Association of peripheral neuropathy with circulating advanced glycation end products, soluble receptor for advanced glycation end products and other risk factors in patients with type 2 diabetes.
BACKGROUND
The pathogenesis of diabetic peripheral neuropathy remains uncertain and nonenzymatic glycoxidation is one of the contributing mechanisms. The aim of this study was to assess the respective relationship of diabetic peripheral neuropathy with glycoxidation, compared with other identified risk factors, in patients with type 2 diabetes.


METHODS
We included 198 patients with type 2 diabetes and high risk for vascular complications. Circulating concentrations of three advanced glycation end products (carboxymethyllysine, methyl-glyoxal-hydroimidazolone-1, pentosidine) and of their soluble receptor (sRAGE) were measured. Peripheral neuropathy was assessed by the neuropathy disability score and by the monofilament test and defined as either an abnormal monofilament test and/or a neuropathy disability score ≥6. Multivariate regression analyses were performed adjusting for potential confounding factors for neuropathy: age, gender, diabetes duration, current smoking, systolic blood pressure, waist circumference, height, peripheral arterial occlusive disease, glycated haemoglobin, estimated glomerular filtration rate and lipid profile.


RESULTS
Prevalence of peripheral neuropathy was 20.7%. sRAGE and carboxymethyllysine were independently and positively associated with the presence of peripheral neuropathy. No significant association was found between peripheral neuropathy and methyl-glyoxal-hydroimidazolone-1 or pentosidine. Waist circumference, height and peripheral arterial occlusive disease were independently associated with peripheral neuropathy.


CONCLUSIONS
Carboxymethyllysine and sRAGE were independently associated with peripheral neuropathy in patients with type 2 diabetes. Although the conclusions are limited by the absence of a healthy control population, this study confirms the relationship between advanced glycoxidation and diabetic peripheral neuropathy, independently of other risk factors.
Diabetes and Metabolic Diseases Department, AP-HP, Pitié-Salpêtrière Hospital, Paris, France; Internal Medicine Department, Fribourg Cantonal Hospital, Fribourg, Switzerland.
C E
CE
Aubert
P-L
PL
Michel
P
P
Gillery
S
S
Jaisson
M
M
Fonfrede
F
F
Morel
A
A
Hartemann
O
O
Bourron
D000368:Aged; D001157:Arterial Occlusive Diseases / Q000150:complications / Q000503:physiopathology; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications* / Q000652:urine; D003925:Diabetic Angiopathies / Q000150:complications / Q000503:physiopathology; D003929:Diabetic Neuropathies / Q000150:complications / Q000453:epidemiology / Q000503:physiopathology*; D005260:Female; D017127:Glycation End Products, Advanced / Q000097:blood*; D006801:Humans; D008239:Lysine / Q000031:analogs & derivatives* / Q000097:blood; D008297:Male; D008875:Middle Aged; D010297:Paris / Q000453:epidemiology; D017933:Peripheral Nervous System / Q000503:physiopathology*; D015995:Prevalence; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000097:blood* / Q000737:chemistry; D012307:Risk Factors; D012720:Severity of Illness Index; D012737:Sex Factors; D012995:Solubility; D055105:Waist Circumference
D017127:Glycation End Products, Advanced; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; C048496:N(6)-carboxymethyllysine; D008239:Lysine
advanced glycation; advanced glycation end products; peripheral neuropathy; risk factors; type 2 diabetes