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

Metabolism. 2017 Jul:72:75-82. doi: 10.1016/j.metabol.2017.03.016. Epub 2017 Apr 2.

Abstract

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-III, 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≥25V 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) μg/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.

Keywords: Apolipoprotein-CIII; Diabetic peripheral neuropathy; Endothelial dysfunction; Endothelium-dependent vasodilation; Type 2 diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Apolipoprotein C-III / blood*
  • Apolipoprotein C-III / metabolism
  • Diabetes Mellitus, Type 2 / complications*
  • Diabetes Mellitus, Type 2 / ethnology
  • Diabetes Mellitus, Type 2 / physiopathology
  • Diabetic Neuropathies / ethnology
  • Diabetic Neuropathies / etiology*
  • Dyslipidemias
  • Endothelium, Vascular / physiology*
  • Humans
  • Middle Aged
  • Peripheral Nervous System Diseases / ethnology
  • Peripheral Nervous System Diseases / etiology*
  • Vasodilation*

Substances

  • Apolipoprotein C-III