No clear evidence of neuropathy among patients with high risk for the development of prediabetes/diabetes—a pilot study

**Background:** Both prediabetes and diabetes are associated with increased risk of sensory and cardiac autonomic neuropathy (CAN). However, it is unknown whether individuals at moderate-to-high risk of developing diabetes, but without current prediabetes or diabetes, have an increased prevalence of neuropathy. This pilot study aimed to evaluate neuropathy in such individuals using the FINDRISC questionnaire.

**Methods:** From 2020 to 2023, 44 patients with FINDRISC ≥12 (high-risk) and 28 with FINDRISC <12 (controls) were enrolled from a university outpatient clinic in Budapest. Exclusion criteria included HbA1c >5.6%, fasting glucose ≥5.9 mmol/L, known glucose metabolism abnormalities, or conditions predisposing to neuropathy. A 75-g OGTT was performed in high-risk patients. CAN was assessed using standard cardiovascular reflex tests (Ewing battery, excluding handgrip): parasympathetic function via heart rate responses to deep breathing (beat-to-beat variation), standing (30:15 ratio), and Valsalva maneuver; sympathetic function via orthostatic hypotension. DSPN was evaluated using Neurometer CPT (median and peroneal nerves at 2000, 250, and 5 Hz), Q-Sense thermal thresholds, tuning fork, monofilament, and NTSS-6 symptom questionnaire. Statistical analyses included Mann-Whitney U, t-tests, χ², and multiple logistic regression for CAN.

**Key Results:** High-risk participants were older (55.7±14.1 vs. 46.7±14.3 years), had higher BMI (29.9±12.5 vs. 25.9±8.9 kg/m²), more hypertension (68.2% vs. 17.9%), and worse lipid profiles. Parasympathetic neuropathy was present in 56.8% of high-risk vs. 32.1% of controls (p=0.035). Sympathetic neuropathy was absent in both groups. DSPN occurred only in 8 high-risk patients. In multiple logistic regression, only HbA1c was independently associated with parasympathetic CAN (OR 5.9; 95% CI 1.08–32.68; p=0.041). Age, hypertension, and FINDRISC score were not significant.

**Clinical Implications:** This pilot study suggests that high diabetes risk alone does not clearly increase neuropathy prevalence, but parasympathetic dysfunction is more common and linked to HbA1c even within normal range. The findings highlight the need for larger prospective studies to clarify the role of glycemia in early neural dysfunction and to determine whether subtle autonomic changes in high-risk individuals predict future neuropathy or diabetes.