The relationship between right ventricular deformation and heart rate variability in asymptomatic diabetic patients.

OBJECTIVE: To investigate heart rate variability (HRV) and right ventricular (RV) remodeling in asymptomatic diabetic patients, as well as the relationship between HRV indices and RV structure, function and deformation. METHOD: This cross-sectional study included 59 asymptomatic patients with type 2 diabetes and 45 healthy controls without cardiovascular risk factors. All study subjects underwent 24-h Holter monitoring, laboratory analyses and complete two-dimensional echocardiography examination (2DE). RESULTS: RV diastolic function and longitudinal deformation were significantly impaired in diabetic individuals comparing with controls. RV global longitudinal strain and layer-specific longitudinal strains were significantly decreased in diabetic group. The same trend of changes in RV deformation was observed for global RV and lateral wall. All parameters of time and frequency domain of HRV were reduced in diabetic subjects. RV endocardial longitudinal strain together with LV mass index, mitral E/e' ratio and HbA1c correlated with HRV parameters. However, multivariate linear regression analysis showed that only RV endocardial longitudinal strain and LV mass index are associated with HRV parameters independently of age, BMI, HbA1c, RV free wall thickness and pulmonary artery pressure. CONCLUSIONS: RV subendocardial strain is independently associated with HRV parameters in the whole study population. This reveals potentially important role of determination of layer-specific RV longitudinal function as important marker of preclinical cardiac damage, but also indirectly show the impairment of cardiac autonomic function in diabetic patients.

The influence of white-coat hypertension on left atrial phasic function.

We aimed to investigate the association between white-coat hypertension (WCH) and left atrial (LA) phasic function assessed by the volumetric and speckle tracking method. This cross-sectional study included 52 normotensive individuals, 49 subjects with WCH and 56 untreated hypertensive patients who underwent a 24-h ambulatory BP monitoring and complete two-dimensional echocardiographic examination (2DE). WCH was diagnosed if clinic blood pressure (BP) was elevated and 24-h BP was normal. We obtained that maximum, minimum LA and pre-A LAV volumes and volume indexes gradually and significantly increased from the normotensive subjects, throughout the white-coat hypertensive individuals to the hypertensive patients. Passive LA emptying fraction (EF), representing the LA conduit function, gradually reduced from normotensive to hypertensive subjects. Active LA EF and the parameter of the LA booster pump function increased in the same direction. Similar results were obtained by 2DE strain analysis. The LA stiffness index gradually increased from normotensive controls, throughout white-coat hypertensive subjects to hypertensive patients. Clinic systolic BP was associated with LA passive EF (ß= -0.283, p = 0.001), LA active EF (ß = 0.342, p < 0.001), LA total longitudinal strain (ß= -0.356, p < 0.001), LA positive longitudinal strain (ß= -0.264, p = 0.009) and LA stiffness index (ß = 0.398, p < 0.001) without regard to age, BMI, left ventricular structure and diastolic function in the whole study population. In the conclusion, WCH significantly impacts LA phasic function and stiffness. Clinic systolic BP was associated with functional and mechanical LA remodeling in the whole study population.

Masked Hypertension and Left Atrial Dysfunction: A Hidden Association.

Masked hypertension (MH) is a clinical condition that indicates normal values of clinic blood pressure (BP) but elevated 24-hour BP. The purpose of this study was to investigate the relationship between MH and left atrial (LA) phasic function evaluated by both the volumetric and speckle tracking method. This cross-sectional study included 49 normotensive individuals, 50 patients with MH, and 70 untreated sustained hypertensive patients adjusted by age and sex. MH was diagnosed if clinic BP was normal and 24-hour BP was increased. LA reservoir function was lower in patients with MH and those with sustained hypertension compared with the normotensive group. LA conduit function gradually decreased, while LA booster pump function progressively increased, from normotension to sustained hypertension. Similar results were obtained by two-dimensional echocardiographic strain analysis. Independently of main clinic and echocardiographic characteristics, 24-hour systolic BP was associated with LA passive ejection fraction, LA total longitudinal strain, LA positive longitudinal strain, and LA stiffness index. In conclusion, MH is associated with impairment of LA phasic function and stiffness, and 24-hour systolic BP increment was closely related with LA remodeling.

Improvement of Glycemic Control in Insulin-Dependent Diabetics with Depression by Concomitant Treatment with Antidepressants.

BACKGROUND It is still disputable whether negative effects of comorbid depression in diabetics can be diminished by successful treatment of depression. The primary aim of this study was to assess whether addition of antidepressants to existing insulin treatment would further improve glycemic control in these patients. A secondary objective was to assess whether such treatment impairs their lipid and inflammatory status. MATERIAL AND METHODS Total of 192 patients with poorly controlled diabetes (defined as HbA1c ≥8%) in the absence of any uncontrolled medical condition entered the 6-month run-in phase with optimization of diabetic therapy. Depression status was screened at the end of this phase by BDI-II depression testing. Patients with BDI-II ≥14 and psychiatric confirmation of depression (58 patients) entered the 6-month interventional phase with SSRI class antidepressants. RESULTS Fifty patients completed the study. During the run-in phase, HbA1c dropped from 10.0±1.8% to 8.5±1.2% (p<0.001), and during the interventional phase it dropped from 8.5±1.2% to 7.7±0.7% (p<0.001). BDI-II scores improved significantly from 30.4±13.2 to 23.5±11.0 (p=0.02) during the interventional phase. A positive linear correlation between improvement in depression scale and improvement in glycemic control was observed (R²=0.139, p=0.008). Lipid profile and inflammatory status did not change significantly during the interventional phase. CONCLUSIONS Patients with poorly controlled diabetes and comorbid depression might benefit from screening and treatment of depression with SSRI antidepressants by achieving an incremental effect on glycoregulation. This therapy did not have any adverse effects on lipid profile or inflammatory status.

Right heart mechanics in untreated normotensive patients with prediabetes and type 2 diabetes mellitus: a two- and three-dimensional echocardiographic study.

BACKGROUND: The aim of this study was to determine right ventricular (RV) and right atrial (RA) deformation assessed by two-dimensional echocardiographic and three-dimensional echocardiographic (3DE) imaging in patients with prediabetes and type 2 diabetes mellitus. METHODS: This cross-sectional study included 47 untreated normotensive subjects with prediabetes, 57 recently diagnosed normotensive patients with diabetes, and 54 healthy controls of similar sex and age distributions. All subjects underwent laboratory analyses and complete two-dimensional echocardiographic and 3DE examinations. RESULTS: Three-dimensional echocardiographic RV end-diastolic volume index gradually decreased from controls across patients with diabetes to those with diabetes (69 ± 10 vs 63 ± 8 vs 58 ± 8 mL/m(2), P < .001), whereas 3DE RV end-systolic volume index was higher in controls compared with patients with diabetes and those with diabetes (25 ± 4 vs 23 ± 4 vs 22 ± 4 mL/m(2), P < .001). However, there was no difference in 3DE RV ejection fraction among the three groups (63 ± 4% vs 62 ± 4% vs 61 ± 5%, P = .063). RV and RA global strain and systolic and early diastolic strain rates were decreased in patients with prediabetes and in those with diabetes compared with controls, whereas RV and RA late diastolic strain rates were increased in these patients. Multivariate regression analysis showed that RV global strain was associated with glycated hemoglobin, independent of left ventricular parameters. CONCLUSIONS: RV and RA myocardial deformation and function obtained by 3DE and two-dimensional echocardiographic strain, even in normal ranges, were decreased in patients with prediabetes and in those with diabetes compared with controls. The long-term parameter of glucose control was correlated with the right heart mechanics.

Impact of acute exercise on antioxidant enzymes activity and lipid status in blood of patients with hypertension.

BACKGROUND/AIM: Many studies support the hypothesis that oxidative stress is involved in the pathogenic process of a variety of diseases including hypertension. In humans, hypertension is also considered a state of oxidative stress that can contribute to the development of arteriosclerosis and other hypertension-induced organ damage. The aim of this study was to evaluate an influence of acute physical exercise on antioxidative enzymes activity and lipid status in patients with hypertension. METHODS: Fourty patients with hypertension and 20 age-matched controls were included in the study. To assess an influence of acute exercise on lipids and antioxidative enzymes activity the following parameters were determined at rest and immediately after the acute cardiopulmonary exercise cycloergometer test: triglycerides (TG), total cholesterol, low density cholesterol (LDL), oxidised LDL cholesterol (OxLDL), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and plasminogen activator inhibitor (PAI). RESULTS: In basal condition, hypertensive patients compared to the control group had increased, but not significantly, level of Ox LDL (88.61 +/- 14.06 vs 79.00 +/- 29.26 mmol/L), PAI (3.06 +/- 0.56 vs 2.6 +/- 0.35 U/mL) and activity of GSH-Px (50.22 +/- 15.20 vs 44.63 +/- 13.73 U/g Hb). After acute exercise test, there was significantly greater level of Ox LDL (79.0 +/- 29.26 vs 89.3 +/- 29.07 mmol/L; p < 0.05) only in the control group. GSH-Px activity was significantly decreased only in hypertensive patients after acute exercise (50.22 +/- 15.2 vs 42.82 +/- 13.42 U/g Hb; p < 0.05), but not in the controls. CONCLUSION: No significantly elevated Ox LDL, GSH-Px and PAI-1 levels were found in hypertensive patients during basal condition in comparison with healthy subjects. Decreased GSH-Px activity was associated with those in acute exercise only in hypertensive patients. It could be an important indicator of deficiency of physiological antioxidative defense mechanism in hypertensive patients during an acute exercise.

Clinical evaluation of oxidative stress in patients with diabetes mellitus type II -- impact of acute exercise.

BACKGROUND/AIM: Exercise is a well recognized model of oxidative stress and, also, an important tool in diabetes management. The aim of our study was to evaluate oxidative stress in patients with diabetes mellitus type 2 and to determine influence of acute exercise training on the investigated parameters. METHODS: To evaluate oxidative stress in the patients, we determinated following parameters: triglycerides (TG), total cholesterol, low density lipoprotein cholesterol (LDL), oxidized LDL cholesterol (Ox LDL), superoxide dismutase (SOD), glutathione peroxidase (GSHPx), plasminogen activator inhibitor (PAI) which were measured at rest and immediately after the acute bout of cardiopulmonary exercise cycle-ergometer test. RESULTS: In basal condition, diabetic patients compared to controls have significant higher values of TG (3.12 +/- 1.09 vs 1.74 +/- 0.9 mmol/L, p < 0.01), Ox LDL (84.73 +/- 16.90 vs 79.00 +/- 29.26 mmol/L, p < 0.05) and SOD enzyme activity (913.38 +/- 120.36 vs 877.14 +/- 153.18 U/g Hb, p < 0.05). During the acute exercise test, there was significant increase of Ox LDL in both the study patients (from 84.73 +/- 16.90 to 92.33 +/- 23.29 mmol/L, p < 0.05) and in the control group (from 79.00 +/- 29.26 to 89.30 +/- 29.07 mmol/L, p < 0.05). SOD activity was significantly increased in both groups during exercise, in diabetic patients from 913.38 +/- 120.36 to 921.50 +/- 130.03 U/gHb, p < 0.05, and in the controls from 877.14 +/- 153.18 to 895.00 +/- 193.49, U/gHb, p < 0.05. GSH-Px activity was significantly increased only in the diabetic patients after the acute exercise (from 45.04 +/- 11.19 to 51.81 +/- 15.07 U/gHb, p < 0.01), but not in the controls (from 44.63 +/- 13.73 to 43.97 +/- 25.97 U/gHb, p = ns). PAI significantly decreased during the exercise test, only in the healthy subjects (from 2.60 +/- 0.35 to 2.22 +/- 0.65, p < 0.05). Type 2 diabetic patients with complications had only significant increase in GSH-Px activity (from 47.10 +/- 7.37 to 54.52 +/- 11.97 U/gHb, p < 0.01). CONCLUSION: Elevated Ox LDL, SOD and GSH-Px levels are associated with acute exercise in type 2 diabetic patients. We suggest that it could be a compensatory mechanism to preventing free radicals tissue damage. We hypothesize that a physical training program induces an enhance of muscular and liver antioxidant enzymes activity and reduces oxidative stress. Further studies are needed to explore the relationship between exercise and antioxidant system in diabetic patients with and without complications.

[Exercise-induced oxidative stress and antioxidant enzyme activity in type 2 diabetic patients with and without diastolic dysfunction and hypertension].

INTRODUCTION: Antioxidant systems are important factors affecting the oxidation of lipoproteins and thereby the progression of atherosclerotic disease. It has been suggested that physical activity might maintain and promote the antioxidant defence capacity against the oxidative stress. Left ventricular dysfunction (LVDD) and hypertension are more common in subjects with diabetes mellitus (DM) type 2. OBJECTIVE: To evaluate the oxidative stress in patients with DM type 2, particularly with LVDD and hypertension and to determine the influence of acute exercise training on the investigated parameters. METHODS: To assess the oxidative stress of patients, we determined the following antioxidative parameters: triglycerides (TG), total cholesterol, low density cholesterol, OxLDL cholesterol, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), plasminogen activator-type 1 (PAI-1) which were measured at rest and immediately after the acute bout of the cardiopulmonary exercise cycle ergometer test. RESULTS: In basal conditions, diabetic patients had a significant increase of TG (3.12 +/- 1.09 vs 1.74 +/- 0.9 mmol/l; p < 0.01), OxLDL cholesterol (84.73 +/- 16.9 vs 79.00 +/- 29.26 mmol/l; p < 0.05) and SOD enzyme activity (913.38 +/- 120.36 vs 877.14 +/- 153.18; p < 0.05) compared to controls. During the acute exercise test, there were significantly greater levels of OxLDL (84.73 +/- 16.90 vs 92.33 +/- 23.29 mmol/l; p < 0.05) in study patients. SOD significantly increased in both groups during exercise, in diabetic patients (913.38 +/- 120.36 vs 921.50 +/- 130.03 U/g Hb; p < 0.05) and in controls (877.14 +/- 153.18 vs 895.00 +/- 193.49 U/g Hb; p < 0.05). GSH-Px significantly increased only in diabetic patients after acute exercise (45.04 +/- 11.19 vs 51.81 +/- 15.07 U/g Hb; p < 0.01), but not in controls. PAI significantly decreased during the exercise test only in healthy subjects (2.60 +/- 0.35 vs 2.22 +/- 0.65; p < 0.05). Type 2 diabetic patients with cardiovascular complications (LVDD and hypertension) had a significant increase of GSH-Px activity (47.10 +/- 7.37 vs 54.52 +/- 11.97 U/g Hb; p < 0.01). CONCLUSION: Elevated enzyme levels are associated with exercise in type 2 diabetic patients. We suggest that it could be a compensatory mechanism to prevent free radical tissue damage. We hypothesize that a physical training programme induces the enhancement of muscular and liver antioxidant enzymes and reduces the oxidative stress.

[Oxidized LDL and C-reactive protein level in relation to carotid intima-media thickness in population with risk factors for atherosclerosis].

INTRODUCTION: Elevated levels of oxidized LDL cholesterol (OxLDL) are considered to be a key factor of initiating and accelerating atherosclerosis. It promotes atherosclerosis through inflammatory and immunologic mechanisms that lead to the formation of macrophage foam cells. OBJECTIVE: To determine the relationship among OxLDL, C-reactive protein (CRP) level and carotid intima-media thickness (IMT) in population with risk factors for atherosclerosis. METHODS: The study group consisted of 125 clinically healthy, hypercholesterolaemic subjects (49.3 +/- 5.7 years; 75 females and 50 males) compared with 100 age-matched population-based control subjects. The study group was divided into two subgroups: subgroup A (the levels of LDL cholesterol > 5 mmol/L) and subgroup B (the levels of LDL cholesterol < 5 mmol/L). None of the subjects had history of cerebrovascular, ischaemic heart disease, hypertension or diabetes mellitus. Lipid profiles were measured by enzymatic methods. OxLDL was measured by using a specific monoclonal antibody, mAb4E6. CRP was measured using hemiluminescent methods (Immulite-DPC). The common carotid IMT was measured by the B-mode ultrasound. RESULTS: Compared to controls, the study group had higher levels of OxLDL (119.97 +/- 43.15 vs. 82.03 +/- 25.99 IU/L; p < 0.01) and CRP (6.20 +/- 3.55 vs. 2.68 +/- 3.04 mg/ml; p < 0.05). IMT was significantly higher in study subjects (1.14 +/- 0.38 vs. 0.72 +/- 0.24 mm; p < 0.05). We also found that, in the whole study group, IMT significantly positively correlated with OxLDL (r = 0.442; p < 0.05). We found that in the study subgroup A, IMT positively correlated with CRP (r = 0.792; p < 0.01). In controls, we found a significantly positive association between IMT and OxLDL (r = 0.781; p < 0.01) and CRP (r = 0.748; p < 0.01). CONCLUSION: The elevated levels of OxLDL and CRP are associated with higher common carotid intima-media thickness in population with risk factors for atherosclerosis.

[Diagnosis of osteoporosis occurring in autoimmune thyroid gland disease].

Osteoporosis or porotic bone is a general, systemic bone disease, which is manifested by fracture as its consequence. The main characteristic of this disease is the loss of bone microarchitecture, bone mass reduction, and its increased fragility. The result, thereof, is susceptibility to fracture. Etiology of osteoporosis is polymorph. Its socio-medical importance is enormous, since there is one osteoporotic fracture every 20 sec. worldwide. Million and six hundred thousand osteoporotic fractures occur annualy throughout the world. Thyroid gland is susceptible to autoimmune reactions that lead to autoimmune diseases, just like many other organs. The autoimmune disorder is a final consequence of a failure, in some instance, within the crucial mechanism of regulation of self tissue tolerance. The main goal is to prove the presence of osteoporosis, its inexpensive and quick diagnostics; to make a distinction among the causes that lead to it. In addition, to indicate the importance of osteoporosis that is caused by normal, metabolic processes which are an inevitable part of ageing. Diagnosis of osteoporosis can be done through laboratory, which is a tiresome, time consuming task. Measurements of BMD could be also performed by using new devices. Osteometers could be constructed on the basis of X-ray photon energy or US. Utilization most contemporary one uses laser beam, and it approximates the distance of additional tissue that also absorbs part of energy changing absorption of the reception unit and thus making the measurement results accurate. In diagnosing BMD by osteometer, one faces with certain difficulties. When axial quantitative CT is used, the value may be falsely lower, because of the loss of energy absorbed by aorta which is often calcified in elderly people. In devices with transversal scanning, of the same nature and technology, a part of the energy is being absorbed by transversal and spinal vertebrals. After the research, one may conclude that the most accurate results can not be achieved. But, this is not considered so important. Values that are to be compared are available anyway. Therapy, if adequate, will show certain improvement which can not be detected even by osteometers. Following the physiatrist treatment, particularly by exercise of muscle strength, the muscle structure will be enhanced and, consequently, a part of pressure will be handled, which would be otherwise taken over by the bone. The movements of the patients will be better in coordinated, which undoubtedly reduces the number of falls and fractures. Results of the research that was conducted at the Clinical Hospital Centre "Dr. Dragisa Misovic" in Belgrade, with over 200 cases, two years, are compatible with literature data. Working with MediTech osteometer DTU ONE that uses ultrasound source in demineralized medium, with indispensable US gel, on constant temperatures, yielded results corresponding to those in patients that were treated by Bisphosphonates, Alphacalcidol and Calcium therapy.