Low-grade inflammation in persons with recently diagnosed type 2 diabetes: The role of abdominal adiposity and putative mediators

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  • Sidsel L. Domazet
  • Thomas B. Olesen
  • Jacob V. Stidsen
  • Camilla K. Svensson
  • Jens S. Nielsen
  • Reimar W. Thomsen
  • Niels Jessen
  • Peter Vestergaard
  • Lepola, Mette Andersen
  • Hansen, Torben
  • Charlotte Brøns
  • Verena H. Jensen
  • Allan A. Vaag
  • Michael H. Olsen
  • Kurt Højlund

Aims: To determine the magnitude of the association between abdominal adiposity and low-grade inflammation in persons with recently diagnosed type 2 diabetes (T2D) and to determine to what extent this association is mediated by low physical activity level, hyperinsulinaemia, hyperglycaemia, dyslipidaemia, hypertension, and comorbidities. Materials and Methods: We measured waist circumference, clinical characteristics, and inflammatory markers i.e. tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and high-sensitivity C-reactive protein (hsCRP), in >9000 persons with recently diagnosed T2D. We applied multiple mediation analysis using structural equation modelling, with adjustment for age and sex. Results: Waist circumference as a proxy for abdominal adiposity was positively associated with all inflammatory markers. Hence, a one-standard deviation (SD) increase in waist circumference (SD = 15 cm) was associated with a 22%, 35%, and 46% SD increase in TNF-α (SD = 1.5 pg/mL), IL-6 (SD = 4.4 pg/mL), and hsCRP (SD = 6.9 mg/L), respectively. The level of hyperinsulinaemia assessed by fasting C-peptide was quantitatively the most important mediator, accounting for 9%–25% of the association between abdominal adiposity and low-grade inflammation, followed by low physical activity (5%–7%) and high triglyceride levels (2%–6%). Although mediation of adiposity-induced inflammation by greater comorbidity and higher glycated haemoglobin levels reached statistical significance, their impact was minor (1%–2%). Conclusions: In persons with recently diagnosed T2D, there was a clear association between abdominal adiposity and low-grade inflammation. A considerable part (20%–40%) of this association was mediated by other factors, with hyperinsulinaemia as a potentially important driver of adiposity-induced inflammation in T2D.

TidsskriftDiabetes, Obesity and Metabolism
Udgave nummer6
Sider (fra-til)2092-2101
StatusUdgivet - 2024

Bibliografisk note

Funding Information:
The authors wish to thank all participants in the DD2 study and the healthcare personnel who recruited the participants at the general practices, outpatient clinics, and pharmacies. The authors sincerely thank the DD2 management and the DD2 data managers. An abstract version of this study was presented at the EASD 2023 annual meeting in Hamburg, 5 October 2023. The DD2 study was supported by the Danish Agency for Science (grant no. 09–067009 and 09–075724), the Danish Health and Medicines Authority, the Danish Diabetes Association, the Region of Southern Denmark, and the Novo Nordisk Foundation (grant no. NNF17SA0030962‐2, NNF20O0063292 and NNF17SA0030364). Project partners are listed on the www.DD2.dk website. The study funders were not involved in the design of the study, the collection, analysis and interpretation of data, nor in the writing of this manuscript.

Funding Information:
Charlotte Brøns owns stock in Novo Nordisk. Michael Olsen has received payment or honoraria for lectures, presentations or educational events from AstraZeneca, Teva A/S, Novo Nordisk A/S and Boehringer Ingelheim, and has unpaid positions as chairperson of the Danish Hypertension Society and is a Nucleus Member of the Working Group for Prevention and Rehabilitation, Danish Society of Cardiology. Peter Vestergaard is head of research at Steno Diabetes Centre North Denmark funded by the Novo Nordisk Foundation. The remaining authors declare no conflicts of interest relevant to this work.

Publisher Copyright:
© 2024 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

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