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). Therefore, 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 (GDS) at baseline (diabetes duration ≤1 year) and in glucose-tolerant controls: CON/T1D-B: n=96/360; age [median (1st; 3rd 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; diabetes duration: -/173 (114; 173) days; HbA1c: 5.1 (5.0; 5.3)/6.4 (5.9; 7.2)%; M-value (hyperinsulinemic-euglycemic clamp): 11.6 (9.1; 13.6)/8.2 (6.5; 10.4) mg*kg-1*min-1. 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 to 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 indices (e.g., standard deviation of normal RR intervals (SDNN): 69.3±2.4 vs. 62.0±2.1 ms; root mean square of successive differences (RMSSD): 42.8±2.3 vs. 34.7±2.0 ms) (all 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).
In conclusion, within the first 5-6 years of type 1 diabetes despite good glycemic control, the deterioration in median and ulnar MNCV was related to worsening HbA1c levels, while cardiac autonomic dysfunction progressed in relation to increasing insulin resistance.
G.J. Bönhof: None. A. Strom: None. O.P. Zaharia: None. J. Szendroedi: None. K. Muessig: None. M. Roden: Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Poxel SA, Servier. Board Member; Self; Eli Lilly and Company. Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Sanofi. Speaker's Bureau; Self; Novo Nordisk Inc. D. Ziegler: Advisory Panel; Self; Allergan, TrigoCare. Consultant; Self; Mitsubishi Tanabe Pharma Corporation, Mylan, Novartis Pharmaceuticals Corporation, Wörwag. Speaker's Bureau; Self; Berlin-Chemie AG.
German Ministry of Culture and Science of the State of North Rhine-Westphalia; German Federal Ministry of Health; German Federal Ministry of Education and Research