Improvement of the quality of diabetes control and decrease in the concentrations of AGE-products in patients with type 1 and insulin-treated type 2 diabetes mellitus: results from a 10 year-prospective, population-based survey on the quality of diabetes care in Germany (JEVIN).
BACKGROUND
Advanced glycation end (AGE)-products are a complex group of compounds that have been implicated in diabetes related long-term complications. Up to the present only few data exist about serum levels of the AGE-proteins N-epsilon-Carboxymethyllysine (CML) and pentosidine in patients with diabetes mellitus.


METHODS
In the present 10-year, population-based trial of a selection-free cohort of patients with insulin-treated diabetes mellitus, serum CML and pentosidine levels were examined in correlation to the patients' quality of diabetes control and the prevalence of diabetes related long-term complications.


RESULTS
Following the reunification of Germany in 1989 the health care system was decentralised. Up to 1994/95 the relative HbA1c (HbA1c/mean normal) of patients with type 1 diabetes increased (1.65 +/- 0.35 versus 1.52 +/- 0.31, p = 0.002). For patients with type 2 diabetes it remained constant (1.75 +/- 0.4 versus 1.78 +/- 0.31, p = 0.669). During the following period (from 1994/95 to 1999/2000) specialised diabetes care, structured treatment and teaching programmes (TTP), intensified insulin therapy and blood glucose self-monitoring for all patients were broadly implemented. This was accompanied by a substantial improvement in the relative HbA1c of both, patients with type 1 (1.48 +/- 0.3, p<0.0001), and insulin-treated type 2 diabetes mellitus (1.47 +/- 0.25, p<0.0001). During the same period the mean concentration of the AGE-product CML in the sera of patients with type 1 and insulin-treated type 2 diabetes decreased (type 1: 1994/95: 1158.1 +/- 410.0 ng/ml versus 1999/2000: 938.5 +/- 422.4 ng/ml, p<0.0001, type 2: 1994/94: 1244.7 +/- 1231.3 ng/ml versus 1999/2000: 970.9 +/- 458.6 ng/ml, p = 0.007). For pentosidine the same tendency was found for patients with type 1 diabetes (1994/95: 253.6 +/- 280.7 pmol/ml versus 1999/2000: 148.2 +/- 91.4 pmol/ml, p<0.0001). For patients with type 1 diabetes there was a positive correlation between the relative HbA1c-value calculated over the total follow-up period of 10 years and the CML-concentration in 1999/2000 (r = 0.405, p = 0.017). In 1999/2000 a reduced creatinine clearance (</=80 ml/min) was found in 7.8% of patients with type 1 and 14.9% of patients with insulin-treated type 2 diabetes. In comparison to patients with a normal creatinine clearance, patients with a reduced creatinine clearance had not only higher creatinine-concentrations in the sera and higher values of albuminuria but also significantly higher pentosidine levels.


CONCLUSIONS
Comparing the data of 1999/2000 with those from 1994/95, there was not only a substantial improvement in patients' quality of diabetes control but also a decrease in the concentration of AGE-products. In patients with diabetes mellitus the AGE-products seem to be mainly influenced by the quality of diabetes control. The decline in renal function leads to increased serum pentosidine levels in patients with insulin-treated diabetes mellitus. Thus it seems that in patients with reduced renal function, higher levels may either play a causal role in the development and progression of nephropathy or they are an epi-phenomenon caused by the decrease in urinary excretion.
Schiel
Ralf
R
University of Jena Medical School, Department of Internal Medicine III, Germany. inselklinik.Schiel@medigreif.de
Franke
S
S
Appel
T
T
Voigt
U
U
Ross
I S
IS
Kientsch-Engel
R
R
Müller
U A
UA
Stein
G
G
D000293:Adolescent; D000328:Adult; D001120:Arginine / Q000031:analogs & derivatives / Q000097:blood; D003404:Creatinine / Q000378:metabolism; D048909:Diabetes Complications / Q000188:drug therapy; D003920:Diabetes Mellitus / Q000097:blood* / Q000188:drug therapy*; D005260:Female; D005858:Germany; D017127:Glycation End Products, Advanced / Q000097:blood*; D006306:Health Surveys; D006801:Humans; D007328:Insulin / Q000627:therapeutic use*; D008137:Longitudinal Studies; D008239:Lysine / Q000031:analogs & derivatives / Q000097:blood; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D013997:Time Factors
D017127:Glycation End Products, Advanced; D007328:Insulin; C048496:N(6)-carboxymethyllysine; D001120:Arginine; D003404:Creatinine; C062187:pentosidine; D008239:Lysine