Effect of smoking on risk factors for cardiovascular disease in patients with diabetes mellitus and renal insufficiency.
BACKGROUND
Many studies have been published demonstrating a strong correlation between smoking, renal lesions and cardiovascular morbidity and mortality. Possible contributing factors are elevated blood pressure values, changes in vascular reactivity, concentrations of lipids, fibrinogen and carboxyhemoglobin, in patients with diabetes mellitus, the quality of diabetes control and insulin resistance. Other possible risk factors may include advanced glycation end (AGE)-products, total plasma homocysteine and metabolites as well as symmetrical (SDMA) and asymmetrical (ADMA) dimethylarginine. It was the goal of the present trial to investigate the serum concentrations of these >new<, possible risk factors in a selection free population of patients with type 1 and insulin-treated type 2 diabetes mellitus, in patients with chronic renal insufficiency and in renal transplant recipients. The second aim was to analyse the effect of cigarette smoking on the levels of these laboratory parameters.


METHODS
A total of 544 subjects (n = 98 patients with chronic renal insufficiency without hemodialysis, n = 84 patients with hemodialysis, n = 50 renal transplant recipients, n = 114 patients with type 1 and n = 147 patients with insulin treated type 2 diabetes mellitus, n = 51 healthy controls) participated in the trial.


RESULTS
Patients with renal insufficiency had significantly higher concentrations of the AGE-products N-epsilon-Carboxymethyllysine (CML) and pentosidine compared with both groups of patients with insulin-treated diabetes mellitus and the healthy controls. In patients with type 1 diabetes there was a positive correlation between HbA1c and the concentration of CML (r = 0.405, p = 0.017) and between the pentosidine-concentration and the serum creatinine-level (r = 0.482, p = 0.001). In type 2 diabetes there was a correlation between CML and diastolic blood pressure (r = 0.239, p = 0.039). In comparison to the healthy controls, patients with renal diseases and patients after kidney transplantation had higher concentrations of total plasma homocysteine and its metabolites. Similar results were found for SDMA and ADMA: Patients with chronic renal insufficiency both with and without hemodialysis had significantly higher values than the renal transplant recipients and healthy controls. A clear influence of cigarette smoking on the levels of the laboratory parameters measured could not be determined in any group; neither in the patients with diabetes mellitus, nor in the patients with renal diseases, nor in the healthy controls.


CONCLUSIONS
The present trial demonstrates an increase in the parameters linked to the development of cardiovascular diseases including total plasma homocysteine, its metabolites, the dimethylarginines SDMA and ADMA and advanced glycation end-products depending on the degree of renal insufficiency. Moreover, in patients with insulin-treated diabetes mellitus, the concentrations of the AGE-products CML and pentosidine seem to be strongly influenced by the quality of diabetes control and blood pressure levels. There was no influence of cigarette smoking on the levels of the laboratory parameters measured.
Schiel
R
R
University of Jena Medical School, Department of Internal Medicine III, Jena, Germany. ralf.schiel@med.uni-jena.de
Franke
S
S
Busch
M
M
Müller
A
A
Fleck
C
C
Müller
U A
UA
Braun
A
A
Stein
G
G
D000328:Adult; D000368:Aged; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood / Q000737:chemistry / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000097:blood / Q000209:etiology / Q000503:physiopathology*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000150:complications / Q000503:physiopathology*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000503:physiopathology*; D005260:Female; D017127:Glycation End Products, Advanced / Q000378:metabolism; D006710:Homocysteine / Q000378:metabolism; D006801:Humans; D016030:Kidney Transplantation; D008239:Lysine / Q000031:analogs & derivatives* / Q000097:blood; D008875:Middle Aged; D006435:Renal Dialysis; D051437:Renal Insufficiency / Q000097:blood / Q000150:complications / Q000503:physiopathology*; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects
D017127:Glycation End Products, Advanced; D006710:Homocysteine; C048496:N(6)-carboxymethyllysine; D001120:Arginine; C062187:pentosidine; D008239:Lysine