Possible synergistic effect of apoE and LRP1 genotypes on metabolic syndrome development in Serbian patients.

The modern way of life contributes to the higher frequency of a complex state medically called metabolic syndrome (MetS), which is an inevitable consequence of several most common diseases of modern civilization. Patients with MetS have three times higher risk of experiencing a heart attack or a stroke and twice higher possibility to die from them. Serbia holds the infamous third place in Europe in mortality from heart disease, just behind Russia and Ukraine. The study explores the correlation of every combination of genotypes of apoE (apolipoprotein E) and LRP1 (low density receptor- related protein 1) genes with presence of MetS, and the connection with each anthropometric and biochemical parameter in both tested groups. Study demonstrates the impact of genotype combinations on the emergence and development of the MetS in Serbia. 63 patients and 30 controls were included in the study, aged from 19 to 65. Each person genotype was determined by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) profile. Odds ratio (OR) values showed that the presence of apoE e3e4/LRP1 CC genotype combination of genotypes in patients multiplies the chance (7.6 times) for the occurrence of the MetS in comparison to the presence of other genotype combinations. Determining the genetic basis of MetS is one of the necessary steps in the prevention of disease, saving the cost of treatment, and in the design of targeted therapies.

DIABETIC NEPHROPATHY IN PREGNANT WOMEN WITH TYPE 1 DIABETES (MULTIPLE CASES REVIEW AND DISCUSSION).

Pregnancy in women with pre-existing diabetes is associated with a doubled, or even up to four-fold increased risk of preeclampsia, preterm delivery, and perinatal mortality compared to the risk observed in a background population. Diabetic nephropathy (DN) is a progressive disease that affects about one third of diabetic patients and is among the most frequent causes of the end stage renal disease (ESRD) worldwide. In the random population, it is present in up to 7% of women with type 1 diabetes mellitus (T1DM), and it represents the most common chronic kidney disease occurring in graviditas, complicating between 2.5% and 5% of T1DM pregnancies. Although maternal and perinatal morbidity and mortality rates in the pregnancies complicated with DN have declined over time, pregnancy related health complications are still more common in women with DN compared to those observed among diabetic women without DN. The adequate pre-pregnancy counseling and a tailored approach to the treatment of women with DN during the pregnancy are crucial for an avoidance of the adverse maternal and fetal outcomes. This paper is highlighting the impact of DN on maternal and fetal outcomes in women with T1DM, through presentation of the cases from a real-world clinical practice.

The LRP1 Gene Polymorphism is associated with Increased Risk of Metabolic Syndrome Prevalence in the Serbian Population.

The determination of genetic background in metabolic syndrome (MetS) represents one of the necessary steps to prevent the disorder, thus reducing the cost of medical treatments and helping to design targeted therapy. The study explores the association between individual alleles of the LRP1 gene and the diagnosis of MetS to find correlation between the low-density lipoprotein receptor-related (LRP1) gene polymorphism and each individual anthropometric and biochemical parameter. The study included 93 males and females, aged from 19 to 65, divided into two groups. The genotype of each person was determined from the restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) profile. Results indicated the association of the T allele form of exon 3 LRP1 gene with development and progression of MetS that further pointed out its negative impact on tested anthropometric and biochemical parameters. The presence of the T allele in patients multiplies the chance of occurrence of deviations from the reference values of body mass index (BMI), (4.24-fold) and low-density lipoprotein (LDL) (20.26-fold) compared to C allele carriers. The results showed that T allele presence multiplies the chance (4.76 fold) for the occurrence of MetS in comparison to C allele carriers. Correlation found that the T allele of the LRP1 gene with MetS determinants is not negligible, therefore, the T allele may be considered as a risk factor for MetS development.

HEART RATE VARIABILITY IN METABOLICALLY HEALTHY AND METABOLICALLY UNHEALTHY OBESE PREMENOPAUSAL WOMEN.

CONTENT: Metabolically healthy obese (MHO) individuals are characterized by absence of metabolic syndrome. The role of autonomic nervous system in metabolic profile of obese subjects has not been sufficiently investigated. OBJECTIVE: We analyzed heart rate variability (HRV) in MHO and metabolically unhealthy obese (MUO) premenopausal women. DESIGN: In 42 women metabolic profile was defined as MHO and MUO. SUBJECTS AND METHODS: For metabolic profile Wildman, IDF and HOMA-IR criteria were used. Autonomic nervous system activity was assessed by analysis of heart rate variability. RESULTS: There was no significant difference in HRV between MHO and MUO premenopausal women. In Wildman division, after adjustment for systolic blood pressure, RRNN and LF/HF were statistically different between groups (p=0.0001; p=0.029). In IDF division, adjusting for waist circumference, LF was significantly different between groups (p=0.004). In HOMA division, adjusting for HOMA, groups were different in SDNN (p=0.009), RMSSD (p=0.002), pNN50 (p=0.003), HF(p=0.002) and TP (p=0.005). CONCLUSIONS: Autonomic nervous system does not share the leading role in premenopausal women metabolic profile. The differences in HRV between MHO and MUO women depend on the metabolic health criteria. Systolic blood pressure, HOMA and waist circumference have significant effect on HRV differences between MHO and MUO premenopausal women.

Association between vitamin D hypovitaminosis and severe forms of COVID-19.

OBJECTIVE: Hypovitaminosis D may be associated with an increased susceptibility to infection, more severe COVID-19 forms, and a higher risk of death. The objective of this study was to investigate any possible connections between vitamin D status [as measured by serum 25-hydroxyvitamin D (25(OH)D) levels] and COVID-19 severity. PATIENTS AND METHODS: In 2021, a cross-sectional study of consecutive adult COVID-19 patients was conducted. Anthropometric data, comorbidities, hospital setting, length of stay, respiratory support, outcome data, and vitamin D status were all evaluated. RESULTS: The length of hospitalization among participants (n = 74; mean age 57.64 ± 17.83 years, 55.4% male) was 18.58 ± 10 days, the majority of the hospital setting was a medical ward (67.6%), and the respiratory support in the form of mechanical ventilation was represented by 12.2%. Hypertension (54.1%), obesity (64.9%), and overweight (64.9%) were the most common cardiometabolic risk factors. In the study group, 44.6% of participants had severe vitamin D deficiency (< 30 nmol/l), while 8.1% had vitamin D insufficiency (50 - 74.9 nmol/l). Furthermore, patients with severe COVID-19 (semi-intensive care unit, intensive care unit) had significantly lower serum 25(OH)D levels (32.9 vs. 20.5 nmol/l; p = 0.007). Participants with severe vitamin D deficiency were older and had more prevalent hypertension, requiring mechanical ventilation; 24.2% experienced a fatal outcome. CONCLUSIONS: Severe vitamin D deficiency may contribute significantly to the influence of other cardiometabolic risk factors in COVID-19.

Polymorphism Val103Ile of the melanocortin-4 receptor gene in the Serbian population.

The melanocortin-4 receptor (MC4R) plays an important role in weight and energy homeostasis and it is associated with lower risk to develop obesity and lower body mass index. The contribution of MC4R mutation to obesity in Vojvodina (Northern Province of Serbia), known as a region with the largest number of overweight people, has not been previously investigated. The objective of this study was to examine the Val103Ile polymorphism of MC4R in a population of Vojvodina and its association with obesity. The study was carried out in a group of 96 persons: 62 obese and 34 normal weight men and women. Anthropometric measurements and cardiovascular risk factors assessment were done. The genotypes were determined by PCR-RFLP. In our on going study, three subjects were heterozygous for Val103Ile mutation (3.12%), and one was homozygous for 103Ile allele (1.04%). Among obese patients no isoleucine allele homozygous was found. The frequencies of the 103Ile allele in a group of obese and normal weight persons were found to be 1.61 and 4.41%, respectively. Val103Ile polymorphism of melanocortin-4 receptor is unlikely to be a major cause of overweight and obesity in Vojvodina, but further studies on larger groups of patients are needed.

Risk characterization for mercury, dichlorodiphenyltrichloroethane and polychlorinated biphenyls associated with fish consumption in Serbia.

The aim of this work was to assess the risk due to mercury (Hg), dichlorodiphenyltrichloroethane (DDT) and non-dioxin-like polychlorinated biphenyls (ndl PCBs) intake via fish consumption in Serbia. We have developed 24 scenarios using four concentration levels (mean, maximum, 50th and 95th percentile) of contaminants, determined in 521 samples of fish products available on Serbian market; two consumption levels (Food and Agriculture Organization/World Health Organization data and recommendation of American Heart Association); and three body weights (5th, 50th and 95th percentile). All the values concerning the intake of DDT are below the corresponding health based guidance value. Calculated weekly intake of Hg using maximal concentration, intake of 340g/week and 5th percentile of body weight exceeded the provisional tolerable weekly intake (PTWI). When maximal and 95th percentile concentration of ndl PCBs was used, weekly intakes exceeded a "guidance value" with one exception i.e., when 95th percentile of concentration along with 95th percentile of body weight were used. Concerning Hg and ndl PCBs, when extreme concentrations were used, HIs exceeded the value of 1, indicating that fish and fishery products may pose a threat to consumer's health.

Morphological characteristics of abdominal adipose tissue in normal-weight and obese women of different metabolic profiles.

BACKGROUND AND AIMS: Morphological changes in adipose tissue reflect functional disorders that correlate with cardiometabolic complications of obesity. The metabolic risks vary among the obese individuals. Furthermore, normal-weight individuals are not necessarily metabolically healthy. Therefore, the aim of this study was to analyze morphological characteristics of the abdominal adipose tissue in normal-weight and obese individuals in regards to metabolic risks. METHODS AND RESULTS: The study group consisted of 30 overweight or obese and 20 normal-weight women undergoing elective surgery. Women of each group were divided into metabolically healthy and metabolically obese, based on the homeostasis model assessment of insulin resistance (HOMA-IR), triglyceride, total-, LDL- and HDL-cholesterol levels. The size and numerical density of adipocytes, as well as volume density of blood vessels in subcutaneous and visceral adipose tissue were compared among subgroups. The results showed hypertrophy of adipocytes of visceral adipose tissue in metabolically obese normal-weight women. At the same time, metabolically healthy obese women had smaller adipocytes in both depots in comparison with "at risk" obese women. The lowest volume density of blood vessels correlated with the largest diameter of adipocytes in "at risk" obese women indicating hypoxic changes in visceral adipose tissue. The observed differences of the adipose tissue morphology did not correlate with considerable phenotypic differences within either the normal-weight or obese women group. CONCLUSION: Changes in adipocyte size, cellular and vascular density of adipose tissue in relation with metabolic disorders, regardless of nutritional level, suggest limited capacity of fat deposition and adipose tissue response to hypoxia.

[Relation between the abdominal sagittal diameter, fat tissue distribution and metabolic complications]. / Odnos sagitalnog abdominalnog dijametra, distribucije masnog tkiva i metabolickih komplikacija.

Numerous epidemiological and clinical studies point to association of android type of obesity with metabolic complications, such as glyco-regulation, hyperlipoproteinemia, accelerated atherosclerosis which all lead to cardiovascular diseases. As the waist-hip ratio did not prove to be specific enough for determining association between fat tissue distribution and risk from development of obesity complications, measurement of the sagittal abdominal diameter has been established. Studies carried out up to now reveal that there is a better connection between these measurements and obesity complications. A group of 45 women was examined: 30 obese and 15 healthy non-obese women being the control group. The following was measured: body height, body weight, waist and hip circumferences, blood pressure, body mass index (BMI), waist-hip ratio (WHR) and a special caliper was used to measure the sagittal abdominal diameter. In order to study glyco-regulation all obese women underwent GTT (Glucose tolerance test) with determination of insulinemia; in regard to lipidic parameters total cholesterol, high-density lipoproteins (HDL) and low-density lipoproteins (LDL) cholesterol and index of atherosclerosis were determined. Gathered results show that in the group of obese women values of sagittal abdominal diameter were significantly higher than in the control group, while metabolic parameters show that in these patients there is a metabolism disorder of lipids and lipoproteins as well as hyperinsulinemia and reactive hyperinsulinemia and higher values of systolic and diastolic blood pressure. Our results of examination in the group of android obese women show that there is a significant association among values of sagittal abdominal diameter and lipid disorders, disorders of glycoregulation, especially hyperinsulinism and insulin resistance.

[Hypophyseal pseudomacroadenoma in primary hypothyroidism--2 case reports]. / Pseudomakroadenomi hipofize u primarnom hipotireoidizmu--povodom dva slucaja.

Primary hypothyroidism is often accompanied with hyperprolactinemia and if the untreated disease persists longer hypophyseal adenoma consisting of thyreotropic cells might develop. On the other hand, although rarely, simultaneous occurrence of primary hypothyroidism and hypophyseal prolactin adenoma might be encountered. If substitutional therapy, after the establishment of euthyroid status, does not eliminate clinical signs of hyperprolactinemia and normalize prolactin levels, a decision can be made in favor of hyperprolactinemia within primary hypothyroidism. In that case possible tumor changes in the hypophysis will show regressive tendency towards final disappearance. However if clinical signs and hyperprolactinemia persist after the establishment of euthyroid status, especially if accompanied with compressive signs this should be regarded as a coincidence of primary hypothyroidism and hypophyseal prolactin tumor. We report two female patients with primary hypothyroidism and hypophyseal pseudomacroadenoma.

[Case report of pheochromocytoma with an atypical localization]. / Slucaj feohromocitoma s atipicnom lokalizacijom.

One of the endocrine causes of arterial hypertension is pheochromocytoma, usually located in the adrenal gland medulla. Extra-adrenal tumor locations are seldom encountered, and this can considerably complicate the diagnostic procedure. If a distinct clinical manifestation exists, supported by the finding of elevated catecholamine values, it is essential to persistently and carefully search for the place of their increased production. Such an attitude is completely justified in regard to the knowledge that this endocrinologically conditioned hypertension can be permanently and successfully solved with a surgical procedure. A case of pheochromocytoma has been presented with an atypical mediastinal location, prolonged and complicated diagnostic procedure, which has been successfully solved by surgery.

[Drug therapy of obesity--results of treatment with dexfenfluramine]. / Medikamentska terapija gojaznosti--rezultati lecenja s deksfenfluraminom.

The paper presents the results of treatment in 22 obese persons with hypoenergetical nutrition of 4200 kJ with the simultaneous application of dexfenfluoramine in the daily dose of 30 mg in the course of three months. During this period of time an average weight loss of 7.5 kg was achieved, and a loss of 10 kg and more in one third of the patients. The controlled laboratory parameters did not show any significant deviations, and side effects in the form of mouth dryness and diarrhea were rare, and of a lighter intensity so that they did not demand the stop of therapy. When correctly indicated, dexfenfluoramine presents a valuable supplement in the therapeutic arsenal for obesity treatment, because thanks to its anorexigenic effect it eases the conducting of hypoenergetical nutrition and improves the treatment effect of this pathological condition.

[Epidemiologic analysis of emergency conditions in the diabetic population as observed in the work of emergency medical services in the area of Novi Sad]. / Epidemioloska analiza urgentnih stanja u dijabetesnoj populaciji posmatrana kroz rad hitne medicinske sluzbe na teritoriji Novog Sada.

The authors analyzed a group of 236 diabetic patients in the municipality of Novi Sad who asked for the help of the Emergency medical service of the Health Center "Novi Sad". A special emergency team which manages vitally endangered patients acted on their requests. After anamnestic data were gathered and physical examination done, electrocardiographic monitoring was performed. Glycemia was determined from semiquantitative analysis of the capillary blood, while glycosuria and acetonuria from urine. In regard to these patients the gathered results point to predominant presence of chronic, degenerative complications, especially of the cardiovascular apparatus. However, this was the case due to the fact that these were elderly persons (62.78 +/- 12.21 years of age) suffering from diabetes mellitus for about 8 years, which is sufficient for development of chronic, degenerative complications of diabetes. Although the studied group was metabolically unregulated (glycemia: 18.13 +/- 5.43 mmol/l, glycosuria positive in 4.54%, acetonuria in 2.20% of patients) there were no elements for diagnosis of some acute metabolic complications. The decrease of acute metabolic complications may be connected to better organization of the antidiabetic service in the municipality of Novi Sad. It is especially important to point out the occurrence of serious hypoglycemias caused by oral hypoglycemics (64.28%) which require, according to contemporary approach, a long-term hospital treatment.

[The role and significance of sagittal abdominal diameter in the determination of adipose tissue distribution]. / Mesto i znacaj sagitalnog abdominalnog dijametra u detekciji distribucije masnog tkiva.

Up-to-now trials have pointed out the importance of determining the type of obesity because the central type of obesity is joined with glucose tolerance disturbance, hyperinsulinemia and insulin resistance. The sagittal abdominal diameter proved to be the method of choice in routine clinical practice for visceral fat tissue detection. We examined a group of 60 females in whom, apart from standard measures (body weight, height, body mass index, perimeters of waist and hips), the sagittal abdominal diameter was measured by means of specially constructed caliper (Holtain Kahn Abdominal Caliper). Gathered parameters were compared with the results of an examination performed on 30 healthy females of normal body weight (control group). Results show a statistically significant higher sagittal abdominal diameter in females with central type of obesity in comparison to the control group, which points to greater quantity of visceral fat tissue in this type of obesity.

[Prolactin secretion in hyperthyroid individuals]. / Stanje prolaktinske sekrecije kod hypertireoidnih osoba.

Several endocrine and metabolic changes occur in hyperthyroidism, among which also changes in prolactin secretion are present. Causes are numerous. However, a decreased content of prolactin in secretory granules of the lactotrophic cells in the adeno-hypophysis gland, e.i. a decreased prolactin pool, should be especially emphasized. Prolactin secretion of the adeno-hypophysis gland was examined in 30 hyperthyroid patients. Normoprolacinaemia was diagnosed in basal conditions, but prolactin response was not so great during stimulation tests (test with thyrotropic hormone and eglonylic test) and suppression tests (L-DOPA and bromo-cryptic test). This finding suggests the existence of a decreased prolactin pool in hyperthyroidism.

[Psychological characteristics of obese persons with special reference to periods of modified fasting]. / Neke psiholoske karakteristike gojaznih osoba s posebnim osvrtom na period sprovodenja modifikovanog gladovanja.

It is well known fact that the results of modified fasting can be improved if the basic therapeutic method is combined with psychotherapeutic procedures. We have analyzed the data taken by a poll from 55 extremely obese women treated by modified fasting regimen. The results absolutely justify the above mentioned remark that radical reduction cures may cause critical moments most frequently recognized in hunger crisis when patients feel a need for conversion with medical staff. With no doubt, any help from a qualified person might be perfectly beneficial. Besides, obese persons are more inclined to depressive moods which may aggravate during these cures. In order to maintain the achieved result for a longer period of time if not for good, a continuous team work which include psychotherapeutic measures is of special significance. On the highest level it would be smart to establish an association of treated obese people, which would be a link between a patient and a professional.

[The metabolic X syndrome--4 case reports]. / Metabolicki sindrom X--povodom cetiri slucaja.

The study reviews current knowledge about metabolic X syndrome characterized by android obesity, arterial hypertension, insulin resistance with hyperinsulinemia and disturbed carbohydrate tolerance, a decrease of HDL cholesterol and an increase of the triglyceride rich VLDL particle level. The study describes 4 female patients having been diagnosed for this syndrome. Only an ontime and vigorous reduction of overweight, along with intensified physical activity can prevent later development of serious complications, first of all, in cardiovascular system.

Orlistat, a gastrointestinal lipase inhibitor, in therapy of obesity with concomitant hyperlipidemia.

Orlistat, a gastrointestinal lipase inhibitor, decreases fat absorption and thus it reduces caloric intake. The objectives of this placebo-controlled, double-blind, multicentre trial were to evaluate the efficacy of orlistat in terms of weight reduction, the effects on serum lipid levels and its tolerability profile. 119 obese patients (body mass index, BMI > or = 30 kg/m2) with hyperlipidemia (LDL-cholesterol > or = 4, 2 mmol/l) were randomized to receive either orlistat capsules 120 mg (n = 60) or placebo capsules (n = 59), three times daily, during 24 weeks. All patients were also on a mild hypocaloric diet. Mean weight reduction was 10.75 kg (10.7%) in orlistat group and 7.34 kg (7.5%) in placebo group. All serum lipid parameters improved in the orlistat group. The only adverse event more frequently noted with orlistat was stool fat. Orlistat in combination with diet provides increased weight loss than diet alone, improvements of serum lipids in subjects with hyperlipidemia and it has a good tolerability profile without systemic effects.

[Hyperinsulinemia as a key factor in the development of many metabolic disorders]. / Hiperinsulinemija kao kljucni faktor u nastanku brojnih metabolickih poremecaja.

Insulin resistance and consequent hyperinsulinemia present a frequent disorder and according to some investigations it is present in a quarter of whole population. Leaving aside numerous genetic syndromes caused by pronounced insulin resistance, this paper surveys the influence of specific arrangement of fat tissue in the development of this disorder, its role in insulin-independent form of diabetes, development of lipidic and lipoproteinic disorders, in the essential arterial hypertension, and finally, in the appearance of accelerated and premature atherosclerosis. Further intensive investigations of this problem will probably result in achieving a definite explanation of the importance of hyperinsulinemia as a marker of cardiovascular risk.