.
HSV kategori
Identifikatorer
urn:nbn:se:uu:diva-234027 (URN)978-91-554-9083-6 (ISBN)
Disputas
2014-12-04, sal IV, Universitetshuset, Biskopsgatan 3, 751 05 Uppsala, 13:00 (svensk)
Opponent
Veileder
Tilgjengelig fra: 2014-11-12 Laget: 2014-10-13 Sist oppdatert: 2018-06-25

Open Access i DiVA

fulltext(222 kB)136 nedlastinger
Filinformasjon
Fil FULLTEXT01.pdfFilstørrelse 222 kBChecksum SHA-512
6bf621d3dcaa4c966e7a52ff4fd6454b3937da5b436b41c2bcfc1fb184a13d068929a3173e2c7d1c57a3e1d6f88c8cfd0a009d626cac065174dddeae1d7baab5
Type fulltextMimetype application/pdf

Andre lenker

Forlagets fulltekstPubMed

Søk i DiVA

Av forfatter/redaktør
Jobs, ElisabethRisérus, UlfIngelsson, ErikSundström, JohanNerpin, ElisabetIggman, DavidBasu, SamarLarsson, AndersLars, LindÄrnlöv, Johan
Av organisasjonen
I samme tidsskrift
Diabetes Care

Søk utenfor DiVA

GoogleGoogle Scholar
Totalt: 136 nedlastinger
Antall nedlastinger er summen av alle nedlastinger av alle fulltekster. Det kan for eksempel være tidligere versjoner som er ikke lenger tilgjengelige

doi
pubmed
urn-nbn

Altmetric

doi
pubmed
urn-nbn
Totalt: 602 treff
RefereraExporteraLink to record
Permanent link

Direct link
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annet format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annet språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf