424-P: Autoantibodies to Glutamic Acid Decarboxylase in Type 1 Diabetes Are Not a Marker of Asymptomatic Cardiac Autonomic Neuropathy

Aim: To clarify whether autoantibodies against glutamic acid decarboxylase (GAD-ab) are associated with cardiac autonomic neuropathy (CAN).

Methods: 319 consecutive patients with type 1 diabetes (DM1) were included. We assessed CAN by responses of heart rate variability to deep breathing (E/I index), Valsalva maneuver, standing (30:15 ratio), low-frequency activity (LFa), and high-frequency activity (HFa). We assayed GAD-ab by immunoprecipitation radioligand.

Results: Mean age was of 40 ± 14 years, with 20 ± 12 years as mean duration of diabetes. Mean A_1c was 7.2 ± 1.0%. We confirmed CAN in 66 patients resulting in a 21% (95% CI 17-25) prevalence of asymptomatic CAN. GAD-ab were present in 199 individuals (62%), with no significant differences as a function of the presence of CAN or not [44 (70%) vs. 144 (66%), respectively; P = 0.544]. GAD-ab titles were similar between both groups (431 ± 695 U/mL in CAN subjects vs. 390 ± 662 U/mL in subjects without CAN, P = 0.688). Considering all patients as a whole, GAD-ab titles only correlated with duration of DM1 (r = -0.346, P < 0.001). HFa correlated with age (r = -0.523, P < 0.001), duration of DM1 (r = -0.374, P < 0.001), and A_1c (r = -0.261, P < 0.001), but not with GAD-ab. Similarly, LFa correlated with age (r = -0.473, P < 0.001), duration of DM1 (r = -0.223, P < 0.001), and A_1c (r = -0.294, P < 0.001). Age, sex, A_1c, duration of DM1, GAD-ab, and systolic blood pressure were introduced as independent variables into a binary regression analysis. The stepwise model (R²: 0.106, P < 0.001) retained only age (β: -0.933, 95% CI: 0.933-0.976) as the significant predictor of the presence of CAN.

Conclusion: GAD-ab unlikely have a role as a CAN marker in patients with DM1.