scholarly journals Impact of metformin versus repaglinide on non-glycaemic cardiovascular risk markers related to inflammation and endothelial dysfunction in non-obese patients with type 2 diabetes

2008 ◽  
Vol 158 (5) ◽  
pp. 631-641 ◽  
Author(s):  
Søren S Lund ◽  
Lise Tarnow ◽  
Coen D A Stehouwer ◽  
Casper G Schalkwijk ◽  
Tom Teerlink ◽  
...  

ObjectiveIn patients with type 2 diabetes mellitus (T2DM), biomarkers reflecting inflammation and endothelial dysfunction have been linked to cardiovascular disease (CVD biomarkers) and metabolic regulation. In T2DM patients, metformin and insulin secretagogues have demonstrated equal anti-hyperglycaemic potency. Here, we report the effect of metformin versus an insulin secretagogue, repaglinide, on CVD biomarkers in non-obese T2DM patients.Design and methodsSingle-centre, double-masked, double-dummy, crossover study during 2×4 months involving 96 non-obese (body mass index≤27 kg/m2) insulin-naïve T2DM patients. At enrolment, previous oral hypoglycaemic agents were stopped and the patients entered a 1-month run-in on diet-only treatment. Hereafter, patients were randomized to either 2 mg repaglinide thrice daily followed by 1 g metformin twice daily or vice versa each during 4 months with a 1-month washout between interventions.ResultsLevels of tumour necrosis factor-α, plasminogen activator inhibitor-1 antigen, tissue-type plasminogen activator antigen, von Willebrand factor, soluble intercellular adhesion molecule-1 and soluble E-selectin were significantly lower during metformin versus repaglinide treatments. In contrast, Amadori albumin and heart rate were higher during metformin versus repaglinide. Levels of interleukin-6, fibrinogen, soluble vascular cell adhesion molecule-1, asymmetric dimethylarginine and advanced glycation end products as well as glycaemic levels (previously reported) and 24-h blood pressure were similar between treatments. Adjustment for known macrovascular disease did not affect the between-treatment effects.ConclusionsIn non-obese T2DM patients, metformin was more effective in reducing selected biomarkers reflecting inflammation and endothelial dysfunction compared with repaglinide despite similar glycaemic levels between treatments.

2001 ◽  
Vol 86 (11) ◽  
pp. 5491-5497 ◽  
Author(s):  
Warwick Bagg ◽  
Claudio Ferri ◽  
Giovambattista Desideri ◽  
Greg Gamble ◽  
Paul Ockelford ◽  
...  

The aims of this study were to elucidate the factors that contribute to endothelial activation and fibrinolytic abnormalities in patients with poorly controlled type 2 diabetes and to determine whether improved glycemic control reduces endothelial activation. Adhesion molecules [E-selectin, intracellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1], von Willebrand factor, total nitric oxide (NO), endothelin-1, tissue plasminogen activator, and plasminogen activator inhibitor-1 were measured in 43 type 2 diabetic subjects with hemoglobin A1c of 9.0% or more at baseline (compared with 21 healthy controls) who after 20 wk had been randomized to either improved (IC) or usual (UC) glycemic control. At baseline, type 2 diabetic patients had significant endothelial activation and abnormal fibrinolysis compared with control subjects. Body mass index in the diabetic patients was the only independent predictor of E-selectin (P = 0.007), ICAM-1 (P = 0.01), and NO (P = 0.008) concentrations, but not vascular cell adhesion molecule-1, plasminogen activator inhibitor-1, or tissue plasminogen activator (all P > 0.05). Type 2 diabetic patients with a body mass index of 28 kg/m2 or less had concentrations of E-selectin, ICAM-1, endothelin-1, and NO similar to those in healthy controls. After 20 wk, hemoglobin A1c was significantly lower in IC vs. UC (IC, 8.02 ± 0.25%; UC, 10.23 ± 0.23%; P < 0.0001), but there were no significant changes in markers of endothelial activation or indexes of fibrinolysis. Obesity appears to be the most important predictor of endothelial activation in patients with type 2 diabetes. Short-term improvement in glycemic control does not appear to reduce endothelial activation.


Author(s):  
Ifeanyichukwu Martin Ositadinma ◽  
Ngwu Amauche Martina ◽  
Eluke Blessing Chekwube

Background: A number of processes regulating the thrombolytic balance are impaired in diabetic patients as a result of dysfunction of endothelial cells leading to a hypercoagulative state. Von Willebrand factor (VWF) is an important marker of endothelial dysfunction. Plasminogen activator inhibitor-1 antigen (PAI-1-Ag), the major physiological inhibitor of tissue plasminogen activator (tPA), is mainly produced by endothelium. The aim of this study is to measure plasma levels of von Willebrand factor, Plasminogen activator inhibitor-1 antigen in type 2 diabetes mellitus patients and to correlate with glycated haemoglobin (HbA1c). Study Design: This prospective cohort study was conducted on 30 diagnosed type 2 DM patients who were about to start treatment. Place and Duration of Study: Medical outpatient (MOP) clinic of Enugu State University of Science and Technology Teaching Hospital (ESUTTH), between January and December 2016. Methodology: We included 30 patients (13 men, 17 women; age range 40-80 years) with type 2 diabetes mellitus. Blood samples were drawn from the patients before they commenced treatment, six months into the treatment and at twelve months of the treatment. Blood samples were also drawn from 25 age matched non diabetic patients. Plasma von Willebrand factor and Plasminogen activator inhibitor-1 antigen levels were determined by Enzyme linked immunosorbent assay. Glycated haemoglobin (HbA1c) and fasting blood sugar (FBS) levels were also evaluated along with them. Results: This study was conducted on 30 type 2 DM patients consisting of 13 males and 17 females. At treatment naïve, mean levels of vWF were significantly increased (45.48 +/- 6.46) in male type 2 Diabetic patients compared to the control (20.45 +/- 0.26). Six months into treatment mean levels of vWF were significantly increased (48.18 +/- 4.99) in female type 2 Diabetic patients compared to the control (37.64 +/- 7.93). The plasma levels of vWF were significantly and positively correlated with HbA1c at six months into treatment in male type 2 DM patients. The plasma levels of vWF were also significantly and positively correlated with PAI-1 at six and twelve months into treatment in both genders. Conclusion: There was strong significant positive correlation between plasma levels of vWF and PAI-1 in type 2 diabetes mellitus patients.


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