Abstract
BACKGROUND: Increased glucagon levels are now recognized as a pathophysiological adaptation to counteract overnutrition in type 2 diabetes (T2D). This study aimed to elucidate the role of glucagon in peripheral nerve function in patients with T2D with different body mass indices (BMIs). METHODS: We consecutively enrolled 174 individuals with T2D and obesity (T2D/OB, BMI ≥ 28 kg/m(2)), and 480 individuals with T2D and nonobesity (T2D/non-OB, BMI < 28 kg/m(2)), all of whom underwent oral glucose tolerance tests to determine the area under the curve for glucagon (AUC(gla)). Electromyography was utilized to assess overall composite Z-scores for latency, amplitude, and nerve conduction velocity (NCV) across all peripheral nerves, specifically examining the median, ulnar, common peroneal, posterior tibial, superficial peroneal, and sural nerves. RESULTS: In the T2D/OB group, the AUC(gla) exhibited a significant correlation with the latency, amplitude and NCV of each peripheral nerve, as well as with the overall composite Z-scores for latency (r = -0.283, p < 0.001), amplitude (r = 0.295, p < 0.001), and NCV (r = 0.362, p < 0.001). In contrast, the T2D/non-OB group did not exhibit obvious correlations between the AUC(gla) and the overall composite Z-scores for latency (r = -0.088, p = 0.056), amplitude (r = 0.054, p = 0.251), and NCV (r = 0.116, p = 0.012). Furthermore, multivariate linear regression analyses indicated that elevated AUC(gla) was independently associated with a lower overall composite Z-score for latency (β = -0.304, t = -3.391, p = 0.001), as well as higher overall composite Z-scores for amplitude (β = 0.256, t = 2.630, p = 0.010) and NCV (β = 0.286, t = 3.503, p = 0.001), after adjusting for other clinical covariates within the T2D/OB group. CONCLUSION: Increased glucagon levels may be a potential protective factor against peripheral nerve compromise in patients with T2D and obesity.