Session: MON 818-841-Diabetes Pathophysiology & Complications
Poster Board MON-828
Pathogenesis of diabetic peripheral neuropathy (DPN) in humans is poorly understood and regulation of inflammation likely has a key role.
We hypothesized that DPN risk may be predicted by biological factors associated with endothelial and vascular dysfunction. We studied the prevalence and associations of DPN with indices of inflammation (eg OPG, PEDF and sRAGE), microcirculatory endothelial dysfunction and vascular stiffness (PWV and AI).
We consecutively enrolled adults with type 2 diabetes seen in our institution’s Diabetes Centre August 2011-2012. All enrolled patients (n=1220) were stratified according to renal function/albuminuria into 3 groups. For analysis of biomarkers, we selected all patients (n=85) with DPN, [defined by a) correctly detecting less than 8 of 10 points tested by monofilament or b) neuothesiometer reading ≥ 25Volts]. Using SPSS 19.0, diabetic controls (n=515) with no DPN were randomly selected from the entire cohort. Fasting blood, endothelial function by laser doppler flowmetry, PWV, AI by applanation tonometery (SphygmoCor®), were evaluated.
Prevalence of DPN was 9.1% (95% CI 7.3-11.1). DPN patients were older [60.0 (9.7) vs 57.5 (11.0) p<0.05)], more commonly males. Malays [14.5% (95%CI 10.1-20.2)], and Indians [11.1% (95%CI 7.3-16.4%)] had higher prevalence than Chinese [6.3% (95%CI 4.4-9.0)]. DPN patients had significantly higher systolic pressure, pulse pressure, heart rate, PWV, HbA1c (8.2% vs 7.9%), serum creatinine and urine ACR, but reduced HDL-C, endothelium-dependent and independent vascular reactivity. Serum OPG, PEDF and sRAGE were significantly higher in DPN, 6.3 (2.6) vs 5.1 (1.9) pmol/l ; 18.0 (5.5) vs 15.6 (5.0) µg/ml and 1267 (719) vs 1063 (609) pg/ml p<0.01 respectively. Serum OPG, urine albumin and TBI remained significant DPN predictors after adjusting for ethnicity, gender and age.
Increased risk of DPN is associated with poorer glycemic control, and increased inflammation. Higher OPG and reduced endothelial function was associated with increased risk of DPN. Further studies are needed to explore the pathobiological role of OPG in neuropathy, whether it could serve as an early predictor and target for diagnosing and management of DPN.
Abbreviations: PWV -pulse wave velocity
AI -Augmentation index
TBI -Toe brachial Index
ACR -Albumin-creatinine ratio
PEDF -Pigment epithelium-derived factor
sRAGE-soluble receptor for Advanced glycated end-products
Nothing to Disclose: ECKY, ST, SCL, LYY, XWN, WCT, JJL, SLTP, CFS
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