Homocysteine as a non-classical risk factor for atherosclerosis in relation to pharmacotherapy of type 2 diabetes mellitus.

AIMS: The aim of our study was to evaluate which of the pharmacotherapeutic methods that are frequently used to treat type 2 diabetes is associated with the most beneficial profile in relation to pro-atherogenic homocysteine levels. PATIENTS AND METHODS: We measured the serum homocysteine level in 182 patients with type 2 diabetes treated with metformin (89), treated with insulin in combination with metformin (31), receiving sulfonylureas (31) and treated conventionally with insulin (31). The total homocysteine levels in the serum were assayed. To exclude the influence of selected metabolic and anthropometric factors on the differences between the examined groups, multivariate analysis of covariance was used (ANCOVA). In this analysis, serum homocysteine concentration was the dependent variable, while diabetes duration, waist circumference, HbA1c, 1,5-anhydro-D-glucitol, fasting glycaemia and peptide C were used as covariates. RESULTS: The serum homocysteine levels in patients treated with insulin in monotherapy were significantly higher than what was observed in the metformin treated subjects and in the patients receiving insulin combined with metformin. The analysis of covariance also confirmed that the differences between the therapeutic groups were affected by waist circumference and the C-peptide levels. CONCLUSION: We conclude that conventional insulin therapy may have a negative effect on pro-atherogenic homocysteine levels in patients with type 2 diabetes. This study revealed that pro-atherogenic homocysteine levels may not only be modified by pharmacotherapy of type 2 diabetes, but also by beta cell secretory function and abdominal obesity.

The Impact of Pharmacotherapy of Type 2 Diabetes Mellitus on IL-1ß, IL-6 and IL-10 Secretion.

BACKGROUND: The aim of this study was to assess the impact of pharmacotherapy of diabetes on atherosclerosis, as reflected in interleukin (IL)-1ß, IL-6 and IL-10 serum levels. METHODS: We studied patients with type 2 diabetes, treated with metformin, insulin combined with metformin and conventional insulin. IL-1ß, IL-6 and IL-10 serum levels were assayed using BD™ Cytometric Bead Array. Multivariate analysis of covariance was performed to exclude the impact of some metabolic and anthropometric factors on differences in cytokines concentrations among the participants receiving different pharmacotherapy. RESULTS: The serum concentrations of IL-1ß and IL-6 were significantly higher and IL-10 serum levels were significantly lower in the insulin-treated group than in other therapeutic groups. Covariance analysis confirmed that differences in IL-1ß and IL-6 levels were determined by pharmacotherapy and fasting plasma glucose, whereas in IL-10 levels by the therapy only. Additionally, peptide C modified differences in IL-1ß levels and HbA1c in IL-6 concentrations. CONCLUSION: This study revealed that both pharmacotherapy and glycemic control may modify some pro-atherogenic factors, such as IL-1ß and IL-6. The therapy with metformin and insulin combined with metformin seems to be much more beneficial in terms of their impact on pro-inflammatory cytokines secretion in comparison to conventional insulinotherapy.

Alpha-lipoic acid modifies circulating angiogenic factors in patients with type 2 diabetes mellitus.

AIMS: In recent years interest has been focused on angiogenesis as a process involved in coronary artery disease (CAD) and diabetic distal sensorimotor polyneuropathy (DSPN). Recent studies have demonstrated the possible angiogenesis-modulating potential of alpha-lipoic acid (ALA) for DSPN and CAD. The aim of our study was to investigate the influence of ALA on serum angiogenic factors in patients with DM-2 (type 2 diabetes) with CAD and DSPN. METHODS: Sixty patients with type 2 DM (T2DM) and CAD and 25 non-diabetic subjects were studied. Thirty patients with T2DM, CAD and DSPN were given 600 mg of ALA a day for 90 days. VEGF, bFGF, MCP-1, angiogenin, IL-12 and IL-10 concentrations in the sera were measured by flow cytometry. RESULTS: ALA significantly increased VEGF, bFGF and IL-10 and decreased MCP-1 serum concentrations in patients with T2DM and CAD and DSPN. VEGF and IL-10 serum levels, both before and after ALA-treatment, were higher in this group than in T2DM and CAD patients, while circulating bFGF was higher and MCP-1 serum level lower in patients with T2DM and CAD and DSPN only in the post-ALA-treatment, compared to the T2DM and CAD group. CONCLUSIONS: ALA may influence angiogenesis in type 2 diabetic patients through an effect on some circulating factors including VEGF, bFGF, MCP-1 and IL-10.

Increased circulating RANTES in type 2 diabetes.

AIM: The pro-atherogenic role of RANTES, a chemokine expressing pleiotropic activities, in the course of type 2 diabetes-related atherosclerosis has been well documented. However, it is not known which of the diabetes-related factors primarily influence serum RANTES levels in patients with type 2 diabetes. Our aim was to investigate relationships between several factors known to be related to an increased risk of atherosclerosis and serum RANTES levels in type 2 diabetic patients. METHODS: A total of 168 subjects were examined, which included 138 patients with type 2 diabetes and 30 non-diabetic controls. Measurements of venous, fasting, plasma glucose, HbA1c, lipid profile, 1,5-anhydro-D-glucitol (1,5-AG) plasma levels, homocysteine and the fasting, serum C-peptide levels were performed. Serum concentrations of RANTES were assayed using BD(TM) Cytometric Bead Array tests. Peripheral insulin resistance was expressed according to a new index defined by Ohkura et al. RESULTS: RANTES levels in type 2 diabetic patients correlated with 1,5-AG, fasting glycaemia, HbA1c and the Ohkura index. Multivariate regression analysis was performed taking into consideration several factors related to the inflammatory process and atherosclerosis, namely the patient's age, diabetes duration, waist circumference, 1,5-AG, HbA1c, lipid profile parameters, serum homocysteine levels and Ohkura index, as independent variables potentially influencing serum RANTES levels in type 2 diabetic patients. It is shown that RANTES concentrations in the serum is primarily dependent upon 1,5-AG plasma levels. CONCLUSION: Our results suggest that increased serum levels of RANTES in type 2 diabetic patients are closely related to postprandial (acute) hyperglycaemia.

Circulating monocyte chemotactic protein 1 (MCP-1), vascular cell adhesion molecule 1 (VCAM-1) and angiogenin in type 2 diabetic patients treated with statins in low doses.

Statins are known as agents promoting a biphasic dose-dependent effect on angiogenesis under experimental conditions. Dysregulation of angiogenesis plays an important role in the development of atherosclerosis and it may be affected by metabolic factors. The aim of this research was to explain how low doses of statins modify serum concentrations of pro-angiogenic factors MCP-1 and angiogenin in type 2 diabetic patients. Measurements of metabolic control parameters were performed in 30 patients with type 2 diabetes treated with low doses of statin, and in 34 statin-free patients with type 2 diabetes. The serum levels of MCP-1 and VCAM-1 in statin-treated patients were lower than those of the statin-free group. ANCOVA results revealed that these effects were dependent only on the use of statins. In type 2 diabetic subjects, overall positive correlation was found between total cholesterol or LDL serum concentration and MCP-1 serum level. The angiogenin concentration in the serum did not show differences and was comparable in both groups. The angiogenin serum level correlated negatively with HDL, LDL and with HbA1c. Multivariate regression analysis indicated that angiogenin serum levels in type 2 diabetic patients were determined mainly by HbA1c, HDL-cholesterol and diabetes duration. It has been shown that statins used in low doses in type 2 diabetic subjects decrease MCP-1 and VCAM-1serum levels, most likely due to the statins-related effect on the lipid profile, while angiogenin serum levels in this group are determined rather by the current metabolic control.

Statins in low doses reduce VEGF and bFGF serum levels in patients with type 2 diabetes mellitus.

BACKGROUND/AIMS: Recent experimental research revealed that statins at low doses induce angiogenesis, which in turn may be related to the course of atherosclerosis. There are no clinical studies evaluating the effect of 'low-dose' statins on serum levels of angiogenesis regulators in diabetic subjects. We aimed to explain how low doses of statins modify the serum concentrations of two potent proangiogenic factors, vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), in patients with type 2 diabetes. METHODS: Measurements of fasting glucose level, HbA1c, 1,5-anhydro-D-glucitol and lipid profile were taken from 47 patients with type 2 diabetes treated with low doses of atorvastatin (10 mg daily) or simvastatin (10-20 mg daily), from 45 statin-free patients with type 2 diabetes and from 23 nondiabetic subjects. Measurements of VEGF and bFGF in serum were taken using the BD™ Cytometric Bead Array. RESULTS AND CONCLUSION: Statins used in low doses in patients with type 2 diabetes reduce the serum concentration of VEGF and bFGF which suggests antiangiogenic potential of these doses. Nevertheless, this effect could be neutralized by postprandial hyperglycemia.