The effects of rosiglitazone and metformin on inflammation and endothelial dysfunction in patients with type 2 diabetes mellitus

Abstract

Diabetic patients have a markedly increased risk of cardiovascular disease compared with non-diabetics. Two drug groups today target insulin resistance; biguanides and thiazolidinediones. In addition, these may have other effects on cardiovascular risk factors. The aim of this study was to evaluate the effects of metformin and rosiglitazone on non-traditional cardiovascular risk factors. Forty type 2 diabetic patients were randomized into metformin and rosiglitazone groups. After receiving the optimal doses, the patients were monitored for 12 weeks. Biochemical parameters, lipid parameters, CRP, insulin, c-peptide, and HbA1c levels were analyzed. VWF, PAI-1, ICAM-1, TNF-α, IL-6, E-selectin, and fibrinogen levels were measured in order to assess coagulation status and endothelial dysfunction. In the metformin group, body mass index, PPG, HbA1c, IL-6, ICAM-1, and TNF-α levels were significantly decreased after 12 weeks compared with the basal levels. IL-6 levels decreased from 75 pg/ml ± 20 to 42 pg/ml ± 9 (P 0.023) and TNF- α levels from 61 pg/ml ± 31 to 39 pg/ml ± 10 (P 0.018). In the rosiglitazone group, FPG, PPG, HbA1c, insulin, HOMA-IR, IL-6, and TNF-α levels decreased significantly after 12 weeks compared with the basal levels. IL-6 levels decreased from 78 pg/ml ± 21 to 41 pg/ml ± 9 (P 0.028) and TNF-α levels from 62 pg/ml ± 19 to 37 pg/ml ± 10 (P 0.012). At the end of the study, no significant differences were determined between groups. Insulin resistance and type 2 diabetes are strongly associated with low grade inflammation. Both metformin and rosiglitazone were effective in controlling inflammatory markers in addition to metabolic parameters.

Associations Between Inflammatory Markers, Hemostatic Markers, and Microvascular Complications in 182 Chinese Patients With Type 2 Diabetes Mellitus

“…15 Chronic low-grade inflammation can be the cause and the consequence of endothelial dysfunction. 16 In addition, enhanced activation of the clotting cascade has recently been implicated as an important contributing factor for the occurrence of vascular complications in DM. 17 The present study showed that most markers of low-grade inflammation and clotting activation were significantly higher in patients with T2DM who have microvascular complications compared to T2DM patients without microvascular complications.…”

AMP-activated protein kinase: an emerging drug target to regulate imbalances in lipid and carbohydrate metabolism to treat cardio-metabolic diseases

“…while metformin affects hsCRP levels in much greater extent than insulin secretagoge glibenclamide ( 185,187 ), both metformin and PPAR-␥ agonist rosiglitazone, which also promotes AMPK activity ( 29 ), were similarly effective in controlling infl ammatory markers in addition to metabolic parameters ( 186 ).…”

Efecto de metformina sobre la expresión del factor de necrosis tumoral-α, los receptores Toll-like 2/4 y la PCR ultra sensible en sujetos obesos con diabetes tipo 2

“…Varios estudios han demostrado la utilidad de metformina en la reducción de los factores de riesgo asociados con diabetes, como el estrés oxidativo, la inflamación endotelial y en la expresión de genes de la inflamación [15][16]22 , sin embargo, hay poca información sobre los efectos de metformina sobre la PCRus. Li et al (2009) 23 demostraron en un modelo de ateroesclerosis de conejo, que al administrar metformina había una disminución de la PCRus, pero también había disminución de la activación de NF-aB.-En los sujetos aquí estudiados no encontramos diferencias en la abundancia del RNAm de NF-aB, sin embargo, el estrés oxidativo está muy ligado a la actividad de este factor nuclear ya que los ROS y los AGEs son inductores de NF-aB 24 , en los sujetos diabéticos estudiados no se encontró diferencias ni en la actividad de la enzima hem oxigenasa-1 ni en la concentración de especies reactivas al ácido tiobarbitúrico, ambos marcadores de estrés oxidativo (datos no mostrados).…”

“…En el estudio prospectivo de diabetes del Reino Unido (UKPDS), la metformina fue el único agente que redujo el infarto al miocardio y las muertes asociadas a diabetes 14 . Posteriormente, se observó que el uso de metformina en sujetos diabéticos obesos produjo una reducción del índice de masa corporal (IMC), con una disminución de la grasa tanto periférica como central, lo que se tradujo en una disminución de la resistencia a la insulina y de secreción de citoquinas pro-inflamatorias 15,16 . Asimismo, en ratas a las que se les indujo diabetes mediante la inyección con estreptozotocina, el tratamiento con metformina redujo el estrés oxidativo y la expresión de TNF-a e IL-6 17 .…”