Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Alerts
  • Advertising
  • Job board
  • Subscribe
  • Contact
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Author's Takes
  • Reviews
    • View all reviews ...
    • Aging (Jul 2022)
    • Next-Generation Sequencing in Medicine (Jun 2022)
    • New Therapeutic Targets in Cardiovascular Diseases (Mar 2022)
    • Immunometabolism (Jan 2022)
    • Circadian Rhythm (Oct 2021)
    • Gut-Brain Axis (Jul 2021)
    • Tumor Microenvironment (Mar 2021)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Commentaries
    • Concise Communication
    • Editorials
    • Viewpoint
    • Top read articles
  • Clinical Medicine
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Author's Takes
  • In-Press Preview
  • Commentaries
  • Concise Communication
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Alerts
  • Advertising
  • Job board
  • Subscribe
  • Contact
Therapeutic approaches targeting inflammation for diabetes and associated cardiovascular risk
Allison B. Goldfine, Steven E. Shoelson
Allison B. Goldfine, Steven E. Shoelson
Published January 3, 2017
Citation Information: J Clin Invest. 2017;127(1):83-93. https://doi.org/10.1172/JCI88884.
View: Text | PDF
Review Series

Therapeutic approaches targeting inflammation for diabetes and associated cardiovascular risk

  • Text
  • PDF
Abstract

Obesity-related sub-acute chronic inflammation has been associated with incident type 2 diabetes and atherosclerotic cardiovascular disease. Inflammation is increasingly considered to be a pathologic mediator of these commonly co-occurring diseases. A growing number of preclinical and clinical studies support the inflammatory hypothesis, but clinical trials to confirm the therapeutic potential to target inflammation to treat or prevent cardiometabolic conditions are still ongoing. There are multiple inflammatory signaling pathways. Regulation is complex, with substantial crosstalk across these multiple pathways. The activity of select pathways may be differentially regulated in different tissues. Pharmacologic approaches to diabetes management may have direct or indirect antiinflammatory effects, the latter potentially attributable to an improved metabolic state. Conversely, some antiinflammatory approaches may affect glucose metabolism and cardiovascular health. To date, clinical trials suggest that targeting one portion of the inflammatory cascade may differentially affect dysglycemia and atherothrombosis. Understanding the underlying biological processes may contribute to the development of safe and effective therapies, although a single approach may not be sufficient for optimal management of both metabolic and athrothrombotic disease states.

Authors

Allison B. Goldfine, Steven E. Shoelson

×

Figure 1

Clinical trials to target inflammation in T2D and ASCVD.

Options: View larger image (or click on image) Download as PowerPoint
Clinical trials to target inflammation in T2D and ASCVD.
Heightened infl...
Heightened inflammation that often accompanies obesity or excessive weight gain is a hypothesized mechanism for the associated increase in risk for T2D and ASCVD. Signaling pathways (e.g., NF-κB, inflammasome) and specific proinflammatory cytokines (e.g., TNF-α, IL-1β) have been both implicated in these pathologic processes and are potential targets for reversal and risk reduction. Salicylate and low-dose methotrexate (LDM) inhibit NF-κB as a downstream consequence of AMPK activation. IL-1β blockade mediated by IL-1Ra or specific antibodies inhibits IL-1β action and suppresses IL-1β production by dampening its self-induction; the same effect is potentially true for TNF-α blockade. Randomized, placebo controlled, double-masked clinical trials of salsalate (1–7, 128–132, 134, 137), LDM (8, 144), IL1Ra (9–11, 178, 179, 181) anti–IL-1β (181, 184, 191, 192), and anti–TNF-α (12, 169) are being used to determine whether these antiinflammatory approaches affect disease risk in T2D and ASCVD. Reported randomized trials of 3 months duration or longer are referenced. CANTOS, Canakinumab Anti-inflammatory Thrombosis Outcomes Study; CIRT, Cardiovascular Inflammation Reduction Trial; TINSAL T2D, Targeting Inflammation Using Salsalate for Type 2 Diabetes.

Copyright © 2022 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts