Abstract
Levels of plasma pentosidine, a well-known AGE, were measured in type 2 diabetic patients
in varying states of metabolic control to verify possible relationships between this
parameter and traditional metabolic control parameters such as HbA1c and plasma glucose levels. At baseline, mean values of fasting plasma glucose, HbA1c and pentosidine were significantly higher in diabetic patients than those of controls,
confirming patients’ poor glycemic control. After ten months, patients with good metabolic
control achieved showed near-normal HbA1c levels and reduced but not normalized pentosidine levels. Significant differences
were found in the mean percentage decrease in the parameters. Regarding linear correlation,
HbA1c levels only showed a positive relationship with plasma glucose values at baseline.
Patients affected by chronic complications showed higher levels of pentosidine than
those without complications. Thus, pentosidine plasma levels may be used to evaluate
very long-term metabolic control in diabetic patients. In addition, a period of ten
months of acceptable metabolic control is not enough to normalize pentosidine levels
in diabetics, thus emphasizing the need for a longer period of improved metabolic
control to reduce both this parameter and the burden of chronic diabetic complications.
Key words
Type 2 diabetes - Glycemic control - Advanced glycation end-products (AGEs) - Pentosidine
- Chronic complications
References
- 1
The Diabetes Control and Complications Trial Research Group .
The effect of intensive treatment of diabetes on the development and progression of
long-term complications in insulin-dependent diabetes mellitus.
N Engl J Med.
1993;
329
977-986
- 2
UKPDS Group .
Intensive blood glucose control with sulphonylureas or insulin compared with conventional
treatment and risk of complications in patients with type 2 diabetes (UKPDS 33).
The Lancet.
1998;
352
837-851
- 3
Vlassara H, Bucala R, Striker L.
Pathogenic effects of advanced glycosylation: biochemical, biologic, and clinical
implications for diabetes and ageing.
Lab Invest.
1994;
70
138-151
- 4
Brownlee M, Cerami A, Vlassara H.
Advanced glycosylation end products in tissue and the biochemical basis of diabetic
complications.
N Engl J Med.
1988;
318
1315-1321
- 5
Thornalley P J.
Advanced glycation and the development of diabetic complications. Unifying the involvement
of glucose, methylglyoxal and oxidative stress.
Endocrinol & Metabolism.
1996;
3
149-166
- 6 Njoroge F G, Monnier V M.
The chemistry of the Maillard reaction under physiological conditions: a review. In: Baynes JW, Monnier VM (eds) The Maillard reaction and Aging, Diabetes and Nutrition. New
York; AR Liss 1989: 85-109
- 7
Reiser K M.
Nonenzymatic glycation of collagen in aging and diabetes.
Proc Soc Biol Med.
1998;
218
23-37
- 8
Baynes J W, Thorpe S R.
Role of oxidative stress in diabetic complications: a new perspective on an old paradigm.
Diabetes.
1999;
48
1-9
- 9
Sell D R, Lapolla A, Odetti P, Fogarty J, Monnier V M.
Pentosidine formation in skin correlates with severity of complication in individuals
with long-standing IDDM.
Diabetes.
1992;
41
1286-1292
- 10
Makita Z, Vlassarq H, Cerami A, Bucala R.
immunochemical detection of advanced glycosylation end products in vivo.
J Biol Chem.
1992;
267
5133-5138
- 11
Ono Y, Aoki S, Ohnishi K, Yasuda T, Kawano K, Tsukada Y.
Increased serum levels of advanced glycation end-products and diabetic complications.
Diabetes Res Clin Pract.
1988;
41
131-137
- 12
Koenig R J, Peterson C M, Jones R L, Saudek C, Lehrman M, Cerami A.
Correlation of glucose regulation and hemoglobin A in diabetes mellitus.
N Engl J Med.
1976;
295
417-420
- 13
Wolffenbuttel B H, Giordano D, Founds H W, Bucala R.
Long-term assessment of glucose control by hemoglobin-AGE measurement.
Lancet.
1996;
347
513-515
- 14
Miura J, Yamagishi S, Uchigata Y, Takeuchi M, Yamamoto H, Makita Z, Iwamoto Y.
Serum levels of non-carboxymethyllysine advanced glycation endproducts are correlated
to severity of microvascular complications in patients with Type 1 diabetes.
J Diabetes Compl.
2003;
17
16-21
- 15
Tsukahara H, Sekine K, Uchiyama M, Kawakami H, Hata I, Todoroki Y, Hiraoka M, Kaji M,
Yorifuji T, Momoi T, Yoshihara K, Beppu M, Mayumi M.
Formation of advanced glycosylation end products and oxidative stress in young patients
with type 1 diabetes.
Pediatr Res.
2003;
54
419-24
- 16
Weiss M F, Rodby R A, Justice A C, Hricik D E.
Free pentosidine and neopterin as markers of progression rat diabetic nephropathy.
Collaborative Study Group.
Kidney Int.
1998;
54
193-202
- 17
Takeuchi M, Makita Z, Yanagisawa K, Kameda Y, Koike T.
Detection of noncarboxymethyl lysine and carboxymethyl lysine advanced glycation end
products (AGE) in serum of diabetic patients.
Mol Med.
1999;
5
393-405
- 18
Daimon M, Sugiyama K, Kameda W, Saitoh T, Oizumi T, Hirata A, Yamaguchi H, Ohnuma H,
Igarashi M.
Increased urinary levels of pentosidine, pyrraline and acrolein adduct in type 2 diabetes.
Endocr J.
2003;
50
61-67
- 19
Schiel R, Franke S, Appel T, Voigt U, Ross I S, Kientsch-Engel R, Stein G, Müller U A.
Improvement in quality of diabetes control and concentrations of AGE-products in patients
with type 1 and insulin-treated type 2 diabetes mellitus studied over a period of
10 years (JEVIN).
J Diab Compl.
2003;
17
90-97
- 20
Odetti P, Fogarty J, Sell D S, Monnier V M.
Chromatographic quantitation of plasma and erythrocyte pentosidine in diabetic and
uremic subjects.
Diabetes.
1992;
41
153-159
- 21
Huggett A, Nixon D A.
Use of glucose oxidase, peroxidase and o-dianisine in the determination of blood and
urine glucose.
Lancet.
1957;
2
368-370
- 22
Janes P K, Willis M C, Chon P P.
Evaluation of minicolumn chromatographic procedure for the measurement of HbA1c.
.
Clin Biochem.
1985;
18
32-36
- 23
Keen H, Chlouverakis C.
An immunoassay method for urinary albumin at low concentrations.
Lancet.
1963;
I
913-914
- 24
Lapolla A, Flamini R, Dalla V edova , Senesi A, Reitano R, Fedele D, Basso E, Seraglia R,
Traldi P.
Glyoxal and methylglyoxal levels in diabetic patients: quantitative determination
by a new GC/MS method.
Clin Chem Lab Med.
2003;
41 (9)
1166-1173
- 25
Zdenka T, Misur I, Turk N, Benko B.
Rat tissue collagen modified by advanced glycation: correlation with duration of diabetes
and glycemic control.
Clin Chem Lab Med.
1999;
37 (8)
813-820
- 26
Monnier V M, Bautista O, Kenny D, Sell D R, Fogarty J, Dahms W, Cleary P A, Lachin J,
Genuth S. and the DCCT Skin Collagen Ancillary Study Group .
Skin collagen glycation, glycoxidation and crosslinking are lower in subjects with
long-term intensive versus conventional therapy of type 1 diabetes.
Diabetes.
1999;
48
870-880
- 27
Berg T J, Bangstad H J, Torjensen P A, Osterby R, Bucala R, Hanssen K F.
Advanced glycation end products in serum predict changes in the kidney morphology
of patients with insulin-dependent diabetes mellitus.
Metabolism.
1997;
46 (6)
661-665
- 28
Berg T J, Snorgaard O, Faber J, Torjensen P A, Hildebrandt P, Mehlsen J, Hanssen K F.
Serum levels of advanced glycation end products are associated with left ventricular
diastolic function in patients with type 1 diabetes.
Diabetes Care.
1999;
22 (7)
1186-1190
- 29
Aso Y, Inukai T, Tayama K, Takemura Y.
Serum concentrations of advanced glycation end products are associated with the development
of atherosclerosis as well as diabetic microangiopathy in patients with type 2 diabetes.
Acta Diabetol.
2000;
37
87-92
- 30
Jeffcoate S L.
Diabetes control and complications: the role of glycated haemoglobin, 25 years on.
Diab Med.
2003;
21
657-665
A. Lapolla
Department of Medical and Surgical Sciences, University of Padua
Via Giustiniani 2 · 35100 Padua · Italy
Telefon: +39 (49) 821 68 57
Fax: +39 (49) 821 68 38
eMail: annunziata.lapolla@unipd.it