Association of apolipoprotein-CIII (apoC-III), endothelium-dependent vasodilation and peripheral neuropathy in a multi-ethnic population with type 2 diabetes

Background. Diabetic peripheral neuropathy (DPN) is a common complication of Type 2 diabetes (T2D). Apart from hyperglycemia, its pathogenesis is poorly understood. Apolipoprotein-CIII (apoC-III) associated with triglyceride metabolism, is a risk factor for cardiovascular disease. Its role in DPN is not well-established. We studied the associations of apoC-Ill, endothelial function and DPN. Methods. In patients with T2D, anthropometric data, fasting blood, and urine were collected for biochemistry and urine albumin/creatinine measurements (uACR). Endothelial function assessments were performed by laser Doppler flowmetry/imaging. DPN was considered present if there was an abnormal finding in monofilament (<= 8 of 10 points) or neurothesiometer testing >= 25 V on either foot. Plasma apoC-III was assessed by ELISA. Results. Monofilament and neurothesiometer readings were measured in 1981 patients, mean age 57.4 +/- 10.8 years old. DPN prevalence was 10.8% (n = 214). Patients with DPN compared to those without, were significantly older (p < 0.0001), with longer duration of T2D (p < 0.0001), had higher BMI (p = 0.006), higher glucose (p = 0.015) and HbA1c (p < 0.0001), Systolic blood pressure (SBP) (p < 0.0001), lower eGFR (p < 0.0001), higher urine ACR (p < 0.0001), poorer endothelium-dependent and endothelium-independent vasodilation (both p < 0.0001), higher VCAM-1 (p < 0.0001) and higher apoC-III [285.3 (195.2-405.6) vs 242.9(165.0-344.0) mu g/ml]. After adjustment, log transformed apoC-III, remained independently associated with the presence of DPN (B = 0.965, SE = 0.397, p = 0.015). Conclusion. Plasma apoC-III is higher in patients with DPN. Apart from its known association with lipids and macrovascular complications, this study suggests its association with DPN. Whether regulating apoC-III metabolism may be an important new therapeutic approach to managing dyslipidemia and microvascular complications in T2D remains to be proven in future mechanistic and clinical studies. (C) 2017 Elsevier Inc. All rights reserved.