Accumulation of advanced glycation end products (AGEs) may contribute to diabetic foot ulceration (DFU). Our goal was to determine whether AGEs measurement by skin autofluorescence (SAF) would be an additional marker for DFU management.
Patients and Methods:
We performed SAF analysis in 66 patients with a history of DFU prospectively included and compared the results with those of 84 control patients with diabetic peripheral neuropathy without DFU. We then assessed the prognostic value of SAF levels on the healing rate in the DFU group.
Results:
Mean SAF value was significantly higher in the DFU group in comparison with the control group, even after adjustment for other diabetes complications (3.2±0.6 arbitrary units vs. 2.9±0.6 arbitrary units; P=0.001). In the DFU group, 58 (88%) patients had an active wound at inclusion. The mean DFU duration was 14±13 weeks. The healing rate was 47% after 2 months of appropriate foot care. A trend for a correlation between SAF levels and healing time in DFU subjects was observed but was not statistically significant (P=0.06).
Conclusions:
Increased SAF levels are associated with neuropathic foot complications in diabetes. Use of SAF measurement to assess foot vulnerability and to predict DFU events in high-risk patients appears to be promising.
Get full access to this article
View all access options for this article.
References
1.
BoultonAJ. The diabetic foot: grand overview, epidemiology and pathogenesis. Diabetes Metab Res Rev, 2008; 24,Suppl 1:S3–S6.
2.
PrompersL, SchaperN, ApelqvistJ, EdmondsM, JudeE, MauricioD, UccioliL, UrbancicV, BakkerK, HolsteinP, JirkovskaA, PiaggesiA, Ragnarson-TennvallG, ReikeH, SpraulM, Van AckerK, Van BaalJ, Van MerodeF, FerreiraI, HuijbertsM. Prediction of outcome in individuals with diabetic foot ulcers: focus on the differences between individuals with, without peripheral arterial disease. The EURODIALE Study. Diabetologia, 2008; 51:747–755.
3.
StevensMJ, EdmondsME, DouglasSLE, WatkinsPJ. Influence of neuropathy on the microvascular response to local heating in the human diabetic foot. Clin Sci, 1991; 80:249–256.
4.
TahraniAA, ZengW, ShakherJ, PiyaMK, HughesS, DubbK, StevensMJ. Cutaneous structural and biochemical correlates of foot complications in high-risk diabetes. Diabetes Care, 2012; 35:1913–1918.
5.
PetersEJ, LaveryLA. International Working Group on the Diabetic Foot: Effectiveness of the diabetic foot risk classification system of the International Working Group on the Diabetic Foot. Diabetes Care, 2001; 24:1442–1447.
6.
LaveryLA, PetersEJ, WilliamsJR, MurdochDP, HudsonA, LaveryDC. International Working Group on the Diabetic Foot: Reevaluating the way we classify the diabetic foot: restructuring the diabetic foot risk classification system of the International Working Group on the Diabetic Foot. Diabetes Care, 2008; 31:154–156.
7.
PetersEJ, ArmstrongDG, LaveryLA. Risk factors for recurrent diabetic foot ulcers. Diabetes Care, 2007; 30:2077–2079.
8.
ManteyI, FosterAVM, SpencerS, EdmondsME. Why do foot ulcers recur in diabetic patients?Diabet Med, 1999; 16:245–249.
9.
FagliaE, FavalesF, MorabitoA. New ulceration, new major amputation, and survival rates in diabetic subjects hospitalized for foot ulceration from 1990 to 1993. Diabetes Care, 2001; 24:78–83.
10.
BrownleeM. The pathobiology of diabetic complications: a unifying mechanism. Diabetes, 2005; 54:1615–1625.
HuijbertsMS, SchaperNC, SchalkwijkCG. Advanced glycation end products and diabetic foot disease. Diabetes Metab Res Rev, 2008; 24,Suppl 1:S19–S24.
13.
AbateM, SchiavoneC, PelottiP, SaliniV. Limited joint mobility in diabetes and ageing: recent advances in pathogenesis and therapy. Int J Immunopathol Pharmacol, 2010; 23:997–1003.
14.
ChaoCY, ZhengYP, CheingGL. Epidermal thickness and biomechanical properties of plantar tissues in diabetic foot. Ultrasound Med Biol, 2011; 37:1029–1038.
15.
BirkeJA, FranksBD, FotoJG. First ray joint limitation, pressure, and ulceration of the first metatarsal head in diabetes mellitus. Foot Ankle Int, 1995; 16:277–284.
GerritsEG, LutgersHL, KleefstraN, GraaffR, GroenierKH, SmitAJ, GansRO, BiloHJ. Skin autofluorescence: a tool to identify type 2 diabetic patients at risk for developing microvascular complications. Diabetes Care, 2008; 31:517–521.
18.
LutgersHL, GraaffR, LinksTP, Ubink-VeltmaatLJ, BiloHJ, GansRO, SmitAJ. Skin autofluorescence as a noninvasive marker of vascular damage in patients with type 2 diabetes. Diabetes Care, 2006; 29:2654–2659.
19.
MeerwaldtR, LutgersHL, LinksTP, GraaffR, BaynesJW, GansRO, SmitAJ. Skin autofluorescence is a strong predictor of cardiac mortality in diabetes. Diabetes Care, 2007; 30:107–112.
20.
Executive summary:. standards of medical care in diabetes—2013. Diabetes Care, 2013; 36,Suppl 1:S4–S10.
21.
BakkerK, ApelqvistJ, SchaperNC. International Working Group on Diabetic Foot Editorial Board: Practical guidelines on the management and prevention of the diabetic foot 2011. Diabetes Metab Res Rev, 2012; 28,Suppl 1:225–231.
22.
GhanassiaE, VillonL, Thuan Dit DieudonnéJF, BoegnerC, AvignonA, SultanA. Long-term outcome and disability of diabetic patients hospitalized for diabetic foot ulcers: a 6.5-years follow-up study. Diabetes Care, 2008; 31:1288–1292.
23.
NiuY, CaoX, SongF, XieT, JiX, MiaoM, DongJ, TianM, LinY, LuS. Reduced dermis thickness and AGE accumulation in diabetic abdominal skin. Int J Low Extrem Wounds, 2012; 11:224–230.
24.
HuH, HanCM, HuXL, YeWL, HuangWJ, SmitAJ. Elevated skin autofluorescence is strongly associated with foot ulcers in patients with diabetes: a cross-sectional, observational study of Chinese subjects. J Zhejiang Univ Sci B, 2012; 13:372–377.
25.
BoykoEJ, AhroniJH, StenselV, ForsbergRC, DavignonDR, SmithDG. A prospective study of risk factors for diabetic foot ulcer. The Seattle Diabetic Foot Study. Diabetes Care, 1999; 22:1036–1042.
26.
DubskýM, JirkovskáA, BemR, FejfarováV, SkibováJ, SchaperNC, LipskyBA. Risk factors for recurrence of diabetic foot ulcers: prospective follow-up analysis of a Eurodiale subgroup. Int Wound J, 2012; 19:1742–1748.
27.
TanKC, ChowWS, AiVH, MetzC, BucalaR, LamKS. Advanced glycation end products and endothelial dysfunction in type 2 diabetes. Diabetes Care, 2002; 25:1055–1059.
28.
KuzuyaM, SatakeS, AiS, AsaiT, KandaS, RamosMA, MiuraH, UedaM, IguchiA. Inhibition of angiogenesis on glycated collagen lattices. Diabetologia, 1998; 41:491–499.
29.
MoritaK, UrabeK, MoroiY, KogaT, NagaiR, HoriuchiS, FurueM. Migration of keratinocytes is impaired on glycated collagen I. Wound Repair Regen, 2005; 13:93–101.
30.
GoovaMT, LiJ, KislingerT, QuW, LuY, BucciarelliLG, NowygrodS, WolfBM, CalisteX, YanSF, SternDM, SchmidtAM. Blockade of receptor for advanced glycation end-products restores effective wound healing in diabetic mice. Am J Pathol, 2001; 159:513–525.
31.
PeppaM, BremH, EhrlichP, ZhangJG, CaiW, LiZ, CroitoruA, ThungS, VlassaraH. Adverse effects of dietary glycotoxins on wound healing in genetically diabetic mice. Diabetes, 2003; 52:2805–2813.
32.
GillSE, ParksWC. Metalloproteinases and their inhibitors: regulators of wound healing. Int J Biochem Cell Biol, 2008; 40:1334–1347.
33.
LobmannR, SchultzG, LehnertH. Proteases and the diabetic foot syndrome: mechanisms and therapeutic implications. Diabetes Care, 2005; 28:461–471.
34.
ZhuP, RenM, YangC, HuYX, RanJM, YanL. Involvement of RAGE, MAPK and NF-κB pathways in AGEs-induced MMP-9 activation in HaCaT keratinocytes. Exp Dermatol, 2012; 21:123–129.
