Association Between Sleep Patterns and the Risk of Cardiometabolic Diseases or Cardiometabolic Multimorbidity and the Mediating Role of Metabolic Biomarkers: A Prospective Study of the UK Biobank Cohort

Q: What is the clinical evidence from this study?

Study design: Cohort. Population: Cardiometabolic diseases (CMDs) and cardiometabolic multimorbidity (CMM) (n=190827). Intervention: Joint sleep pattern (per 1-decrement in healthy sleep score, or poor sleep pattern with score = 4 out of 5 low-risk sleep factors). Primary outcome: Incidence of cardiometabolic multimorbidity (CMM, defined as >=2 of T2DM, stroke, and CHD) and total cardiometabolic diseases (CMDs) (HR 1.151, 95% CI 1.108-1.196).

Duqiu Liu; Yi Guo; Guochen Li; Chenxing Yang; Jingjie Xiong; Shan Deng; Ru Chen

doi:10.3390/healthcare14152296

July 29, 2026HealthcareOpen Access

Association Between Sleep Patterns and the Risk of Cardiometabolic Diseases or Cardiometabolic Multimorbidity and the Mediating Role of Metabolic Biomarkers: A Prospective Study of the UK Biobank Cohort

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Key result

Worse sleep score linked to ~15% higher cardiometabolic multimorbidity risk per 1-point drop.

HR 1.151
95% CI 1.108-1.196
n=190,827

Why the study?

Does a poor joint sleep pattern increase the risk of incident cardiometabolic diseases and cardiometabolic multimorbidity in middle-aged and older adults, and is this association mediated by circulating metabolic biomarkers?

Key Points

To evaluate the prospective associations between joint sleep patterns and incident cardiometabolic diseases and multimorbidity, and to determine the mediating roles of circulating metabolic biomarkers.
Prospective cohort study of 190,827 participants from the UK Biobank followed for a median of 13.5 years.
Joint sleep patterns were assessed via a healthy sleep score comprising five factors: chronotype, sleep duration, insomnia, snoring, and excessive daytime sleepiness.
Cox proportional hazards models and mediation analyses evaluated links between sleep scores, 152 plasma metabolites, and incident cardiometabolic diseases (type 2 diabetes, coronary heart disease, and stroke) and multimorbidity.
During follow-up, 24,602 incident cardiometabolic disease cases and 2,740 incident multimorbidity cases occurred; each 1-decrement in sleep score was associated with higher risks of cardiometabolic diseases (HR 1.105, 95% CI 1.090–1.119) and multimorbidity (HR 1.151, 95% CI 1.108–1.196).
Compared with healthy sleep, poor sleep was associated with increased risks of multimorbidity (HR 1.653, 95% CI 1.419–1.926) and total cardiometabolic diseases (HR 1.430, 95% CI 1.352–1.512), but sleep score was not associated with progressing from an initial disease to multimorbidity.
Sleep patterns were associated with 152 metabolites, predominantly lipoproteins; 119 metabolites significantly mediated the association with multimorbidity, led by glycoprotein acetyls (mediation proportion 7.68%, 95% CI 5.81–11.13%) and triglycerides in small HDL (7.68%, 95% CI 5.89–10.95%).

Study Design

Type

Cohort (n=190,827)

Multicenter

Yes

Structured PICO

Does a poor joint sleep pattern increase the risk of incident cardiometabolic diseases and cardiometabolic multimorbidity in middle-aged and older adults, and is this association mediated by circulating metabolic biomarkers?

P

Population

190,827 UK Biobank adults aged 40-69 years without baseline type 2 diabetes, stroke, or coronary heart disease, followed for a median of 13.5 years.

E

Exposure

Poor or intermediate joint sleep patterns (or per 1-point decrement in healthy sleep score ranging from 0 to 5, based on 5 self-reported sleep factors: chronotype, sleep duration 7-8 h/day, absence of insomnia, no snoring, and no frequent daytime sleepiness) and associated plasma metabolic biomarkers (168 directly measured NMR metabolites).

C

Comparator

Healthy sleep pattern (healthy sleep score >= 4)

O

Outcome

Incidence of total cardiometabolic diseases (CMDs: presence of CHD, stroke, or T2DM) and cardiometabolic multimorbidity (CMM: presence of at least two of T2DM, stroke, and CHD) over a median follow-up of 13.5 (IQR 12.6-14.2) years, identified via ICD-10 codes linked to self-report, primary care, hospital inpatient data, and death registries.hard clinical

Main Result

Hazard Ratio: 1.151 (95% CI 1.108–1.196)

Limitations

All sleep behaviors were self-reported at baseline, introducing potential recall and reporting bias.
Plasma metabolomics were measured only once at baseline using an NMR platform, preventing assessment of longitudinal changes and leaving possibility of reverse causality.
Plasma samples were collected under non-fasting conditions, which may increase variation in metabolite concentrations.
The majority of participants were white, limiting generalizability to other ethnic populations.
Residual and unknown confounding (e.g., diet quality, sleep apnea severity, mental health status, occupational schedules) could not be completely excluded.
Self-reported sleep behaviors at baseline could introduce potential bias.
Plasma metabolomics were measured only once at baseline using an NMR profiling platform, precluding longitudinal metabolic tracking and allowing potential reverse causality.
Plasma samples were collected under non-fasting conditions, increasing variability in metabolite concentrations.
Study population was predominantly white, limiting generalizability to diverse ethnic populations.
Residual confounding from unmeasured variables (e.g., diet quality, sleep apnea severity, mental health status, occupational schedules) could not be excluded.

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Implication

Poor joint sleep patterns significantly elevate the risk of incident cardiometabolic diseases and multimorbidity in primary prevention, an effect partially mediated by circulating lipoprotein and inflammatory metabolites.

Abstract

Aim: To identify the relationship between joint sleep patterns and the incidence of cardiometabolic diseases (CMDs) and multimorbidity (CMM) as well as the mediating effects of plasma metabolites. Methods: This prospective study included 190,827 participants from the UK Biobank. The joint sleep pattern was evaluated by the healthy sleep score according to five sleep factors (chronotype, sleep duration, insomnia, snoring, and excessive daytime sleepiness). Cox proportional hazards models were utilized to evaluate the relationship between sleep-related metabolites and the incidence of CMM and CMDs. Mediation analyses were conducted to quantify the potential mediating effects of circulating metabolites. Results: After a median follow-up of 13.5 years, 24,602 incident cases of CMDs and 2740 incident cases of CMM were identified. Per 1-decrement of sleep score was associated with 10.5% and 15.1% increased risks of CMDs and CMM, respectively. However, sleep was not associated with the progression from the first disease to CMM. A total of 152 metabolites were identified to be associated with sleep patterns, among which lipoproteins emerged as the predominant class. Most of the metabolites showed mediation effects on the association between sleep and outcomes. Conclusions: Poor sleep pattern was associated with increased risk of CMDs and CMM. Differences in metabolites, especially lipoproteins, might partially explain the association between sleep pattern and cardiometabolic health.

Discussion

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Cite This Study

Liu et al. (2026) conducted a cohort in Cardiometabolic diseases (CMDs) and cardiometabolic multimorbidity (CMM) (n=190,827). Joint sleep pattern (per 1-decrement in healthy sleep score, or poor sleep pattern with score <= 1) vs. Healthy sleep pattern (score >= 4 out of 5 low-risk sleep factors) was evaluated on Incidence of cardiometabolic multimorbidity (CMM, defined as >=2 of T2DM, stroke, and CHD) and total cardiometabolic diseases (CMDs) (HR 1.151, 95% CI 1.108-1.196). Each 1-point decrement in healthy sleep score was associated with a 15.1% increased risk of cardiometabolic multimorbidity and a 10.5% increased risk of total CMDs.

synapsesocial.com/papers/6a6c4787747664a1aa73cfd3 https://doi.org/10.3390/healthcare14152296

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Association Between Sleep Patterns and the Risk of Cardiometabolic Diseases or Cardiometabolic Multimorbidity and the Mediating Role of Metabolic Biomarkers: A Prospective Study of the UK Biobank Cohort

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

Association Between Sleep Patterns and the Risk of Cardiometabolic Diseases or Cardiometabolic Multimorbidity and the Mediating Role of Metabolic Biomarkers: A Prospective Study of the UK Biobank Cohort

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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