Urinary sulphated glycosaminoglycans excretion in obese patients with type 2 diabetes mellitus treated with metformin.

OBJECTIVE: The pattern of urinary excretion of total sulphated glycosaminoglycans (GAGs) and their particular types: chondroitin sulphate/dermatan sulphate (CS/DS) and heparan sulphate (HS) was analysed in obese patients with type 2 diabetes mellitus (T2DM) treated with metformin in monotherapy for the period of six months. METHODS: The urinary sulphated glycosaminoglycans were quantitated using standardised dye (1.9-dimethylmethylene blue)-binding method and normalised to creatinine level. RESULTS: Urinary total GAGs, CS/DS and HS levels were significantly higher in untreated diabetic patients in comparison to healthy subjects. Moreover, it was observed that urinary total GAGs, CS/DS and HS levels in diabetic patients after six-month metformin therapy were significantly decreased versus pre-treatment situation. CONCLUSIONS: The obtained results suggest that the six-month treatment with metformin in obese patients with T2DM has a regulating influence on the systemic changes in proteoglycans/glycosaminoglycans, resulting in a decrease in the urinary excretion of total GAGs, CS/DS and HS.

Circulating C1q/TNF-Related Protein 3, Omentin-1 and NGAL in Obese Patients with Type 2 Diabetes During Insulin Therapy.

The aim of the study was to quantify the plasma concentration of omentin-1, neutrophil gelatinase-associated lipocalin (NGAL), and complement C1q tumor necrosis factor-related protein-3 (CTRP3) in obese patients with type 2 diabetes, before introducing insulin therapy, in relation to the plasma expression profiles of these regulatory molecules in the same patients after a 6-month insulin mixture therapy and in obese controls. Elevated plasma NGAL concentrations were found in type 2 diabetic patients as compared with subjects with metabolically healthy obesity. In turn, a 6-month insulin mixture therapy has shown a marked increase in the plasma concentration of omentine-1 and a significant decrease in plasma CTRP3 concentration in obese patients with type 2 diabetes, in relation to the values found in these patients before the implementation of insulin therapy. Insulin mixture therapy has also proved to be an important factor modifying the plasma profile of NGAL, increasing the concentration of this bioactive molecule in the plasma of patients with type 2 diabetes, after 6 months of its use, in relation to the concentration before treatment. The significant changes in the plasma profile of omentin-1, NGAL and CTRP3 during insulin therapy suggest their potential diagnostic utility in monitoring metabolic changes associated with the introduction of insulin treatment in type 2 diabetic patients.

Adiponectin, Leptin, and Leptin Receptor in Obese Patients with Type 2 Diabetes Treated with Insulin Detemir.

The aim of the present study is to quantitatively assess the expression of selected regulatory molecules, such as leptin, leptin receptor, and adiponectin in the blood of obese patients with type 2 diabetes both before treatment and after six months of pharmacological therapy with the long-lasting insulin analogue, insulin detemir. A significant decrease in the analysed regulatory molecules, i.e., leptin receptor and adiponectin, was found in blood plasma of the patients with untreated type 2 diabetes. These changes were accompanied by an increase in plasma leptin concentrations. Insulin treatment resulted in the normalization of plasma leptin receptor and adiponectin concentrations. The circulating leptin level did not change following anti-diabetic therapy with insulin detemir. Gender was a significant factor modifying the circulating level of all the analysed regulatory active compounds. Bioinformatic analysis was performed using Matlab with the Signal Processing Toolbox. The conducted discriminant analysis revealed that the leptin receptor, Δw(19), and adiponectin, Δw(21), were the parameters undergoing the most significant quantitative changes during the six-month therapy with insulin detemir. The conducted examinations indicated the contribution of adipocytokines-the biologically-active mediators of systemic metabolism, such as leptin and adiponectin in the pathomechanism of disorders being the basis for obesity which leads to development of insulin resistance, which, in turn, results in the occurrence of type 2 diabetes.

Endothelium dysfunction markers in patients with diabetic retinopathy.

Diabetes mellitus leads to endothelium dysfunction and an accelerated progression of atherosclerosis. Vascular complications of diabetes mellitus can affect not only large and medium arteries resulting in coronary heart disease and peripheral arteries diseases, but also small vessels leading to retinopathy and nephropathy. Intercellular adhesion molecule-1 (ICAM-1), vascular adhesion molecule-1 (VCAM-1), E-selectin and von Willebrand factor (vWF) are considered as markers of endothelium dysfunction. The aim of our study was to evaluate plasma levels of ICAM-1, VCAM-1, E-selectin and vWF in patients with type 2 diabetes mellitus receiving insulin therapy and who had diabetic non-proliferative retinopathy, proliferative retinopathy, or did not develop diabetic retinopathy. There were no statistically significant differences between studied groups in any of evaluated endothelium dysfunction markers. There was no statistically significant correlation between measured parameters and a period of diabetic history. None of the studied markers presented a significant correlation with a period of insulin treatment.

Blood antioxidant parameters in patients with diabetic retinopathy.

It has been postulated that enhanced generation of reactive oxygen species (ROS) may take part in a pathogenesis of diabetic microvascular complication - retinopathy. There are two types of diabetic retinopathy, non-proliferative (simplex) and proliferative. ROS are anihilated by an intracelluar enzymatic system composed mainly of glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT). Beta-carotene, tocopherols and ascorbic acid are major components of serum antioxidants. All serum antioxidants are usually measured together as total antioxidant status (TAS). Erythrocyte activities of GPx, SOD, CAT and TAS were measured in diabetic patients without retinopathy, with non-proliferative and proliferative retinopathy. Obtained results were correlated with a period of diabetic history and a period of insulin treatment. SOD was significantly elevated in diabetics with non-proliferative retinopathy compared to patients without retinopathy. TAS was significantly lower in patients with proliferative retinopathy than in diabetics not developing retinopathy. Only CAT was significantly negatively correlated with the period of insulin treatment. This significant negative correlation was also observed in a subgroup of patients with proliferative retinopathy.