Interleukin-6 and its considerable role in the pathogenesis of thyrotoxicosis-related disturbances of bone turnover in postmenopausal women

Background: Thyrotoxicosis is more frequent in postmenopausal women than in the general population, effectively accelerating bone turnover. Interleukin-6 has been shown to be involved in the pathogenesis of bone disorders. Thus, the aim of the present study was to assess the role of IL-6 and its soluble receptor in the pathogenesis of thyrotoxicosis-related disturbances of bone turnover in oestrogen-deficient women. Material and methods: The study was carried out in 40 subjects with toxic nodular goitre in three groups: Group 1 &#8212; 13 premenopausal females, mean age 36 &#177; 15 years (PremTx&#8594;PremEu); Group 2 &#8212; 12 postmenopausal females, mean age 66 &#177; 14 years (PostTx&#8594;PostEu); and Group 3 &#8212; 15 males, mean age 45 &#177; 21 years (MTx&#8594;MEu). Overt thyrotoxicosis and euthyreosis after treatment with thyrostatics were confirmed by thyrotropin, free thyroxine and free triiodothyronin concentrations. Serum levels of bone turnover markers: TRACP5b and osteocalcin as well as serum IL-6 and IL-6sR were determined using ELISA kits. Results: TRACP5b/osteocalcin quotient was significantly elevated in the PostTx females compared to the PremTx women (p < 0.02). There was a positive correlation between serum TRACP5b and osteocalcin in the studied patients (R = 0.45, p < 0.001). Levels of serum IL-6 values were significantly elevated in PostTx: 3.0 (2.14&#8211;6.40) and MTx: 2.24 (1.60&#8211;5.10), compared to PremTx females: 1.39 (0.96&#8211;2.14) (p < 0.01 and p < 0.05 respectively). There were significant positive correlations between IL-6 and IL-6sR concentrations (R = 0.22, p < 0.05) and between IL-6sR and TRACP5b serum levels (R = 0.23, p < 0.05). Conclusions: The results of our study suggest that interleukin-6 plays a considerable role in the pathogenesis of thyrotoxicosis-related disturbances of bone turnover in oestrogen-deficient women. (Pol J Endocrinol 2011; 62 (4): 299&#8211;302)Wstęp: Nadczynność tarczycy występuje częściej u kobiet po menopauzie w porównaniu z populacją ogólną, skutecznie przyspieszając obrót kostny. Wykazano, że interleukina 6 (IL-6) odgrywa istotną rolę w regulacji obrotu kostnego. Uwzględniając ten fakt, celem obecnej pracy była próba oceny roli IL-6 i jej rozpuszczalnego receptora w patogenezie zaburzeń obrotu kostnego w przebiegu tyreotoksykozy u kobiet po menopauzie. Materiał i metody: Badanie przeprowadzono u 40 osób z nadczynnym wolem guzkowym w 3 grupach: 1 &#8212; 13 kobiet przed menopauzą w wieku 36 &#177; 15 lat (PremTx&#198;PremEu), 2 &#8212; 12 kobiet po menopauzie w wieku 66 &#177; 14 lat (PostTx&#198;PostEu) i 3 &#8212; 15 mężczyzn w wieku 45 &#177; 21 lat (MTx&#198;MEu). Stan czynnościowy tarczycy potwierdzono oznaczeniem TSH, fT3 i fT4 w surowicy. Markery obrotu kostnego: TRACP5b i osteokalcyna oraz IL-6 i IL-6sR w surowicy, oznaczono zestawami ELISA. Wyniki: Iloraz TRACP5b/osteokalcyna był istotnie zwiększony u kobiet PostTx w porównaniu z grupą PremTx (p < 0,02). Stwierdzono dodatnią korelację między TRACP5b i osteokalcyną (R = 0,45, p < 0,001). Stężenie IL-6 było istotnie zwiększone w grupie PostTx: 3,0 (2,14&#8211;6,40) i MTx: 2,24 (1,60&#8211;5,10) w porównaniu z odnotowanym u kobiet z grupy PremTx: 1,39 (0,96&#8211;2,14) (odpowiednio: p < 0,01 i p < 0,05). Wykazano istotną dodatnią korelację pomiędzy IL-6 i IL-6sR (R = 0,22, p < 0,05) oraz pomiędzy IL-6sR i TRACP5b (R = 0,23, p < 0,05). Wnioski: Podsumowując, wyniki obecnej pracy wskazują, że IL-6 odgrywa ważną rolę w patogenezie zaburzeń obrotu kostnego w przebiegu tyreotoksykozy u kobiet po menopauzie. (Endokrynol Pol 2011; 62 (4): 299&#8211;302

Phenotype variability and neonatal diabetes in a large family with heterozygous mutation of the glucokinase gene

Monogenic diabetes caused by mutations in the glucokinase gene (GCK-MODY) is usually characterized by a mild clinical phenotype. The clinical course of diabetes may be, however, highly variable. The authors present a child with diabetes manifesting with ketoacidosis during the neonatal period, born in a large family with ten members bearing a heterozygous p.Gly223Ser mutation in GCK. DNA sequencing and multiplex ligation-dependent probe amplification were used to confirm GCK mutation and exclude other de novo mutations in other known genes associated with monogenic diabetes. Continuous glucose monitoring (CGM) was used to assess daily glycemic profiles. At the onset of diabetes the child had hyperglycemia 765 mg/dl with pH 7.09. Her glycated hemoglobin level was 8.6% (70.5 mmol/mol). The C-peptide level was below normal range (<0.5 pmol/ml) at onset, and the three- and 6-month follow-up examinations. Current evaluation at age 3 still showed unsatisfactory metabolic control with HbA1c level equal to 8.1% (65.0 mmol/mol). CGM data showed glucose concentrations profile similar to poorly controlled type 1 diabetes. The patient was confirmed to be heterozygous for the p.Gly223Ser mutation and did not show any point mutations or deletions within other monogenic diabetes genes. Other family members with p.Gly223Ser mutation had retained C-peptide levels and mild diabetes manageable with diet (five individuals), oral hypoglycemizing agents (five patients), or insulin (one patient). This mutation was absent within all healthy family members. Heterozygous mutations of the GCK gene may result in neonatal diabetes similar to type 1 diabetes, the cause of such phenotype variety is still unknown. The possibility of other additional, unknown mutations seems to be the most likely explanation for the unusual presentation of GCK-MODY

The association of thyroid-stimulating hormone (TSH) and free thyroxine (fT4) concentration levels with carbohydrate and lipid metabolism in obese and overweight teenagers.

Introduction: Obesity has increased rapidly among children and adolescents during the last 30 years. Paediatric patients with a BMI above the 85th centile are more often diagnosed with increased TSH levels than are children with proper body weight. Material and methods: The data of 961 overweight and obese children, aged 13 years, recruited in four cities in Poland as part of PoZdro!, a two-year prophylactic program, were analysed to observe the relationship between serum TSH and fT4 concentration and carbohydrate and lipid metabolism parameters, as well as anthropometric parameters.Results: TSH concentration in the study group was positively correlated, whereas fT4 concentration was negatively correlated with WHR and WHtR values, fasting serum glucose concentrations and one-hour glucose concentration, fasting serum insulin concentrations, one-hour and two-hour insulin concentration, ALT serum activity, as well as total cholesterol, LDL cholesterol, and triglyceride serum concentrations. An increased risk of metabolic syndrome was diagnosed previously in patients with TSH concentrations &gt; 2.5 mUI/L. Conclusions: TSH concentration in the upper half of the current reference range (&gt; 2.50 mIU/L) is associated with an increased risk of lipid and carbohydrate metabolism disorders and therefore increased chances of developing metabolic syndrome. It seems advisable to regularly monitor thyroid function in overweight and obese paediatric patients

Differential regulation of serum microRNA expression by HNF1β and HNF1α transcription factors.

We aimed to identify microRNAs (miRNAs) under transcriptional control of the HNF1β transcription factor, and investigate whether its effect manifests in serum.This article is freely available via Open Access. Click on the 'Additional Link' above to access the full-text via the publisher's site.Published (Open Access

The Role of Forkhead Box O in Pathogenesis and Therapy of Diabetes Mellitus

Type 2 diabetes is a disease that causes numerous complications disrupting the functioning of the entire body. Therefore, new treatments for the disease are being sought. Studies in recent years have shown that forkhead box O (FOXO) proteins may be a promising target for diabetes therapy. FOXO proteins are transcription factors involved in numerous physiological processes and in various pathological conditions, including cardiovascular diseases and diabetes. Their roles include regulating the cell cycle, DNA repair, influencing apoptosis, glucose metabolism, autophagy processes and ageing. FOXO1 is an important regulator of pancreatic beta-cell function affecting pancreatic beta cells under conditions of insulin resistance. FOXO1 also protects beta cells from damage resulting from oxidative stress associated with glucose and lipid overload. FOXO has been shown to affect a number of processes involved in the development of diabetes and its complications. FOXO regulates pancreatic &beta;-cell function during metabolic stress and also plays an important role in regulating wound healing. Therefore, the pharmacological regulation of FOXO proteins is a promising approach to developing treatments for many diseases, including diabetes mellitus. In this review, we describe the role of FOXO proteins in the pathogenesis of diabetes and the role of the modulation of FOXO function in the therapy of this disease

Assessment of Sclerostin and Interleukin 6 Levels and Selected Anthropometric Parameters in Patients Receiving Hemodialysis Replacement Therapy—Pilot Study

Background and Objectives: Chronic kidney disease (CKD) is an important public health problem associated with, e.g., progressive renal insufficiency, bone mineral disorders, and increased inflammatory marker levels. The objective of this study was to compare selected biochemical parameters and to evaluate potential correlations between selected anthropometric parameters and levels of sclerostin and interleukin 6 (IL-6) in blood plasma. Materials and Methods: The study group consisted of 34 patients aged 59.8 &plusmn; 9.8 years, receiving hemodialysis therapy. The control group consisted of 31 individuals aged 55.4 &plusmn; 9.37 years, presenting with GFR (glomerular filtration rate) of more than 60 mL/min/1.73 m2. Selected anthropometric and biochemical parameters were assessed at baseline, as well as 3 and 6 months into the study. Statistical analyses were performed using the Statistica 2014 software package (StatSoft, Inc.Tulsa, OK, USA). Analyses included descriptive statistics, intergroup comparisons using the Mann-Whitney U-test or the Kruskal-Wallis test, and Spearman&rsquo;s correlation analysis. The significance level was set at p &le; 0.005. Results: At all measurement time points, i.e., at baseline, at month 3, and at month 6, the IL-6 levels in the study group were significantly higher than those in the control group. No correlations were observed in the study group between SCL or IL-6 levels and anthropometric parameters such as body weight, body mass index (BMI), or waist circumference. Conclusions: Patients receiving hemodialysis replacement therapy present with significantly higher levels of IL-6 in their blood. Anthropometric parameters (body weight, BMI, and waist circumference) have no impact on sclerostin and IL-6 levels in patients undergoing hemodialysis therapy. The results obtained are satisfactory, and the research will be continued