Anna Brona

The influence of endocannabinoid receptor 1 gene variations on anthropometric and metabolic parameters of women with polycystic ovary syndrome

INTRODUCTION Polycystic ovary syndrome (PCOS) is associated with an increasing number of metabolic comorbidities. About 50% of PCOS patients are obese, and insulin resistance affects up to 70% of these women. The endocannabinoid system contributes to human energy homeostasis. CNR1 is a biological candidate for human obesity and related metabolic disorders. The aim of this study was to determine the relationships between CNR1 polymorphisms and anthropometric and metabolic parameters in PCOS women. MATERIAL AND METHODS 130 women diagnosed with PCOS according to the Rotterdam criteria were recruited. The control group consisted of 70 healthy women. Medical history was taken, and physical examination as well as assessment of anthropometric (body mass, height, waist and hip circumference, BMI, waist-to-hip ratio [WHR]) and metabolic parameters (glucose and insulin, the insulin resistance index HOMA, lipid profile) was carried out. Genetic studies to detect six CNR1 gene polymorphisms were performed. RESULTS The total cholesterol and low-density lipoprotein (LDL) cholesterol levels in PCOS women carrying T/T genotype of rs2023239CNR1 polymorphism were higher than in those with C/T and C/C. There were no statistical differences in other metabolic parameters or in the value of BMI and WHR between the variants of rs2023239 CNR1 polymorphism. The other studied polymorphisms of the CNR1 gene were not associated with anthropometric or metabolic parameters in PCOS women. There were no differences in anthropometric or metabolic parameters between the variants of studied polymorphisms of the CNR1 gene in control women. CONCLUSIONS On the basis of our study, it seems that CNR1 polymorphisms are not associated with obesity and metabolic disorders, including insulin resistance, in PCOS women.

In contrast to matrix metalloproteinases, serum adiponectin concentrations increase after radioiodine treatment of thyrotoxicosis

BackgroundMatrix metalloproteinases (MMPs), together with their tissue inhibitors (TIMPs), remodel extracellular matrix under physiological and pathological conditions and are implicated in pathogenesis of cardiovascular diseases, cancer and in chronic inflammation. We have endeavoured to assess whether concentrations of MMPs, TIMPs, and anti-inflammatory adiponectin are altered by pharmacological treatment of acute thyrotoxicosis or by radioiodine therapy (RIT).Material and methodsWe measured serum concentrations of MMP-2, MMP-9, TIMP-1, TIMP-2, and adiponectin, TSH, free T4 (FT4) and free T3 (FT3) in 15 patients (4 males), age (years) 51.8±15.3 (mean±SD) with hyperthyroidism treated with thiamazole (Group 1) and in 20 subjects (2 males), treated for thyrotoxicosis with radioiodine, age 52.3±12.4 (Group 2), where blood samples were taken before RIT, visit 1 (V1), seven days post RIT, visit 2 (V2), and two to three months post RIT, visit 3 (V3).ResultsIn Group 1 there was no significant change in concentrations of MMP-2, MMP-9, TIMP-1, TIMP-2 or adiponectin, despite a fall in FT4 and FT3 (8.74±4.79 pg/ml vs 3.54±2.40 pg/ml, for FT3, and 4.48 ±2.21 ng/ml vs 1.02±1.07 ng/ml, for FT4, p<0.001). In Group 2 RIT did not cause any acute change in serum MMP-2, MMP-9, TIMP-1 and TIMP-2 or adiponectin (V1 vs V2). However, there was a significant increase in serum adiponectin [from 15201±8860 ng/ml (V1) to 19373±8657 ng/ml (at V3), p<0.05], and TIMP-2 at V3 [from 129±45 ng/ml (V1) to 149±38 ng/ml (V3), p<0.01]. There was no significant change MMP-2, MMP-9 and TIMP-1 between V1 and V3. There was a decrease in FT4 and FT3 from 24.4±15.4 pmol/l (V1) to 14.7±10.6 pmol/l (V3), and from 10.0±5.65 (V1) to 6.1±4.8 pmol/l (V2), p<0.01, for FT4 and FT3, respectively.ConclusionsRadioiodine therapy of thyrotoxicosis does not alter serum MMP-2, MMP-9 or TIMP-1 concentrations either acutely or after about three months of observation. An increase in serum adiponectin might reflect favourable effects of radioiodine administration on cardiovascular risk factors, while an increase in TIMP-2 (principal MMP-2 inhibitor) might lead to a decrease in free MMP-2 concentrations.

Effects of radioiodine administration on serum concentrations of matrix metalloproteinases, adiponectin and thrombospondin-1

BackgroundIn order to assess safety of radioactive iodine administration in the treatment of thyrotoxicosis, we measured concentrations of matrix metalloproteinase-2 (MMP-2), its main inhibitor – TIMP-2 (tissue inhibitor of MMP-2), matrix metalloproteinase-9 (MMP-9), its main inhibitor – TIMP-1, adiponectin, as well as pro-inflammatory and procancerogenic thrombospondin-1 (TSP-1).Design and patientsThe study involved 23 patients treated with radioiodine for thyrotoxicosis. Serum concentrations of TSH, free T4, free T3, MMP-2, MMP-9, TIMP-1, TIMP-2, total adiponectin and TSP-1 were measured by immunoassays just before radioiodine administration (visit 1), and subsequently, after 7 days (visit 2), 3 months (visit 3), 6 to 8 months (visit 4) and 15–18 months after radioiodine administration (visit 5).ResultsThere were no acute changes in serum concentrations of MMP-2, MMP-9, TIMP-1, TIMP-2, adiponectin and TSP-1 (visit 1 vs. 2). Subsequently, there was an increase in MMP-2 (from 393±106 ng/ml to 774±424 ng/ml), TIMP-1 (from 177±76 ng/ml to 296±118 ng/ml), and adiponectin (from 16442±9490 ng/ml to 23518±9840 ng/ml), visit 1 to 5, respectively (p < 0.01). Further analysis revealed no significant change in MMP-2/TIMP-2 ratio, but there was a significant decrease in MMP-9/TIMP-1 ratio (p < 0.05), suggestive of possible decrease in free MMP-9 concentrations.ConclusionsOur data reveal a significant and sustained increase in serum adiponectin, as well as possible decrease of free MMP-9 concentration after radioiodine administration. In contrast, there was no significant change of TSP-1. This might indicate overall safety of radioiodine treatment of thyrotoxicosis in terms of the risks of subsequent cardiovascular and neoplastic disease.

Thyroid Disorders in Climacteric Women

The appearance of menopause is combined with the incidence of many diseases typical of middle age, i.e., thyroid disorders, osteoporosis, and cardiovascular diseases. Thyroid disorders, especially subclinical hypothyroidism and subclinical hyperthyroidism, are frequent medical conditions among postmenopausal women. The prevalence of metabolic syndrome and osteoporosis significantly increases in postmenopausal women [1]. Many symptoms appear due to decreased estrogen level; however, chronic diseases influence quality of life as well. One of them is thyroid diseases, which are associated with risk factors for osteoporosis and cardiovascular diseases. Some symptoms of chronic diseases may mimic or modify the clinical expression of climacteric symptoms. Menopause and thyroid disease may present with similar symptoms, i.e., sweating, heart palpitations, insomnia, irritability, or mood changes, which suggest menopause, hyperthyroidism, or both. In addition, weight gain, constipation, skin atrophy, and hair atrophy are climacteric symptoms as well as symptoms of hypothyroidism [2]. With aging, the level of thyroid-stimulating hormone (TSH) remains within normal range and occasionally has a tendency to increase [3]. Reduction of thyroid iodine uptake, free thyroid hormone synthesis, and catabolism of free thyroxine (FT4) are observed. In addition, reverse triiodothyronine (rT3) level increases [3].

Why Metformin Is so Important for Prevention and Therapy in Climacteric Women

Metformin (MET) is the most widely used oral antidiabetic agent, currently recommended as first-line therapy not only for all newly diagnosed type 2 diabetes mellitus (DM2) patients but also for prediabetic syndromes associated with insulin resistance (IR). MET has been used in the treatment of DM2 for over 50 years and has been found to be safe and efficacious both as monotherapy and in combination with other oral antidiabetic agents and insulin. Its major clinical advantage is not causing hypoglycemia or weight gain. Besides its use in DM2, there is interest in the use of MET for the treatment of polycystic ovary syndrome, diabetic nephropathy, and gestational diabetes [1]. This drug also counteracts the cardiovascular complications associated with DM2 [2]. Another possible benefit for MET use is the prevention of DM2 in obese prediabetic patients, antiproliferative effect associated with decreased cancer risk and improved cancer prognosis, and anabolic impact on bones [3, 4].

Do thyroid peroxidase antibodies influence risk of cardiovascular diseases before and after treatment of hyperthyroidism

We have evaluated how levels of predictors of the cardiovascular risk such as: glucose, insulin, total cholesterol, high-density cholesterol, low-density cholesterol and triglycerides as well as adiponectin, fibrinogen, D-Dimers and CRP changed 24-28 weeks after treatment of hyperthyroidism in women with low and high titer of antibodies, and if their levels were different in these groups before and after treatment of hyperthyroidism. We compared also fT4 level before and after treatment in study groups. We investigated 35 postmenopausal women (non-smoking, aged 51-69 years) with subclinical and overt hyperthyroidism. We divided them into two groups according to titer of thyroid peroxidase antibodies: with low titer of antibodies (27 women) and high titer of antibodies (8 women). Statistical analysis revealed no difference in lipids profile, coagulation-fibrinolytic system, glucose, insulin, CRP and adiponectin level (before and after treatment) between groups with low and high titer of antibodies. No difference in fT4 level before and after treatment was found. In women with low titer of antibodies significant decrease was observed only in fT4 level (20.38 vs. 13.23 ng/ml). Levels of other factors did not differ before and after treatment. Triglycerides level decreased (133.00 vs. 89.13 mg/dl) and CRP level increased (2.95 vs. 4.48 mg/l) significantly after treatment in women with high titer of antibodies. Data suggest that it is more difficult to become euthyroid for women with hyperthyroidism and high titer of antibodies (there is no significant difference between fT4 level before and after treatment). Changes in metabolic profile and increase in inflammatory process are observed in women with hyperthyroidism and high titer of antibodies.