Chronic widespread pain linked to higher cardiovascular risk in type 2 diabetes

People with type 2 diabetes who report chronic widespread pain may face substantially higher odds of developing atherosclerotic cardiovascular disease, according to a large UK Biobank cohort study published in Frontiers in Cardiovascular Medicine. The research, which followed more than 17,000 participants with diabetes for a median of 13.4 years, suggests that simple questionnaire-based pain assessments could help flag a clinical phenotype associated with elevated cardiovascular risk.

The researchers also measured chronic pain burden using the number of pain sites, with multisite chronic pain defined as pain involving three or more sites.

During follow-up, the cohort experienced 4,223 atherosclerotic cardiovascular disease (ASCVD) events, 1,389 heart failure events, and 2,632 microvascular events. Using Cox proportional hazards models, the team found a clear gradient of ASCVD risk across pain categories. Compared with participants reporting no pain, the fully adjusted hazard ratio for ASCVD was 1.16 (95% confidence interval 1.05–1.27) for short-term pain, 1.32 (1.22–1.41) for chronic localized pain, and 1.77 (1.49–2.10) for chronic widespread pain.

The burden of pain also mattered. Multisite chronic pain involving three or more sites was associated with ASCVD risk, with a hazard ratio of 1.43 (95% CI 1.22–1.67). In other words, the more widespread and persistent the pain, the stronger the statistical association with subsequent atherosclerotic cardiovascular events, even after adjustment for established risk factors.

Associations with heart failure and with a composite of diabetic microvascular complications were weaker and less consistent across pain phenotypes. Among the microvascular subtypes, however, one stood out: diabetic neuropathy showed the strongest association, with a hazard ratio of 2.28 (95% CI 1.54–3.39) for chronic widespread pain. The authors caution that this finding may partly reflect symptom overlap or early, subclinical neuropathic disease rather than a directional relationship, since nerve damage itself can produce widespread pain.

To probe how pain relates to the progression of vascular disease, the researchers built a clock-reset multistate model that tracked transitions from a complication-free baseline state to microvascular complications, to ASCVD or heart failure, and to death. In these analyses, chronic widespread pain was associated with the transition from baseline to ASCVD or heart failure (1.63, 95% CI 1.36–1.95) and with the transition from existing microvascular complications to ASCVD or heart failure (1.78, 95% CI 1.10–2.91). Notably, CWP was not associated with transitions to death.

The multistate results are particularly intriguing because they suggest pain may be linked not only to the initial onset of cardiovascular disease but also to progression among people who already have microvascular complications.

Chronic pain is common in type 2 diabetes, yet its cardiovascular relevance across different pain phenotypes and disease-progression pathways had remained uncertain. The study’s authors conclude that questionnaire-defined chronic widespread pain and greater chronic pain burden were the pain characteristics most consistently associated with incident ASCVD and with transitions toward ASCVD or heart failure in this population.

The researchers emphasize that these readily assessed pain characteristics may identify a clinical phenotype associated with higher cardiovascular risk, but they note that the incremental value of pain assessment beyond established risk factors remains to be determined.

Subject of Research: Associations between pain phenotypes, chronic pain burden and cardiovascular and microvascular complications in people with type 2 diabetes

Article Title: Pain phenotypes and chronic pain burden are associated with atherosclerotic cardiovascular disease and vascular disease progression in participants with type 2 diabetes: a UK Biobank cohort study with multistate analysis

Article References: Tang, B., Liu, D., Zhao, P., Zhang, Z., Deng, C., Chen, J., Xiao, Y., & Zhang, J. (2026). Pain phenotypes and chronic pain burden are associated with atherosclerotic cardiovascular disease and vascular disease progression in participants with type 2 diabetes: a UK Biobank cohort study with multistate analysis. Frontiers in Cardiovascular Medicine, 13, Article 1942167. https://doi.org/10.3389/fcvm.2026.1942167

Image Credits: AI Generated

DOI: 10.3389/fcvm.2026.1942167

Keywords: type 2 diabetes, chronic pain, chronic widespread pain, atherosclerotic cardiovascular disease, heart failure, microvascular complications, diabetic neuropathy, UK Biobank, cohort study, multistate model, cardiovascular risk, Pain