Combined effects of atorvastatin and metformin on glucose-induced variations of inflammatory process in patients with diabetes mellitus.

BACKGROUND: Statin treatment improves survival in patients with atherosclerosis, but their effect on the glucose-induced variations of inflammatory markers, is unknown. We examined the effect of combined therapy with atorvastatin and metformin on glucose-induced variations of inflammatory molecules in patients with newly diagnosed diabetes mellitus type 2 (DM). METHODS: Thirty five subjects with newly diagnosed DM were randomized to receive metformin 850 mg/d (M, n=17) or metformin 850 mg/d+atorvastatin 10mg (n=18). All subjects underwent glucose loading (75 g oral glucose) at baseline and after 12 weeks of treatment. Blood samples were obtained at baseline and 3h post-loading, while serum tumor necrosis factor alpha (TNF-α) levels were determined at baseline and at 3h. RESULTS: Serum TNF-α remained unchanged in metformin at baseline (1.36±0.18 to 1.47±0.21 pg/ml p=NS) and after treatment (1.44±0.71 to 1.31±0.17 pg/ml, p=NS), while it was reduced in metformin+atorvastatin (2.3±0.3 to 2.0±0.4 pg/ml, p=NS at baseline and 1.80±0.2 to 1.65±0.2 pg/ml, p=0.03 after treatment). CONCLUSIONS: Interestingly, the combination of metformin and atorvastatin partly prevents the glucose-loading induced elevation of glucose levels (at 1 h), suggesting a better response to glucose intake than monotherapy with metformin. In addition, combined treatment with atorvastatin and metformin reduces the post-glucose loading levels of TNF-α compared to metformin monotherapy.

Impact of 6 weeks of treatment with low-dose metformin and atorvastatin on glucose-induced changes of endothelial function in adults with newly diagnosed type 2 diabetes mellitus: A single-blind study.

BACKGROUND: Statin treatment has been reported to improve survival in patients with atherosclerosis, partly by improving vascular endothelial function. Elevation of blood glucose concentrations impairs endothelial function and promotes atherogenesis, but the effect of statins on glucose-induced endothelial dysfunction is unknown. Endothelium-dependent dilation (EDD) measured by gauge-strain plethysmography in the forearm is considered to be a reliable marker of endothelial function in forearm resistance vessels. OBJECTIVE: This study examined the combined effects of metformin and atorvastatin treatment on glucose-induced endothelial dysfunction (as EDD) in patients with newly diagnosed type 2 diabetes mellitus (DM). METHODS: Patients with newly diagnosed DM were recruited and were randomly assigned to receive metformin 850 mg/d or metformin 850 mg/d + atorvastatin 10 mg/d for 6 weeks in a single-blind study. All patients underwent glucose loading (75 g oral glucose after 12 hours of fasting) at baseline and at the end of the treatment period. Blood samples were obtained at baseline before glucose loading and 3 hours after loading to determine serum concentrations of cholesterol, lipoproteins, triglycerides, glucose, and glycosylated hemoglobin. EDD was evaluated at baseline and at 1, 2, and 3 hours after loading. The investigators were blinded to the treatment group assignments, and all analyses were performed in a blinded manner. Adverse events (eg, gastrointestinal disorders, myopathy, liver disorders) were monitored based on reported symptoms or signs (eg, myalgias, muscle cramps), clinical examination, and laboratory parameters (eg, increased liver and muscle enzymes). RESULTS: Thirty-two white patients with newly diagnosed type 2 DM were randomly assigned to receive metformin 850 mg/d (n = 17 [12 men]; mean [SD] age, 53.88 [45] years; body mass index [BMI], 28.7 [4.5] kg/m²) or metformin 850 mg/d + atorvastatin 10 mg/d (n = 15 [6 men]; mean age, 52.53 [37] years; BMI, 28.5 [2.1] kg/m²). At baseline, EDD was reduced 1 and 2 hours after glucose loading in both study groups (P < 0.01). Glucose loading was associated with an elevation of blood glucose concentrations at 1 and 2 hours (P < 0.01 vs resting levels before loading), and concentrations returned to resting levels at 3 hours, in both groups at baseline and after treatment. Metformin alone or in combination with atorvastatin was associated with a significant reduction in resting glucose concentrations after 6 weeks (both, P < 0.05 vs baseline), but only the combination of metformin + atorvastatin partly prevented the glucose-induced elevation of serum glucose at 1 hour after loading and the glucose-induced decrease in EDD (both, P < 0.01 vs baseline). CONCLUSIONS: Glucose loading blunted endothelial function, with a deterioration in EDD, in these patients with newly diagnosed type 2 DM. However, combined treatment with metformin and atorvastatin for 6 weeks partly prevented the glucose-induced impairment of EDD in these patients, with a significant difference compared with monotherapy with metformin.

Common community infections and the risk for coronary artery disease and acute myocardial infarction: evidence for chronic over-expression of tumor necrosis factor alpha and vascular cells adhesion molecule-1.

BACKGROUND: Although several common community infections have been associated with the risk for coronary artery disease (CAD), their role in the development of acute myocardial infarction (AMI) is still unclear. We examined the prevalence of IgG and IgM (or IgA) antibodies against common infections such as HSV, Hepatitis A (HAV), Helicobacter pylori (HP), cytomegalovirus (CMV) and Chlamydia pneumoniae (CP), in CAD and AMI patients, and their relationship with pro-atherogenic inflammatory molecules. METHODS: A total number of 337 subjects were included in this study: 150 patients with angiographically documented stable CAD, 138 patients admitted with AMI and 49 healthy individuals. Serum IgG and IgM against HAV, CMV and HSV, IgG against HP and IgG/IgA against CP were determined in all participants. Serum tumor necrosis factor alpha (TNF-alpha) and soluble vascular cells adhesion molecule (sVCAM-1), were determined by ELISA. RESULTS: Patients with CAD were more likely to have anti-HAV IgG (94.4%), anti-HSV IgG (97.2%) and anti-HP IgG (55.1%) compared to healthy individuals (70.8%, 89.6% and 39.6% respectively, p<0.05 for all). In multivariate analysis, anti-HAV IgG was an independent predictor of CAD (beta(SE): 0.187(0.075), p=0.015). Among the CAD patients, the presence of anti-CP IgA was more frequent in those admitted with AMI (39%) compared to those with stable CAD (21%, p<0.05). Finally, both patients and controls had significantly higher levels of sVCAM-1 and TNF-alpha in the presence of anti-HAV IgG, compared to those without anti-HAV IgG (p<0.05 for all). CONCLUSION: Past infections with HAV, HSV and HP are associated with higher risk for coronary atherosclerosis, while the presence of anti-HAV IgG is also associated with higher levels of TNF-alpha and sVCAM-1. Furthermore, the presence of recent infection by CP is associated with higher risk for AMI among CAD patients. These findings are important since they demonstrate that past HAV, HSV and HP infections may affect cardiovascular risk, while recent CP infection may be implicated in the triggering of AMI among CAD patients.