Mitochondrial dysfunction and oxidative stress participate in the development of diabetic complications, however, the mechanisms of their origin are not entirely clear. Coenzyme Q has an important function in mitochondrial bioenergetics and is also a powerful antioxidant. Coenzyme Q (CoQ) regenerates alpha-tocopherol to its active form and prevents atherogenesis by protecting low-density lipoproteins against oxidation. The aim of this study was to ascertain whether the experimentally induced diabetes mellitus is associated with changes in the content of endogenous antioxidants (alpha-tocopherol, coenzymes Q9 and Q10) and in the intensity of lipoperoxidation. These biochemical parameters were investigated in the blood and in the isolated heart and liver mitochondria. Diabetes was induced in male Wistar rats by a single intravenous injection of streptozotocin (45 mg.kg-1), insulin was administered once a day for 8 weeks (6 U.kg-1). The concentrations of glucose, cholesterol, alpha-tocopherol and CoQ homologues in the blood of the diabetic rats were increased. The CoQ9/cholesterol ratio was reduced. In heart and liver mitochondria of the diabetic rats we found an increased concentration of alpha-tocopherol, however, the concentrations of CoQ9 and CoQ10 were decreased. The formation of malondialdehyde was enhanced in the plasma and heart mitochondria. The results have demonstrated that experimental diabetes is associated with increased lipoperoxidation, in spite of the increased blood concentrations of antioxidants alpha-tocopherol and CoQ. These changes may be associated with disturbances of lipid metabolism in diabetic rats. An important finding is that heart and liver mitochondria from the diabetic rats contain less CoQ9 and CoQ10 in comparison with the controls. We suppose that the deficit of coenzyme Q can participate in disturbances of mitochondrial energy metabolism of diabetic animals., J. Kucharská, Z. Braunová, O. Uličná, L. Zlatoš, A. Gvozdjáková., and Obsahuje bibliografii
Diabetes mellitus type 2 ranks among the strongest predictors of cardiovascular diseases (CVD) while the association of type 1 diabetes with CVD is more complex. We studied differences between type 1 and 2 diabetic women regarding association of cardiovascular risk factors with preclinical atherosclerosis expressed as intima-media thickness of common carotid (IMT CCA) and femoral arteries (IMT CFA) measured by high resolution ultrasound. Women with type 1 (n=203) and type 2 diabetes (n=123) were examined with regard to the presence of cardiovascular risk factors. In type 1 diabetic women strong association between IMT CCA and body mass index, waist circumference, and total body fat was found in contrast to type 2 diabetic women. In type 2 diabetic women strong association between IMT CCA and fasting glucose, glycated hemoglobin, and atherogenic index of plasma (log TG/HDL cholesterol) was observed in contrast to type 1 diabetic women. In type 1 diabetic women, IMT CFA was associated with body fat in contrast to type 2 diabetic women. Preclinical atherosclerosis in type 1 diabetic women was strongly associated with factors reflecting body fat and its distribution, while in type 2 diabetic women preclinical atherosclerosis was associated with markers reflecting glucose and lipid metabolic disorders., P. Piťhová, K. Štechová, J. Piťha, V. Lánská, M. Kvapil., and Obsahuje bibliografii
1a_Caveolin-1 (CAV-1) is the main structural component of caveolae, acting as a modulator of signal transduction. CAV-1 might be involved in the pathophysiology of microvascular complications in Type 1 diabetes (DM). We sought to determine whether fractionation on sucrose gradient (SF), a method routinely utilized for isolation of caveolar fractions in homogenous cell lines, is applicable for CAV-1-related studies in tissues with multiple cell types, such as the normal rat kidney cortex (C). Using this method, we also determined whether streptozotocin- induced DM in rats (4-week duration) leads to changes in renal subcellular targeting of CAV-1, and evaluated the effects of tight metabolic control (insulin, 12 IU /day) and angiotensin receptor blocker, losartan (4 weeks, 20 mg/kg/day). Immunoblotting of individual fractions obtained from C revealed CAV-1 expression in fractions 4-6 that corresponded to light scattering band that typically forms after separating cellular fractions on SF. These fractions were considered to be caveolar fractions. In C, CAV-1 was also detectable in fracti ons 8-10. These and all other fractions except caveolar fractions were considered to be non-caveolar fractions. A ratio of caveolar/non-caveolar expression of CAV-1 (CNCR) was computed for each renal cortex allowing comparisons of CAV-1 subcellular distribution in C and DM rats, and effects of treatments., 2a_Using this approach, DM was characterized by marked increases in CNCR as compared to C (5.54±1.56 vs. 2.65±1.33, p<0. 05) that were reduced by treatment with insulin (0.78±0. 24, p<0.01 vs. DM) or losartan (0.84±0.06, p<0.01 vs. DM). In summary, analysis of CAV-1 following the SF of renal cortex detected similar distribution of the protein as in homogenous cell lines, DM-induced changes in CAV-1 targeting, and the effects of pharmacological treatments. This suggests applicability of SF in studies focusing on CAV-1 targeting in organs with various cell lines in vivo., H. Demová, R. Komers., and Obsahuje seznam literatury
The aim of our work was to provide data from women of fertile age with type 1 diabetes mellitus about the endogenous androgens and on their relations to the parameters of diabetes control. Forty-two women were examined, they did not use contraceptives for at least three months prior to the examination. A multivariate regression analysis showed that the daily insulin dose, the fasting glycemia and the HbA1c values and patient´s age correlated negatively with dehydroepiandrosterone sulfate, dehydroepiandrosterone and prolactin levels. The testosterone/ dehydroepiandrosterone sulfate ratio correlated positively with daily insulin dose and patient´s age. In contrast to adrenal androgens the values of other hormones, including total and free testosterone, androstenedione, dihydrotestosterone, estradiol, LH, FSH, 17-OH-P, progesterone and cortisol revealed no significant correlation. To conclude, significant relations between the glucose control parameters and the adrenal androgens and prolactin were demonstrated. These relationships should be considered as an important factor influencing diabetes control so the additional cardiovascular risk in women with DM1., H. Kvasnickova, R. Hampl, K. Vondra., and Obsahuje bibliografii
Decreased baroreflex sensitivity is an early sign of autonomic dysfunction in patients with type-1 diabetes mellitus. We evaluated the repeatability of a mild baroreflex sensitivity decrease in diabetics with respect to their heart rate. Finger blood pressure was continuously recorded in 14 young diabetics without clinical signs of autonomic dysfunction and in 14 age-matched controls for 42 min. The recordings were divided into 3-min segments, and the mean inter-beat interval (IBI), baroreflex sensitivity in ms/mm Hg (BRS) and mHz/mm Hg (BRSf) were determined in each segment. These values fluctuated in each subject within 42 min and therefore coefficients of repeatability were calculated for all subjects. Diabetics compared with controls had a decreased mean BRS (p=0.05), a tendency to a shortened IBI (p=0.08), and a decreased BRSf (p=0.17). IBI correlated with BRS in diabetics (p=0.03); th is correlation was at p=0.12 in the controls. BRSf was IBI independent (controls: p=0.81, diabetics: p=0.29). We conclude that BRS is partially dependent on mean IBI. Thus, BRS reflects not only an impairment of the quick baroreflex responses of IBI to blood pressure changes, but also a change of the tonic sy mpathetic and pa rasympathetic heart rate control. This is of significance during mild changes of BRS. Therefore, an examination of the BRSf index is highly recommended, because this examin ation improves the diagnostic value of the measurement, particul arly in cases of early signs of autonomic dysfunction., J. Svačinová ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Type I diabetes mellitus (DM1) is a complex disease with adverse effects on organs and tissues despite compensation by insulin treatment. The goal of our study was to study how kidney diseases change 31P MR parameters of muscle metabolism in DM1 patients with respect to gender. 51 DM1 patients (19 m/14 f without and 13 m/5 f with nephropathy) and 26 (14 m/12 f) healthy volunteers were examined using 31P magnetic resonance spectroscopy at 3T tomograph at rest, and during and after a calf muscle exercise. The exercise consisted of a six-minute plantar flexion using a pedal ergometer followed by a six-minute recovery. It is reflected by reduced relative β-ATP and increased Pi and phosphodiester signals to phosphocreatine (PCr) at rest and prolongation of the PCr recovery time after the exercise. Measurement on healthy volunteers indicated differences between males and females in pH at the rest and after the exercise only. These differences between patients groups were not significant. We have proven that nephropathy affects the metabolism in diabetic patients and our results confirm significant difference between patients with and without nephropathy. Gender differences in pH were observed only between male and female healthy volunteers., P. Sedivy, M. Dezortova, M. Drobny, Z. Vlasakova, V. Herynek, M. Hajek., and Obsahuje bibliografii
a1_Diabetes mellitus is a risk factor of cardiovascular diseases. ECG of patients with diabetes mellitus type 1 (DM 1) shows tachycardia (block of parasympathetic innervation) and abnormal repolarization (increased QT interval and QT dispersion (QTd)) indicating a risk of ventricular tachycardia and sudden death in young people with DM 1. The aim of the present report was to measure 145 parameters of the heart electric field in 22 patients (14 men, 8 women) with DM 1 without complications (mean age 32.8±11.4 years) and in 22 controls (11 men, 11 women, mean age 30.1±3.4 years). The duration of diabetes was 13.9 ±7.8 years. The parameters were regist ered by the diagnostic system Cardiag 112.2 and statistically evaluated by the Student and Mann-Whitney test. Tachycardia (86.3±2.7 beats.min-1), shortening of both QRS (79.9±1.6 ms) and QT (349.0±5.9 ms) and increased QT dispersion (115±36 ms) were observed in DM 1 when compared with the controls (75.0±2.1 beats. min -1, QRS 89.9±2.7 ms, QT 374.0±4.4 ms, QTd 34.0±12.0 ms, p<0.01). The QTc was 415.2±4.1 ms in DM 1 and 401.4±6.6 ms in controls (NS)., a2_Other significant findings in DM 1 were: higher maximum of depolarization isopotential maps (DIPMmax) in the initial phase of QRS and less positive in the terminal phase, more negative minimum (DIPMmin) during QRS similarly as the minimum in depolarization isointegral maps (DIIMmin) and the minimum in isointegral map of the Q wave (Q-IIMmin), lower maximum in repolarization isopotential maps (RIPMmax) and less negative minimum (RIPMmin), more negative amplitude of Q wave (Q-IPMAM) and more pronounced spread of depolarization (activation time). Our results confirmed a decreased parasympathetic to sympathetic tone ratio (tachycardia, shortening of the activation time) and revealed different depolarization and repolarization patterns in DM 1. The differences in heart electric field parameters measured by the BSPM method in DM 1 and in the controls indicate the importance of ECG examination of diabetic patients type 1 in the prevention of cardiovascular diseases., D. Žďárská, P. Pelíšková, J. Charvát, J. Slavíček, M. Mlček, E. Medová, O. Kittnar., and Obsahuje bibiografii a bibliografické odkazy
ECG body surface mapping (BSM) parameters in patients with diabetes mellitus Type 1 (DM1) are significantly different comparing to healthy non-diabetic subjects. Hypothesis that these changes are more pronounced in DM1 patients with autonomic neuropathy (AN) was tested. The parameters of BSM were registered by diagnostic system Cardiag 112.2 in 54 DM1 patients including 25 with AN and 30 control subjects. AN was diagnosed according to Ewing criteria when two or more Ewing tests were abnormal. In classic 12-lead ECG the heart rate was increased, QRS and QT shortened (p<0.01) and QTC prolonged in DM1 patients. The VCG measurement of QRS-STT angles and spatial QRS-STT angle showed non-significant differences. The absolute values of maximum and minimum in depolarization and repolarization isopotential, isointegral, isoarea maps were significantly different in DM1 patients in comparison with controls (p<0.01). The changes were more pronounced in DM1 patients with AN than in DM patients without AN (p<0.05). The QT duration measured in 82 leads of thorax was significantly shortened in 68 leads of both groups of DM 1 patients (p<0.01) when compared with controls. In 34 of them this shortening was more pronounced in DM1 patients with AN than in DM1 patients without AN (p<0.05). The results showed that the method of ECG BSM is capable to confirm the presence of autonomic neuropathy in diabetic patients., S. Palová ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Women with gestational diabetes mellitus (GDM) are at increased risk for cardiovascular diseases (CVD) events compared with women without GDM. The aim of the present study was to evaluate 200 parameters of the heart electric field in 35 women with GDM under optimal glycemic compensation compared to 32 healthy pregnant women. All examinations were performed in the 36th week of gestation. The parameters in ECG body surface mapping (BSM) were registered by the diagnostic system Cardiag 112.2. The absolute values of maximum and minimum in depolarization and repolarization isopotential, isointegral and isoarea maps were not significantly different between the groups. These findings correspond to the result of heart rate variability examination. However BSM revealed the significant prolongation of QRS complex (p=0.05), shortening of ventricular myocardial activation time (ICHVAT) (p=0.01), prolongation of mean QT duration (p=0.01) and increase of QT interval dispersion (p=0.01) in women with GDM. Duration of QRS and ICHVAT significantly correlated with interventricular septum and posterior wall thickness in GDM group, QTd interval correlated significantly with HbA1C level. We conclude that despite of optimal metabolic control several significant abnormalities detected by ECG BSM are still present in patients with GDM., E. Žákovičová, O. Kittnar, J. Slavíček, E. Medová, P. Šváb, J. Charvát., and Obsahuje bibliografii
To determine whether acutely-induced supraphysiological hyperinsulinemia influences brain metabolism in patients with type 1 diabetes (D) and healthy controls (C) as detected by MR Spectroscopy. Group D consisted of 4 patients with the average duration of diabetes for 7 years. They were matched according to age, sex and BMI to 4 healthy controls. 1H MR Spectroscopy was performed with a 1.5 Tesla. Spectra were obtained from parietooccipital white matter repeatedly during a 3-h hyperinsulinemic euglycemic clamp with 2 mU.kg-1.min-1. In group D, significantly lower basal concentrations of N-acetylaspartate (p=0.02), choline (p=0.03), creatine (p=0.002) and inositol (p=0.007) were detected compared to C. After the induction of hyperinsulinemia, concentrations of choline, creatine, GABA, inositol, lactate, NAA and composite signal glutamate + glutamine (Glx) stayed stable. The detection of glucose signal is less realiable at 1.5 Tesla but we registered the alteration in glucose concentration (p=0.003) in the whole group. Originally sightly elevated glucose concentration in D decreased on the contrary to the increase of originally lower glucose level in C. In conclusions, brain metabolism was altered in D. Short term supraphysiological euglycemic hyperinsulinemia induced changes in the concentration of brain glucose in both C and D., S. Kratochvílová, A. Škoch, M. Dezortová, E. Švehlíková, M. Hill, J. Brunová, M. Hájek, T. Pelikánová., and Obsahuje bibliografii