Circulating P-Selectin and Its Glycoprotein Ligand in Nondiabetic Obstructive Sleep Apnea Patients.

Selectins and their ligands play an important role in atherosclerosis. The role of these adhesion molecules in the pathogenesis of obstructive sleep apnea (OSA) may be of clinical relevance. Therefore, the aim of this study was to assess the serum content of platelet P-selectin (P-SEL) and P-selectin glycoprotein ligand 1 (PSGL-1) in different OSA stages. The study was performed in nondiabetic patients, aged 32-71, in whom OSA was verified by polysomnography. The apnea/hypopnea index (AHI) was used to stratify OSA stages: AHI <5, no sleep pathology (OSA-0); AHI 5-15, (OSA-1); AHI 16-30, (OSA-2); and AHI >30, (OSA-3). There were 16 patients in each group. P-SEL and PSGL-1 were assessed by ELISA kits. There were no appreciable differences in the patients' glucose or high-specificity C-reactive protein content. We found that P-SEL and PSGL-1 significantly increased from OSA-0 to OSA-3. There were the following positive associations in all OSA patients: P-SEL vs. AHI, PSGL-1 vs. AHI, and P-SEL vs. PSGL-1. In addition, the adhesion molecules are associated with the anthropometric parameters, oxygen saturation, and sleep architecture in the OSA-1 group. We conclude that the adhesion molecules consistently increase in the blood of nondiabetic OSA patients, along with progression of disorder severity.

Oxidative Stress Markers and Severity of Obstructive Sleep Apnea.

Oxidative stress underlies both obstructive sleep apnea (OSA) and atherosclerosis. The aim of the study was to assess the markers of oxidative stress in plasma at different stages of OSA in non-smoking obese Caucasian males aged 41-60, with normal oral glucose tolerance test. All patients were subjected to clinical and polysomnographic examinations. The stage of OSA severity was set according to the following criteria of the apnea-hypopnea index (AHI): AHI < 5/h - no disease (OSA-0; n = 26), AHI 5-15/h - mild disease (OSA-1; n = 26), AHI 16-30/h - moderate disease (OSA-2: n = 27), and AHI > 30/h obstructive episodes per hour - severe disease (OSA-3; n = 27). Plasma total antioxidant status (TAS) and thiobarbituric acid-reacting substances (TBARS), reflecting the level of lipid peroxides, were determined spectrophotometrically. We found that TAS decreased and TBARS increased significantly from OSA-0 to OSA-3. We conclude that the oxidative stress markers are conducive to setting the severity of OSA in normoglycemic patients.

Paraoxonase 1 Gene L55M Polymorphism and Paraoxonase 1 Activity in Obstructive Sleep Apnea Patients.

The antioxidant enzyme paraoxonase-1 (PON1) may limit oxidative stress in the development of cardiovascular diseases (CVD) and obstructive sleep apnea (OSA). The aim of the study was to determine PON1 gene L55M polymorphism in OSA-positive and OSA-negative subjects, along with paraoxonase activity of the enzyme (PON1-act). Caucasians aged 25-75, with BMI 19.0-53.0 kg/m2 and no acute or severe chronic disorder underwent polysomnography, and OSA-negative (n = 44) and OSA-positive (n = 57) groups were established. The following parameters were assessed: arterial blood pressure and serum glucose, lipids, C-reactive protein, and homocysteine. Genomic DNA was extracted and amplified, and automatic sequencing was used to confirm the LL, LM, MM genotypes. PON1-act was measured spectrophotometrically using paraoxon as a substrate. We found that frequency of polymorphisms differed significantly between the OSA-negative and OSA-positive patients (p < 0.05). Increased PON1-act was observed in the LL-genotype versus the LM + MM-genotype in the study population (p < 0.05). PON1-act was higher in the OSA-negative compared with OSA-positive patients (p < 0.001); in general and in the subgroups presenting the LL or LM genotype. In addition, there was an inverse relationship between PON1-act and LDL-cholesterol in the entire study population. The OSA-positive group presented an inverse relationship between PON1-act and fasting glucose. We conclude that patients could benefit from the LL genotype related with higher activity of PON1. OSA pathology might decrease the enzyme activity, despite the presence of L allele.

Disproportionately elevated proinsulin levels in type 2 diabetic patients treated with sulfonylurea.

OBJECTIVE: Hyperproinsulinemia in type 2 diabetic subjects has recently been accepted as an independent cardiovascular risk factor. Moreover, it has been confirmed that high proinsulin concentrations stimulate amylin secretion by pancreatic beta-cells and amyloid accumulation within pancreatic islets leading to impairment of pancreatic islets secretory function. The association between sulfonylureas administration and secretory function of pancreatic beta-cells, especially concerning insulin precursor peptides, is not sufficiently elucidated. Preliminary studies by our research group revealed that the fasting proinsulin serum concentration is significantly higher in type 2 diabetic patients treated with sulfonylureas than in a well-matched group treated with insulin only. METHODS: A total of 101 subjects with type 2 diabetes were treated either with sulfonylureas (n = 32), with insulin (n = 40), with sulfonylureas + insulin (n = 17) or with diet alone (n = 12). RESULTS: The basal secretory function in the four groups were comparable (C-peptide fasting serum level > 0.5 ng/l). An effect of fasting glycemia, long-term metabolic control (HbA1c), postprandial hyperglycemia (1,5-anhydro-D-glucitol), insulin resistance (HOMA(IR)score) and diabetes duration on the fasting proinsulin serum level in the subjects treated could be excluded. CONCLUSION: The disproportionately high proinsulin levels are due to sulfonylureas therapy. The effect is independent of fasting glycemia, long-term metabolic control, postprandial hyperglycemia, diabetes duration and peripheral insulin resistance.

Circulating CD3+56+ cell subset in pre-diabetes.

The CD3+56+ cells are a small but significant population of T lymphocytes encompassing NKT-like and NKT cells, which may play the essential role at the very early stages of atherosclerotic plaque development. The frequency and activity of CD3+56+ cells in atherosclerosis-inducing dysglycaemic disease (diabetes type 2 or pre-diabetes) is largely unknown.We analysed CD3+56+ cell count, granzyme, perforin and annexin V profiles in the peripheral blood from a group of patients with pre-diabetes, with diabetes type 2 and from non-dysglycaemic controls. Measurements were made of fasting glucose levels, HbA1c, 1,5-anhydroglucitol and lipid profile.The mean counts of CD3+56+ cells were significantly higher in patients with pre-diabetes compared to both patients with diabetes and to control group. There was an increase in the number of CD3+56+ cells producing granzyme and perforin in pre-diabetic patients compared to other groups, while there were no difference in annexin V+ populations within examined groups. It was confirmed that CD3+56+ cells count is modified by metabolic factors and their parameters, namely HbA1c and 1,5-anhydroglucitol values.It could be stated that the alterations of CD3+ 56+ cells count in peripheral blood of pre-diabetic and type 2 diabetic patients are related to different grades of carbohydrate deteriorations - postprandial hyperglycaemia and chronic hyperglycaemia.

Plasma anhydro-D-glucitol (1,5-AG) as an indicator of hyperglycaemic excursions in pregnant women with diabetes.

AIMS: To evaluate the use of the plasma 1,5-anhydro-d-glucitol (1,5-AG) level as a possible marker for glucose excursions in pregnant women with diabetes. METHODS: The study group consisted of 55 pregnant women with diabetes (gestational diabetes mellitus-GDM, n = 28 or pre-gestational diabetes mellitus -PGDM, n = 27), without hepatic or renal insufficiency, gestational age range 5-38 weeks. In each patient, 24-h glucose profile, glycated haemoglobin and 1,5-AG plasma levels were measured. Mean blood glucose (MBG) and M-value (by Schlichtkrull) were calculated. MBG, M-value and maximal daily glycaemia (MxG) were used as indexes of daily glycaemic excursions. RESULTS: A significant correlation was found between the 1,5-AG plasma level and MxG [r = (-0.3)] and between the 1,5-AG level and M-value [r = (-0.36)]. There was no association between the 1,5-AG level and gestational age. Multivariate regression analysis, with 24-h glucose profile, gestational age and MxG as independent variables, showed that MxG was the main parameter determining the 1,5-AG plasma level [beta = (-0.68)]. The M-value, the coefficient of glucose fluctuations, also determined the 1,5-AG level but with lower statistical power [beta = (0.41)]. No statistical differences were found in the group with HbA(1c) < 6% or > 6% for 1,5-AG and M-value, while MBG was higher in poorly controlled patients (HbA(1c) > 6%). CONCLUSIONS: The plasma 1,5-AG level may be a useful marker of daily glucose excursion in pregnant women with diabetes, as an adjunct to HbA(1c) monitoring.