The Interconnection between Carotid Intima-Media Thickness and Obesity: Anthropometric, Clinical and Biochemical Correlations.

Background and Objectives: Carotid intima-media thickness (CIMT) and obesity are considered independent determinants of cardio- and cerebrovascular events. The aim of our study was to investigate the effect of obesity on CIMT and to define which traditional cardiovascular risk factors correlate the most with CIMT values in patients with obesity. Materials and Methods: Anthropometric measurements were collected for the whole study group, as well as body composition and blood pressure data, and biochemical blood analyses were also performed. Results: Although our study group was significantly older according to vascular compared with chronological age, the mean CIMT values were lower when compared with the reference values. We found a statistically significant correlation of CIMT with chronological and vascular age, systolic blood pressure, fasting glucose, total cholesterol and triglyceride levels, waist-to-hip ratio, waist circumference, body muscle mass and skeletal muscle mass index. Atherosclerotic Cardiovascular Disease (ASCVD) risk assessment and SCORE (Systematic COronary Risk Evaluation) showed significant positive correlations, but there was only a weak correlation of ASCVD with CIMT. Conclusions: To deduce, since no diagnostic tool currently includes body weight as an individual risk factor, further trials are highly needed to determine if SCORE, SCORE2, ASCVD risk assessment or CIMT would be the most accurate and relevant diagnostic tool for prediction of risk for future CV events in patients with obesity.

FTO Gene Polymorphisms at the Crossroads of Metabolic Pathways of Obesity and Epigenetic Influences.

In this review, we summarize the current state of knowledge on the fat mass and obesity-associated (FTO) gene and its role in obesity. The FTO-encoded protein is involved in multiple molecular pathways contributing to obesity as well as other metabolic complexities. This review emphasizes the epigenetic influence on the FTO gene as a new approach in the treatment and management of obesity. Several known substances have a positive effect on reducing FTO expression. Depending on which variant of the single nucleotide polymorphism (SNP) is present, the profile and level of gene expression changes. Implementation of environmental change measures could lead to reduced phenotypic manifestation of FTO expression. Treating obesity through FTO gene regulation will have to include various complex signal pathways in which FTO takes part. Identification of FTO gene polymorphisms may be useful for the development of individual obesity management strategies, including the recommendation of taking certain foods and supplements.

Combined Approach: FFQ, DII, Anthropometric, Biochemical and DNA Damage Parameters in Obese with BMI ≥ 35 kg m-2.

Although obesity with its comorbidities is linked with higher cancer risk, the data on genome stability in the obese/severely obese are scarce. This is the first study with three DNA damage assessment assays (Fpg-modified and alkaline comet assays and micronucleus cytome assay) performed on a severely obese population (n = 53) where the results were compared with daily intake of food groups, nutrient intake, dietary inflammatory index (DII), and anthropometric and biochemical parameters usually measured in obese individuals. Results demonstrated the association between DNA damage levels and a decrease in cell proliferation with anthropometric measurements and the severity of obese status, together with elevated levels of urates, inorganic phosphates, chlorides, and hs troponin I levels. DII was connected with oxidative DNA damage, while BMI and basal metabolic rate (BMR) were associated with a decrease in cell proliferation and DNA damage creation. Measured daily BMR and calculated daily energy intake from the food frequency questionnaire (FFQ) demonstrated no significant difference (1792.80 vs. 1869.86 kcal day-1 mean values). Groups with higher DNA damage than expected (tail intensity in comet assay >9% and >12.4%, micronucleus frequency >13), consumed daily, weekly, and monthly more often some type of food groups, but differences did not show a clear influence on the elevated DNA damage levels. Combination of all three DNA damage assays demonstrated that some type of damage can start earlier in the obese individual lifespan, such as nuclear buds and nucleoplasmic bridges, then comes decrease in cell proliferation and then elevated micronucleus frequencies, and that primary DNA damage is not maybe crucial in the overweight, but in severely obese. Biochemically changed parameters pointed out that obesity can have an impact on changes in blood cell counts and division and also on genomic instability. Assays were able to demonstrate groups of sensitive individuals that should be further monitored for genomic instability and cancer prevention, especially when obesity is already connected with comorbidities, 13 different cancers, and a higher mortality risk with 7-10 disease-free years loss. In the future, both DNA damage and biochemical parameters should be combined with anthropometric ones for further obese monitoring, better insight into biological changes in the severely obese, and a more individual approach in therapy and treatment. Patients should also get a proper education about the foodstuff with pro- and anti-inflammatory effect.

Association of Vitamins D, B9 and B12 with Obesity-Related Diseases and Oral Microbiota Composition in Obese Women in Croatia.

Research background: Oral microbiota has become an important factor in obesity, but its association with obesity-related diseases and serum 25-hydroxy vitamin D [25(OH)D] and B complex amounts is still uncertain. The main aim of the paper is to determine the variation in oral microbiota composition as a response to the vitamin status and obesity-related diseases in obese females from Croatia. We hypothesized that the prevalence of probiotic or pathogenic bacteria in the oral cavity of obese women in Croatia depends on the amounts of vitamin B9 (folic acid), B12 and 25(OH)D in serum and/or hypertension, diabetes and prediabetes diagnosis. Experimental approach: To test the defined research hypothesis, female individuals with body mass index (BMI)≥30 kg/m2 (N=70) were recruited to participate in this study. Obese women were divided into groups according to BMI value, diagnosis of obesity-related diseases and amount of micronutrient in blood. For the quantitative determination of folic acid, vitamin B12 and 25(OH)D in serum, an electrochemiluminescence protein binding assay (ECLIA) was performed. Microorganisms isolated from the saliva of obese women were analyzed by MALDI-TOF mass spectrometer. Results and conclusions: The presented results do not support the hypothesis that the prevalence of probiotic or pathogenic bacteria in the oral cavity of obese women in Croatia depends on the amount of micronutrients. On the other hand, hypertension and diabetes/prediabetes favour the growth of oral pathogens, specifically increased levels of Candida sp. Novelty and scientific contribution: To the best of our knowledge, this is the first study showing the relationship between obesity, micronutrient amount, oral microbiota composition, and the incidence of obesity-related disease. We included only obese women from Croatia, so it is regionally specific. Also, we have shown that oral microbiota composition is not connected with micronutrient deficiencies but only with obesity-related diseases.

Utility of Screening Questionnaires to Detect Obstructive Sleep Apnea in Patients with Obesity.

BACKGROUND: Obesity is one of today's most concerning health problems due to increased cardiovascular risk, which is still the leading cause of death. Obstructive sleep apnea syndrome (OSAS) is certainly one of the important risk factors that links obesity and cardiovascular risk. There is a great need to evaluate obstructive sleep apnea (OSA) in obese patients. Today, there are easily available and applicable questionnaires (Epworth Sleepiness Scale (ESS), STOP, STOP-Bang (SBQ), Insomnia Severity Index (ISI) and Pittsburgh Sleep Quality Index (PSQI)) that could be very useful in clinical practice for this very purpose. The aim of this paper is to investigate the sensitivity and specificity of the questionnaires for OSA screening in obese patients with and without OSA. PATIENTS AND METHODS: This cross-sectional study was carried out in the tertiary healthcare centre. The following questionnaires were used: ESS, STOP, SBQ, ISI, PSQI. 70 (58 female) adult patients with obesity (body mass index (BMI) > 30 kg/m2) were included. RESULTS: SBQ showed sensitivity of 75%, specificity of 75% at cut-off of 5.5 with the Youden index of 0.5, while PSQI had sensitivity of 78%, specificity of 67% at cut-off of 17.75 with slightly smaller Youden index 0.45. STOP and ESS had a sensitivity of 77% and 75%, respectively but with an even smaller Youden index (0.23 and 0.21), and ISI had the lowest sensitivity of 59% and the lowest Youden index (0.13) of the questionnaires we examined. CONCLUSION: Our study results suggest that SBQ and PSQI are best screening tools in detecting OSA in patients with obesity. Further study of these questionnaires and possible modifications are certainly important for future research.

Sexual Dysfunction in Croatian Patients with Obesity.

BACKGROUND: Patients with obesity may have symptoms of sexual dysfunction (SD). Little is known about these symptoms in obese patients in Croatia and the aim of this study was to explore them. SUBJECTS AND METHODS: This was a cross-sectional study carried out in tertiary healthcare centre at the Croatian Obesity Treatment Referral Center in University Hospital Center of Zagreb. 103 patients (72 female, 31 male, mean age 48.7±11.87 years, mean BMI 40.42) were included. SD symptoms were assessed using the internationally acclaimed questionnaire Arizona Sexual Experience Scale (ASEX), that was recently validated for Croatian language. Patients were also administered a questionnaire, prepared for this purpose, that enquired about their previous known chronic disorders. Statistical analyses included t-test, chi-squared test and bivariate Pearson's correlations. RESULTS: Average total response on the questionnaire was 12.4 (women 13.2, range 3-30; men 10.6, range from 5-19). A total score of 19 or more was present in 5 (4.8 %, range from 19-30, average 22.4; 1 man, 4 women), at least one question with a score 5 or greater on any item was found in 36 (34.9 %, 5 men, 31 women), while a score of 4 or more on three items was found in 20 patients (19.4 %, 2 men, 18 women). Overall median response was 3 (range 1-6). Women were found to have more pronounced symptoms of SD (p<0.05). The overall results on ASEX were found to be in significant correlation with regard to depression (r=0.22, p=0.03), as well as anxiety (r=0.2, p=0.04). Significant correlations were also found with regard to age (r=0.31), mobility (r=0.25), and pain/uneasiness (r=0.22) (p<0.05). CONCLUSIONS: This study brings valuable observations on the presence of SD symptoms in obese patients in Croatia. SD symptoms were found to be present in up to one-third of our patients, more pronounced in women, and in significant correlation with depression and anxiety. However, median response on ASEX suggests that overall SD symptoms in our group of patients are not that expressed.

Count Ivan VIII Draskovic: a case of Graves' orbitopathy?

There is a possibility that Count Ivan VIII Draskovic (1740-1787), a member of one of the oldest and most famous Croatian noble families, had Graves' disease and suffered from a thyroid disorder. Our suspicions were aroused by certain data, including his personal history, his lifestyle, including use of tobacco and iodine, as well as stress, and, finally, two portraits. If he was affected by Graves' disease and orbitopathy, his poor health might have been a consequence of thyroid disease, which was further worsened by injury and tobacco use. Later spontaneous remission could have been induced by higher iodine intake and bed rest.

Lower Urinary Tract Symptoms in Croatian Obese Patients.

BACKGROUND: Patients with obesity may experience lower urinary tract symptoms (LUTS). Little is known about these symptoms in obese patients in Croatia. The aim of this study was to asses LUTS in this group of patients. SUBJECTS AND METHODS: This cross-sectional study was carried out in a tertiary healthcare centre. 111 participants were included (81 women and 30 men, age 23-78 years), with BMI>30 kg/m2. LUTS were evaluated using International consultation on incontinence questionnaires (ICIQ) investigating symptoms of overactive bladder (OAB) and urinary incontinence (UI): ICIQ-OAB and ICIQ-UI Short Form (SF). We evaluated also some of the questions on the EQ-5D-5L questionnaire. RESULTS: On ICIQ-OAB patients most often reported:UI (46.85% (N=52)), nocturia (42.34% (N=47)) and increased frequency of urination (34.23% (N=38)), and on ICIQ-UI SF: UI when coughing and sneezing (44.44% (N=32)), urgency UI (43.06% (N=31)) and UI during exercise/physical activity (22.22% (N=16)). Women were found to be more significantly affected by OAB symptoms (p<0.05). Significant correlations were found between the overall results on ICIQ-OAB and hypertension (r=0.32). CONCLUSIONS: The results of this study confirm that obese patients in Croatia experience LUTS as well. A higher incidence of LUTS was found among women and gender-independent among hypertensive obese patients.

Vitamin B12 Supplementation in Addition to Folic Acid and Iron Improves Hematological and Biochemical Markers in Pregnancy: A Randomized Controlled Trial.

Vitamin B12 plays an important role in cell division and is of vital importance during pregnancy. Iron and B12 deficiency increase the risk of neonatal morbidity and the outcome of the overall pregnancy. The aim of our study was to analyze whether the use of vitamin B12, with standard supplements of folic acid and iron among nonanemic pregnant women, will result in improvements of hemogram parameters in terms of hematological and biochemical markers. Study participants were 200 healthy pregnant women, randomized into an intervention group and a control group, recruited from gynecological primary care practices in Split, Croatia. In addition to standard supplementation (350 mg/day ferrous iron, 5 mg folic acid), participants in the intervention group were given 5 µg of vitamin B12 each morning for 100 days. Both biochemical and hematological measurings were conducted in two intervals: 8th-10th week of gestation and then again in the 34th-36th week of gestation. Participants in the control group were given only standard-of-care iron and folic acid supplementation. Significantly lower values of haptoglobin postintervention, compared with baseline, were found only in the intervention group; for erythrocytes, significantly lower values postintervention were found only in the control group. For parameter hematocrit, we found decreased values postintervention, compared with baseline, in both intervention and control group; however, this decrease was within the reference range for the control group, whereas it was above the reference range for the intervention group. The results of this study indicated that intervention with vitamin B12 in pregnancy reduces possibilities of the onset of anemia, but within reference range.

Decrease in growth hormone and insulin-like growth factor (IGF)-1 release and amelioration of acromegaly features after rosiglitazone treatment of type 2 diabetes mellitus a patient with acromegaly.

A 28-year-old woman with clinical features of acromegaly and diabetes mellitus was admitted to our Reference Center for Clinical Neuroendocrinology and Pituitary Diseases at Sisters of Mercy University Hospital, Zagreb, Croatia. Magnetic resonance scan of the brain showed pituitary macroadenoma. After transsphenoidal resection, histological analysis confirmed it was a growth hormone (GH)-secreting pituitary adenoma. The tumor could not be completely removed, but the hormonal status normalized. A month after the surgery, octreotide was introduced because of a further increase in GH and insulin-like growth factor-I (IGF-I), but discontinued after a week due to intolerance. Alternative treatment with oral antidiabetic agent, rosiglitazone, was introduced two weeks after octreotide was discontinued, and the fasting blood glucose concentration decreased from 8.4 mmol/L before the treatment to 6.7 mmol/L after 90 days of treatment. The concentration of GH and IGF-I in the week before rosiglitazone was introduced was 5.96 ng/mL and 990 ng/mL, respectively, and decreased to 2.92 ng/mL and 180.0 ng/mL, respectively, after 90 days of treatment. There was also a pronounced improvement in acromegalic features. It is possible that rosiglitazone induced the decrease in GH and IGF-I concentrations and its role in the long-term medical therapy of patients with pituitary tumors should be further investigated.

Incidence of pituitary tumors in the human population of Croatia.

Pituitary tumors are rare tumors (less then 10%) of the central nervous system (CNS), which malignicity depends on their localization, meanwhile, their biological nature is benign. The diameter they have is mostly less then 10 mm (microadenomas), but sometimes could be 10 mm (macroadenomas) to 5 cm and more and then are usually nonfunctional (about 20% of all pituitary tumors). Clinical presence depends on their localisation and hormonal activity. In the Center for Clinical Neuroendocrinology and Pituitary Diseases, in the last working 10 years, there were treated and examined 504 patients from Croatia, all with pituitary tumors: 182 patients with prolactinomas, 137 with acromegaly, 70 with Morbus Cushing (Mb. Cushing), and 115 patients with nonfunctional pituitary tumors. The patient's classification is based on regional (Mediterranean and continental region, 20 counties) and the state level. In our analysis we haven't found difference in incidence of tumors between Mediterranean and continental region.