Effects of insulin dependence on inflammatory process, thrombotic mechanisms and endothelial function, in patients with type 2 diabetes mellitus and coronary atherosclerosis.
BACKGROUND
Type 2 diabetes mellitus (T2DM) is characterized by endothelial dysfunction, increased thrombogenicity and abnormal inflammatory response.


OBJECTIVE
We hypothesizsed that insulin dependence/exogenous insulin administration may affect thrombotic/inflammatory status and endothelial function in patients with T2DM and coronary artery disease (CAD).


METHODS
Fifty-five patients with T2DM + CAD (26 insulin-treated (INS) and 29 under oral biguanide + sulphonylurea (TABL)) were recruited. Endothelial function was assessed by gauge-strain plethysmography, and serum levels of inflammatory and thrombotic markers were determined by enzyme linked immunosorbent assay.


RESULTS
There was no significant difference in endothelium-dependent dilation (EDD) between the study groups, while EDD was correlated with fasting glucose levels in both INS (r = - 0.776, p = 0.0001) and TABL (r = - 0.702, p = 0.0001). Patients in INS group had higher levels of interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha), monocyte chemoattractant protein (MCP-1) and vascular cell adhesion molecule (sVCAM-1), compared to TABL. However, TNF-alpha was negatively correlated with protein C (PrtC) only in INS (r = - 0.726, p = 0.01) but not in TABL group (r = - 0.066, p = 0.738). Similarly, sVCAM-1 was correlated with PrtC only among INS patients (r = - 0.451, p = 0.046) but not in TABL (r = 0.069, p = 0.727). In multivariate analysis, insulin dependence was a predictor of IL-6, TNF-alpha, MCP-1 and sVCAM-1 levels independently from the patients' demographic characteristics, the angiographic extend of CAD or the duration of diabetes.


CONCLUSIONS
Insulin treatment in patients with type 2 diabetes mellitus affects the expression of inflammatory cytokines and subsequently modifies the thrombotic mechanisms in patients with coronary atherosclerosis, independently from the duration of diabetes and the extend of coronary artery disease.
Antoniades
Charalambos
C
A' Cardiology Department, Athens University Medical School, Athens, Greece. antoniades@panafonet.gr
Tousoulis
Dimitris
D
Marinou
Kyriakoula
K
Papageorgiou
Nikos
N
Bosinakou
Erini
E
Tsioufis
Costas
C
Stefanadi
Elli
E
Latsios
George
G
Tentolouris
Costas
C
Siasos
Gerasimos
G
Stefanadis
Christodoulos
C
D000368:Aged; D001645:Biguanides / Q000494:pharmacology / Q000627:therapeutic use*; D001779:Blood Coagulation Factors / Q000378:metabolism; D003324:Coronary Artery Disease / Q000097:blood / Q000209:etiology* / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D004359:Drug Therapy, Combination; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D005260:Female; D005542:Forearm / Q000098:blood supply; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D007249:Inflammation / Q000097:blood / Q000209:etiology* / Q000503:physiopathology; D007328:Insulin / Q000494:pharmacology / Q000627:therapeutic use*; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D011486:Protein C / Q000378:metabolism; D012039:Regional Blood Flow / Q000187:drug effects; D012042:Registries; D013453:Sulfonylurea Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D013927:Thrombosis / Q000097:blood / Q000209:etiology* / Q000503:physiopathology; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood; D014664:Vasodilation / Q000187:drug effects
D001645:Biguanides; D001779:Blood Coagulation Factors; D007004:Hypoglycemic Agents; C508600:IL6 protein, human; D007328:Insulin; D015850:Interleukin-6; D011486:Protein C; D013453:Sulfonylurea Compounds; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1