Cardiac autonomic neuropathy is a significant independent risk factor for the development of diabetic sensorimotor polyneuropathy: findings from a cross-sectional and prospective cohort study.

Background: Even though they share common risk factors and overlapping pathogenetic features, the relationship between cardiac autonomic neuropathy (CAN) and peripheral sensorimotor polyneuropathy (DSPN) in diabetes mellitus (DM) remains poorly characterized, since prospective studies are absent.

Methods: 276 individuals with DM (DM1 n=60, DM2 n=216) underwent CAN tests (30:15 and E:I ratio, orthostatic blood pressure drop) at baseline. DSPN diagnosis was established via i) clinical scales (NDS≥6 or NSS≥5 plus NDS≥3), ii) sensory loss phenotype at the foot, based on quantitative sensory testing (QST), iii) combination of pathological electrophysiology findings and clinical deficits (Toronto consensus criteria). Those without DSPN based on each definition were followed up for a mean of 3 years. The effect of CAN diagnosis (based on≥2 pathological cardiovascular tests) on the prospective probability of DSPN diagnosis was estimated via Cox proportional hazards models, adjusted for multiple confounders (age, sex, BMI, waist-to-hip ratio, DM type and duration, beta blocker therapy, HbA1c, eGFR and ACR).

Results: A total of n=51 (18.5%) had≥2 pathological CAN tests while an additional n=83 (30.1%) had a single pathological test. Apart from higher BMI and HbA1c values in the CAN group, the two groups were comparable in terms of their basic clinical and laboratory characteristics. In cross-sectional analysis, the presence of≥2 pathological tests was an independent predictor of somatic neuropathy based on all 3 definitions, specifically i) NSS/NDS-based: aOR 2.22, 95% c.i. 1.04-4.31, p=0.039, ii) QST-based Sensory Loss phenotype: aOR 2.50, 95% c.i. 1.08-5.81, p=0.033) and iii) Toronto consensus-defined DSPN (aOR 2.90, 95% c.i. 1.23-6.82, p=0.015). In longitudinal analysis among those without DSPN based on any one of the three definitions (total n=180), the presence of≥2 abnormal CAN tests was independently predictive of new onset of somatic neuropathy based on any definition during a mean of 3 years follow-up, specifically: NSS/NDS-based: aHR 4.49, 95% c.i. 1.81-11.13, p=0.001, ii) QST-based Sensory Loss phenotype: aHR 2.86, 95% c.i. 1.04-7.90, p=0.042) and iii) Toronto consensus-defined DSPN (aHR 8.84 (1.88-41.56), p=0.006).

Conclusions: In individuals with DM without DSPN, cardiac autonomic dysfunction is a significant risk factor for the future development of DSPN, according to various diagnostic criteria. This highlights the importance of incorporating CAN testing in clinical practice to screen patients at high risk for developing DSPN.

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Artikel online veröffentlicht:
28. Mai 2025