11ß-Hydroxysteroid dehydrogenase type 2 in hypertension: comparison of phenotype and genotype analysis.

11ß-Hydroxysteroid dehydrogenase type 2 (11ß-HSD2) catalyzes the inactivation of cortisol (F) to cortisone (E) in aldosterone target tissues, thereby protects mineralocorticoid receptor from F. Failure of 11ß-HSD2 function is the basis of apparent mineralocorticoid excess, and its mild disturbances are suggested to lead to hypertension. The aim of the study was to analyze the 11ß-HSD2 activity in hypertensives and healthy volunteers. Glucocorticoids (GCs) profile was estimated to verify whether the disorders of GCs balance may be involved in essential hypertension etiology. Exons and short introns of HSD11B2 were sequenced to evaluate existing mutations and their potential implications in the disease. The identified polymorphisms were assessed in case-control study to determine their relevance to hypertension. No significant differences in values of plasma F/E and UFF/UFE (urinary free F to free E) were observed between hypertensives and controls. The value of (THF+allo-THF)/(THE+allo-THE) (urinary tetrahydro-metabolites of F to tetrahydro-metabolites of E) in hypertensives was higher than in normotensives. Logistic regression demonstrated that the increase of one unit of (THF+allo-THF)/(THE+allo-THE) value increases the risk of hypertension over 11-fold. Genotyping indicated no hypertension related mutations in the coding region and short introns of HSD11B2.

Serum adiponectin concentrations are not related to glycosylated hemoglobin levels (HbA1c) in obese diabetic and non-diabetic caucasians.

UNLABELLED: Although circulating adiponectin has been inversely correlated with obesity, type 2 diabetes and serum glycosylated hemoglobin (HbA1c) in humans, contradictory reports on that subject exist. In this study, serum concentrations of adiponectin in obese non-diabetic and diabetic humans were measured to examine whether they were associated with levels of HbA1c. The WHO definitions of obesity and diabetes were used. One hundred and five obese euglycemic subjects and 49 obese diabetics (aged 51+/-6.9, and 52+/-6.7 years, respectively) were studied. Their BMI, HbA1c and % of body fat were measured. Adiponectin was determined by an enzyme-linked immunosorbent assay. Although the serum adiponectin concentrations differed between diabetics and non-diabetics ( P<0.01), they were not correlated with HbA1c (r=-0.0814; P=0.5823, and r=-0.1861; P=0.1099, for diabetics and non-diabetics, respectively). Both diabetics and non-diabetics were segregated into tertiles according to their HbA1c levels. Plasma adiponectin did not differ significantly between the high (H), intermediate (I), and low (L) HbA1c tertiles. CONCLUSION: Concentrations of adiponectin were not correlated with levels of glycosylated hemoglobin in the diabetic and non-diabetic subjects examined.

The impact of the sleep apnea syndrome on oxidant-antioxidant balance in the blood of overweight and obese patients.

The aim of the study was to assess the markers of oxidant-antioxidant status in excess body mass index (BMI) persons with and without the obstructive sleep apnea syndrome (OSAS). In overweight (BMI-1: 25.0-29.9 kg/m(2)) control and OSAS and obese (BMI-2: 30.0-34.9 kg/m(2)) control and OSAS subjects with no acute or chronic disorder the following markers were determined: concentration of plasma total antioxidant status, TAS, (Randox); activity of erythrocyte Cu, Zn-superoxide dysmutase, SOD, (Randox); plasma concentration of thiobarbituric acid reacting substances, TBARS, (Yagi method). BMI-1-OSA presented decreased SOD, compared with the BMI-1-C group (P=0.006). BMI-2-OSA showed both SOD (P=0.002) and TAS (P=0.047) decreased, and elevated TBARS (P=0.03) compared with the BMI-2-C group. There was a positive correlation between TAS & SOD and a negative one between TAS & TBARS in the BMI-1-C group. In BMI-2-C, a negative correlation between TAS & TBARS was observed. We conclude that OSAS decreases the blood antioxidant status in high BMI persons and may change the relationship between oxidative stress markers.

The Y111 H (T415C) polymorphism in exon 3 of the gene encoding adiponectin is uncommon in Polish obese patients.

The genetic background of obesity is under research. Obesity-related phenotype candidate genes include the gene encoding adiponectin (AdipoQ). In this study, exon 3 of the adiponectin gene was screened for the Y111 H (Tyr111His, or T415C, rs17366743) polymorphism, and adiponectin serum concentrations were measured in 206 obese subjects (110 women and 96 men, aged 50.5+/-16.9 years). Their BMI, % of body fat, plasma glucose, insulin, and glycosylated hemoglobin were measured. Adiponectin was determined by enzyme-linked immunosorbent assay. Genomic DNA was extracted from peripheral blood leukocytes. A fragment of exon 3 of the adiponectin gene was amplified in PCR and screened for the Y111 H polymorphism in SSCP analysis. Genetic screening revealed a different SSCP pattern in 2 subjects. Subsequent genotyping disclosed the TC genotype in both subjects, resulting in Y111 H heterozygote variant frequency of 0.01 in the whole cohort. Other results for SNP (single nucleotide polymorphism) positive and negative subjects were as follows, respectively: BMI (kg/m (2)) 39.95+/-9.83 vs. 38.12+/-8.56; waist circumference (cm) 122+/-18.4 vs.115+/-16; glucose (mmol/l) 7.51+/-1.86 vs. 5.56+/-0.74; HbA1c (%) 7.55+/-1.86 vs. 6.58+/-1.36; body fat (%) 51+/-2 vs. 44+/-10; plasma insulin (mU/l) 28.92+/-16.50 vs. 37.59+/-47.34; adiponectin (ng/ml) 1301+/-15.8 vs. 5682+/-4156. Due to a proportion of 2 vs. 204, statistical calculations were not possible. The Y111 H adiponectin gene variant is uncommon in Polish obese subjects. Although we observed low adiponectin concentrations in Y111 H SNP heterozygote carriers, this finding was not confirmed by statistics.

Circulating serum adiponectin concentrations do not differ between obese and non-obese caucasians and are unrelated to insulin sensitivity.

Reduced serum levels of adiponectin in obesity and insulin resistance seem paradoxical, since adipose tissue is the only source of adiponectin, and reports on that subject are contradictory. The aim of this study was to investigate the concentrations of adiponectin in non-obese and obese normoglycemic humans, and to determine the correlation between adiponectin and HOMA index of insulin sensitivity. Based on the WHO definition of obesity, 145 obese subjects and 49 non-obese controls (aged 20-55 years) were studied. The serum adiponectin concentrations did not differ between subjects and controls (p=0.6398) and were not correlated with HOMA index (r=-0.0211; p=0.8048, and r=-0.0523; p=0.4757, for subjects and controls, respectively). Adiponectin was not correlated with HOMA index in females (r=-0.0521; p=0.6546, and r=-0.0825; p=0.3981, for female subjects and controls, respectively) as well as in males (r=0.0033; p=0.9791, and r=0.0123; p=0.9131, for male subjects and controls, respectively). These results lead to the conclusion that neither the concentrations of adiponectin differ between obese and non-obese humans, nor does any relationship between adiponectin concentration and insulin sensitivity exist.

[The role of rheological factors in the pathogenesis of diabetic nephropathy]. / Rola czynników reologicznych w patogenezie nefropatii cukrzycowej.

In this paper the stages and pathogenesis of diabetic nephropathy have been presented. Factors which influence blood rheology and hemorheologic abnormalities founded in diabetic patients have been reviewed. Attention was paid to the role of rheological parameters in initiating and progression of diabetic nephropathy. The possibilities of prevention of diabetic microvascular complications by influencing blood rheology have been presented.