Early parallel progression of peripheral and cardiac autonomic nerve dysfunction in recent-onset type 1 diabetes patients

Aims:

We previously demonstrated an early parallel involvement of small and large fibers in recent-onset type 2 diabetes. Here we hypothesized that this pattern may also be pertinent to type 1 diabetes (T1D).

Methods:

Motor and sensory nerve conduction velocity (MNCV, SNCV), vibration perception thresholds (VPT), thermal detection thresholds (TDT), intraepidermal nerve fiber density (IENFD), and heart rate variability (HRV) were assessed in participants with T1D from the German Diabetes Study at baseline (diabetes duration ≤1 year) and glucose-tolerant controls: CON/T1D-B: n = 96/360; age [median (1st; 3 rd quartile)]: 34.5 (26.0; 46.8)/34.6 (26.5; 45.3) years; male: 72/58%; BMI: 25.0 (22.9; 28.3)/24.0 (22.0 (22.0; 27.0)kg/m²; HbA1c: 5.1 (5.0; 5.3)/6.4 (5.9; 7.2)%; M-value: 11.6 (9.1; 13.6)/8.2 (6.5; 10.4)mg*kg-1*min-1.

Results:

T1D-B showed lower peroneal MNCV ([mean ± SEM]: 45.8 ± 0.2 vs. 47.0 ± 0.3 m/s), median MNCV (55.1 ± 0.2 vs. 56.0 ± 0.7 m/s), and IENFD (10.0 ± 0.5 vs. 11.2 ± 0.5 fibers/mm) than CON (p ≤0.05). In T1D, a deterioration from baseline over 5 years (n = 151) was noted for ulnar and median MNCVs and SNCVs (e.g. ulnar MNCV: 57.4 ± 0.4 vs. 56.3 ± 0.3 m/s), malleolar VPT (0.76 ± 0.07 vs. 1.12 ± 0.12 µm), and HRV (e.g. standard deviation of normal RR intervals (SDNN): 69.3 ± 2.4 vs. 62.0 ± 2.1 ms) (p ≤0.05). Peroneal MNCV, sural SNCV, and TDT remained unchanged. The decline in MNCV was associated with an increase in HbA1c (e.g. median nerve: β=-0.316, P = 0.004) and the deterioration in HRV with decreasing M-value (e.g. SDNN: β= 0.246, P = 0.041).

Conclusions:

Within the first 5 – 6 years of type 1 diabetes, the deterioration in median and ulnar MNCV was related to worsening HbA1c levels, while cardiac autonomic dysfunction progressed in relation to increasing insulin