Pro-atherogenic alterations in T-lymphocyte subpopulations related to acute hyperglycaemia in type 2 diabetic patients.

BACKGROUND: T cells are among the earliest cells to infiltrate the arterial intima during the initial stages of atherosclerosis. Alterations in the peripheral blood lymphocyte distribution might be associated with intensive lymphocytes extravasation and stimulation of atherosclerotic plaque development. Epidemiological data reveal that short-term postprandial hyperglycemia is a significant risk factor for coronary heart disease. Using a parameter that indicates recently-past acute hyperglycemia, 1,5-anhydro-D-glucitol (1,5-AG), the aim of the present study was to elucidate which alterations in peripheral blood T-lymphocytes, if any, are associated with acute hyperglycemia in patients with type 2 diabetes mellitus (DM) and, thus, might be involved in the progression of atherosclerosis. METHODS AND RESULTS: Measurement of fasting glucose level, glycated hemoglobin A(1c), 1,5-AG, lipid profile and lymphocyte receptors expression (CD3+, CD4+, CD8+, CD8+28+, CD+28 -) was performed in 97 patients with type 2 DM, 23 patients with coronary heart disease, and 15 healthy controls. The mean CD3+, CD4+, CD8+28 - and CD8+28+ lymphocyte counts were significantly higher in the DM patients than in both control groups. Multiple regression analysis revealed that CD4+ and CD8+28- lymphocyte counts primarily were dependent on 1,5-anhydro-D-glucitol plasma levels. CONCLUSIONS: These results suggest that acute hyperglycemia results in the progression of atherosclerosis in type 2 DM, at least in part through changes in CD4+ and CD8+28- lymphocyte subsets.

Hypoglycaemic effect of quinolizidine alkaloids--lupanine and 2-thionosparteine on non-diabetic and streptozotocin-induced diabetic rats.

The hypoglycaemic effects of two quinolizidine alkaloids: lupanine and 2-thionosparteine were examined in non-diabetic and in streptozotocin-induced diabetic rats. The model of experimental diabetes can be considered to be related to diabetes mellitus type 2 with regards to the impairment of beta-cells' secretory function. A single intraperitoneal injection of 2-thionosparteine at a dose of 8.6 mg/kg lowered the blood glucose levels in diabetic rats at 90 and 120 min after administration and showed similar hypoglycaemic effects to glibenclamide and sparteine, which were used as reference substances. In contrast to glibenclamide, 2-thionosparteine did not result in a significant increase in plasma insulin levels in diabetic rats; an increase was only observed in the non-diabetic group. It was found that lupanine did not exert hypoglycaemic potency in diabetic and in non-diabetic animals and did not significantly increase plasma insulin concentration independent of the group examined. From this study we can state that 2-thionosparteine, but not lupanine, is confirmed to be a possible plasma glucose lowering agent. It is possible that 2-thionosparteine-dependent decrease in blood glucose level is not the only result of this drug's related insulin secretion.

IL-15 is elevated in serum patients with type 1 diabetes mellitus.

IL-15 is a 14-15 kD cytokine produced by monocytes/macrophages and shares some biological actions with IL-2. The serum concentration of IL-15 in type 1 diabetic patients has not been reported seriously. Our studies were performed on 51 patients (28 women and 23 men) with type 1 diabetes mellitus. Healthy control subjects (n=22, 12 women and 10 men, mean age 29 years, range 24-32 years) were recruited from medical staff. IL-15 serum levels were detected by ELISA (R & D systems, USA). Short-term and long-term metabolic control parameters, lipid profile and C-reactive protein levels were also estimated. There was a statistically significant increase of serum IL-15 in type 1 diabetic patients in comparison to the control subjects (4.4 (1.5-11.8) versus 2.9 (1.5-6.0) pg/ml, p<0.05). Diabetic patients with higher IL-15 serum levels had higher HbA1c values. A correlation was found between IL-15 serum concentration and HbA1c (N(s)=0.31, p=0.029). There was no relation between acute hyperglycaemic episodes and IL-15 serum level. The potential associations between IL-15 serum level and long-term diabetic control lead us to speculate that IL-15 may serve as a target for future treatment in patients with prediabetes and/or for prevention of late diabetic complications.