Interleukin-1β in circulating mononuclear cells predicts steatotic liver disease improvement after weight loss in subjects with obesity and prediabetes or type 2 diabetes
- Design
- Randomized trial · 16 participants · Mixed outcome
- Match to healthy normal-weight adults aged 55–75
- Different population[Auto] Participants had obesity/overweight (age/BMI not reported in abstract).
- Could weight loss explain it?
- Possibly[Auto] Participants had obesity and/or type 2 diabetes and the abstract does not separate direct drug effects from weight loss or glycaemic improvement.
- Study tier
- Study tier 3[Auto] Small or short randomized trial (auto-provisional).
- Assessment
- Version 1 · automatic, not yet reviewed by a person · Sep 13, 2026
Study facts come from the paper. Population match, weight-loss explanation and study tier are our judgments, made against the reference group of healthy normal-weight adults aged 55–75.
[Auto, unreviewed; quoted from abstract conclusions] 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.
01Findings
What the study reported
- Drugs
- Liraglutide
- Primary outcome
- Not extracted
- Effect
- Not extracted
- 95% confidence interval
- Not extracted
- Follow-up
- Not stated
- Adverse events
- Not extracted
- Limitations
- Auto-classified from abstract only; effect estimates, adverse events and limitations not extracted. Requires manual review.
Who was studied
- Obesity status
- obesity/overweight present (all or most)
- Diabetes status
- diabetes mentioned
- Baseline condition
- MASH / MASLD
- Sample size
- 16
Study quality details
- Study design
- Randomized controlled trial
- Sample size
- 16
- Randomization
- yes
- Blinding
- not stated
- Comparator
- not stated
- Follow up duration
- not stated
- Outcome type
- mixed
- Replication
- not assessed (auto)
- Consistency with other evidence
- not assessed (auto)
- Population applicability
- INDIRECT
- Statistical precision
- CI reported: 95% CI - 12
- Funding conflicts
- no
- Peer review status
- yes
01bRisk of bias
How much the result can be relied on
Risk of bias is judged per result, not per paper: the same study can report one marker at low risk and another at high. Two reviewers assess each result independently against a written guide, and every domain judgment below carries its reasoning and the sentences it rests on.
These words are not quality scores. On the RoB 2 scale, High risk of bias is the worst rating a result can receive and Low risk of bias is the best — the opposite of how the same words read on some other scales. Levels are always written out in full here for that reason.
hs-C-reactive protein (circulating, high-sensitivity immunoassay), change from baseline to achievement of the 7% weight-loss target · end of intervention = achievement of 7% weight loss; median time-to-weight-loss 4 months
High risk of bias · RoB 2 · Two reviewers agreed on every domain
How the overall was reached: High at D2, D3 and D5 independently. Beyond the domain algorithm, the result as framed for O4 has a defect the domains do not capture and the guide (v1.3 ruling 7, Limit) directs be carried in the overall judgment with a written reason: for hs-CRP there is no between-arm analysis of any kind in this paper — no treatment difference, no CI, no p. The weight-matched design is genuinely the right design for C-001, and a null from it would be informative; but nothing was tested between arms for the graded circulating marker, and a comparison that was never made cannot be reported as a null. What the paper supports is that hs-CRP fell within both arms after a 7% weight loss, which is CONSISTENT_WITH_BUT_DOES_NOT_TEST for C-001.
| Domain | Judgment and reasoning |
|---|---|
| D1 · Randomisation process Some concerns about risk of bias | Sequence generation is adequately described (computer-generated block randomization, 1:1). Allocation concealment is not described: the paper says subjects were assigned a consecutive random number by order of inclusion, which describes sequence application, not a concealment mechanism (no sealed envelopes, no central/pharmacy allocation, no IVRS/IWRS). RULE USED: the guide's D1 large-industry-trial presumption (domain rule, plus v1.2 ruling 6) does NOT apply — this is a small single-centre investigator-initiated academic trial funded by the Italian Ministry of University and Research (PRIN 2010JS3PMZ), with no registration number given anywhere in the bundle, so nothing is inherited and the "small academic trials must describe their method, or the answer is NI" limb governs. Concealment is therefore NI. Baseline table is mostly balanced but smoking differs (0.0% lifestyle vs 23.5% liraglutide, p=0.045) in a 32-person sub-sample; this is a sub-study imbalance rather than evidence against the parent randomization, but it is not reassuring. Per guide ruling 4, D1 stays trial-level: the non-randomized character of the target-achiever subset is carried in D3, D5 and overall, not here.Block randomization was performed by computer-generated random allocation sequence. The subjects were assigned a consecutive random number based on the order of inclusion in the study and were then allocated to one of the two treatment groups. |
| D2 · Deviations from intended interventions High risk of bias | Open-label by construction: daily subcutaneous liraglutide versus nutritionist-led lifestyle counselling, with no blinding of participants or carers claimed anywhere. Per the guide's D2 domain rule, awareness alone rarely biases a laboratory biomarker, so the judgment rests on the analysis population. It fails there. The analysis is not an intention-to-treat estimate of the effect of assignment: participants who did not reach the 7% target within 15 months were "considered withdrawn", and only target-achievers with isolable PBMCs (32/62, 52%) appear. Analysing a set defined by attaining a post-randomization, outcome-correlated criterion is precisely an inappropriate analysis for the assignment effect; no ITT analysis of this sub-study exists. The co-interventions also differ in a way that the design intends but the contrast cannot separate: the lifestyle arm received a structured programme while the liraglutide arm received unstructured advice, so the "weight-matched" contrast is liraglutide+advice versus an active behavioural intervention, not liraglutide versus an inert comparator.Patients not achieving the weight loss goal within 15 months of the initiation of the randomized treatment, as well as those not completing the study for decision of the patient and/or of the investigator, were considered withdrawn from the study. Patients in the liraglutide arm received some advises on physical activity and diet, without a structured intervention program. |
| D3 · Missing outcome data High risk of bias | Both prongs of the guide's D3 rule are engaged on the first limb and the second cannot be checked. Outcome data are available for 32 of 62 randomized participants (51.6%), so 48% are missing — far beyond the 20% threshold, hence PN to "data available for nearly all". The per-arm denominators of the parent 62 are not reported, so whether missingness differs by more than 5 points between arms is NI; the analysed split (15 lifestyle vs 17 liraglutide) is not the randomized split. Missingness is very likely to depend on the true value: participants enter the analysis only if they achieved a 7% weight loss, and weight loss is the variable this design uses to explain inflammatory change, so the excluded are systematically those in whom the metabolic and inflammatory response was smallest. The stated reason for the subset (PBMC isolation feasibility) covers only part of the attrition and is itself unverified. No sensitivity analysis of any kind addresses value-dependent missingness.The number of participants included in the analysis (32 out of 62) was determined by the feasibility of isolating PBMCs from blood samples at the time of scheduled visits in the main study. 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. |
| D4 · Measurement of the outcome Low risk of bias | hs-CRP is an objective central-laboratory high-sensitivity immunoassay, and per the guide's D4 rule measurement bias is Low unless the assay changed partway through or differed between arms; neither is reported or suggested. Samples in both arms were drawn fasting at the same two protocol points and handled identically. Outcome assessors are not described as blinded, but an immunoassay result is not susceptible to assessor judgment. One residual caveat that does not change the judgment: the two measurement points are not at a fixed calendar time but at whenever each participant hit the target, so the interval differs between and within arms.Serum hs-CRP concentrations were measured using highly sensitive immunoassay. At admission to the study and after the achievement of the weight loss goal, venous blood samples were collected after an overnight fasting and frozen at - 20 degrees C for subsequent biochemical measurements. |
| D5 · Selection of the reported result High risk of bias | Guide v1.3 ruling 7, first limb: the authors state in their own words that this is a post hoc analysis and that no a priori power analysis was performed. That is affirmative evidence of non-prespecification, and D5 is High — not the Some-concerns floor that mere protocol unretrievability would give. The paper's own claim of "two pre-specified intergroup contrasts" is a claim, not verification (ruling 7, third limb): no protocol, SAP or registry entry was retrievable, and no registration number is given. Compounding this, the sub-study's declared outcomes of interest are delta MASLD and PBMC IL-1beta; hs-CRP is reported only as one row among ~30 in a table of within-arm p values with no multiplicity control and no between-arm estimate, which is selective in shape even if not in intent. The post hoc power statement also shows the analysis is powered only to detect a 1-SD between-group difference — a very large effect — so any absence of a between-arm difference here is uninformative rather than null.This is a post-hoc analysis of a published study [ 18 ]. Although no a priori (prospective) power analysis was performed for this sub-study, a post hoc power analysis indicated that with 32 participants we had approximately 90% power (alpha = 0.05) to detect a mean difference of 1 standard deviation (SD) in the changes in MASLD extent and IL-1beta expression between the liraglutide and lifestyle intervention groups. |
02Funding
Funding and conflicts
- Funding
- Italian Ministry of University and Research
- Industry funded
- No
- Manufacturer
- None identified
- Sponsor role
- no manufacturer funding identified
- Author conflicts
- Declarations. Ethics approval and consent to participate: The trial was approved by the Italian Ethics Committee of the University of Chieti (Approval n. 10 (protocol 20131) 23.05.2013). Each patient provided written informed consent before participation. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.
- Independent replication
- unknown
Funding is shown on every study and never used to score it.
04Source
The source, as retrieved
Abstract
[BACKGROUND] Metabolic dysfunction-associated steatotic liver disease (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.
Where this record came from
| Source | Retrieved | Identifier |
|---|---|---|
| pubmed | Sep 13, 2026 | 40514652 first ingestion |