# Incidence and predictors of cardiovascular disease mortality and all-cause mortality in patients with type II diabetes with peripheral arterial disease

**Authors:** Amaraporn Rerkasem, Ampica Mangklabruks, Supawan Buranapin, Kiran Sony, Nimit Inpankaew, Rath Rerkasem, Sasinat Pongtam, Kochaphan Phirom, Kittipan Rerkasem, Shukri AlSaif, Shukri AlSaif, Shukri AlSaif, Shukri AlSaif

PMC · DOI: 10.1371/journal.pone.0322502 · PLOS One · 2025-05-16

## TL;DR

This study found that patients with type 2 diabetes and severe peripheral arterial disease face significantly higher risks of death from cardiovascular disease and all causes.

## Contribution

The study identifies critical limb ischemia as a strong predictor of mortality in type 2 diabetes patients with peripheral arterial disease.

## Key findings

- The cumulative all-cause mortality rate over seven years was 36%.
- Critical limb ischemia patients had 5.26 times higher all-cause mortality risk.
- Asymptomatic PAD patients had similar mortality risk to those with intermittent claudication.

## Abstract

This cohort study estimated the incidence and predictors of cardiovascular disease (CVD) and all-cause mortality among patients with type 2 diabetes mellitus (T2DM) and various stages of peripheral arterial disease (PAD) at the largest tertiary referral hospitals in upper-northern Thailand.

This study recruited 278 T2DM and PAD patients for a 7-year cohort study. These patients completed health questionnaires and underwent physical examinations including ankle-brachial index measurements and clinical assessment to determine PAD severity. Mortality endpoints were determined using hospital death registers and national death records. The Cox proportional hazards and subdistribution hazard models were used to estimate PAD’s effect on mortality, quantifying the association with hazard ratios (HR) and subdistribution hazard ratios (SHR).

PAD patients were categorized into three subgroups. Over seven years, the cumulative all-cause mortality rate was 36%, or 6.4 deaths per 100 person-years. Multivariable analysis revealed critical limb ischemia (CLI) patients had significantly higher risks of all-cause (HR 5.26, 95%CI 3.10–8.94) and CVD mortality (SHR 6.20, 95%CI 3.20–12.03) compared to their asymptomatic peers. No statistically significant differences in non-CVD mortality were noted across PAD subgroups.

CLI, chronic kidney disease, and underweight (body mass index < 18.5 kg/m2) emerged as independent mortality predictors. Conversely, asymptomatic PAD patients had a similar overall mortality risk as those with intermittent claudication. These findings highlight the need for risk stratification and patient empowerment to optimize management of these complex conditions.

## Linked entities

- **Diseases:** type 2 diabetes mellitus (MONDO:0005148), peripheral arterial disease (MONDO:0005386), cardiovascular disease (MONDO:0004995), chronic kidney disease (MONDO:0005300)

## Full-text entities

- **Genes:** INS (insulin) [NCBI Gene 3630] {aka IDDM, IDDM1, IDDM2, ILPR, IRDN, MODY10}, REN (renin) [NCBI Gene 5972] {aka ADTKD4, HNFJ2, RTD}, P2RY12 (purinergic receptor P2Y12) [NCBI Gene 64805] {aka ADPG-R, BDPLT8, HORK3, P2T(AC), P2Y(12)R, P2Y(AC)}, DPP4 (dipeptidyl peptidase 4) [NCBI Gene 1803] {aka ADABP, ADCP2, CD26, DPPIV, TP103}, ACE (angiotensin I converting enzyme) [NCBI Gene 1636] {aka ACE1, CD143, DCP, DCP1}
- **Diseases:** albuminuria (MESH:D000419), End-stage renal disease (MESH:D007676), tissue loss (MESH:D017695), atherosclerosis (MESH:D050197), PAD (MESH:D058729), TIA (MESH:D002546), HIV infection (MESH:D015658), necrosis (MESH:D009336), diabetic (MESH:D003920), heart failure (MESH:D006333), MI (MESH:D009203), ischemic heart disease (MESH:D017202), diabetic peripheral neuropathy (MESH:D010523), CL (MESH:D007383), bone loss (MESH:D001847), abdominal aortic aneurysms (MESH:D017544), cancer (MESH:D009369), CLI (MESH:D000089802), DM (MESH:D009223), fungal arteritis (MESH:D009181), infections (MESH:D007239), stroke (MESH:D020521), hypertension (MESH:D006973), OACs (MESH:C536683), vasculopathy (MESH:D000090122), hyperglycemic (MESH:D006944), ischemic rest pain (MESH:D010146), kidney damage (MESH:D007674), cerebrovascular and coronary artery disease (MESH:D003324), muscle wasting (MESH:D009133), death (MESH:D003643), CKD (MESH:D051436), T2DM (MESH:D003924), malnutrition (MESH:D044342), obese (MESH:D009765), sudden cardiac arrest (MESH:D016757), COPD (MESH:D029424), rest (MESH:D014202), insulin resistance (MESH:D007333), PADs (MESH:C567780), AIDS (MESH:D000163), foot ulcers (MESH:D016523), amputation (MESH:C565682), cerebrovascular disease (MESH:D002561), gangrene (MESH:D005734), thoracic aortic aneurysms (MESH:D017545), CVD (MESH:D002318), hyperlipidemia (MESH:D006949), dyslipidemia (MESH:D050171), underweight (MESH:D013851), chronic ulcers (MESH:D014456), overweight (MESH:D050177)
- **Chemicals:** insulins (MESH:D061385), warfarin (MESH:D014859), glucose (MESH:D005947), aldosterone (MESH:D000450), sulfonylureas (MESH:D013453), biguanides (MESH:D001645), DDP-4 (-), ASA (MESH:D001241), thiazolidinediones (MESH:D045162), blood sugar (MESH:D001786), lipid (MESH:D008055)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12083800/full.md

## References

35 references — full list in the complete paper: https://tomesphere.com/paper/PMC12083800/full.md

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Source: https://tomesphere.com/paper/PMC12083800