TOPLINE

Adults with type 2 diabetes and overweight or obesity who had higher concentrations of interleukin-6 (IL-6) had an increased risk for incident heart failure (HF), and an intensive weight-loss lifestyle program was linked to a reduction in concentrations of IL-6 at 1 year. Concentrations of high-sensitivity C-reactive protein (hs-CRP) did not independently predict the risk for HF.

METHODOLOGY

• Look AHEAD, a randomized trial, assessed whether intensive lifestyle changes reduced the cardiovascular risk in adults with type 2 diabetes and obesity. In this post hoc analysis, researchers assessed whether concentrations of hs-CRP and IL-6 at baseline were associated with atherosclerotic events and HF and how the lifestyle program affected IL-6 concentrations.
• The original trial included adults aged 45-76 years with type 2 diabetes and BMI of 25 or above across 16 sites in the US between 2001 and 2004.
• Measurements of hs-CRP at baseline were available for 1902 patients (mean age, 58 years; 57.6% women). Measurements of IL-6 at baseline were available for 1507 patients, with a similar distribution of age and sex.
• Patients were randomly assigned to receive either an intensive lifestyle intervention targeting a weight loss of at least 7% through diet and exercise or diabetes support and education with general guidance.
• Key clinical outcomes included a composite outcome of atherosclerotic cardiovascular disease (ASCVD) and incident events of HF over a median follow-up of 12 years.

TAKEAWAY

• In fully adjusted analyses, the concentration of hs-CRP at baseline was not significantly associated with the composite ASCVD outcome or incident HF.
• Each 1-SD higher log-transformed concentration of IL-6 was associated with a 43% increased risk for incident HF (P < .001) in analyses adjusted for multiple variables including the use of statins. The risk was 92% higher in patients without prior cardiovascular disease (P < .001).
• At 1 year, patients who received an intensive lifestyle intervention had a greater reduction in concentrations of IL-6 than those who received diabetes support and education (median change, -28.7% vs -11.8%; P = .01).
• In adjusted analysis including both inflammatory biomarkers, IL-6 remained significantly associated with an increased risk for incident HF (P = .004), whereas hs-CRP was not.

IN PRACTICE

"[The] study findings highlight the effect of a weight-loss strategy on IL-6 and the role of this inflammatory biomarker in HF risk assessment among adults with type 2 diabetes," the researchers wrote.

"This study supports the concept that residual inflammatory risk should no longer be viewed solely through the lens of atherosclerosis," Jelani K. Grant, MD, MHS, and Michelle D. Kelsey, MD, wrote in an editorial comment.

SOURCE

The study was led by Kershaw V. Patel, MD, MSCS, of Houston Methodist DeBakey Heart and Vascular Center in Houston. It was published online on September 3 in JACC: Heart Failure.

LIMITATIONS

The analysis was post hoc, and the original trial did not meet its primary endpoint. IL-6 concentrations were assessed over only 1 year and may not have reflected chronic inflammation. The study was performed in a subset of participants and may not have represented the full cohort.

DISCLOSURES

The original study received support from the National Heart, Lung, and Blood Institute. Multiple authors reported serving in advisory roles for, or receiving consulting fees, research support, or honoraria from various research organizations and pharmaceutical and medical device companies. Additionally, one author reported being the founder of ReCODE Medical, outside of the submitted work. Detailed author disclosures are reported in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.