Skin collagen pentosidine and fluorescence in diabetes were predictors of retinopathy progression and creatininemia increase already 6years after punch-biopsy.
OBJECTIVE
Advanced glycation end products (AGEs) of collagens appear to contribute to microvascular complications in diabetes. Do high concentrations of AGEs in skin collagen predict accelerated progression of these complications after 6 years and indicate the need for tighter anti-diabetic treatment?


METHODS
We measured two AGE parameters in collagen extracted from skin punch-biopsies: pentosidine and fluorescence at 370/440nm, as markers and predictors of microvascular complications, in 30 patients with diabetes (14 type-1, 16 type-2) without renal insufficiency, and in age- and gender-matched normoglycemic controls, followed at Hôtel-Dieu in Paris.


RESULTS
At the time of biopsy, marked increases in pentosidine (p=0.0014) and fluorescence (p=0.0001) expressed per collagen hydroxyproline, were found in the patients with diabetes versus the controls. A significant effect of age was found for pentosidine, but not fluorescence, measurements in the normoglycemic controls. Therefore pentosidine but not fluorescence results were corrected for age in the patients. Pentosidine and fluorescence were correlated with diabetes duration. Fluorescence was significantly dependent on retinopathy presence and score in type-1 and type-2 diabetes, whereas pentosidine was not. Fluorescence was correlated with microalbuminuria only in type-1 diabetes. Neither fluorescence nor pentosidine were correlated with creatininemia. Already six years after biopsy, retinopathy score progression and creatininemia increase were significantly correlated with initial pentosidine and fluorescence measurements.


CONCLUSIONS
These AGEs are good predictors of progression of microvascular complications and appear to be pathogenic. High skin concentrations of AGEs should induce tighter anti-diabetic treatment.
Équipe "Protéines Modifiées, Protéases et Physiopathologie de l'Endothélium Vasculaire", Laboratoire de Pharmacologie, Faculté de Pharmacie, Université René Descartes, Paris, France. Electronic address: michel.sternberg@wanadoo.fr.
Michel
M
Sternberg
Centre de Diagnostic et de Thérapeutique, Diabétologie, Hôtel-Dieu de Paris, France.
Jocelyne
J
M'bemba
Équipe "Protéines Modifiées, Protéases et Physiopathologie de l'Endothélium Vasculaire", Laboratoire de Pharmacologie, Faculté de Pharmacie, Université René Descartes, Paris, France; Laboratoire de Biochimie, Hôpital Bichat, Paris, and Université Paris VI, France.
Paul
P
Urios
Équipe "Protéines Modifiées, Protéases et Physiopathologie de l'Endothélium Vasculaire", Laboratoire de Pharmacologie, Faculté de Pharmacie, Université René Descartes, Paris, France; Laboratoire de Biochimie, Hormonologie et Génétique Moléculaire, Hôpital Ambroise-Paré, 92100 Boulogne and Université Paris VI, France.
Anne-Marie
AM
Borsos
Centre de Diagnostic et de Thérapeutique, Diabétologie, Hôtel-Dieu de Paris, France.
Jean-Louis
JL
Selam
Équipe "Protéines Modifiées, Protéases et Physiopathologie de l'Endothélium Vasculaire", Laboratoire de Pharmacologie, Faculté de Pharmacie, Université René Descartes, Paris, France.
Jacques
J
Peyroux
Centre de Diagnostic et de Thérapeutique, Diabétologie, Hôtel-Dieu de Paris, France.
Gérard
G
Slama
D000328:Adult; D000419:Albuminuria / Q000097:blood / Q000378:metabolism / Q000473:pathology; D001120:Arginine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D015415:Biomarkers / Q000032:analysis; D001706:Biopsy; D016022:Case-Control Studies; D003094:Collagen / Q000378:metabolism*; D003404:Creatinine / Q000097:blood*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000378:metabolism / Q000473:pathology; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000378:metabolism / Q000473:pathology; D003925:Diabetic Angiopathies / Q000097:blood / Q000378:metabolism / Q000473:pathology; D003928:Diabetic Nephropathies / Q000097:blood / Q000378:metabolism / Q000473:pathology; D003930:Diabetic Retinopathy / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D018450:Disease Progression; D005260:Female; D005453:Fluorescence; D006801:Humans; D008137:Longitudinal Studies; D008239:Lysine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D012867:Skin / Q000378:metabolism* / Q000473:pathology; D013050:Spectrometry, Fluorescence
D015415:Biomarkers; D003094:Collagen; D001120:Arginine; D003404:Creatinine; C062187:pentosidine; D008239:Lysine
Creatininemia,; Diabetic nephropathy; Diabetic retinopathy,; Fluorescence; Microalbuminuria,; Pentosidine; Progression of microvascular complications; Skin collagen,