Branka Kovacev-Zavisic

Vitamin D and Dysfunctional Adipose Tissue in Obesity.

Vitamin D deficiency and dysfunctional adipose tissue are involved in the development of cardiometabolic disturbances (eg, hypertension, insulin resistance, type 2 diabetes mellitus, obesity, and dyslipidemia). We evaluated the relation between vitamin D and adipocytokines derived from adipose tissue. We studied 50 obese individuals who were classified into different subgroups according to medians of observed anthropometric parameters (body mass index, body fat percentage, waist circumference, and trunk fat mass). There was a negative correlation between vitamin D level and leptin and resistin (r = −.61, P < .01), while a positive association with adiponectin concentrations was found (r = .7, P < .001). Trend estimation showed that increase in vitamin D level is accompanied by intensive increase in adiponectin concentrations (growth coefficient: 12.13). In conclusion, a positive trend was established between vitamin D and the protective adipocytokine adiponectin. The clinical relevance of this relationship needs to be investigated in larger studies.

Risk factors for accelerated atherosclerosis in young women with hyperprolactinemia

Prolactin is a metabolic hormone. The hypothesis is that hyperprolactinemia can cause metabolic and inflammatory changes which are associated with accelerated atherosclerotic process, but the treatment of hyperprolactinemia with dopamine agonists, leads to reversibility of these processes. The first aim of this study was to determine whether hyperprolactinemia in premenopausal women is accompanied with the increase in body mass index (BMI), changes in body composition, lipid disturbances, the presence of inflammation and changes in systolic and diastolic blood pressure as risk factors for the development of early atherosclerosis. The second aim was to know whether the therapy of hyperprolactinemia and prolactin normalization lead to improvement of the observed parameters. Twenty female patients with prolactinomas, before and during treatment with dopamine agonists and 16 healthy controls were evaluated. Prolactin, BMI, total body fat, free fat mass, total body water, total cholesterol, triglycerides, high density lipoprotein (HDL), low density lipoprotein (LDL) and fibrinogen as well as systolic and diastolic blood pressure were measured at baseline and during the therapy. Hyperprolactinemic patients had pathologic and significantly higher levels of prolactin (PRL) than the controls (p=0.000). The BMI, body fat, total body water (TBW), total cholesterol, triglycerides, LDL were in normal range and higher in the patients than in the controls. HDL was lower in hyperprolactinemic females than controls. The difference was significant only for body fat (fat % p=0.006; fat kg p=0.009). Fibrinogen was slightly increased in patients compared with the controls. Hyperprolactinemic patients had normal, but increased levels of systolic and diastolic blood pressure compared with the controls. The difference with border significance was found in diastolic blood pressure (p=0.065). The correlation of PRL with all the observed parameters was positive apart from HDL, but relatively significant only with diastolic blood pressure (r=0.31). The therapy with dopamine agonists caused the decrease of all the observed parameters, but significant decreases was achieved only in BMI (p=0.028), total cholesterol levels (p<0.001) and LDL (p<0.002). Changes in BMI, body composition, serum lipids and lipoproteins, fibrinogen level and blood pressure confirm our hypothesis about the possible role of hyperprolactinemia in developing adverse metabolic disturbances which are reversible after treatment.

The Wnt/β-catenin Signalling Pathway Inhibitor Sclerostin is a Biomarker for Early Atherosclerosis in Obesity

BACKGROUND Sclerostin is an inhibitor of the wingless-type mouse mammary tumor virus integration site family/β-catenin signalling pathway (WβcSP), which plays an important role in bone metabolism and in vascular biology. It could act protective regarding atherosclerosis development through its effect on WβcSP in vascular cells. Nevertheless, results of studies analyzing association between circulating sclerostin level (CSL) and atherosclerotic diseases (AD) are showing conflicting results. The aim of this study is to test the value of CSL as a biomarker of subclinical carotid atherosclerosis (SCA) in obese persons. METHODS The cross-sectional study included 50 obese persons without previous history of diabetes and AD. Participants underwent adequate anthropometrical, ultrasound and laboratory examinations, including 2h 75 g oral glucose tolerance test (OGTT). RESULTS Only the presence of SCA significantly indirectly correlated with CSL (p<0.05). Based on the median value of CSL, we formed two groups: low CSL (CSL<7.9 pmol/l) and high CSL (CSL>7.9 pmol/l). There were no statistically significant differences in general (gender, age and current smoking) and anthropometrical characteristics (body mass index, waist circumference, systolic and diastolic blood pressure), inflammatory (total white blood cell count, erythrocyte sedimentation rate, fibrinogen, C-reactive protein and uric acid), glucose metabolism (fasting and 2h OGTT blood glucose, glycated hemoglobin and presence of dysglycemia) and lipid metabolism (low density lipoprotein cholesterol, high density lipoprotein cholesterol, triglycerides, apolipoprotein A-I, apolipoprotein B and lipoprotein (a)) parameters between low and high CSL groups. Low CSL group had significantly higher incidence of SCA (p<0.05). CONCLUSION CSL could serve as a useful biomarker of early atherosclerosis in obese persons without previous history of cardiometabolic disorders but the final conclusion requires further testing.

Physical activity and bone turnover in women with osteopenia

Background/Aim. Osteoporosis is a systemic disease of the skeleton characterized by a decrease in bone mass and changes in the bone structure. An increased tendency of the bone tissue for fractures occurs as a consequence of these changes. The initial phase of physiological aging of the bones that gradually leads to osteoporosis is osteopenia. This paper tracks the effects of a specific kind of physical exercise program in women with osteopenia. The aim was to quantify the impact of this program on: the concentration of bone metabolism blood markers, muscle strength, aerobic capacity, and physical dimensions. Methods. The sample consisted of 26 women in postmenopause (age 46–58) divided into two groups – experimental group (n = 15) and control group (n = 11). A combined program of exercise consisting of aerobic activities and strength training was applied in the experimental group, while the control group did not join in the exercise program. The program lasted for 7 weeks, three times a week with a break day between the trainings. The intensity of the aerobic training was in the span of 60% to 70% of heart rate reserve (HRR), and the intensity of the strength training was in the span of 60% to 85% of one repetitive maximum (1RM). Osteopenia was diagnosed prior to the experiment by applying a dual energy X-ray absorptiometry of the lumbar spine and the hip. The following was measured before and after the experiment: the level of biochemical markers in the serum [Beta-aspartic acid β-cross laps (CTx), total procollagen type 1 N-terminal peptide (tP1NP) and bone isoenzyme of alkaline phosphatase (ALP), 1RM of leg extensors, maximum oxygen consumption (VO2 max), bodily height and mass, and a calculated Body Mass Index (BMI). Results. Significant changes were determined only in the experimental group. During the experimental period, there was a significant increase of muscle strength and VO2 max, with a decrease of Beta-CTx concentration. No statistically significant changes were recorded in the control group. Conclusion. A 7week period of systematic exercise showed to be sufficient to increase muscle strength and VO2 max, partially also to decrease bone resorption, but insufficient to alter bone volume, bodily mass, and BMI.

Multiple Causes of Hyponatremia: A Case Report

Objective: To present a case with 4 different potential causes of hyponatremia. Clinical Presentation and Intervention: The patient presented with the following symptoms: nausea, vomiting, diarrhea, and dark urine after drinking large amounts of fluids that included alcohol and caffeine. Laboratory, microbiological, and morphological examinations revealed the existence of severe hyponatremia and acute poststreptococcal glomerulonephritis. The patient developed acute symptomatic seizures and coma. Gradual normalization of the sodium level led to a recovery of consciousness. Conclusion: Treatment with hypertonic sodium, fluid restriction, and antibiotics led to a complete recovery. In the case of multiple causes of hyponatremia, it is necessary to treat all causes.

Surrogates of Insulin Sensitivity and Indices of Cardiometabolic Profile in Obesity

BACKGROUND AND OBJECTIVES Obesity is often associated with insulin resistance (IR). We considered different IR indexes: the Homeostasis Model Assessment-Insulin Resistance (HOMA-IR) index, the two specimen (0 and 120 min) oral glucose tolerance test Matsuda Index (MI) and the Homeostasis Model Assessment-Adiponectin (HOMA-AD) index. These IR indexes were compared with indicators of the cardiometabolic profile. METHOD This cross-sectional study enrolled 60 obese individuals without previous history of diabetes. Anthropometrical, ultrasound and laboratory examinations were conducted. RESULTS All 3 indexes significantly correlated with indicators of central obesity, systolic and diastolic blood pressure, inflammation parameters, liver enzymes, HbA1c and some lipid parameters. The majority of correlation coefficients were the highest for HOMA-AD, but only the difference in correlation with waist circumference comparing with MI was statistically significant. HOMA-IR directly, and MI indirectly, significantly correlated with age, while HOMA-AD significantly directly correlated with the mean carotid artery intima media thickness (CAIMT). MI showed the best performances in predicting non-alcoholic fatty liver disease and pathologically increased CAIMT; HOMA-AD was the best in predicting metabolic syndrome, while HOMA-IR demonstrated the poorest performances in the prediction of all 3 conditions. There were no statistically significant differences in predicting performances of the analysed indexes. CONCLUSION The HOMA-AD and MI are not superior compared with the HOMA-IR, in the identification of obese individuals with a proatherogenic cardiometabolic profile.

Vitamin D and Dysfunctional Adipose Tissue in Obesity (Authors’ Reply)

Response to Editor to the Comment “Vitamin D Trials and Their Limitations” by Kucukseymen et al We thank Kucukseymen et al for their interest in our paper entitled “Vitamin D and Dysfunctional Adipose Tissue in Obesity.” We assessed vitamin D levels in obese individuals and evaluated the relationship between this vitamin and adipose tissue dysfunction. We showed that an increase in vitamin D level is accompanied by intensive increase in adiponectin concentrations. Therefore, we suggested that vitamin D supplementation may have a beneficial effect on obesity via modulation of adipocytokine secretion. However, a recent meta-analysis did not demonstrate such a link. We mentioned that previous studies reported that intra-abdominal obesity has a direct impact on increased cardiovascular risk due to the increased action of pro-inflammatory and proatherogenic cytokines. Kucukseymen et al mentioned that in our study, there were no details about serum inflammation markers such as highsensitivity C-reactive protein (hsCRP), white blood cells, and neutrophil-to-lymphocyte ratio (NLR). Our unpublished data show that hsCRP was significantly increased (P < .001) in obese compared to nonobese, control participants (control: 0.82 + 1.28 mg/L, obese: 7.67 + 6.92 mg/L). We also measured plasma level of nitric oxide (NO) as an inflammatory marker, and our unpublished data show that the level of NO was significantly increased (P < .001) in obese compared to nonobese control participants (control: 5.67 + 4.52 mmol/L, obese: 13.75 + 9.06 mmol/L). However, we agree with the comment that even if we measure hsCRP, white blood cell, and NLR, this will not be enough because some intestinal diseases (eg, Crohn disease or celiac disease) impair dietary vitamin D absorption. Kucukseymen et al mention that it would be helpful to know during which season this study was carried out. The study was carried out from March to June (ie, spring). We do not have specific information about sunlight exposure and vitamin D obtained from food. Finally, Pereira-Santos et al reported a systematic review and meta-analysis of studies that examined the relationships between vitamin D deficiency and obesity. As is in our study, they pointed out the fact that the prevalence of vitamin D deficiency was higher in obese participants compared to normal-weight participants. In addition, they concluded that the vitamin D deficiency was associated with obesity irrespective of age, latitude, and cutoff values to define vitamin D deficiency and the Human Development Index of the study location.

Influence of some traditional risk factors for osteoporosis on bone metabolism during substitution therapy of primary hypothyroidism

INTRODUCTION The relation between thyroid hormones and bone metabolism markers in hyperthyroidism is well known. Earlier studies indicate the possibility of bone metabolism acceleration during the excessive replacement therapy with l-thyroxin in hypothyroid patients especially in one with other risk factors for bone metabolism impairment. This study evaluated the effect of physiological l-thyroxine treatment on bone metabolism in patient with primary hypothyroidism. MATERIAL AND METHODS In the study group of 30 hypothyroid patients individual thyroxine replacement was performed targeting euthyroid status. Bone and calcium metabolism parameters (osteocalcin-OC, alkaline phosphates-ALP, C-terminal cross-linking telopeptide type l-CL, parathormone-PTH, Ca, ionized Ca, P), thyroid hormone levels (T3, T4, TSH) were measured before treatment and when euthyroid status was achieved. RESULTS AND DISCUSSION A significant treatment effect was observed for bone formation and resorption parameters before and during the therapy; OC (p = 0.000024), CL (p = 0.002648). Ionized calcium levels also showed significantly higher values in euthyroid status confirming bone metabolism acceleration during the l-thyroxine therapy (p = 0.020). Thus, calcium metabolism hormone regulators were not significantly different before and after the therapy; PTH (p = 0.27). Thyroid hormone levels showed significant correlation with bone metabolism parameters before the therapy whereas this correlation was not found during therapy because of different individual l-thyroxine doses. CONCLUSION It can be concluded that physiological doses of l-thyroxine therapy accelerate bone metabolism in hypothyroid patients. Thus, the argument against bone loss during physiological substitution is highly specific mutual correlation between bone formation and resorption parameters. These assumptions require further investigations in long-term prospective studies in patients on replacement l-thyroxine therapy.

Bone metabolism during substitution therapy of primary hypothyroidism

Introduction. The relation between thyroid hormones and bone metabolism markers in hyperthyroidism is well known. Earlier studies indicate the possibility of bone metabolism acceleration during the excessive replacement therapy with l-thyroxin in hypothyroid patients especially in one with other risk factors for bone metabolism impairment. This study evaluated the effect of physiological l-thyroxine treatment on bone metabolism in patient with primary hypothyroidism. Material and methods. In the study group of 30 hypothyroid patients individual thyroxine replacement was performed targeting euthyroid status. Bone and calcium metabolism parameters (osteocalcin-OC, alkaline phosphates-ALP, C-terminal cross-linking telopeptide type I-CL, parathormone-PTH, Ca, ionized Ca, P), thyroid hormone levels (T3, T4, TSH) were measured before treatment and when euthyroid status was achieved. Results and discussion. A significant treatment effect was observed for bone formation and resorption parameters before and during the therapy; OC (p=0.000024), CL (p=0.002648). Ionized calcium levels also showed significantly higher values in euthyroid status confirming bone metabolism acceleration during the l-thyroxine therapy (p= 0.020). Thus, calcium metabolism hormone regulators were not significantly different before and after the therapy; PTH (p=0.27). Thyroid hormone levels showed significant correlation with bone metabolism parameters before the therapy whereas this correlation was not found during therapy because of different individual l-thyroxine doses. Conclusion. It can be concluded that physiological doses of l-thyroxine therapy accelerate bone metabolism in hypothyroid patients. Thus, the argument against bone loss during physiological substitution is highly specific mutual correlation between bone formation and resorption parameters. These assumptions require further investigations in long term prospective studies in patients on replacement l-thyroxine therapy.