Reduced heart rate variability predicts incident diabetic polyneuropathy

Q: What is the clinical evidence from this study?

Study design: Cohort. Population: Diabetes mellitus (n=288). Intervention: Cardiovascular autonomic neuropathy (CAN) vs. No cardiovascular autonomic neuropathy. Primary outcome: Incident distal symmetrical polyneuropathy (DSPN) based on clinical criteria (HR 6.20).

Q: What does this research mean for the field?

Baseline cardiovascular autonomic neuropathy and reduced heart rate variability strongly and independently predict the development of incident distal symmetrical polyneuropathy in individuals with diabetes. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

Dimitrios Tsilingiris; D Schmalzridt; Omar Eldesouky; Florian Kalb; Viktoria Flegka; Ekaterina von Rauchhaupt; Theresa Hoefer; Stefan Kopf; Thomas Fleming; Stephan Herzig; A L Hohneck; Julia Szendroedi; Ζoltan Κender

doi:10.3389/fendo.2026.1880532

July 16, 2026Frontiers in EndocrinologyOpen Access

Reduced heart rate variability predicts incident diabetic polyneuropathy

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Key result

Cardiovascular autonomic neuropathy linked to ~6-fold higher risk of incident distal polyneuropathy in diabetes.

HR 6.20
n=288

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Why the study?

Cardiovascular autonomic neuropathy and reduced heart rate variability may predict the development of distal symmetrical polyneuropathy in individuals with diabetes, but prospective data are limited.

Does cardiovascular autonomic neuropathy and reduced heart rate variability predict incident distal symmetrical polyneuropathy in individuals with diabetes mellitus?

Key Points

To determine whether cardiovascular autonomic neuropathy (CAN) and reduced heart rate variability (HRV) predict the development of distal symmetrical polyneuropathy (DSPN) in individuals with diabetes mellitus.
A total of 288 participants with diabetes (mean age 58.1 ± 13.4 years, 41.3% women, 78.5% type 2 diabetes) were assessed at baseline for CAN using reflex tests and HRV indices (CVRR, rMSSD, HF power, LF power).
DSPN was characterized by three definitions: clinical criteria, sensory-loss phenotype from quantitative sensory testing, and the Toronto consensus definition requiring abnormal nerve conduction plus signs or symptoms.
A longitudinal subset of 194 individuals free of DSPN at baseline was followed for 3.0 ± 1.3 years to evaluate incident DSPN.
Incident DSPN occurred at rates of 8.4, 5.7, and 3.3 per 100 person-years across clinical, sensory-loss, and Toronto consensus definitions, respectively.
Baseline CAN independently predicted incident DSPN with adjusted HRs of 6.20, 3.30, and 7.33 across the three diagnostic criteria.
Lower HRV indices also predicted future DSPN, with reduced rMSSD, HF power, and LF power predicting clinical and Toronto-defined DSPN, whereas reduced CVRR predicted sensory-loss DSPN.

Study Design

Type

Cohort (n=288)

Multicenter

No

Structured PICO

Does cardiovascular autonomic neuropathy and reduced heart rate variability predict incident distal symmetrical polyneuropathy in individuals with diabetes mellitus?

P

Population

288 individuals with type 1 or type 2 diabetes (mean age 58.1 years, 41.3% female) followed for a mean of 3.0 years to assess incident distal symmetrical polyneuropathy.

E

Exposure

Presence of cardiovascular autonomic neuropathy (CAN) and reduced heart rate variability (HRV)

C

Comparator

Absence of cardiovascular autonomic neuropathy (CAN) and normal heart rate variability (HRV)

O

Outcome

Incident distal symmetrical polyneuropathy (DSPN) assessed by three definitions (clinical criteria, sensory-loss phenotype, Toronto consensus definition)hard clinical

Main Result

Hazard Ratio: 6.2

Limitations

Absence of the Valsalva manoeuvre may have reduced the sensitivity of CAN detection and introduced some misclassification.
Some variables included in multivariable models may function as mediators rather than confounders.
Frequency-domain HRV data were missing in a small subset of participants.
DSPN incidence varied by diagnostic definition, reflecting phenotypic heterogeneity.
Absence of the Valsalva manoeuvre may have reduced the sensitivity of CAN detection
Relationship of further HRV metrics (MCR) remains to be investigated
Some variables included in multivariable models may function as mediators rather than confounders
Frequency-domain HRV data were missing in a small subset of participants
Exploratory models yielded unstable odds ratios for WHR and certain HRV parameters

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Implication

Established cardiovascular autonomic neuropathy and reduced heart rate variability are strong, independent predictors of future distal symmetrical polyneuropathy in individuals with diabetes.

Abstract

Objective: To determine whether cardiovascular autonomic neuropathy (CAN) and reduced heart rate variability (HRV) predict the development of distal symmetrical polyneuropathy (DSPN) in individuals with diabetes mellitus (DM). Methods: A total of 288 individuals with DM (mean age 58.1 ± 13.4 years, 41.3% women, 78.5% with type 2 diabetes) underwent baseline assessment of CAN using cardiovascular autonomic reflex tests and HRV indices (CVRR, rMSSD, high- and low-frequency power). DSPN was characterized using three definitions: (i) clinical criteria based on symptoms and signs, (ii) the sensory-loss phenotype derived from quantitative sensory testing, and (iii) the Toronto consensus definition requiring abnormal nerve conduction plus symptoms or signs. A total of 194 participants without DSPN at baseline were followed for 3.0 ± 1.3 years to assess incident DSPN. Results: At baseline, CAN prevalence was 16.3%, and low HRV indices were present in 18.6-40.2% of participants. DSPN prevalence was 27.7%, 17.6%, and 20.8% for definitions (i), (ii), and (iii), respectively. Cross-sectionally, CAN and reduced HRV were associated with DSPN (unadjusted ORs 1.8-4.0), with associations largely persisting after adjustment. Incident DSPN occurred at 8.4, 5.7, and 3.3 per 100 person-years. Baseline CAN independently predicted incident DSPN (adjusted HRs 6.20, 3.30, and 7.33 across definitions). Lower rMSSD, HF power, and LF power predicted incident DSPN according to definitions (i) and (iii), whereas reduced CVRR predicted DSPN defined by criteria (ii). Conclusions: Established CAN is a strong predictor of future DSPN. Reduced HRV provides a practical, accessible alternative marker for identifying individuals at elevated neuropathy risk.

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Cite This Study

Tsilingiris et al. (2026) conducted a cohort in Diabetes mellitus (n=288). Cardiovascular autonomic neuropathy (CAN) vs. No cardiovascular autonomic neuropathy was evaluated on Incident distal symmetrical polyneuropathy (DSPN) based on clinical criteria (HR 6.20). Baseline cardiovascular autonomic neuropathy strongly predicted the development of incident distal symmetrical polyneuropathy in individuals with diabetes.

synapsesocial.com/papers/6ac470939b242b2e45466c5f https://doi.org/10.3389/fendo.2026.1880532

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Reduced heart rate variability predicts incident diabetic polyneuropathy

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

Reduced heart rate variability predicts incident diabetic polyneuropathy

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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