Osteoprotegerin Predicts Peripheral Neuropathy In Type 2 Diabetes

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: MON 818-841-Diabetes Pathophysiology & Complications
Basic/Clinical
Monday, June 17, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board MON-828
Ester Chai Kheng Yeoh*1, Subramaniam Tavintharan1, Su Chi Lim2, Lee Ying Yeoh2, Xiao Wei Ng2, Wan Ching Toy3, Jian-Jun Liu4, Sharon Li Ting Pek2 and Chee Fang Sum1
1Khoo Teck Puat Hospital, Singapore, 2Khoo Teck Puat Hospital, Singapore, Singapore, 3Khoo Teck Puat hospital, Singapore, Singapore, 4Khoo Teck Puat Hospital/Alexandrahealth Ptd Ltd, Singapore, Singapore
Objectives

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).

Methods

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.

Results

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.

Conclusions

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

                       OP       -Osteoprotegerin

                      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

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm