Higher levels of interleukin-1β in blood immune cells predict liver fat improvement after weight loss in people with obesity and prediabetes or type 2 diabetes
A median decrease of -23.0 in (MASLD) extent was observed in subjects with low baseline IL-1β levels after weight loss.
IL-1β levels were positively correlated with body mass index, fasting plasma glucose, HbA1c, visceral adipose tissue, and MASLD extent at baseline.
Both liraglutide and lifestyle changes led to a significant but comparable reduction in IL-1β levels following weight loss.
Weight loss was associated with improvements in glycaemic control, C reactive protein, body mass index, and MASLD in both groups.
Baseline IL-1β levels independently predicted the extent of MASLD decrease, with higher levels associated with less improvement.
Subjects in the highest tertile of IL-1β had a median MASLD decrease of -8.0, compared to -23.0 in the lowest tertile.
Simplified
BACKGROUND: (MASLD) is a major cardiovascular risk (CV) factor. Interleukin-1β (IL-1β), a cytokine involved in the pathogenesis of obesity-associated inflammation and type 2 diabetes (T2D), promotes hepatic steatosis. The Canakinumab Anti-inflammatory Thrombosis Outcome (CANTOS) trial showed that the inhibition of the IL-1β pathway was associated with a reduction of CV events in high-risk patients. The present study was designed to determine: (i) whether an equal degree of weight loss by liraglutide or lifestyle changes has a different impact on MASLD extent and IL-1β expression in peripheral blood mononuclear cells from obese subjects with prediabetes or early T2D; (ii) whether baseline IL-1β levels may predict the extent of weight loss and related metabolic changes.
METHODS: Thirty-two obese subjects with prediabetes (n = 16) or newly diagnosed T2D (n = 16), were randomized to the glucagon-like peptide receptor agonist (GLP1-RA) liraglutide or lifestyle counselling until achieving a comparable weight loss. Visceral adipose tissue (VAT) and gene expression of IL-1β in peripheral blood mononuclear cells were assessed by magnetic resonance and real time PCR, respectively.
RESULTS: At baseline, IL-1β was positively correlated to body mass index (BMI), fasting plasma glucose, HbA1c, VAT, MASLD extent, platelet count, chemerin and interleukin-1 receptor antagonist (IL1-RA). After achievement of the weight loss target in the two groups, a significant but comparable reduction of IL-1β (p for difference = 0.56) was observed in both arms, in parallel with a comparable improvement in glycaemic control, C reactive protein (CRP), BMI and MASLD. Furthermore, basal IL-1β levels independently predicted the extent of MASLD decrease (p = 0.030); subjects in the highest tertile showed a median decrease of - 8.0 (95% CI - 12.3 to - 4.8) compared with - 23.0 (95% CI - 39.5 to - 16.3) in the lowest tertile.
CONCLUSION: In patients with obesity with initial impairment of glucose metabolism successful weight loss is associated with a reduction of both IL-1β levels and MASLD degree. Of interest, basal levels of IL-1β predict the extent of MASLD improvement, regardless of the intervention. Our results may set the stage for ad-hoc studies investigating the usefulness of baseline IL-1β a level as a drug-response biomarker.
Key numbers
-8.0
Median Decrease
Median decrease in for patients in the highest IL-1β tertile.
7%
Weight Loss Target
Weight loss goal for participants in both intervention groups.
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