Circulating Growth Differentiation Factor 15 Is Associated with Diabetic Neuropathy

Background: Growth differentiation factor (GDF15) is a superfamily of transforming growth factor-beta which has been suggested to be correlated with various pathological conditions. The current study aimed to investigate the predicted role of circulating GDF15 in diabetic metabolism characteristics and diabetic neuropathy. Methods: 241 diabetic patients and 42 non-diabetic subjects were included to participate in the study. The plasma GDF15 levels were measured using ELISA. Chronic kidney disease and albuminuria were defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) guideline. The nerve conductive study (NCS) was performed with measurement of distal latency, amplitude, nerve conduction velocity (NCV), H-reflex, and F-wave studies. Results: The diabetic group had a significantly higher prevalence of chronic kidney disease and higher plasma GDF15 level. After adjusting for age and BMI, GDF15 was significantly positively correlated with waist circumference (r = 0.332, p = <0.001), hip circumference (r = 0.339, p < 0.001), HbA1c (r = 0.302, p < 0.001), serum creatine (r = 0.146, p = 0.017), urine albumin/creatinine ratio (r = 0.126, p = 0.040), and HOMA-IR (r = 0.166, p = 0.007). As to NCS, GDF15 was significantly correlated with all latency and amplitude of sensory and motor nerves, as well as F-wave and H-reflex latencies. The area under the curve (AUC) in predicting tibial motor nerve neuropathy (MNCV) in all subjects and in the diabetic group for GDF15 was 0.646 (p = 0.001) and 0.610 (p = 0.012), respectively; for HbA1c was 0.639 (p = 0.001) and 0.604 (p = 0.018), respectively. Predicting ulnar sensory nerve neuropathy for GDF15 was 0.639 (p = 0.001) and 0.658 (p = 0.001), respectively; for HbA1c was 0.545 (p = 0.307) and 0.545 (p = 0.335), respectively. Predicting median sensory nerve neuropathy for GDF15 was 0.633 (p = 0.007) and 0.611 (p = 0.032), respectively; for HbA1c was 0.631 (p = 0.008) and 0.607 (p = 0.038), respectively. Predicting CKD for GDF15 was 0.709 (95% CI, 0.648-0.771), p < 0.001) and 0.676 (95% CI, 0.605-0.746), p < 0.001), respectively; for HbA1c was 0.560 (95% CI, 0.493-0.627); p = 0.080) and 0.515 (95% CI, 0.441-0.588); p = 0.697), respectively. Conclusions: We suggest that there is a significant association between the increased serum GDF-15 level and metabolic parameters and diabetic neuropathy. Plasma GDF15 may be an independent predictor of diabetic neuropathy.