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Insulin detemir (Levemir®) is a long-acting insulin analogue indicated for use as basal insulin therapy in patients with type 1 or 2 diabetes mellitus. The protracted action of insulin detemir is explained by increased self-association and reversible binding to albumin, which slows its systemic absorption from the injection site. In glucose-clamp studies, less within-patient variability in glucose-lowering effect was seen with insulin detemir than with neutral protamine Hagedorn (NPH) insulin or insulin glargine in patients with type 1 or 2 diabetes. The beneficial effect of insulin detemir on glycaemic control was shown in numerous randomized, open-label, multicentre trials, including when used as basal- bolus therapy in patients with type 1 or 2 diabetes and as basal therapy in addition to oral antidiabetic drugs in insulin-naive patients with type 2 diabetes. In terms of glycosylated haemoglobin (HbA1c) [primary endpoint in most trials], insulin detemir was generally at least as effective as NPH insulin, insulin glargine or insulin lispro protamine suspension in patients with type 1 or 2 diabetes, and at least as effective as biphasic insulin aspart in patients with type 2 diabetes. Less within-patient variability in blood glucose was also generally seen with insulin detemir than with NPH insulin in patients with type 1 or 2 diabetes. Significantly less weight gain was generally seen with insulin detemir than with NPH insulin in patients with type 1 diabetes or with insulin detemir than with NPH insulin, insulin glargine, insulin lispro protamine suspension or biphasic insulin aspart (in one study) in patients with type 2 diabetes (i.e. insulin detemir generally had a weight-sparing effect). The addition of insulin detemir to liraglutide plus metformin improved glycaemic control in insulin-naive patients with type 2 diabetes and inadequate glycaemic control, although a significantly greater reduction in bodyweight was seen in patients receiving liraglutide plus metformin than in those receiving add-on therapy with insulin detemir. Results of two trials in patients aged 2-16 or 6-17 years (and a subgroup analysis in children aged 2-5 years) indicate that a basal-bolus insulin regimen incorporating insulin detemir appears to be a suitable option for use in paediatric patients with type 1 diabetes. Less within-patient variation in self-measured fasting plasma glucose was seen with insulin detemir than with NPH insulin in one of the studies. Insulin detemir was noninferior to NPH insulin in pregnant women with type 1 diabetes in terms of the HbA1c value achieved at 36 gestational weeks. In addition, maternal and neonatal outcomes with insulin detemir were similar to those seen with NPH insulin. Subcutaneous insulin detemir was generally well tolerated in the treatment of patients with type 1 or 2 diabetes, including in paediatric patients and pregnant women with type 1 diabetes. The majority of adverse events, including serious adverse events, reported in insulin detemir recipients were not considered to be related to the study drug. Insulin detemir was generally associated with a significantly lower risk of nocturnal hypoglycaemia than NPH insulin in patients with type 1 or 2 diabetes, particularly nocturnal minor hypoglycaemia. In conclusion, insulin detemir is a useful option for use as basal insulin therapy in patients with type 1 or 2 diabetes. [ABSTRACT FROM AUTHOR]

The aim of this study was to examine the effect of antioxidant supplementation on oxidative damage and chromosome stability in middle-aged men, smokers and non-smokers. A total of 124 men aged 48±6 years from Bratislava and from the rural population near Bratislava were investigated; 64 men (22 smokers and 42 non-smokers) were supplemented for 12 weeks with antioxidants, while 60 (25 smokers and 35 non-smokers) were given placebo. The daily antioxidant supplementation consisted of vitamin C (100 mg), vitamin E (100 mg), β-carotene (6 mg), and selenium (50 μg). Samples of blood were taken on two occasions: At the beginning and at the end of the supplementation trial. Concentrations of dietary antioxidants, ferric reducing ability, malondialdehyde as an indicator of lipid peroxidation in plasma, micronuclei and chromosome aberrations in lymphocytes were measured. Antioxidant supplementation significantly increased the levels of vitamin C, β-carotene, a-tocopherol and selenium in plasma. The overall antioxidant status of plasma measured as ferric reducing ability of plasma (FRAP) increased significantly (p<0.001) after antioxidant supplementation as well. The increase in antioxidant parameters after supplementation were consistently more pronounced in non-smokers than in smokers. There was a significant decrease of malondialdehyde concentration in the non-smokers, while in smokers the decrease of malondialdehyde concentration was not significant. Antioxidant supplementation did not affect the proportion of lymphocytes with micronuclei or the total number of micronuclei; however, there was a significant positive correlation (p<0.001) between the malondialdehyde concentration at the beginning of the supplementation trial and the difference in number of cells with micronuclei before and after the supplementation. The percent of cells with chromosome aberrations decreased significantly after antioxidant supplementation in smokers. These results indicate that a combined antioxidant supplementation (a) is effective even at very moderate doses; (b) significantly diminishes oxidative damage to lipids when it is high initially; and (c) is effective in decreasing chromosomal instability in lymphocytes of middle-aged men. [ABSTRACT FROM AUTHOR]

The effect of ciprofibrate therapy on plasma lipids and lipoproteins, HDL and LDL subfraction profile, fractional esterification rate of HDL cholesterol (FERHDL) and the resistance of LDL and serum lipids to oxidation was studied in 24 males with type 2 diabetes and atherogenic lipoprotein phenotype (ALP). We also examined the effect of ciprofibrate therapy on oxidative DNA damage in peripheral lymphocytes. No differences in glucose, HbA1C and BMI levels were found after three months of ciprofibrate therapy. Ciprofibrate significantly decreased total cholesterol and triglyceride levels by 5.5% and 50% ( p = 0.05; 0.001, respectively) and increased HDL-cholesterol levels by 8.5% ( p = 0.05). FERHDL and LDL subfraction profile were also favorably affected, However, no effect on HDL subclasses was found. There were no statistically significant differences in lipid resistance to oxidation measured in serum and in LDL (lag time and Vmax) before and after therapy. No significant effect of ciprofibrate was found on oxidative DNA damage. The evaluation of the relationship between oxidative damage purines with lag time in LDL and maximal rate of serum lipid oxidation showed significant correlations after therapy (r = −0.58; 0.47, p = 0.01; 0.05, respectively), but only trends before starting ciprofibrate treatment. Type 2 diabetes mellitus represents a complex metabolic disorder expressed in glucose and lipoprotein disturbances and increased oxidative stress. Ciprofibrate therapy favorably affected major features of lipid abnormalities of diabetic patients, but the level of oxidative stress assessed by in vitro and in vivo methods was not changed. The evaluation of expected logical correlations between the parameters of lipoprotein metabolism, lipid resistance in serum and LDL, and oxidative DNA damage showed that those correlations were more relevant and significant after ciprofibrate treatment and were not related with glucose homeostasis. [ABSTRACT FROM AUTHOR]

Objective: We examined the relationship between plasma levels of fenofibric acid, the active metabolite of fenofibrate, and differences in concentrations of plasma lipids, in subjects with primary type IIA or IIB hyperlipoproteinemia (HLP). Subjects and methods: Twenty-nine patients (13 with type IIA and 16 with type IIB HLP) were treated with a single daily 200-mg dose of micronized fenofibrate for 3␣months, after which the plasma levels of fenofibric acid were determined by HPLC after an overnight fast. Results: In the type IIA HLP phenotype, statistically significant correlations were found between fenofibric acid levels and changes in total cholesterol, LDL-C and apo-B at all three control visits, with the highest correlation coefficients at V3 visit (total cholesterol , LDL-C , apo-B ). In type IIB HLP, statistical significance was confirmed only when performing an analysis of pooled values for total cholesterol and LDL-C ( , , respectively). The high correlation between plasma fenofibric acid levels and its effect on betalipoprotein changes might reflect the effect of fenofibrate on the catabolism of plasma LDL by the LDL receptor, since that type of relationship is typical of drugs which directly influence the target compartment without an effect on intermediary steps of metabolism. An explanation for the different levels of correlations in type IIA and IIB patients might be found in their different metabolic defects. The fact that fenofibrate's impact on VLDLs is such an important part of its effect on lipoprotein metabolism supports the concept that the effect of circulating fenofibric acid is less pronounced on the LDL receptor in type IIB HLP. [ABSTRACT FROM AUTHOR]

Objectives: This study was conducted to examine a complex effect of ciprofibrate therapy in patients with atherogenic lipoprotein phenotype. Methods: Effects of ciprofibrate were studied on HDL subpopulations, HDL ability to esterify cholesterol (FERHDL), susceptibility of LDL to oxidation as well as on in vivo oxidative DNA damage in peripheral lymphocytes, measured as strand breaks (SBs) by the comet assay. Results: Ciprofibrate treatment significantly decreased total cholesterol, and triglycerides, and increased HDL-cholesterol. The FERHDL showed a significant reduction (29.5 ± 7.4 to 23 ± 7.5% · h−1, P = 0.0001). The relative concentrations of HDL subclasses did not differ between baseline and after treatment. Ciprofibrate induced a significant increase in LDL oxidation lag time (93 ± 7 to 102 ± 11 min, P = 0.02) and a decrease in DNA strand breaks (34.0 ± 16.2 to 17.8 ± 7.5, P = 0.02). A significant correlation between maximal rate of diene production and strand breaks was found ( r = 0.55, P = 0.01). These findings may be explained by an improvement of LDL resistance to oxidation, resulting in a decrease in oxidatively modified LDL's cytotoxic effect. Conclusion: Ciprofibrate treatment favourably affected the quality of plasma HDL, probably by the improvement of triglyceride rich lipoprotein metabolism and/or LDL subpopulation profile, increased LDL resistance to oxidation, and decreased the level of DNA damage in peripheral lymphocytes. [ABSTRACT FROM AUTHOR]