Five-Year Outcomes in Bariatric Surgery Patients.

Background and objectives: Obesity presents as a multifactorial, pandemic disease that arises as a consequence of unequal energy intake and energy consumption. Obesity adversely affects the quality of life, leading not only to disability, but also to various other disorders. Bariatric surgery is the most effective method for achieving significant and sustained weight loss in individuals with extreme obesity. The aim of this study was to examine how well surgically induced weight loss is maintained after five years of follow-up and its effects on cardiovascular risk factors and outcome. Materials and Methods: This is a retrospective cross-sectional study of 66 patients with morbid obesity, with body mass index (BMI) ≥ 40 kg/m2 or BMI ≥ 35 kg/m2 and obesity-related health conditions, aged 20 to 61 years, mostly women (77.3%) who underwent laparoscopic Roux-en-Y gastric bypass surgery. Results: Average follow-up was 6.42 years (95% CI 6.30-6.54 years) after surgery, with survival rate of 97% in operated individuals. There was a statistically significant reduction of weight and body mass index 6 months and 5 years after surgery in comparison to the initial values (p < 0.001). Of 62 patients who presented weight loss at the end of the follow-up period, 38 were able to maintain the amount of weight loss that was attained 6 months after surgery, while 24 patients regained weight compared to their postoperative weight at 6 months. Two patients reported no weight loss after treatment. Significant weight reduction was associated with better control of diabetes and increased self-reported physical activity at 6 months and 5 years after surgery, as well as with a reduction of the use of anti-diabetic and anti-hypertensive medications. Conclusions: Our research demonstrates a positive long-term impact of bariatric surgery on patients' health conditions, significant and sustained weight loss, and decrease in BMI, which were associated with a reduction of co-morbidities and risk factors for cardiovascular diseases.

AGING, HEART RATE VARIABILITY AND METABOLIC IMPACT OF OBESITY.

The relationship between aging and changes in heart rate variability (HRV) could depend on the metabolic profile of obese people, i.e. metabolically healthy obese (MHO) and metabolically unhealthy obese (MUO). We aimed to determine the age at which obesity related autonomic dysfunction becomes significant and whether it decreases differently according to metabolic profile. We analyzed HRV in 99 adults using Wildman's criteria for metabolic profile and 5-minute HRV for autonomic nervous system. In MHO, high frequency (HF) decreased in the 4th decade of life. In MUO, standard deviation of R-R intervals (SDNN), root mean square of successive differences of all R-R intervals (RMSSD), number of adjacent intervals differing by more than 50 ms expressed as percentage of all intervals in the collecting period (pNN50), HF, low frequency (LF), LF/HF (LF divided by HF) and total power (TP) decreased in the 4th decade of life (partial shared variance 28%-36%). In conclusion, an age dependent decrease of HRV occurs in MUO between the third and fifth decade of life. In MHO, HF significantly decreases around the age of 40 years. Cardiometabolic profile influences metabolic aging, altering the autonomic nervous system.

Combined Administration of Ghrelin and Corticotropin-Releasing Hormone in the Diagnosis of Cushing's Disease.

BACKGROUND/AIMS: Exaggerated adrenocorticotropic hormone (ACTH) and cortisol responses to ghrelin in Cushing's disease (CD) have previously been reported, similarly to responses to corticotropin-releasing hormone (CRH). We assessed the ability of ghrelin to enhance ACTH and cortisol responses when added to CRH stimulation in CD patients. METHODS: In 21 CD patients (18 females, 3 males; age 49.8 ± 10.2 years; BMI 29.8 ± 0.8) and 8 healthy subjects (7 females, 1 male; age 40.6 ± 5.3 years; BMI 29.9 ± 1.2), we administered (1) ghrelin 100 µg i.v. bolus, (2) CRH 100 µg i.v. bolus, and (3) ghrelin + CRH combination. ACTH and cortisol were analyzed by commercially available kits from samples taken at 0, 15, 30, 45, 60, 90 and 120 min. ACTH and cortisol responses were calculated as peak and area under the curve (AUC0-120 min). RESULTS: ACTH and cortisol at baseline and stimulated with ghrelin and/or CRH (peak and AUC0-120 min) were significantly higher in CD patients compared to controls (p < 0.01). ACTH and cortisol responses to ghrelin or CRH were similar in CD patients. Combined ghrelin + CRH administration in CD patients produced the highest ACTH response (peak and AUC0-120 min) compared to ghrelin or CRH alone (p < 0.01). Cortisol responses after ghrelin + CRH were uncoupled with ACTH responses and similar to the response to ghrelin or CRH alone in both groups. ACTH and cortisol responses, during all three tests, were similar in CD patients with micro- or macroadenomas. CONCLUSION: Ghrelin administration causes exaggerated ACTH and cortisol responses in CD patients compared to healthy controls. In combination with CRH, it additionally enhances ACTH secretion without further additive effect on cortisol output.

Retinal Perfusion Analysis of Children with Diabetes Mellitus Type 1 Using Optical Coherence Tomography Angiography.

(1) Background: This study aims to evaluate retinal perfusion by optical coherence tomography angiography (OCTA) in pediatric patients with type 1 diabetes mellitus (T1D) without diabetic retinopathy (DR). (2) Methods: Thirty-one patients affected by T1D were enrolled. All participants were evaluated using OCTA. The foveal avascular zone (FAZ) and superficial and deep macular vessel density (VD) were analyzed. The correlation of these parameters with metabolic factors such as body mass index (BMI), glycated hemoglobin (HbA1c), and the type of insulin therapy (multiple daily injections, MDI vs. continuous subcutaneous insulin infusion, CSII) was determined. (3) Results: None of the OCTA parameters were significantly different between the groups. The patients' HbA1C level did not influence any of the OCTA parameters. The use of MDI tended to reduce the parafoveal and perifoveal deep VD (p = 0.048 and p = 0.021, respectively) compared to CSII. An elevated BMI tended to increase the deep macular (p = 0.005) and perifoveal VD (p = 0.006). (4) Conclusion: VD and FAZ are normal in pubescent children with T1D without signs of DR. Treatment with CSII may be a better choice compared to MDI, as CSII may be protective against retinal microvascular damage. Our results indicate the need for new clinical parameters of glycemic control in addition to HbA1c which could assess the risk of DR.

Beneficial effects of a new probiotic formulation on adipocytokines, appetite-regulating hormones, and metabolic parameters in obese women.

Obesity is often accompanied by low-grade chronic inflammation and metabolic syndrome. It has been established that microbiota influences many physiological processes, including the development of obesity, and dysbiosis has been observed in obese individuals. In this study, we aimed to evaluate the impact of a new probiotic formulation, containing two probiotic strains and the bioactive compound octacosanol, on body weight, metabolic parameters, and concentrations of certain adipocytokines and appetite-regulating hormones in obese women. This double blind placebo-controlled supplementary intervention study included twenty-five women in the intervention group and twenty-three in the placebo group, and it lasted 12 weeks. Daily oral supplementation included 7 × 1010 CFU of Lactiplantibacillus plantarum 299v (DSM9843), 5 × 109 CFU of Saccharomyces cerevisiae var. boulardii (DBVPG6763), and 40 mg of octacosanol or placebo. Body weight, metabolic parameters, adipocytokines, and appetite-regulating hormones were assessed before (T0) and after the intervention (T1). After the intervention, significantly lower median concentrations of CRP (p = 0.005) and IL-6 (p = 0.012) were measured in the intervention group than the baseline, while the median concentrations of ghrelin (p = 0.026) and HDL-cholesterol (p = 0.03) were significantly increased. The intervention group had lower CRP levels (p = 0.023) and higher ghrelin levels (p = 0.006) than the placebo group. Significant changes in BMI between groups were not observed. In summary, although the new probiotic formulation showed beneficial effects on IL-6, CRP, HDL, and ghrelin levels, its potential effects on regulating triglyceride, insulin, and glucose levels require further studies before the novel dietary intervention could be considered a useful adjuvant therapy and an effective strategy for the management of obesity and obesity-associated comorbidities.

Epigenetic Aspects of a New Probiotic Concept-A Pilot Study.

Several studies report the important role of an altered gut microbiota in the development of obesity, highlighting the potential use of probiotics in the treatment of obesity. The aim of this study is to investigate the effect of a novel probiotic approach on the expression of specific miRNAs and mRNAs associated with obesity in combination with the hypocholesterolemic octacosanol. Twenty overweight/obese women participated in a randomized, placebo-controlled, double-blind study and were randomly divided into two groups: the intervention group (daily one capsule containing Lactobacillus plantarum 299v (DSM9843), Saccharomyces cerevisiae var. boulardii, and 40 mg octacosanol; N = 12) and the placebo group (N = 8). Changes in lipid parameters and expression of miRNAs and mRNAs were assessed before (T0) and after the 12-week intervention (T1). After the intervention, the expression of miR-155-5p (9.38 ± 0.85 vs. 8.38 ± 1.06, p = 0.05) and miR-24-3p (3.42 ± 0.38 vs. 2.71 ± 0.97, p = 0.031) showed significant decreases in the intervention group when compared to the control group. At T1, the expression of miR-155-5p (8.69 ± 1.31 vs. 9.3 ± 0.85, p = 0.04), miR-125b-5p (5.41 ± 1.18 vs. 5.99 ± 1.36, p = 0.049), and TNF-α (10.24 ± 1.66 vs. 11.36 ± 1.12, p = 0.009) were significantly decreased in the intervention group. No changes in lipids and anthropometric parameters were observed. The novel probiotic approach had a positive effect on regulating the expression of certain miRNAs and mRNAs important for regulating inflammation and adipogenesis, which are essential for obesity onset and control.

Reproductive outcomes after bariatric surgery in women.

The presence of obesity may significantly influence female fertility through various mechanisms. Impairment of the hypothalamic-pituitary-ovarian axis in obese women may induce anovulation and infertility. Obesity may have an effect on women's spontaneous and assisted conception rates, increased miscarriage rates, premature labor, stillbirth and perinatal risks, and menstrual irregularity. It has been suggested that weight loss improves reproductive outcomes due to fertility amelioration and an improvement in menstrual irregularity and ovulation. It is still not known which weight reduction procedures (changes in lifestyle, pharmacological management or bariatric intervention) result in optimal outcome on infertility. Currently, bariatric surgery is defined as the best available method for the management of obesity and its associated diseases.We have analyzed literature facts about effects of bariatric surgery on the function of the hypothalamic-pituitary-ovarian axis, polycystic ovary syndrome (PCOS), anti-Mullerian hormone (AMH) and sexual dysfunction in obesity and pregnancy in obesity. Immediate positive effects of bariatric surgery are evident at the moment, while for long-term outcomes more prolonged follow-up investigations should be done.

Cross-cultural validation of the Retinopathy Treatment Satisfaction Questionnaire status version (RetTSQs) in Serbian community: a cross-sectional study.

OBJECTIVE: Cross-cultural translation and validation of the Serbian version of the Retinopathy Treatment Satisfaction Questionnaire status version (RetTSQs). DESIGN: Cross-sectional study. SETTINGS: The study was conducted between June 2017 and June 2018 at tertiary care centre in Serbia, Belgrade. PARTICIPANTS: A total of 101 patients with diabetic retinopathy (DR) were included. All subjects were evaluated in two consecutive visits, the first during the initial contact to the clinic, while the second 4-6 weeks later. MAIN OUTCOME MEASURES: Validation of Serbian version of the RetTSQs was the major outcome. RESULTS: Cronbach alpha coefficient of the subscales ranged from 0.783 (positive scale) to 0.811 (negative scale) and for all domains it was excellent at α=0.829. The intraclass correlation coefficient was greater than 0.8 for all of the subscales. Univariable analyses revealed that age, gender, education, marital status and working status did not affect the RetTSQ scores, whereas participants with non-proliferative DR reported significantly higher treatment satisfaction (TS) than those with proliferative retinopathy (p=0.001). The group who received laser treatment scored significantly lower than the group without it (p=0.004) regardless of type of performed laser. Positive and statistically significant correlations were found between the RetTSQ score and most of the National Eye Institute Visual Functioning Questionnaire-25 subscales. CONCLUSION: Translated Serbian adaptation of the RetTSQs showed adequate psychometric characteristics as an acceptable, reliable and valid questionnaire. It was well understood by Serbian diabetic patients and it promises to be used in daily clinical work as an instrument for the assessment of TS for patients with DR.

The Amount of Weight Loss Six Months after Bariatric Surgery: It Makes a Difference.

BACKGROUND: Bariatric surgery, especially Roux-en-Y gastric bypass (RYGB), has become the most frequently used therapy for morbid obesity. OBJECTIVES: The aim of this study was to examine the effects of surgically induced weight loss on cardiopulmonary function 6 months after the procedure, as well as the effect of such an intervention on well-known risk factors for cardiovascular diseases. METHODS: This is a cross-sectional study on 66 morbidly obese patients (BMI ≥40 or ≥35 kg/m2 with present comorbidities), comparing their cardiopulmonary function prior to and 6 months after RYGB surgery. RESULTS: The substantial amount of weight loss (29.80 ± 13.27 kg) after RYGB surgery was associated with significant reduction of comorbidities, especially diabetes and sedentary lifestyle (p = 0.005 and p = 0.002, respectively). Regarding functional capacity, there was significant increase in peak oxygen uptake (VO2 peak, p = 0.003), duration of exercise testing, metabolic equivalents (exercise time and METs, p < 0.001), and in peak O2 pulse. These findings were particularly pronounced in a group of patients who had lost more than 18% of initial weight. CONCLUSIONS: Reduction of body weight after RYGB surgery is associated with significantly improved cardiorespiratory function 6 months after surgery, especially in patients who lost more than 18% of their initial body weight. In addition, substantial decreases in body weight were also associated with a reduction of cardiovascular risk factors such as diabetes, smoking, hypertriglyceridemia, and sedentary lifestyle.

Prognostic Value of Preoperative Neutrophil-to-lymphocyte Ratio for Prediction of Severe Cholecystitis.

BACKGROUND: The predictive value of preoperative neutrophil-to-lymphocyte ratio (NLR) in patients with cholecystitis has not been established. The aim of this study was to investigate preoperative NLR in patients with cholecystitis and to identify a relevant NLR value that discriminates between simple and severe cholecystitis. METHODS: This study included 136 patients who under went laparoscopic cholecystectomy due to cholecystitis. The Receiver Operating Characteristic (ROC) analysis was performed to identify the most useful NLR cut-off value in relation to the severity of cholecystitis. The patients were di vided into two groups according to the cut-off NLR value: high NLR group (≥4.18, n=23) and low NLR group (<4.18, n=113). Severe cholecystitis was defined as a state which includes inflammation, empyema, gangrene, perforation of gallbladder, adhesions or difficulty in dissecting Calot's triangle. RESULTS: In the high NLR group, severe cholecystitis (p<0.0001) and higher C-reactive protein level (CRP) and white blood cells count (WBC) (p<0.0001) were significantly more frequent. There was no difference in homeostatic model assessment-insulin resistance index (HOMA-IR) between both groups before the operation (p<0.634). The incidence of severe cholecystitis was 16.9%. The NLR of 4.18 could predict severe cholecystitis with 78.3% sensitivity and 74.3% specificity. Spearman's correlation revealed significant association between the preoperative NLR and HOMA-IR on day 1, (r=0.254, p=0.030) and between preoperative NLR and CRP on day 1 (ρ=0.355; p<0.0001). CONCLUSIONS: NLR ≥4.18 was significantly associated with severe cholecystitis. The preoperative NLR in patients under going cholecystectomy due to cholecystitis could be a useful surrogate marker of severe cholecystitis.

Influence of IL-6, TNF-α and Hs-CRP on Insulin Sensitivity in Patients after Laparoscopic Cholecystectomy or Open Hernia Repair.

BACKGROUND: The aim of this study was to investigate the influence of IL-6, TNF-α and hs-CRP on insulin sensitivity during postoperative follow-up in patients with laparoscopic cholecystectomy (LC) or open hernia repair (OHR). METHODS: 65 patients were studied: after laparoscopic cholecystectomy (LC; n=40) or open hernia repair (OHR; n=25). Glucose, insulin, hs-CRP, IL-6 and TNF-a were determined at day 0 (before the operation) and at days 1, 3 and 7 (after the operation). RESULTS: There were no difference between LC and OHR groups concerning age, BMI, glucose, insulin, hs-CRP, IL-6 and TNF-α at day 0. hs-CRP increased at day 1, 3 and 7 vs. day 0 (p<0.0005), without difference between groups (p=0.561). IL-6 increased at day 1 and day 3 vs. day 0 (p<0.005). IL-6 was higher at day 1 in OHR group in comparison with LC group (p=0.044). There were no differences in TNF-a levels between LC and OHR groups (p=0.056). There was increase of HOMA-IR at day 1, 3 and 7 vs. day 0 (p<0.0005) in both groups. Significantly higher increase of HOMA-IR was in OHR group compared with LC group at day 1 (p=0.045). There was a positive correlation between hs-CRP and HOMA-IR (r=0.46; p=0.025) and between IL-6 and HOMA-IR at day 1 in OHR group (r=0.44; p=0.030). CONCLUSIONS: Significantly higher HOMA-IR was found in OHR group compared with LC. Positive correlation between hs-CRP and IL-6 with HOMA-IR in OHR group at day 1, indicate possible influence of this mediators on impairment of insulin sensitivity.

The impact of thyroid autoimmunity (TPOAb) on bone density and fracture risk in postmenopausal women.

OBJECTIVE: Skeletal development, linear growth, cartilage biology and bone turnover are highly dependent on the activity of thyroid hormones. Thyroid dysfunction affects the skeleton, and autoimmune thyroid disease, manifesting as a chronic inflammatory condition, may be an important contributing factor to impaired bone quality in these patients. MATERIALS AND METHODS: Measurement of TSH, FT4, TPOAb and bone mineral density and FRAX score calculations were performed in 189 postmenopausal women (110 euthyroid women and 79 women diagnosed with subclinical hypothyroidism) divided into subgroups according to the presence of TPOAb. RESULTS: In multivariate logistic regression analysis only TPOAb were found to be significantly related to fracture, independently of TSH values (p=0.018; OR=7.800; 95% CI 1.424-42.721). Lower bone mineral density and FRAX score for hip and for major osteoporotic fractures were associated with the presence of TPOAb in euthyroid postmenopausal women in an unadjusted logistic regression model, as well as in a model adjusted for age, BMI and smoking. TSH was a better predictive factor for fractures in women with subclinical hypothyroidism (FRAX main p <0.001; 95% CI for SE 0.858-0.959 and FRAX hip p <0.001; 95% CI for SE 0.628-0.854). CONCLUSION: Autoimmune thyroid disease is associated with decreased bone mineral density at both spine and hip and risk of future fracture incidence in euthyroid postmenopausal women. Presence of TPOAb is a potential marker of higher fracture risk in these patients. However, in subclinical hypothyroidism, TSH is a better indicator of future fragility fractures than TPOAb.

Non-functional parathyroid cyst--diagnostic pitfall: A case-report.

INTRODUCTION: Parathyroid cysts are relative rare and they may be misdiagnosed with thyroid nodules. Parathyroid cysts are characterized by elevated level of parathyroid hormone (PTH) in cystic fluid. CASE REPORT. We reported about middle-aged woman with palpable node in the left thyroid lobe. Ultrasound showed anechoic 40 x 25 mm lesion in the left thyroid lobe. Fine needle aspiration (FNA) obtained 13 mL colorless, watery cystic fluid. PTH value in cystic fluid was ten fold more in comparison with serum PTH. Serum PTH was slightly elevated, D vitamin was under the reference range, serum calcium and phosphorus were normal as well as thyroid hormones. Thyroglobulin antibodies (TgAb) and thyroid peroxidase antibodies (TPOAb) were not detected. Radionuclide parathyroid scintigraphy indicated at physiological metaiodbenzyl-guamidine (MIBG) distribution. After six monthsof vitamin D supplementation, serum calcium, phosphorus, vitamin D and PTH were normal. This finding was indicative that was a nonfunctional parathyroid cyst. CONCLUSION: This case report points out that thyroid cystic lesions with thin walls, and reverberation in ultrasound, must be observed as a potential parathyroid cyst. These cysts require caution during diagnostic aspiration because of danger of hypercalcemic crises due to FNA, which can be a life-threatening condition.

Risk factors clustering within the metabolic syndrome: a pattern or by chance?

INTRODUCTION: An accumulation of various cardiovascular risk factors has been noted to occur within the clinical diagnosis of metabolic syndrome. However, it remains unclear whether specific risk factors aggregate following a predefined pattern or whether this happens by chance. METHODS: This cross-sectional study involved 1715 adults, 37% males and 63% females, aged 34-80 years, who were consecutively recruited from cardiology and endocrinology outpatient clinics, and from internal medicine specialists in the primary healthcare physician office setting in Serbia, on a one-third basis. According to the AHA/NHLBI criteria, the actual prevalence of a combination of 3 or more of the following risk factors was determined: abnormal waist circumference, hypertension, high triglycerides, low high-density lipoprotein cholesterol, and abnormal fasting glucose. In addition, the prevalence of a corresponding combination of 3 factors was predicted from the prevalence of each factor in a given population, assuming that their combination occurred as the result of chance. RESULTS: The most frequent risk factor was hypertension (87%), followed by waist circumference (60%), dyslipidemia (55%), and abnormal fasting glucose level (50%). Metabolic syndrome was identified in 1135 participants (66.2%). The actual prevalence of the combination of increased waist circumference, elevated blood sugar and hypertension was found to be 5 times more frequent than would be expected to occur by chance (10% actual vs. 2% predicted; p<0.0001). CONCLUSIONS: A predefined aggregation pattern of risk factors within the metabolic syndrome was found for abdominal obesity, abnormal fasting glucose and hypertension. These risk factors do cluster more frequently than coincidental phenomena in the subjects of the given population, implying common underlying pathophysiological mechanisms.

Frax score calculations in postmenopausal women with subclinical hypothyroidism.

OBJECTIVE: The aim of our study was to evaluate the relationship between the elevated TSH and fracture risk in postmenopausal women with subclinical hypothyroidism for evaluation of individuals with a high risk for osteoporotic fractures. DESIGN: FRAX score calculation (10-year estimated risk for bone fracture) and measurement of bone markers (osteocalcin and beta cross-laps) were performed in 82 postmenopausal women with newly discovered subclinical hypothyroidism (mean age 59.17±7.07, mean BMI 27.89±3.46kg/m2, menopause onset in 48.05±4.09 years of age) and 51 matched controls (mean age 59.69±5.72, mean BMI 27.68±4.66kg/m2, menopause onset in 48.53±4.58 years of age) with normal thyroid function. RESULTS: The main FRAX score was significantly higher in the group with subclinical hypothyroidism than in the controls (6.50±4.58 vs. 4.35±1.56; p=0.001). Hip FRAX score was significantly higher in the group with subclinical hypothyroidism (1.11±1.94 vs. 0.50±0.46; p=0.030). There was no significant difference in bone markers: osteocalcin (23.99±12.63 vs. 21.79±5.34 ng/mL; p=0.484) and beta cross-laps (365.76±184.84 vs. 306.88±110.73 pg/mL; p=0.21) between the two groups. CONCLUSIONS: Postmenopausal patients with subclinical hypothyroidism, in particular of autoimmune origin, have higher FRAX scores and a thus greater risk for low-trauma hip fracture than euthyroid postmenopausal women. Our results point to the need to monitor postmenopausal patients with subclinical hypothyroidism for avoidance of fractures.

[Sleep and metabolic disorders].

In the 20th century, the prevalence of obesity has been increasing worldwide at an alarming rate and it is followed by an increase in the diseases for which obesity is major risk factor, like metabolic syndrome, diabetes type 2 and hypertension. These facts has been resulting in explosion of investigation devoted to explanation of pathogenetic mechanisms of this serious social and medical problems with the main idea to find adequate way of prevention as well as of treatment. Together with the observed epidemy of obesity and Type 2 diabetes, it was found parallel tendency for sleep curtailment, that was confirmed in numerous epidemiological studies, that coincide with its beginning and progress with this two epidemies. This facts lead to investigations with the idea to try to explaine possible mechanisms of the association between sleep curtailment, obesity, type 2 diabetes, metabolic syndrome and polycistic ovary syndrome. Having in mind that insulin resistance is one of the fundamental pathogenetic mechanism in these disorders, numerous studies were done with the aim to explain association between sleep curtailment and insulin resistance in obesity, Type 2 diabetes, metabolic syndrome and polycistic ovary syndrome. It was demonstrated that sleep curtailment may affect energy homeostasis of human organism with the effects on body weight increase through three different ways: appetite increase, prolongation of time for food intake and through decrease of energy expenditure. There are several postulated mechanism for the effect of sleep curtailment on development of insulin resistance as well as for predisposition for Type 2 diabetes. Among possible mechanism are included: increase of sympathetic neuronal acitvity, decreased cerebral utilisation of glucose, increase in evening cortisol values, growth hormone increase and disorder of neuroendocrine control of appetite which increases the risk for getting the body weight. Metabolic systems are of particular interest in the discussion of possible mechanisms to account for elevated inflammatory mediators during sleep deprivation, particularly because of the contributory role of insulin resistance in the development of impaired vascular function and increased inflammation.

Metformin: its emerging role in oncology.

Metformin is considered, in conjunction with lifestyle modification, as a first-line treatment modality for type 2 diabetes mellitus (DM). Recently, several clinical studies have reported reduced incidence of neoplastic diseases in DM type 2 patients treated with metformin, as compared to diet or other antidiabetic agents. Moreover, in vitro studies have disclosed significant antiproliferative and proapoptotic effects of metformin on different types of cancer. Metformin acts by activating AMP-activated protein kinase (AMPK), a key player in the regulation of energy homeostasis. Moreover, by activating AMPK, metformin inhibits the mammalian target of rapamycin complex 1 (mTORC1) resulting in decreased cancer cell proliferation. Concomitantly, metformin induces activation of LKB1 (serine/threonine kinase 11), a tumor suppressor gene, which is required for the phosphorylation and activation of AMPK. These new encouraging experimental data supporting the anti-cancer effects of metformin urgently require further clinical studies in order to establish its use as a synergistic therapy targeting the AMPK/mTOR signaling pathway.

[The influence of diet with reduction in calorie intake on metabolic syndrome parameters in obese subjects with impaired glucose tolerance].

INTRODUCTION: Current therapy of metabolic syndrome includes the assessment of cardiovascular risk together with control of high blood pressure, hyperlipidaemia and prevention of type 2 diabetes with adequate diet and increase in physical activity. AIM OF THE STUDY: To investigate the influence of medical nutritive therapy in obese people with impaired glucose tolerance risk factor for Type 2 Diabetes mellitus and potential consecutive lowering of cardiometabolic risk. MATERIAL AND METHODS: The 55 obese (body mass index greater than 30 kg/m2) subjects were divided into two groups, the study group A (n = 35), and the control group B (n = 20). Group A was on diet for a period of 12 weeks (1200-1500 kcal/day diet with 55-65% carbohydrates, 15-18% proteins and 22-23% predominantly unsaturated fats, and 20-40 g fibers/day.). Before and after 12 weeks the following parameters were determined: waist circumference, blood pressure, fasting plasma glucose, Index HOMA-IR, HDL cholesterol and triglycerides. RESULTS: After 12 weeks on low calorie diet in Group A there was a decrease in the waist circumference (p = 0.001); systolyc blood pressure (p = 0.001); diastolic blood pressure (p = 0.01); fasting blood glucose (p = 0.001); Index HOMA IR (p < 0.001); triglycerides (p < 0.001) and increase in HDL cholesterol (p < 0.05). CONCLUSION: These results suggest that implementation of low calorie-high fibers diet with balanced nutritive elements have a positive effect on visceral obesity, fasting glucose, lipid profile, and hypertension in obese people with impaired glucose tolerance and lead to consecutive lowering of cardiometabolic risk.

[Obesity and coronary heart disease: the mechanism of atherogenic impact].

The epidemic of obesity and overweight leads to many diseases including cardiovascular disease. Having an influence on function and heart structure, obesity and overweight are in connection with coronary heart disease, heart failure and sudden heart death. Cardiomyopathy in obesity (adipositas cordis) appears due to accumulation of adipose tissue between the heart muscle fibers and degeneration of myocites. The degeneration of myocardial could be due to lipotoxicity of free fatty acids in adipose tissue. The left ventricle hypertrophy, diastolic dysfunction, increasing blood volume, ejection fraction lead to heart failure. Obesity is low inflammation state with increased adipocitokine production from truncal adipose tissue which causes endothelial dysfunction and insulin resistance. Adipocitokines include leptin, adiponectin, resistin, visfatin, RBP 4 (retinol binding protein), angiotenzinogen, TNF alpha (tumor necrosis factor), PAI 1 (plazminogen activator inhibitor), fatty acids, sex steroids and different growth factors. Adipocitokines act synergistically or competitively with insulin, that explaining their impact on insulin resistance. Inflammatory citokines from adipose tissue could have influence on blood vessels endothelial function without their increase in plasma concentrations.