TLR4 polymorphisms seem not to be associated with prediabetes and type 2 diabetes but predispose to diabetic retinopathy; TLR4 polymorphisms in glucose continuum.

OBJECTIVES: Compared to type 1 diabetes, the role of the immune and autoimmune pathogenetic mechanisms is much less studied in the type 2 diabetes. Toll-like receptors 4 (TLR4) have a leading role in inflammation, insulin resistance, and vascular damage. This study aimed to analyze the relationship between the polymorphisms in TLR4 gene and different stages in the glucose continuum from prediabetes to the type 2 diabetes and chronic microvascular complications. MATERIALS AND METHODS: The study included 113 patients with the type 2 diabetes, 29 participants with prediabetes, and 28 controls. Polymerase chain reaction (PCR) was used for genotyping Asp299Gly and Thr399Ile polymorphism, followed by restriction analysis. RESULTS: The difference in the genotype frequency for both polymorphisms in patients with the type 2 diabetes or prediabetes compared to that in controls was not significant. Patients with heterozygous genotype of Asp299Gly polymorphism had a higher prevalence of diabetic retinopathy (42.9%) than participants with homozygous genotype (9.0%) (OR [95%CI]=7.61 [1.41-41.08]; p=0.018). No association was established for diabetic polyneuropathy and nephropathy. Prevalence of chronic diabetes complications was not related to Thr399Ile polymorphism. CONCLUSION: Our study demonstrates that Asp299Gly and Thr399Ile polymorphisms seem not to be associated with the type 2 diabetes and prediabetes but Asp299Gly may contribute to diabetic retinopathy predisposition.

Serum Paraoxonase-1 Levels are Significantly Decreased in the Presence of Insulin Resistance.

UNLABELLED: Paraoxonase-1 (PON1) is an extracellular esterase contributing to the anti-atherogenic and anti-inflammatory properties of HDL and has a protective role in the progression of atherosclerosis. The aim of the present study was to compare serum paraoxonase-1 levels between obese subjects with prediabetes and normal glucose tolerance. METHODS: In this study were included 76 patients with mean age 50.7±10.7 years, divided into 2 age and BMI-matched groups - group 1 with obesity without glycemic disturbances (n=38) and group 2 with prediabetes (n=38). Oral glucose tolerance test (OGTT) with measurement of immunoreactive insulin was performed in all participants and levels of PON1 were measured using ELISA method. RESULTS: There was only a tendency towards higher PON1 levels in patients with prediabetes compared to controls. However, individuals with insulin resistance had significantly lower levels of PON1 compared to those without. The levels of PON1 showed a negative correlation with the blood glucose on 120th minute of OGTT, fasting IRI, HOMA index, BMI, WSR, WHR and particularly with waist circumference and positive with HDL-cholesterol. CONCLUSIONS: The levels of PON1 are similar in patients with and wthout prediabetes, but are significantly decreased in patients with insulin resistance and correlate with anthropometric markers of visceral adiposity.

Irisin in the Glucose Continuum.

AIM: Irisin, a novel myokine has been involved in the pathogenesis of type 2 diabetes (T2D) and metabolic syndrome. The aim of the current study was to investigate this association by comparing individuals from the whole spectrum of carbohydrate disturbances. METHOD: A total of 160 subjects participated in the study - 50 had normal glucose tolerance (NGT), 60 had prediabetes (PreDM), 50 had T2D. Subjects in the 3 groups were age, sex and BMI-matched. Standard OGTTs were performed for the distribution of patients in each group. Circulating serum irisin was measured by ELISA method. RESULTS: Mean age of the participants of the study was 48.8 (± 7.97) years. Circulating irisin levels were statistically different in the 3 study groups - highest in NGT - median 619 ng/ml (IQR=567), lower in PreDM - 314 ng/ml (IQR=577) and lowest in T2D - 228 ng/ml (IQR=200). In males, irisin correlated positively with BMI (r=0.475, p<0.001), negatively with fasting glucose (r=- 0.547, p<0.001) and negatively with hepatic enzymes: ALT (r=- 0.281, p<0.05), AST (r=- 0.153, p>0.05), GGT (r=- 0.293, p<0.05). Similar correlations were observed in females. ROC analyses established irisin suitable for distinguishing T2D subjects from those without the condition (AUC=0.779, p<0.001) and insulin resistance (AUC=0.679, p=0.009), but not for MetS or dyslipidaemia. In a binary logistic regression model, after adjustment for confounders, irisin of ≤658 ng/ml had an OR of 7.125 for T2D in females. CONCLUSION: Circulating irisin levels progressively decreased with the worsening of the glucose tolerance. Irisin correlated well with traditional biochemical and anthropometric parameters of metabolic health.

Treatment outcome results from the Bulgarian Acromegaly Database: adjuvant dopamine agonist therapy is efficient in less than one fifth of non-irradiated patients.

OBJECTIVE: We described biochemical outcome in regards to different treatment modalities in patients with acromegaly in Bulgaria. PATIENTS AND METHODS: It was a retrospective analysis using data from the Bulgarian Acromegaly Database. Patients with eligible data on at least one treatment modality were included in the study. Disease control was assessed by both GH and IGF-1 values or by GH/IGF-1 alone in cases with one marker. Last follow-up was median 7.0 (range 0.5-51) years after diagnosis. RESULTS: We identified 534 patients with interpretable data, 65.4% of whom were females. Overall surgical cure rate was 28.8%. Adjuvant bromocriptine and cabergoline treatment was analyzed in 133 and 70 patients with disease control achieved in 18.8% and 31.4% respectively. Patients without prior radiotherapy had 16.3% and 18.2% control rates respectively. Predictors of response to dopamine agonist (DA) therapy were disease activity, radiotherapy and medication dose. Adjuvant somatostatin analog (SSA) treatment led to biochemical control in 38.6% of 70 patients. Combination of SSA and cabergoline led to remission in 25% of 20 patients. Growth hormone receptor antagonist (GHRA) alone or in combination resulted in remission in 61.5% of 13 patients. Approximately one third of the patients were cured median 10 years after irradiation. Overall disease control was observed in 51.4% of our patients increasing to 70.3% in the last 5 years of the study period. CONCLUSION: DAs are efficient in less than 20% of non-irradiated patients. They are a good cost-effective alternative for carefully selected patients.

A comprehensive review of erectile dysfunction in men with diabetes.

Erectile dysfunction (ED) is more common in men with diabetes (DM). Dependent on the selected population, age, DM type and duration, the prevalence of diabetic ED (DED) varies from 32 to 90%. In 12-30% of men ED is the first sign of diabetes, diagnosed later. Today men with diabetes live longer than ever, and develop more late diabetic complications. Having in mind also the global ageing of the world population all this data suggests an increasing number of men with DED in the future. The main factors playing in the complex pathogenesis of DED are diabetic neuropathy (oxidative stress, polyol pathway, advanced glycation end-products, nerve growth factor deficiency, dysfunction of protein kinase C, tissue remodeling, etc.), macrovascular arterial disease (endothelial dysfunction, abnormal collagen deposition and smooth muscle degeneration, dyslipidemia, arterial hypertension, veno-occlusive dysfunction, etc.), hypogonadism, structural remodeling of the corporeal tissue, psychogenic components and adverse drug reactions. The diagnostic process is based on the results of questionnaires, neurological, vascular (Doppler) and other more rarely used investigations.Because of the complex pathogenesis of DED diabetic men represent a "difficult" treatment group. The difficulties are from the "beginning", because patients do not talk about their problem spontaneously, and doctors do not ask about it. The treatment of DED should be team work, preferably including also specialists in sexual medicine. Psychological support and counseling of the couple is necessary in most cases. The general measures include implementation of a healthier lifestyle, improved glycemic-, lipids-, and arterial pressure control, and careful re-evaluation of the concomitant medications. The specific treatment includes as first line therapy the inhibitors of phosphodiesterase type 5 (PDE-5) with lesser effectiveness compared to non-DM men. There are rare studies with selected diabetic populations and even less with head-to-head comparisons between the PDE-5 inhibitors. Men with DM have a higher prevalence of hypogonadism. Testosterone replacement therapy should be started in symptomatic men with proven hypogonadism and no contraindications. Vacuum constriction devices and intracavernous or intraurethral applications of vasoactive drugs are the second line therapy. Vascular surgery rarely comes into consideration. The penile implant is the last and effective option in men with severe DED.

NT-proBNP levels in premenopausal women with polycystic ovarian syndrome and/or obesity.

According to some studies, polycystic ovarian syndrome (PCOS) patients have an increased risk for diabetes mellitus and often show an adverse cardiovascular risk profile. NT-proBNP was shown to have a high predictive value regarding cardiovascular events, especially in those without overt cardiovascular disease. The aim of this study was to investigate the levels of NT-proBNP in 70 women with PCOS and/or obesity in relation to other classical cardiovascular risk factors. There was no statistical difference between NT-proBNP levels between obese, lean PCOS and obese PCOS patients; between patients with or without metabolic syndrome; or between patients with different cardiovascular risk, according to The Androgen Excess and PCOS Society consensus. NT-proBNP does not show significant correlation to age, weight, BMI, WHR, WSR, systolic or diastolic blood pressure and results from oral glucose tolerance test (OGTT), except for immunoreactive insulin (IRI) at 120 min. NT-proBNP correlates weakly with HDL, but not with other indices of lipid metabolism.

[Polycystic ovarian syndrome and obstructive sleep apnea].

Polycystic ovarian syndrome (PCOS) is one of the most common endocrine disturbances in women of reproductive age. Recently it has been postulated that its presence is linked to increased risk for cardiovascular diseases and type 2 diabetes in affected women. This makes necessary that PCOS is accepted not only as a reproductive issue, bus as a serious metabolic disease that carries important health risks with increasing age. In the contemporary studies much attention is given to PCOS comorbidites, including cardiovascular diseases and obstructive sleep apnea (OSA). OSA is a chronic condition that is characterized by repeating collapsing of upper airways during sleep that leads to severe hypoxemia and frequent awakening. OSA is a relatively rare condition in premenopausal women without PCOS and is commonly associated with obesity. On the other hand it is thought that PCOS patients have significantly higher risk. OSA severity is directly linked to plasma glucose and insulin levels and homeostatic model assessment (HOMA)-index in PCOS patients. It appears that the progressive worsening of PCOS clinical presentation leads to OSA that in turn aggravates the metabolic disturbances, associated with the syndrome.

Take action to prevent diabetes--the IMAGE toolkit for the prevention of type 2 diabetes in Europe.

When we ask people what they value most, health is usually top of the list. While effective care is available for many chronic diseases, the fact remains that for the patient, the tax payer and the whole of society: prevention is better than cure. Diabetes and its complications are a serious threat to the survival and well-being of an increasing number of people. It is predicted that one in ten Europeans aged 20-79 will have developed diabetes by 2030. Once a disease of old age, diabetes is now common among adults of all ages and is beginning to affect adolescents and even children. Diabetes accounts for up to 18 % of total healthcare expenditure in Europe. The good news is that diabetes is preventable. Compelling evidence shows that the onset of diabetes can be prevented or delayed greatly in individuals at high risk (people with impaired glucose regulation). Clinical research has shown a reduction in risk of developing diabetes of over 50 % following relatively modest changes in lifestyle that include adopting a healthy diet, increasing physical activity, and maintaining a healthy body weight. These results have since been reproduced in real-world prevention programmes. Even a delay of a few years in the progression to diabetes is expected to reduce diabetes-related complications, such as heart, kidney and eye disease and, consequently, to reduce the cost to society. A comprehensive approach to diabetes prevention should combine population based primary prevention with programmes targeted at those who are at high risk. This approach should take account of the local circumstances and diversity within modern society (e.g. social inequalities). The challenge goes beyond the healthcare system. We need to encourage collaboration across many different sectors: education providers, non-governmental organisations, the food industry, the media, urban planners and politicians all have a very important role to play. Small changes in lifestyle will bring big changes in health. Through joint efforts, more people will be reached. The time to act is now.

A European evidence-based guideline for the prevention of type 2 diabetes.

BACKGROUND: The prevalence and socioeconomic burden of type 2 diabetes (T2DM) and associated co-morbidities are rising worldwide. AIMS: This guideline provides evidence-based recommendations for preventing T2DM. METHODS: A European multidisciplinary consortium systematically reviewed the evidence on the effectiveness of screening and interventions for T2DM prevention using SIGN criteria. RESULTS: Obesity and sedentary lifestyle are the main modifiable risk factors. Age and ethnicity are non-modifiable risk factors. Case-finding should follow a step-wise procedure using risk questionnaires and oral glucose tolerance testing. Persons with impaired glucose tolerance and/or fasting glucose are at high-risk and should be prioritized for intensive intervention. Interventions supporting lifestyle changes delay the onset of T2DM in high-risk adults (number-needed-to-treat: 6.4 over 1.8-4.6 years). These should be supported by inter-sectoral strategies that create health promoting environments. Sustained body weight reduction by >or= 5 % lowers risk. Currently metformin, acarbose and orlistat can be considered as second-line prevention options. The population approach should use organized measures to raise awareness and change lifestyle with specific approaches for adolescents, minorities and disadvantaged people. Interventions promoting lifestyle changes are more effective if they target both diet and physical activity, mobilize social support, involve the planned use of established behaviour change techniques, and provide frequent contacts. Cost-effectiveness analysis should take a societal perspective. CONCLUSIONS: Prevention using lifestyle modifications in high-risk individuals is cost-effective and should be embedded in evaluated models of care. Effective prevention plans are predicated upon sustained government initiatives comprising advocacy, community support, fiscal and legislative changes, private sector engagement and continuous media communication.

Quality indicators for the prevention of type 2 diabetes in Europe--IMAGE.

BACKGROUND: The marked increase of type 2 diabetes necessitates active development and implementation of efficient prevention programs. A European level action has been taken by launching the IMAGE project to unify and improve the various prevention management concepts, which currently exist within the EU. This report describes the background and the methods used in the development of the IMAGE project quality indicators for diabetes primary prevention programs. It is targeted to the persons responsible for diabetes prevention at different levels of the health care systems. METHODS: Development of the quality indicators was conducted by a group of specialists representing different professional groups from several European countries. Indicators and measurement recommendations were produced by the expert group in consensus meetings and further developed by combining evidence and expert opinion. RESULTS: The quality indicators were developed for different prevention strategies: population level prevention strategy, screening for high risk, and high risk prevention strategy. Totally, 22 quality indicators were generated. They constitute the minimum level of quality assurance recommended for diabetes prevention programs. In addition, 20 scientific evaluation indicators with measurement standards were produced. These micro level indicators describe measurements, which should be used if evaluation, reporting, and scientific analysis are planned. CONCLUSIONS: We hope that these quality tools together with the IMAGE guidelines will provide a useful tool for improving the quality of diabetes prevention in Europe and make different prevention approaches comparable.

Diagnosis of diabetic neuropathy using simple somatic and a new autonomic (neuropad) tests in the clinical practice.

AIM: The global spread of diabetes (DM) and the importance of early therapeutic intervention determine the need of simple, inexpensive and sensitive methods for diagnosis of diabetic complications in the general practice. The aim of this study was to assess a new instrument - the plaster Neuropad in diagnosing the sudomotor diabetic dysfunction and to investigate the correlates of Neuropad data with diabetic complications. PATIENTS AND METHODS: In this cross-sectional study participated 264 inpatients (M/F=126/138) with DM type 1/2 (61/203), mean age 55.4+/-12.0 and DM duration of 9.3+/-7.1 years. According to hospital records were registered: anthropometric data; fasting plasma glucose and HbA1c; presence of micro-(retino-, nephro-, neuropathy), and macrovascular (arterial hypertension, coronary artery disease and/or brain vascular disease) complications, and neuropathic symptoms were evaluated. For investigation of somatic DN a modified Neuropathy Disability Score (NDS) and for sudomotor autonomic DN - Neuropad were used. RESULTS: Neuropad showed the highest between-feet correlation of 0.91 compared to all other individual tests and the NDS. Neuropad was able to separate patients in groups with different general risk profile, including age, duration of DM, presence of coronary and/or brain vascular disease, nephropathy, and retinopathy. Moreover, Neuropad differentiated patient groups by their stage of DN, evaluated by symptoms, diagnosis, the individual somatic tests and with the highest significance - by NDS. Most sensitive for detecting DN was NDS > or = 3, followed by Achilles reflexes, vibration perception (128 Hz tuning fork) and Neuropad. A borderline or abnormal result of Neuropad showed sensitivity=76.3/79.3, specificity=56.1/42.9, positive=86.3/62.8 and negative=39.5/63.0 predictive values, and diagnostic accuracy 72.2/62.9%, compared to the indices for presence of somatic DN (NDS > or = 3)/foot at risk (NDS > or = 6) respectively. CONCLUSIONS: Screening for DN must cover somatic and autonomic disturbances. Neuropad is a new sensitive and appropriate for everyday clinical use test for detecting sudomotor DN and identification of patients at higher risk for chronic diabetes complications.

Inflammatory activity and anticardiolipin antibodies during tibolone treatment of healthy postmenopausal women.

The aim of the study was to investigate the inflammatory activity and anticardiolipin antibodies (Acl) during tibolone administration. Twenty seven clinically healthy postmenopausal women were included in the study and were divided into two groups: 16 women (mean age 56.4 +/- 4.6 years) who received tibolone at a dose of 2.5 mg/day for 6 months and an untreated control group (n = 11, mean age 54.8 +/- 4.0 years). Acl of IgG and IgM isotype, and C-reactive protein (CRP) were determined at baseline, 1, 3, and 6 months after treatment. Acl did not change during tibolone treatment, while CRP increased significantly at the 1st, 3rd, and 6th month compared with that at the baseline values. These preliminary data indicate that tibolone administration does not induce increase in Acl. This may counterbalance the adverse influence on CRP.

Physiological characteristics of diabetic neuropathy in sucrose-fed Otsuka Long-Evans Tokushima fatty rats.

Diabetic neuropathy is a very common complication of diabetes mellitus, and animal studies have contributed tremendously to its understanding. The aim of this study was to estimate the neuropathic alterations in the Otsuka Long-Evans Tokushima fatty (OLETF) rats, an animal model of human type 2 diabetes mellitus. For this purpose, four groups of animals were used: untreated OLETF rats, sucrose-fed for 2 months OLETF rats, untreated Long-Evans Tokushima Otsuka (LETO) nondiabetic rats as genetic controls of OLETF, and sucrose-fed LETO rats. All were examined at baseline, at the end of the sucrose treatment, and during a washout period. The following parameters were evaluated: motor nerve conduction velocity (MNCV), sensitivity to noxious thermal and mechanical stimuli using the tail-flick (TF) and tail-pressure (TP) tests, and blood glucose (BG) and HbA1c levels. Our results showed that BG and HbA1c were significantly higher in OLETF rats when compared with those in control LETO rats. Sucrose caused remarkable increase of BG and HbA1c in the OLETF rats, but not in the sucrose-fed LETO rats. MNCV and thermal nociception significantly decreased in OLETF rats in their 10th month, while the values of the TP test did not differ compared with those from LETO rats. Sucrose administration significantly decreased the MNCV, and increased the pain threshold evaluated by the TF and TP tests, compared with those in the control OLETF rats. The studied parameters were not significantly altered in sucrose-fed LETO rats. In conclusion, our findings show that signs of diabetic neuropathy appear late in the individual development of the OLETF rats, and MNCV and thermal nociception are selectively affected in this strain. Sucrose deteriorated the diabetic state, decreased MNCV, and caused thermal and mechanical hypoalgesia.

[Effect of 6-month treatment with oral antiandrogen alone and in combination with insulin sensitizers on body composition, hormonal and metabolic parameters in women with polycystic ovary syndrome (PCOS) in order to determine therapeutic strategy].

UNLABELLED: PCOS is a complex disorder with variability of phenotypes, characterized by hyperandrogenic, anovulatory and metabolic components. The later is a result of specific insulin resistant state with compensatory hyperinsulinaemia. Oral hormonal contraceptives (OHC) are a treatment of first choice in hyperandrogenic PCOS women who do not desire conception. Addition of insulin sensitizers might counteract unfavourable metabolic consequences of OHC monotherapy and could result in additional benefits for treated PCOS women. AIM: To compare the effects of 3 therapeutic regimens widely used in practice--OHC alone and in combination with metformin or rosiglitazone on body weight and anthropometric proportions, hormonal and metabolic alterations. MATERIAL AND METHODS: The study comprised of 44 women with proven PCOS, divided in 3 therapeutic groups: 1st group--with Diane35 alone; 2nd group--with Diane35 + metformin; 3rd group--with Diane35 + rosiglitazone. Body weight, fat mass and distribution, hormonal levels, metabolic parameters (insulin and blood glucose during oGTT lipid profile) were studied before and after a 6-month treatment. RESULTS: Monotherapy with Diane35 did not lead to changes in body weight, fat mass and distribution; had beneficial influence on some of the hormonal alterations in PCOS, but did not achieved significant antiandrogenic effect; did not induce changes in carbohydrate tolerance while having mild negative effect on insulinaemia; had an unfavourable although mild influence on lipid parameters including atherogenic indices except the HDL-cholesterol; did not show side effects on liver and vascular function. Combined treatment with Diane35 and metformin led to reduction of weight, fat mass and abdominal fat distribution; possessed significant antiandrogenic effect; did not decrease blood glucose levels; supressed glucose-stimulated insulin levels; had beneficial effect on HDL-cholesterol and neutral effect on other lipid parameters and atherogenic indices; decreased diastolic blood pressure. Combined treatment with Diane 35 and rosiglitazone did not induce changes in body weight, fat mass and abdominal fat distribution; possessed significant antiandrogenic effect; did not influence fasting and postchalange glucose levels; suppressed fasting hyperinsulinaemia and HOMA-index, respectively; had neutral effect on the levels of lipid parameters and atherogenic indices.

[Emergency contraception with levonorgestrel for teenagers--efficacy, tolerability, and level of information awareness]. / Speshna kontratseptsiia pri tiineidzhuri s levonorgestrel--efektivnost, ponosimost, informiranost.

OBJECTIVE: Assessment of efficacy and side effects of emergency contraception for teenagers with levonorgestrel (LNG) and the level of users' informedness about possibilities and practical application. METHODS: The subjects are healthy girls (n = 49) with regular menstrual cycles at the age between 15 and 19, having had one unprotected or faultily protected sexual intercourse. All of them have administered 0.75 mg LNG within the 72nd hour, repeated after 12 hours. The data have been processed by variational analysis. RESULTS: One pregnancy was registered of a girl with firstintake at the 67th hour - pregnancy rate - 2,0%. The most frequent side effect was nausea - 26,5%, folowed by breast tenderness - 22,4% and fatigue - 20,4%. An up to 7th day delay in menstrual cycle is non significantly more frequent - 14,3%, followed by a delay of more than 7 days breakthrough bleeding - 8,2%. No significant changes were established in the lenght of the menstrual cycle. Emergency contraception is sought for after unprotected sexual intercourse in 69,4%, and condom failure problems in 30,6%. Only 18,4% have sufficient information about the possibilities and practical use of emergency contraception. CONCLUSION: LNG provides effective, highly tolerable contraception with a small number of side effects. Need is felt for serious popularization of the application of emergency contraception with teenagers.

Ambulatory blood pressure monitoring and active renin in menopausal women treated with amlodipine and hormone replacement therapy.

The aim of this study was to follow up the effect of an 8-week treatment with amlodipine given alone or in combination with hormone replacement therapy (HRT) on blood pressure and active renin in postmenopausal women with mild to moderate arterial hypertension using both conventional clinical blood pressure measurements and ambulatory blood pressure monitoring. Twenty-nine hypertensive menopausal women were divided randomly into two groups according to the treatment regimens: amlodipine and amlodipine plus HRT. The combination with HRT led to normalization of 24-h and daytime systolic and diastolic blood pressure. In contrast to the group treated with amlodipine alone, where a significant fall only of systolic night-time blood pressure was observed, in the group treated with amlodipine plus HRT both systolic and diastolic night-time blood pressure decreased significantly. Active renin did not change significantly after treatment in both groups. Triglycerides decreased significantly and high-density lipoprotein-cholesterol increased significantly only after amlodipine treatment. There were no significant differences in serum total cholesterol and low-density lipoprotein-cholesterol after HRT plus amlodipine. In conclusion, amlodipine is effective in reducing blood pressure in postmenopausal women. The maintenance of a normal circadian blood pressure pattern was influenced by HRT.

Hematological alterations in the Otsuka Long-Evans Tokushima fatty (OLETF) rats--a model of type 2 diabetes mellitus.

The OLETF rat develops microangiopathic complications similar to human diabetes and is considered a useful model of Type 2 DM. Erythrocyte, platelet and leucocyte abnormalities described in diabetic patients are thought to play a role in the development of diabetic microangiopathy. This study was designed to investigate whether OLETF rats show hematological alterations and the effect of sucrose treatment on metabolic and blood parameters. Hematological parameters, body weight, food and water intake, fasting and non-fasting blood glucose (BG) and HbA1c were measured in OLETF rats treated for two months with 30% sucrose added to drinking water. Non-treated OLETF rats and non-diabetic Long-Evans Tokushima Otsuka (LETO) rats were used as controls. In the control OLETF rats the number of platelets (Plt) and red blood cells (RBC) was higher, while the mean cell volume (MCV) and the mean cell hemoglobin content (MCH) were lower compared with LETO. Mean cell hemoglobin concentration (MCHC) was significantly higher in the diabetic rats. Sucrose administration decreased food intake and body weight and increased fasting blood glucose and HbA1c. It resulted in a decrease of RBC, Hb, Hct, MCV and MCH compared with control OLETF, while Plt count increased significantly. Our results point to significant alterations in erythrocyte count and morphology and Plt count in diabetic OLETF rats compared with non-diabetic LETO. Sucrose administration accelerated the development of diabetes, affected blood cells inducing the suppression of RBC and an increase in Plt count and some of its effects persisted after sucrose withdrawal.

[Comparative diagnostic characteristics of carbohydrate metabolism disorders in women with polycystic ovary syndrome (PCOS)]. / Sravniavane na diagnostichnite pokazateli za otsenka na narusheniiata vuv vuglekhidratniia metabolizum pri zheni sus sindrom na polikistozni iaichnitsi (PCOS)

The aim of the study was to compare the information provided by both fasting and stimulated during a standard oral glucose tolerance test (oGTT) levels of glucose and insulin as regards glucose tolerance and insulin resistance in women with PCOS. Few criteria are used in practice to verify insulin resistance in PCOS--elevated fasting insulin, decreased basal glucose/insulin ratio (< 6 for glucose in mg/dl or < 0.333 for glucose in mmol/l), insulin increase of more than 100 lul during an oGTT, and HOMA index > 2. The study comprised of 94 women (mean age 21.8 +/- 5 = 8 ys, mean BMI-30.38 +/- 7 = 7 kg/m2), divided in 4 groups according to BMI--group with BMI < 25, n = 21; group with BMI25-30, n = 27; group with BMI = 30-35, n = 23 and group with BMI > 35, n = 23. An oGTT with parallel determination of blood glucose and insulin was performed in all patients. The ratio basal glucose/insulin and HOMA index were calculated. Glucose levels on the 2 md hour during the oGTT pointed at IGT (impaired glucose tolerance) and/or diabetes in 8.5% of the investigated patients while the fasting levels indicated disturbances in only 2.2% of them. Fasting insulin levels were in the normal range in a considerable part of PCOSE women, mainly those with normal weight, and were not predictive for the response of insulin to glucose load. Relative percent of patients with elevated fasting insulin rose with the increasing of BMI. Decreased glucose/insulin ratio, elevated HOMA index, and abnormal stimulation of insulin were seen in more than 2/3 of the PCOS women including nonobese ones. Information provided by the above three markers was similar and they could be used alternatively according to the particular case and assessment of the cost/benefit ratio.

Effect of amlodipine and hormone replacement therapy on blood pressure and bone markers in menopause.

The aim of this study was to observe the effect of an 8-week treatment with amlodipine, alone or in combination with hormone replacement therapy (HRT), on blood pressure (BP), serum osteocalcin, bone-specific alkaline phosphatase (B-ALP) and urine deoxypiridinoline in postmenopausal osteoporotic women with mild-to-moderate arterial hypertension. Both conventional clinical BP measurements and ambulatory blood pressure monitoring (ABPM) were used. Twenty hypertensive menopausal women with osteoporosis were randomly divided in two groups according to the treatment regimens: amlodipine and amlodipine + HRT. Neither treatment regimen significantly changed bone formation or bone resorption markers. There were no significant differences in levels of serum and urinary calcium and phosphorous or serum cholesterol and low-density lipoprotein (LDL)-cholesterol after treatment with amlodipine alone or in combination with HRT. Triglycerides were significantly decreased and high-density lipoprotein (HDL)-cholesterol was significantly increased after amlodipine treatment. Both treatment regimens significantly decreased conventionally measured BP to a similar extent. Amlodipine given alone lowered the midline estimating statistic of rhythm (MESOR; mean 24-level) of systolic BP and induced phase advances of the circadian rhythms of systolic, diastolic and mean BP. When combined with HRT, amlodipine lowered the MESOR and reduced the amplitude of systolic BP without any phase change. In conclusion, amlodipine is effective in reducing BP in postmenopausal women. The maintenance of a normal circadian BP pattern is also influenced by supplementation with 17beta-estradiol. The 8-week treatment with amlodipine alone and in combination with HRT is not associated with a marked influence on bone metabolism.

[Possibilities for an individualized approach to the treatment of climacteric symptoms with phytoestrogens]. / V'zmozhnosti za individualiziran podkhod v lechenieto na klimakterichnata simptomatika s fitoestrogeni.

UNLABELLED: In climacteric women with contraindications and fear or lack of compliance for taking hormonal replacement therapy as well as in those cases where risks exceed benefits, the use of phytoestrogens is appropriate having in mind their especially good effect on neurovegetative symptoms. AIM: The present randomized prospective study is aimed at estimating the possibility for ameliorating climacteric symptoms with Melbrosia and at assessment of its effect on different symptoms in order to individualize the therapeutical approach. PATIENTS AND METHODS: Two groups of women with climacteric complaints were followed-up--control group (n = 32) and treatment group (n = 34). Climateric symptoms were assessed in the beginning and at the end of the study using Kupperman menopausal index. The levels of FSH, LH, oestradiol as well as some parameters of lipid metabolism were determined. RESULTS: A significant decrease of Kupperman index was observed in Melbrosia treatment group in contrast to the control group. No significant changes in gonadotropins, oestradiol and lipid parameters were found in both groups. CONCLUSION: The preparation Melbrosia, consisting of phytoestrogens and amino acids exerts a good therapeutic effect on climacteric symptoms mainly on the nervousness, anxiety, irritability, headache, and hot flashes.