What is the clinical evidence from this study?

Study design: Cohort. Population: Type 2 Diabetes (n=8900). Intervention: High Fibrosis-4 (FIB-4) index (>2.67) vs. Low FIB-4 index (<1.3). Primary outcome: Major adverse cardiovascular events (MACE) (p=≤0.001).

What does this research mean for the field?

In adults with type 2 diabetes, a higher Fibrosis-4 (FIB-4) index is associated with a greater burden of atherosclerotic cardiovascular disease, major adverse cardiovascular events, and all-cause mortality. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

This research aims to clarify the relationship between the FIB-4 index and ASCVD outcomes in adults with type 2 diabetes mellitus (T2DM).

June 7, 2026

1427-P: Fibrosis-4 Index Is Associated with ASCVD Burden, MACE, and Mortality in Real-World Type 2 Diabetes Cohort

Q: What are the key findings of this study?

In adults with T2DM, a higher FIB-4 index was associated with a stepwise increase in the prevalence of MACE (53.6% to 70.3%) and all-cause mortality (4.4% to 14.2%) (p≤0.001).

Q: What does this research mean for the field?

In adults with type 2 diabetes, a higher Fibrosis-4 (FIB-4) index is associated with a greater burden of atherosclerotic cardiovascular disease, major adverse cardiovascular events, and all-cause mortality. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

Q: What question did this study set out to answer?

This research aims to clarify the relationship between the FIB-4 index and ASCVD outcomes in adults with type 2 diabetes mellitus (T2DM).

Key Result

In adults with T2DM, a higher FIB-4 index was associated with a stepwise increase in the prevalence of MACE (53.6% to 70.3%) and all-cause mortality (4.4% to 14.2%) (p≤0.001).

Key Points

This research aims to clarify the relationship between the FIB-4 index and ASCVD outcomes in adults with type 2 diabetes mellitus (T2DM).
Conducted a unicenter retrospective study of 8,900 adults with T2DM from 2016-2023
Identified T2DM and ASCVD using ICD-10 codes and laboratory data
Categorized FIB-4 into low, indeterminate, and high for outcome analysis.
32.3% had low, 42.7% indeterminate, and 11.0% high FIB-4; higher FIB-4 linked to older age and chronic conditions
MACE prevalence increased across FIB-4 categories: 53.6% (low), 58.8% (indeterminate), 70.3% (high)
All-cause mortality rates also rose with FIB-4: 4.4% (low), 6.6% (indeterminate), 14.2% (high).

Study Design

Type

Cohort (n=8,900)

Multicenter

Structured PICO

Does a higher Fibrosis-4 (FIB-4) index predict greater ASCVD burden, MACE, and mortality in adults with Type 2 Diabetes?

Population

8,900 adults with type 2 diabetes receiving care at a single center between 2016 and 2023.

Exposure

High (>2.67) or indeterminate (1.3-2.67) Fibrosis-4 (FIB-4) index

Comparator

Low (<1.3) Fibrosis-4 (FIB-4) index

Outcome

ASCVD, MACE, and all-cause mortalitycomposite

In adults with T2DM, a higher FIB-4 index is significantly associated with increased prevalence of MACE, all-cause mortality, CAD, and stroke, suggesting its utility as an integrative cardiometabolic risk marker.

Main Result

Absolute Event Rate: 70.3% vs 53.6%

p-value: p=≤0.001

Abstract

Introduction and Objective: Advanced liver fibrosis, estimated by the fibrosis-4 (FIB-4) index, is linked to adverse cardiometabolic risk, but its relationship with atherosclerotic cardiovascular disease (ASCVD) burden and outcomes in adults with T2DM remains unclear. We examined the relationship between FIB-4, prevalent ASCVD, major adverse cardiovascular events (MACE), and mortality in a real-world T2DM cohort. Methods: We conducted a unicenter retrospective study of 8,900 adults with T2DM receiving care at Weill Cornell Medicine (2016-2023) using a validated electronic health record registry. T2DM and ASCVD were identified via ICD-10 codes, laboratory data, and medications; baseline data included demographics, cardiometabolic risk factors, and CVD subtypes (67% coronary artery disease CAD, 30% peripheral arterial disease PAD, 40% stroke). The mean age was 71 ± 11 years, 43% were female, and 70% resided in area deprivation index quintile 1. FIB-4 was categorized as low (1.3), indeterminate (1.3-2.67), or high (2.67). Outcomes were ASCVD, MACE, and all-cause mortality, stratified by sex. Results: Among 8,900 adults with T2DM, 32.3% had low, 42.7% indeterminate, and 11.0% high FIB-4. Higher FIB-4 was associated with older age, male sex, White race, lower LDL cholesterol and triglyceride levels, less use of SGLT2 inhibitors and GLP-1 receptor agonists, and greater prevalence of chronic kidney disease, heart failure, and atrial fibrillation (all p0.001), but not with body mass index, HbA1c, or insurance type. Prevalence of MACE (53.6%, 58.8%, 70.3%), all-cause mortality (4.4%, 6.6%, 14.2%), CAD (63.1%, 68.8%, 71.8%), and stroke (35.7%, 38.3%, 42.5%) increased stepwise across FIB-4 categories (all p≤0.001), while PAD did not differ. Associations persisted in men; in women, associations remained for MACE, stroke, and mortality, but not CAD. Conclusion: In adults with T2DM, higher FIB-4 is associated with greater ASCVD burden, MACE, and mortality, and may be a useful integrative cardiometabolic risk marker in secondary prevention. Disclosure M.I. Manolas: None. S. Barenbaum: None. M. Yeung: None. X. Ma: None. S. Kumar: Consultant; Current; Boehringer Ingelheim International GmbH, Gilead Sciences, Inc. Speaker's Bureau; Current; Gilead Sciences, Inc. Research Support; Current; Gilead Sciences, Inc. Advisory Panel; Current; GlaxoSmithKline plc. Speaker's Bureau; Current; GlaxoSmithKline plc. Consultant; Current; Ipsen Biopharmaceuticals, Inc. Speaker's Bureau; Current; Ipsen Biopharmaceuticals, Inc. Consultant; Current; Madrigal Pharmaceuticals, Inc. Research Support; Current; Madrigal Pharmaceuticals, Inc. Speaker's Bureau; Current; Madrigal Pharmaceuticals, Inc. Advisory Panel; Current; Novo Nordisk. Consultant; Current; Novo Nordisk. Research Support; Current; Novo Nordisk. Speaker's Bureau; Current; Novo Nordisk, Boehringer Ingelheim International GmbH. S.R. Kashyap: Other - adjudication committee member; Current; Medpace. Other - advisor; Current; Madrigal Pharmaceuticals, Inc. Other - clinical trial; Ended; Fractyl Health, Inc., Janssen Pharmaceuticals, Inc.

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Cite This Study

Manolas et al. (Fri,) conducted a cohort in Type 2 Diabetes (n=8,900). High Fibrosis-4 (FIB-4) index (>2.67) vs. Low FIB-4 index (<1.3) was evaluated on Major adverse cardiovascular events (MACE) (p=≤0.001). In adults with T2DM, a higher FIB-4 index was associated with a stepwise increase in the prevalence of MACE (53.6% to 70.3%) and all-cause mortality (4.4% to 14.2%) (p≤0.001).

synapsesocial.com/papers/6a250b4c7def13d035e1b3ef https://doi.org/https://doi.org/10.2337/db26-1427-p

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