Publications by authors named "Zdravko Kamenov"

68 Publications

Increased Serum Pentraxin 3 Is Associated with Prediabetes and Type 2 Diabetes in Obese Patients with Nonalcoholic Fatty Liver Disease.

Metab Syndr Relat Disord 2021 Nov 24. Epub 2021 Nov 24.

Department of Internal Medicine, Clinic of Endocrinology and Metabolic Disease, University Hospital "Alexandrovska," Medical University Sofia, Sofia, Bulgaria.

Pentraxin 3 (PTX3) is an acute-phase protein, which resembles C-reactive protein in both structure and function, and belongs to the same family. PTX3 is associated with cardiovascular diseases, obesity, and metabolic syndrome (MetS). This study evaluated the relationship between serum PTX3 levels, prediabetes, newly diagnosed type 2 diabetes mellitus (T2DM), and other biochemical and clinical parameters in obese patients with nonalcoholic fatty liver disease (NAFLD). A total of 77 obese patients with NAFLD were included. Forty-seven of them were with normal glucose levels and 30 were with glycemic disorders, including prediabetes and newly diagnosed T2DM. Serum PTX3 was measured using ELISA method. Higher PTX3 serum levels were found in patients with prediabetes and T2DM compared with those with normal blood glucose (2321.29 ± 926.63 vs. 1877.03 ± 895.45 pg/mL,  = 0.028). There were significant correlations between PTX3 and alanine aminotransferase ( = 0.018), gamma-glutamyl transferase ( = 0.005), and neuropathy disability score ( < 0.05). The presence of hypertension, dyslipidemia, insulin resistance, and MetS, as well as the number of components of the MetS did not affect PTX3 levels. PTX3 serum levels were higher in an obese subject with NAFLD with prediabetes and T2DM.
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http://dx.doi.org/10.1089/met.2021.0086DOI Listing
November 2021

Inositols: From Established Knowledge to Novel Approaches.

Int J Mol Sci 2021 Sep 30;22(19). Epub 2021 Sep 30.

Department of Obstetrics and Gynecology, Santo Spirito Hospital, 00193 Rome, Italy.

Myo-inositol (myo-Ins) and D-chiro-inositol (D-chiro-Ins) are natural compounds involved in many biological pathways. Since the discovery of their involvement in endocrine signal transduction, myo-Ins and D-chiro-Ins supplementation has contributed to clinical approaches in ameliorating many gynecological and endocrinological diseases. Currently both myo-Ins and D-chiro-Ins are well-tolerated, effective alternative candidates to the classical insulin sensitizers, and are useful treatments in preventing and treating metabolic and reproductive disorders such as polycystic ovary syndrome (PCOS), gestational diabetes mellitus (GDM), and male fertility disturbances, like sperm abnormalities. Moreover, besides metabolic activity, myo-Ins and D-chiro-Ins deeply influence steroidogenesis, regulating the pools of androgens and estrogens, likely in opposite ways. Given the complexity of inositol-related mechanisms of action, many of their beneficial effects are still under scrutiny. Therefore, continuing research aims to discover new emerging roles and mechanisms that can allow clinicians to tailor inositol therapy and to use it in other medical areas, hitherto unexplored. The present paper outlines the established evidence on inositols and updates on recent research, namely concerning D-chiro-Ins involvement into steroidogenesis. In particular, D-chiro-Ins mediates insulin-induced testosterone biosynthesis from ovarian thecal cells and directly affects synthesis of estrogens by modulating the expression of the aromatase enzyme. Ovaries, as well as other organs and tissues, are characterized by a specific ratio of myo-Ins to D-chiro-Ins, which ensures their healthy state and proper functionality. Altered inositol ratios may account for pathological conditions, causing an imbalance in sex hormones. Such situations usually occur in association with medical conditions, such as PCOS, or as a consequence of some pharmacological treatments. Based on the physiological role of inositols and the pathological implications of altered myo-Ins to D-chiro-Ins ratios, inositol therapy may be designed with two different aims: (1) restoring the inositol physiological ratio; (2) altering the ratio in a controlled way to achieve specific effects.
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http://dx.doi.org/10.3390/ijms221910575DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8508595PMC
September 2021

Potential role of biochemical placentation markers - pregnancy associated plasma protein-A and human chorionic gonadotropin for early gestational diabetes screening - a pilot study.

Ginekol Pol 2021 Sep 20. Epub 2021 Sep 20.

Department of Internal Medicine, Medical University -Sofia, Sofia, Bulgaria;Clinic of Endocrinology, University Hospital, Sofia, Bulgaria.

Objectives: Gestational diabetes mellitus (GDM) is one of the most common pregnancy complications. The universal screening for GDM is usually performed between 24-28 weeks' gestation. This often delays the diagnosis and could increase the risk of adverse pregnancy outcomes. Some of the biochemical placental markers - pregnancy associated plasma protein A (PAPP-A) and free-β human chorionic gonadotropin (hCG), probably could provide a diagnostic value for GDM. The aim of our study was to assess if PAPP-A and hCG values were different among pregnant women with and without GDM and respectively, to tested their place in the early GDM screening.

Material And Methods: We conducted a retrospective, case-control study by reviewing the clinical database records of 662 pregnant women. The analysis includes the data for a two-year period. The patients included in the observation were divided into two groups - GDM group (n = 412) and Euglycemic group (n = 250). Early screening for GDМ between 9-12 weeks' gestation was performed in 173 of the women in the interventional group due to: registered fasting plasma glucose (FPG) above 5.1 mmol/L, obesity, macrosomia in previous pregnancies or family history for diabetes mellitus. The remaining 239 women underwent universal screening at 24-28 weeks' gestation. Mean serum levels of PAPP-A, hCG, FPG, and body mass index (BMI) were measured between 10-13 gestational weeks. Serum levels of PAPP-A and hCG are presented as multiples of the normal median (MoM), adjusted by maternal baseline characteristics and demographics.

Results: In patients who developed GDM during pregnancy, compared with the control group, we have found significantly lower MoM values of PAPP-A (p < 0.0001), higher levels of FPG (р < 0.0001) and higher BMI (р < 0.0001). Median hCG MoM was similar in both group of pregnant women.

Conclusion: Our findings suggest that low-normal to low reference range values of PAPP-A might be associated with higher risk for GDM. PAAP-A levels can be used as an additional factor to recommend early screening for GDM.
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http://dx.doi.org/10.5603/GP.a2021.0129DOI Listing
September 2021

Usefulness of different adiposity indexes for identification of metabolic disturbances in patients with obesity.

Arch Physiol Biochem 2021 May 12:1-6. Epub 2021 May 12.

Department of Internal Medicine, Medical University - Sofia, Sofia, Bulgaria.

Context: Despite the role of BMI as a classical obesity index, other indexes reflecting mainly abdominal obesity, usually outperform BMI in terms of metabolic complications prediction.

Objective: The aim of the present study is to compare the usefulness of different adiposity indexes for the identification of metabolic disturbances in patients with obesity.

Methods: In the study, we included 461 patients - group 1 with obesity ( = 182), group 2 with prediabetes ( = 193), and group 3 with newly diagnosed type 2 diabetes ( = 86). Different anthropometric and adiposity indexes were calculated - WHR, WSR, VAI, ABSI, BRI, Hip index, WWI, LAP.

Results: VAI and LAP had the highest predictive value for the presence of carbohydrate disturbances. VAI also showed the strongest correlation with Framingham and SCORE compared to other adiposity indexes.

Conclusions: VAI and LAP are most useful for the identification of metabolic disturbances and cardiovascular risk in patients with obesity.
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http://dx.doi.org/10.1080/13813455.2021.1899241DOI Listing
May 2021

Polycystic ovary syndrome and (pre)osteoarthritis: assessing the link between hyperandrogenism in young women and cartilage oligomeric matrix protein as a marker of cartilage breakdown.

Clin Rheumatol 2021 Oct 4;40(10):4217-4223. Epub 2021 May 4.

Clinic of Endocrinology, University Hospital "Alexandrovska", Department of Internal Medicine, Medical Faculty, Medical University of Sofia, Sofia, Bulgaria.

Introduction: OBJECTIVES: Our aim was to analyze the link between hyperandrogenism and early clinical manifestations of osteoarthritis (OA), knee cartilage thickness, and serum cartilage oligomeric matrix protein (sCOMP) levels in patients with polycystic ovary syndrome (PCOS) and to compare them with healthy volunteers.

Methods: Fifty-four PCOS patients who met the Rotterdam criteria with phenotypes A, B, and C were included. They were compared with 26 age- and body mass index (BMI)-matched controls. Detailed anthropometric measurements and clinical evaluation for hyperandrogenism were performed for all participants who also filled in the Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaire. Furthermore, laboratory tests including sCOMP and hormone quantification were performed in a fasting stage. Finally, an ultrasound assessment was carried out in randomly selected 56 study participants.

Results: PCOS women reported more prominent knee-related symptoms (p = 0.035) and more impaired activities of daily living (ADL) (p = 0.001) than controls. Cartilage thickness of the left and right medial condyle and left lateral condyle was significantly greater in PCOS group (n = 41) than in control group (n = 15) (p = 0.05, p = 0.006, and p = 0.036, respectively). COMP correlated significantly and negatively with testosterone levels (p = 0.029, r =  - 0.297) in women with PCOS and the correlation remained significant after controlling for BMI.

Conclusions: Women with PCOS may experience knee-related symptoms and impaired ADL. They had greater knee femoral cartilage thickness. Although sCOMP levels did not significantly differ between the groups, lower levels of sCOMP may be inherent to PCOS patients with higher testosterone levels. Key Points • Although PCOS patients may experience more prominent knee related symptoms, their femoral cartilage of the knee joint is found thicker than controls. • PCOS patients did not have significantly elevated levels of sCOMP. • Lower sCOMP levels were related to higher testosterone levels.
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http://dx.doi.org/10.1007/s10067-021-05753-0DOI Listing
October 2021

The relationship between thyroid dysfunction during pregnancy and gestational diabetes mellitus.

Endokrynol Pol 2021 23;72(3):226-231. Epub 2021 Feb 23.

Department of Internal Medicine, Medical University - Sofia, Sofia, Bulgaria, Bulgaria.

Introduction: Thyroid dysfunction and gestational diabetes (GDM) are the two most common endocrine disorders that can be observed during pregnancy. Thyroid function abnormalities can be associated with insulin resistance (IR) and changes in carbohydrate metabolism. In patients with type 1 diabetes, thyroid function is usually evaluated to rule out abnormalities within a second autoimmune disease. Patients with type 2 diabetes are tested for thyroid function in view of the associated weight gain, IR, and changes in metabolism. The question arises: Should we also look for thyroid dysfunction in patients with gestational diabetes? The aim of the study was to determine whether there are abnormalities in thyroid hormone levels in pregnant women with gestational diabetes.

Material And Methods: A monocentric, retrospective study of the Dr Shterev Hospital electronic database was performed. We analysed the medical records of 662 pregnant women, divided in two groups - 412 with GDM and 250 with normal glucose tolerance, who gave birth in the period 2017-2019. Gestational diabetes mellitus in the study group was diagnosed with a 2-h, 75-g oral glucose tolerance test (OGTT) using the International Federation of Gynaecology and Obstetrics (FIGO) and American Diabetes Association (ADA) criteria. We analysed the mean serum concentrations of thyroid-stimulating hormone (TSH); free thyroxine (FT4), free triiodothyronine (FT3), FT3:FT4 ratio, fasting plasma glucose, age and body mass index in both groups. The groups were compared using the Mann-Whitney U-test.

Results: In patients who developed GDM, significantly higher concentrations of TSH (p < 0.0001) and FT3 (p < 0.0001), lower concentrations of FT4 (p < 0.0001), and higher FT3:FT4 ratios (p < 0.0001) were found.

Conclusion: The results of this pilot retrospective series reveal that high-normal to high concentration of TSH and low-normal to low concentration of FT4 as well as high FT3:Ft4 ratio could indicate increased risk of development of GDM.
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http://dx.doi.org/10.5603/EP.a2021.0016DOI Listing
February 2021

Real-World Effectiveness and Safety of Insulin Glargine 300 U/mL in Patients with T2D Uncontrolled on NPH or Premixed Insulins as Part of Routine Clinical Practice in Bulgaria: ToUPGRADE Study.

Diabetes Ther 2021 Mar 19;12(3):913-930. Epub 2021 Feb 19.

Sanofi, Sofia, Bulgaria.

Introduction: The aim of this study is to demonstrate the real-life effectiveness and safety of insulin glargine 300 U/mL (Gla-300) in patients with type 2 diabetes (T2D) previously uncontrolled on NPH ± prandial insulin or premixed insulins in routine clinical practice in Bulgaria.

Methods: This was a 24-week prospective, observational study performed in 40 inpatient and outpatient sites across the country.

Results: A total of 286 patients were included in the study. The mean age (± SD) was 61.2 ± 10.0 years with duration of diabetes of 11.64 ± 7.5 years and body mass index (BMI) of 32.1 ± 5.7 kg/m. HbA1c before Gla-300 initiation was 9.8 ± 1.0%, and fasting plasma glucose (FPG) was 13.1 ± 3.4 mmol/L. HbA1c and FPG change from baseline to week 24 was - 1.86% (p < 0.001) and - 4.8 mmol/L (p < 0.001), respectively. The proportion of patients reaching their individualized HbA1c at week 24 was 39.1% (95% CI 33.3-45.1%), while the proportion of patients reaching their individualized HbA1c target without confirmed and/or severe hypoglycaemia was 34.8% (95% CI 29.2-40.7%). At study end, 19.0% (95% CI 14.6-24.1%) achieved HbA1c < 7%. Body weight decreased from 88.3 to 87.0 kg from baseline to week 24 with mean change of - 1.3 kg (p < 0.001). The incidence and event rates of anytime confirmed (≤ 3.9 mmol/L) and/or severe hypoglycaemia were low: 7.7% and 0.42 events per patient-year, respectively. The overall Insulin Treatment Satisfaction Questionnaire (ITSQ) score increased from 53.2 to 78.2 from baseline to week 24 and the difference of 25.1 ± 21.5 points was significant (p < 0.001).

Conclusions: In real-life settings, Gla-300 significantly improved glycaemic control and insulin treatment satisfaction in people with T2D who were inadequately controlled with NPH ± prandial insulin or premixed insulin analogues. Improvement of glycaemic control was associated with a very low risk of hypoglycaemia and with significant weight loss irrespective of the previous insulin regimen.
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http://dx.doi.org/10.1007/s13300-021-01022-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947095PMC
March 2021

Neopterin in the Evolution from Obesity to Prediabetes and Newly Diagnosed Type 2 Diabetes.

Metab Syndr Relat Disord 2021 05 16;19(4):249-255. Epub 2021 Feb 16.

Clinic of Endocrinology, Department of Internal Medicine, Medical University of Sofia, University Hospital "Alexandrovska," Sofia, Bulgaria.

Neopterin, marker of cellular immunity and oxidative stress, is mainly produced by activated macrophages. It could play a crucial role in the development of insulin resistance (IR) and type 2 diabetes (T2D). The aim of this study was to investigate the circulating levels of neopterin in different stages of glucose dysregulation from obesity through prediabetes to newly diagnosed diabetes. Neopterin levels were determined using a commercially available human enzyme-linked immunosorbent assay kit. The homeostasis model assessment of IR was used as an index to assess IR. The sample consisted of 163 subjects with mean age 52.5 ± 11.3 years, divided in three age- and body mass index (BMI)-matched groups-obesity, prediabetes, and diabetes. The control group consisted of 42 healthy individuals. Neopterin levels were significantly higher in patients with obesity and/or prediabetes and newly diagnosed diabetes than those in the control group, respectively (4.14 ± 2.51; 4.04 ± 2.80 and 2.17 ± 1.93 vs. 0.87 ± 0.84;  < 0.05). Correlation analysis showed that the level of neopterin positively correlated with BMI, waist, waist-to-stature ratio, waist-to-hip ratio, fasting glucose, and triglycerides. Receiver operating characteristic analysis established neopterin suitable for distinguishing subjects with obesity [area under the curve (AUC) = 0.83;  < 0.001] and carbohydrate disturbances (AUC = 0.59;  < 0.05) from those without these conditions. Neopterin ≥0.47 ng/mL have an odds ratio (OR) of 2.71 for development of dysglycemia, whereas threshold value of neopterin ≥0.56 ng/mL shows an OR of 5.94 for development of obesity. The levels of neopterin were increased in patients with obesity and carbohydrate disturbances. Further studies will elucidate the role of the biomarker in development of T2D and its complications.
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http://dx.doi.org/10.1089/met.2020.0144DOI Listing
May 2021

Inositols in PCOS.

Molecules 2020 Nov 27;25(23). Epub 2020 Nov 27.

Department of Internal Medicine, Clinic of Endocrinology University Hospital Alexandrovska, Medical University-Sofia, 1431 Sofia, Bulgaria.

(1) Background: Myoinositol (MI) and D-chiro-inositol (DCI) are involved in a number of biochemical pathways within oocytes having a role in oocyte maturation, fertilization, implantation, and post-implantation development. Both inositols have a role in insulin signaling and hormonal synthesis in the ovaries. (2) Methods: Literature search (with key words: inositols, myo-inositol, d-chiro-inositol, PCOS) was done in PubMed until Sept. 2020 and 197 articles were identified, of which 47 were of clinical trials (35 randomized controlled trials). (3) Results: Many studies have demonstrated that in patients with polycystic ovarian syndrome (PCOS) MI treatment improved ovarian function and fertility, decreased the severity of hyperandrogenism including acne and hirsutism, positively affected metabolic aspects, and modulated various hormonal parameters deeply involved in the reproductive axis function and ovulation. Thus treating with MI has become a novel method to ameliorate PCOS symptoms, improve spontaneous ovulation, or induce ovulation. The current review is focused on the effects of MI and DCI alone or in combination with other agents on the pathological features of PCOS with focus on insulin resistance and adverse metabolic outcomes. (4) Conclusions: The available clinical data suggest that MI, DCI, and their combination in physiological ratio 40:1 with or without other compound could be beneficial for improving metabolic, hormonal, and reproductive aspects of PCOS.
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http://dx.doi.org/10.3390/molecules25235566DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7729761PMC
November 2020

Dryness of Foot Skin Assessed by the Visual Indicator Test and Risk of Diabetic Foot Ulceration: A Prospective Observational Study.

Front Endocrinol (Lausanne) 2020 8;11:625. Epub 2020 Sep 8.

First Department of Propaedeutic Internal Medicine, Medical School, National and Kapodistrian University of Athens, Laiko General Hospital, Athens, Greece.

Previous cross-sectional studies have shown an association between sudomotor dysfunction and diabetic foot ulceration (DFU). The aim of this prospective multicenter study was to determine the role of dryness of foot skin and of established neurological modalities in the prediction of risk for foot ulceration in a cohort of individuals with diabetes mellitus (DM). The study was conducted from 2012 to 2017. A total of 308 subjects with DM without history of DFU or critical limb ischemia completed the study. Diabetic neuropathy was assessed using the neuropathy symptom score (NSS) and neuropathy disability score (NDS). In a subset of participants, vibration perception threshold (VPT) was evaluated. Dryness of foot skin was assessed by the visual indicator plaster method (IPM). The diagnostic performance of the above neurological modalities for prediction of DFU was tested by receiver operating characteristic curve (ROC) analysis. During the 6-year follow-up, 55 patients (annual ulceration incidence 2.97%) developed DFU. Multivariate Cox-regression analysis after controlling for the effect of age, gender, and DM duration demonstrated that the risk (hazard ratio, 95% confidence intervals) of DFU increased significantly with either abnormal IPM (3.319, 1.460-7.545, = 0.004) or high (≥6) NDS (2.782, 1.546-5.007, = 0.001) or high (≥25 volts) VPT (2.587, 1.277-5.242, = 0.008). ROC analysis showed that all neurological modalities could discriminate participants who developed DFU ( < 0.001). IPM testing showed high sensitivity (0.86) and low specificity (0.49), while high vs. low NDS and VPT showed low sensitivity (0.40 and 0.39, respectively) and high specificity (0.87 and 0.89, respectively) for identification of patients at risk for DFU. Dryness of foot skin assessed by the IPM predicts the development of DFU. IPM testing has high sensitivity, whereas high NDS and VPT have high specificity in identifying subjects at risk for DFU. The IPM can be included in the screening methods for identification of the foot at risk.
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http://dx.doi.org/10.3389/fendo.2020.00625DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7506164PMC
May 2021

Lumican in Obese Patients with Nonalcoholic Fatty Liver Disease With or Without Prediabetes.

Metab Syndr Relat Disord 2020 11 11;18(9):443-448. Epub 2020 Aug 11.

Department of Internal Medicine, Clinic of Endocrinology and Metabolic Diseases, University Hospital "Alexandrovska," Medical University, Sofia, Bulgaria.

Lumican is a small leucine-rich proteoglycan that regulates the assembly of collagen fibers in the extracellular matrix of different tissues. Excess collagen production in the liver is key in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) and might contribute to the risk of type 2 diabetes mellitus and cardiovascular diseases. The aim of this study was to evaluate the relationship between serum lumican and prediabetes, and other biochemical and clinical parameters in obese subjects with NAFLD. The study group included 79 subjects with obesity and NAFLD of which 41 had normal carbohydrate tolerance and 38 had prediabetes. Serum lumican was measured by means of enzyme-linked immunosorbent assay. Higher lumican serum levels were found in patients with prediabetes compared with those with normal carbohydrate tolerance (0.117 ± 0.074 vs. 0.080 ± 0.048 ng/mL,  = 0.010) as well as in subjects with metabolic syndrome (MetS) versus those without MetS (0.113 ± 0.071 vs. 0.079 ± 0.048 ng/mL,  = 0.034). There was also a modest positive association between lumican levels and fasting glucose ( = 0.228,  < 0.05). Lumican levels ≥0.07 ng/mL determine a 3.9-fold higher risk of prediabetes (odds ratio: 3.945, 95% confidence interval: 1.518-10.254,  = 0.005). Lumican levels were higher in obese subjects with NAFLD with prediabetes and MetS. Lumican bears an increased risk for prediabetes in the study population.
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http://dx.doi.org/10.1089/met.2020.0001DOI Listing
November 2020

Relationship between circulating netrin-1 levels, obesity, prediabetes and newly diagnosed type 2 diabetes.

Arch Physiol Biochem 2020 Jul 11:1-6. Epub 2020 Jul 11.

Department of Internal Medicine, Medical University, Sofia, Bulgaria.

Background: Netrin-1 is presumed to have regenerative, angiogenic and anti-inflammatory properties, thus it could play a substantial role in the development of insulin resistance and T2DM.

Objective: The aim of this study was to evaluate the relationship between serum netrin-1 levels and carbohydrate disturbances in patients with obesity.

Methods: Sample size consisted of 163 patients, divided into four groups: obesity without carbohydrate disturbances prediabetes and diabetes and healthy controls Netrin-1 level was determined using ELISA method.

Results: Circulating serum Netrin-1 was significantly lower in patients only with obesity, as well as with those with prediabetes and diabetes in comparison to the control group. Correlation analysis revealed that netrin-1 correlates negatively with BMI, waist, WSR, LDL and positive with sudomotor function. Netrin-1 ≤ 0.17 ng/ml has about 3 fold higher risk for carbohydrate disturbances (OR 3.06, 95% CI 1.48-6.34,  = .003).

Conclusion: Netrin-1 is associated with an increased risk for glycaemic disorders in patients with obesity.
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http://dx.doi.org/10.1080/13813455.2020.1780453DOI Listing
July 2020

Impact of testosterone treatment on circulating irisin in men with late-onset hypogonadism and metabolic syndrome.

Aging Male 2020 Dec 26;23(5):1381-1387. Epub 2020 May 26.

Department of Internal Diseases, Medical University of Sofia, Sofia, Bulgaria.

Objectives: The beneficial effects of testosterone replacement therapy (TRT) in men with late-onset hypogonadism (LOH) on the body composition and metabolic outcomes are well-established. A potential explanation might lie in the hormones, secreted from skeletal muscles, named "myokines". The aim of this study was to evaluate the effects of TRT on the levels of serum irisin in subjects with LOH.

Study Design: A total 40 men with metabolic syndrome (MS) and LOH (measured serum testosterone concentration < 12 nmol/l). TRT with Testosterone Undecanoate (Nebido™) was performed at baseline and at week 6. Irisin serum concentration was determined at baseline and at week 18 by means of ELISA.

Results: Circulating irisin was positively associated with serum testosterone (r = 0.283,  < 0.05). TRT has led to a statistically significant rise in circulating serum irisin levels (7.12 ± 0.76 mcg/ml versus 7.76 ± 0.75 mcg/ml; paired-samples t-test  < 0.001). ROC-analyses determined irisin to be predictive of treatment response (AUC = 0.741,  = 0.014).

Conclusions: Irisin is positively associated with serum testosterone in a population of men with MS and LOH. TRT in these subjects has led to a significant improvement in associated clinical symptoms as well as to a significant rise in serum irisin levels.
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http://dx.doi.org/10.1080/13685538.2020.1770721DOI Listing
December 2020

Inositols in Polycystic Ovary Syndrome: An Overview on the Advances.

Trends Endocrinol Metab 2020 06 9;31(6):435-447. Epub 2020 Mar 9.

University of Lyon, INSERM U1060, CarMeN, INSA de Lyon, Université Claude Bernard Lyon 1, Villeurbanne, France.

This review details the physiologic roles of two insulin sensitizers, myo-inositol (MI) and d-chiro-inositol (DCI). In the human ovary, MI is a second messenger of follicle-stimulating hormone (FSH) and DCI is an aromatase inhibitor. These activities allow a treatment for polycystic ovary syndrome (PCOS) to be defined based on the combined administration of MI and DCI, where the best MI:DCI ratio is 40:1. Moreover, MI enhances the effect of metformin and clomiphene on the fertility of PCOS women seeking pregnancy. As impaired intestinal transport may lead to unsuccessful inositol treatment, we also discuss new data on the use of alpha-lactalbumin to boost inositol absorption. Overall, the physiological activities of MI and DCI dictate the dosages and timing of inositol supplementation in the treatment of PCOS.
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http://dx.doi.org/10.1016/j.tem.2020.02.002DOI Listing
June 2020

Early prevention of diabetes microvascular complications in people with hyperglycaemia in Europe. ePREDICE randomized trial. Study protocol, recruitment and selected baseline data.

PLoS One 2020 13;15(4):e0231196. Epub 2020 Apr 13.

Departamento de Salud Internacional, Escuela Nacional de Sanidad, Instituto de Salud Carlos III, Madrid, Spain.

Objectives: To assess the effects of early management of hyperglycaemia with antidiabetic drugs plus lifestyle intervention compared with lifestyle alone, on microvascular function in adults with pre-diabetes.

Methods: Trial design: International, multicenter, randomised, partially double-blind, placebo-controlled, clinical trial.

Participants: Males and females aged 45-74 years with IFG, IGT or IFG+IGT, recruited from primary care centres in Australia, Austria, Bulgaria, Greece, Kuwait, Poland, Serbia, Spain and Turkey.

Intervention: Participants were randomized to placebo; metformin 1.700 mg/day; linagliptin 5 mg/day or fixed-dose combination of linagliptin/metformin. All patients were enrolled in a lifestyle intervention program (diet and physical activity). Drug intervention will last 2 years. Primary Outcome: composite end-point of diabetic retinopathy estimated by the Early Treatment Diabetic Retinopathy Study Score, urinary albumin to creatinine ratio, and skin conductance in feet estimated by the sudomotor index. Secondary outcomes in a subsample include insulin sensitivity, beta-cell function, biomarkers of inflammation and fatty liver disease, quality of life, cognitive function, depressive symptoms and endothelial function.

Results: One thousand three hundred ninety one individuals with hyperglycaemia were assessed for eligibility, 424 excluded after screening, 967 allocated to placebo, metformin, linagliptin or to fixed-dose combination of metformin + linagliptin. A total of 809 people (91.1%) accepted and initiated the assigned treatment. Study sample after randomization was well balanced among the four groups. No statistical differences for the main risk factors analysed were observed between those accepting or rejecting treatment initiation. At baseline prevalence of diabetic retinopathy was 4.2%, severe neuropathy 5.3% and nephropathy 5.7%.

Conclusions: ePREDICE is the first -randomized clinical trial with the aim to assess effects of different interventions (lifestyle and pharmacological) on microvascular function in people with pre-diabetes. The trial will provide novel data on lifestyle modification combined with glucose lowering drugs for the prevention of early microvascular complications and diabetes.

Registration: - ClinicalTrials.Gov Identifier: NCT03222765 - EUDRACT Registry Number: 2013-000418-39.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0231196PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7153858PMC
July 2020

Experts' opinion on inositols in treating polycystic ovary syndrome and non-insulin dependent diabetes mellitus: a further help for human reproduction and beyond.

Expert Opin Drug Metab Toxicol 2020 Mar 19;16(3):255-274. Epub 2020 Mar 19.

Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.

: This Experts' opinion provides an updated scientific support to gynecologists, obstetricians, endocrinologists, nutritionists, neurologists and general practitioners on the use of Inositols in the therapy of Polycystic Ovary Syndrome (PCOS) and non-insulin dependent (type 2) diabetes mellitus (NIDDM).: This paper summarizes the physiology of Myo-Inositol (MI) and D-Chiro-Inositol (DCI), two important molecules present in human organisms, and their therapeutic role, also for treating infertility. Some deep differences between the physiological functions of MI and DCI, as well as their safety and intestinal absorption are discussed. Updates include new evidence on the efficacy exerted in PCOS by the 40:1 MI/DCI ratio, and the innovative approach based on alpha-lactalbumin to overcome the decreased therapeutic efficacy of Inositols in some patients.: The evidence suggests that MI, alone or with DCI in the 40:1 ratio, offers a promising treatment for PCOS and NIDDM. However, additional studies need to evaluate some still unresolved issues, such as the best MI/DCI ratio for treating NIDDM, the potential cost-effectiveness of reduced gonadotropins administration in IVF due to MI treatment, or the benefit of MI supplementation in ovulation induction with clomiphene citrate in PCOS patients.
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http://dx.doi.org/10.1080/17425255.2020.1737675DOI Listing
March 2020

PNPLA3 I148M Polymorphism in Patients with Nonalcoholic Fatty Liver Disease, Obesity and Prediabetes.

J Gastrointestin Liver Dis 2019 Dec 9;28(4):433-438. Epub 2019 Dec 9.

Clinic of Endocrinology and Metabolic Diseases, Alexandrovska University Hospital, Department of Internal Medicine, Medical University Sofia, Bulgaria.

Background And Aims: Nonalcoholic fatty liver disease (NAFLD) is closely associated with obesity and insulin resistance, and therefore predisposes to type 2 diabetes and cardiovascular diseases. Lipid deposition in the liver seems to be critical in the pathogenesis of NAFLD. A common genetic variant, the patatin-like phospholipase domain-containing protein 3 (PNPLA3) has been associated with NAFLD. The aim of the present study was to evaluate the association between PNPLA3, key gene of lipid metabolism and the metabolic traits in obesity NAFLD patients with and without prediabetes.

Methods: A total of 208 obese NAFLD patients without (n=125) and with prediabetes (n=83) were included. The genotyping of PNPLA3 I148M variant (rs738409) was performed by restriction analysis.

Results: Regarding rs738409 (I148M) polymorphism, CG genotype was positively correlated with prediabetes, insulin resistance, dyslipidemia and metabolic syndrome compared to the wild CC genotype. The carriers of the PNPLA3 I148M variant have 9.6-fold higher risk of glucose disturbances compared to wild genotype (OR 9.649, 95%CI 2.100-44.328, р=0.004). The carriers of the PNPLA3 I148M variant also have a 3 times higher risk for the presence of metabolic syndrome (OR 2.939, 95% CI: 1.590-5.434, p=0.001) and a 2.1-fold higher risk for the presence of insulin resistance (OR 2.127, 95% CI: 1.078-4.194, p=0.029).

Conclusions: PNPLA3 I148M is associated with increased risk of prediabetes, metabolic syndrome and insulin resistance in obese patients with NAFLD.
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http://dx.doi.org/10.15403/jgld-506DOI Listing
December 2019

Fibroblast growth factor 23 and 25(OH)D levels are related to abdominal obesity and cardiovascular risk in patients with polycystic ovarian syndrome.

Gynecol Endocrinol 2020 May 10;36(5):402-405. Epub 2019 Nov 10.

Department of Internal Medicine, Medical University-Sofia, Sofia, Bulgaria.

Fibroblast growth factor 23 (FGF23) and Klotho are extensively studied in relation to bone metabolism and progression of chronic kidney disease. There is very limited information about their role in polycystic ovarian syndrome (PCOS). The aim of the present study was to investigate some bone markers in women with PCOS in relation to obesity and cardiovascular risk. In the study were included 80 patients, divided into three age-matched groups -Non-obese PCOS ( = 40); Obese PCOS ( = 20) and Obese control group ( = 20). Bone marker levels were measured by an enzyme-linked immunosorbent assay. Obese PCOS patients had higher levels of FGF23 and sRANKL, lower levels of 25(OH)D and higher prevalence of vitamin D deficiency compared to non-obese subjects. Patients with abdominal obesity (waist circumference >80 cm) independently of PCOS status had significantly higher levels of FGF23 (112.5 ± 86.5 vs. 73.4 ± 37.9 pg/ml;  = .023) and lower of 25(OH)D (35.8 ± 21.4 vs 47.8 ± 26.5 nmol/l;  = .034). Patients with PCOS at risk of cardiovascular diseases according to AE-PCOS consensus also had increased levels of FGF23 (111.6 ± 84.5 vs. 66.5 ± 35.1 pg/ml;  = .031) and decreased levels of 25(OH)D (31.9 ± 16.8 vs. 47.1 vs 28.4 nmol/l;  = .017) compared to those not at risk. There was no correlation between bone markers and blood glucose levels, insulin resistance or hormonal levels.
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http://dx.doi.org/10.1080/09513590.2019.1689550DOI Listing
May 2020

The association between retinol-binding protein 4 and prediabetes in obese patients with nonalcoholic fatty liver disease.

Arch Physiol Biochem 2019 Oct 7:1-6. Epub 2019 Oct 7.

Department of Internal Medicine, Clinic of Gastroenterology, University Hospital "St. Ivan Rilski", Medical University - Sofia , Sofia , Bulgaria.

Retinol-binding protein 4 RBP4) is associated with visceral fat and insulin resistance (IR) in obesity, type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD), but some of these data remain controversial. This study evaluated the relationship between serum RBP4 levels and prediabetes in obese patients with NAFLD. A total of 79 obese NAFLD patients without ( = 41) and with prediabetes ( = 38) were included. Serum RBP4 was measured using ELISA method. Higher RBP4 serum levels were observed in patients with prediabetes, metabolic syndrome (MetS), or dyslipidaemia. There was correlation between RBP4 levels and visceral adiposity index (VAI), glucose, insulin, HOMA-IR, and Quicki index. RBP4 ≥ 61 mcg/ml have about 3.5-fold higher risk of prediabetes (OR 3.544, 95% CI 1.385-9.072, =.008), and RBP4 ≥ 55 mcg/ml increased the risk for MetS approximately 3.1 times. RBP4 is associated with increased risk for prediabetes and MetS in obese patients with NAFLD.
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http://dx.doi.org/10.1080/13813455.2019.1673429DOI Listing
October 2019

Serum AGEs and sRAGE levels are not related to vascular complications in patients with prediabetes.

Diabetes Metab Syndr 2019 Mar - Apr;13(2):1005-1010. Epub 2019 Jan 18.

Clinic of Endocrinology, University Hospital "Alexandrovska", Medical University-Sofia, 1 Georgi Sofiiski str, 1431, Sofia, Bulgaria.

Background: While hyperglycemia has a key role in the pathogenesis of microvascular complications of diabetes, it is just one of the many factors contributing to macrovascular damage. The aim of the present study is to investigate the link between serum pentosidine and sRAGE levels and vascular complications in patients with prediabetes compared to normal glucose tolerance controls with obesity.

Methods: In this study were included 76 patients with mean age 50.7 ± 10.7 years, divided into two age and BMI-matched groups - group 1 with obesity without glycemic disturbances (n = 38) and group 2 with obesity and prediabetes (n = 38).

Results: There was no significant difference in pentosidine and sRAGE levels between patients with obesity and prediabetes. Patients with hypertension had lower levels of sRAGE compared to nonhypertensive subjects. sRAGE showed a weak negative correlation to blood glucose on 60th min of OGTT and HOMA index. There was no correlation between sRAGE and pentosidine levels and the markers of micro- and macrovascular complications. There was no difference in sRAGE and pentosidine levels between patients with and without endothelial dysfunction.

Conclusions: sRAGE and pentosidine levels are similar in patients with obesity with and without prediabetes and do not correlate to the markers of micro- and macrovascular complications.
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http://dx.doi.org/10.1016/j.dsx.2019.01.014DOI Listing
December 2019

Correction to: Endorsement by Central European experts of the revised ESCEO algorithm for the management of knee osteoarthritis.

Rheumatol Int 2019 Sep;39(9):1661-1662

Division of Public Health, Epidemiology and Health Economics, University of Liège, CHU Sart Tilman B23, 4000, Liege, Belgium.

In the Original Publication, the e-mail address of the author Milan Petronijević is incorrect. The correct e-mail address is [email protected]
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http://dx.doi.org/10.1007/s00296-019-04347-zDOI Listing
September 2019

Relationships between sperm DNA integrity and bulk semen parameters in Bulgarian patients with varicocele.

Arch Ital Urol Androl 2019 Jul 2;91(2). Epub 2019 Jul 2.

Medical University, Sofia.

Objective: This exploratory retrospective study aimed to compare the level of Sperm DNA Fragmentation (SDF) and investigate its association with bulk semen parameters, for the first time in Bulgarian patients with varicocele, using a distinct methodology.

Material And Methods: Standard semen analysis was performed according to the 2010 criteria of the European Society of Human Reproduction and Embryology - Nordic Association for Andrology (ESHRE-NAFA-2010) and DNA fragmentation was assessed using the Halosperm® kit. The total sample included 28 males: the control group consisted of men with normal genital examination and unknown fertility (n = 10), group one consisted of men with varicocele, normozoospermia and DNA fragmentation > 15% (n = 9) and group two consisted of men with varicocele, abnormal sperm parameters and DNA fragmentation > 15% (n = 9).

Results: DNA fragmentation was found to be higher in patients with abnormal sperm parameters (43.78 ± 30.78) compared to the normozoospermic group (21.22 ± 3.93) (p = 0.008). In normozoospermic patients, no statistically significant correlations were observed between SDF and bulk semen parameters. In patients with abnormal sperm parameters, DNA fragmentation exhibited significant very strong negative association with motility (a+b), vitality and typical morphology (p < 0.001).

Conclusions: DNA integrity assays could be used for a better evaluation and management of male infertility, particularly in normozoospermic varicocele patients.
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http://dx.doi.org/10.4081/aiua.2019.2.125DOI Listing
July 2019

The role of Sudoscan feet asymmetry in the diabetic foot.

Prim Care Diabetes 2020 02 29;14(1):47-52. Epub 2019 May 29.

Clinic of Endocrinology, University Hospital "Alexandrovska", Medical University - Sofia, Sofia, Bulgaria. Electronic address:

The aim of this study was to investigate the role of Sudoscan asymmetry parameters in the diabetic foot.

Patients And Methods: In this study we included 165 participants: 84 type 2 diabetes patients divided into three HbA1c matched groups - group 1: newly diagnosed diabetics (n = 31), group 2: people with longer diabetes duration and established neuropathy (n = 33), group 3: patients with diabetic foot ulcer (n = 20), and a control group of 81 people with prediabetes. All subjects underwent peripheral sudomotor evaluation using Sudoscan device (Impeto Medical, Paris).

Results: Patients with diabetic foot had significantly higher Sudoscan feet asymmetry (19.6%) compared to those with only diabetic neuropathy (7.9%), compared to the group with newly diagnosed diabetes (7.44%), and compared to controls (2.5%). This test has shown a good discriminative value (with a threshold of 9.5%) for diabetic foot with area under the ROC curve of 0.955 (p = 0.001). Additionally, in a regression model feet asymmetry proved its predictive value for participants with diabetic foot.

Conclusion: In this study Sudoscan feet asymmetry proved to be a novel discriminator and predictor for diabetic foot patients. It might be considered as a marker for early damage in the neuropathy evaluation protocol.
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http://dx.doi.org/10.1016/j.pcd.2019.05.003DOI Listing
February 2020

Endorsement by Central European experts of the revised ESCEO algorithm for the management of knee osteoarthritis.

Rheumatol Int 2019 07 25;39(7):1117-1123. Epub 2019 May 25.

Division of Public Health, Epidemiology and Health Economics, University of Liège, CHU Sart Tilman B23, 4000, Liege, Belgium.

Osteoarthritis (OA) is characterized by deterioration of the joints and associated with considerable pain and disability. OA is a chronic disease that requires intervention with both non-pharmacological and pharmacological treatment modalities and, inevitably, disease progression may necessitate successive treatments throughout the course of the disease. There is increasing data on the shortfalls of current pharmacological treatment of OA, and safety concerns associated with analgesic therapy use in OA arising from increasing evidence of gastrointestinal, cardiovascular, hepatic and renal adverse events with paracetamol and non-steroidal anti-inflammatory drugs (NSAIDs). Consequently, symptomatic slow-acting drugs for OA (SYSADOAs) may now be considered as a first-line treatment for knee OA, with a particular emphasis placed on the outstanding benefit: risk ratio of pharmaceutical-grade glucosamine and chondroitin sulfate formulations. In this short communication we review recent publications concerned with the safety of paracetamol, NSAIDs and SYSADOAs. Greater understanding of the benefits and limitations of current medications will lead to better disease management in OA. Furthermore, adherence to guideline recommendations across Europe and internationally, such as those from the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO), will promote evidence-based medicine and patient-centric care, ultimately leading to greater physician and patient satisfaction.
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http://dx.doi.org/10.1007/s00296-019-04332-6DOI Listing
July 2019

Peroxiredoxin 4 levels in patients with PCOS and/or obesity.

J Gynecol Obstet Hum Reprod 2019 Nov 11;48(9):739-743. Epub 2019 Apr 11.

Medical University-Sofia, Bulgaria Department of Internal Medicine, Clinic of Endocrinology, University Hospital "Alexandrovska", Bulgaria.

Background: Peroxiredoxin 4 is a part of endogen antioxidant system and its levels are elevated in increased oxidative stress conditions. It is found to be positively associated with cardiovascular risk. The aim of the study was to investigate peroxiredoxin 4 levels in women with polycystic ovarian syndrome (PCOS) and/or obesity.

Methods: In this cros-sesctional study were included 80 patients. Anthropometric measurements and biochemical tests, including peroxiredoxin 4 measurement, were performed.

Results: There was a tendency towards lower peroxiredoxin 4 levels in non-obese PCOS subjects (5674.8 ± 3822.4 pg/ml), higher in obese PCOS (6588.9 ± 3731.0 pg/ml) and even higher in obese patients without PCOS (7724.6 ± 4840.4 pg/ml). Patients with abdominal obesity according to waist circumference and waist-to-hip ratio had significantly higher levels of peroxiredoxin compared to those without (7108.2 ± 4568.0 vs. 5079.8 ± 2555.4 pg/ml; p = 0.015 and 7310.6 ± 2646.2 vs. 4785.0 ± 2646.2 pg/ml; p = 0.013). There was no difference in peroxiredoxin 4 levels in patients with and without insulin resistance, hypertension, dislipidemia, hyperandrogenemia, metabolic syndrome. Peroxiredoxin 4 showed weak positive correlation to weight (r = 0.228; p = 0.044) and visceral adiposity index (r = 0.278; p = 0.031) and higher to erythrocyte sedimentation rate (r = 0.4; p < 0.01), but not to hormonal parameters and insulin sensitivity indexes.

Conclusions: Non-obese patients with PCOS have a tendency towards lower peroxiredoxin 4 levels compared to obese patients with and without PCOS. Patients with abdominal obesity have significantly higher peroxiredoxin 4 levels than those without. We were not able to prove correlation between peroxiredoxin 4 levels and hormonal and carbohydrate status of the PCOS patients.
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http://dx.doi.org/10.1016/j.jogoh.2019.04.002DOI Listing
November 2019

Higher levels of thioredoxin interacting protein (TXNIP) in patients with prediabetes compared to obese normoglycemic subjects.

Diabetes Metab Syndr 2019 Jan - Feb;13(1):734-737. Epub 2018 Nov 30.

Clinic of Endocrinology, University Hospital "Alexandrovska", Medical University-Sofia, 1 GeorgiSofiiski Str., 1431, Sofia, Bulgaria.

Background: Thioredoxin interacting protein (TXNIP) is one of the mediators of oxidative stress induced beta-cell glucotoxisity. TXNIP might play a key role in impaired glucose homeostasis preceding overt T2DM. The aim of the present study was to compare TXNIP levels between patients with prediabetes and obese normoglycemic controls and to evaluate the link between TXNIP and metabolic risk factors.

Patients And Methods: In the present study we included 79 patients with mean age 50.3 ± 10.6 years, divided into two age and BMI matched groups -control group with obesity without glycemic disturbances (NGT) (n = 40) and prediabetes (n = 39).

Results: We found significantly higher levels of TXNIP in patients with prediabetes compared to normoglycemic obese controls (54.2 ± 69.9 vs. 23.9 ± 47.1 pg/ml; p = 0.03). The levels of TXNIP gradually increased from normal glucose tolerance trough IFG/IGT only to IFG + IGT (27,1; 44.0; 49.9 and 95.7 pg/ml respectively; p = 0.025 between NGT and IFG + IGT). TXNIP levels correlated weakly only with fasting blood glucose (r = 0.235; p = 0.04) but not with glucose during OGTT or the markers of insulin resistance.

Conclusions: The levels of TXNIP are higher in patients with prediabetes compared to normoglycemic controls as they increase gradually from NGT trough IFG/IGT only to IFG + IGT.
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http://dx.doi.org/10.1016/j.dsx.2018.11.056DOI Listing
May 2019

Higher levels of IL-18 in patients with prediabetes compared to obese normoglycaemic controls.

Arch Physiol Biochem 2020 Dec 11;126(5):449-452. Epub 2019 Jan 11.

Laboratory of Tumor Immunology and Cell Therapy, Hyogo College of Medicine, Tokyo, Japan.

: Overweight and obesity are linked to low-grade chronic inflammation that can impair normal insulin function and induce insulin resistance. The aim of this study was to compare IL-18 levels between patients with prediabetes and obese normoglycaemic controls.: In this study, we included 131 patients with mean age 54.9 ± 9.1 years, divided into two groups - group 1 with obesity without glycaemic disturbances ( = 66) and group 2 with prediabetes ( = 65). IL-18 was measured using enzyme-linked immunosorbent assay (ELISA) method.: Patients with prediabetes had significantly higher levels of IL-18 compared to obese controls (304.0 ± 220.4 vs. 233.6 ± 103.6 pg/l, =.029). When patients with prediabetes were divided into IFG only, IGT only and IFG + IGT the highest levels of IL-18 were found in IGT only patients.: Patients with prediabetes have higher levels of IL18 compared to obese normoglycemic controls.
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http://dx.doi.org/10.1080/13813455.2018.1555667DOI Listing
December 2020

Prediabetes is Characterized by Higher FGF23 Levels and Higher Prevalence of Vitamin D Deficiency Compared to Normal Glucose Tolerance Subjects.

Horm Metab Res 2019 Feb 20;51(2):106-111. Epub 2018 Dec 20.

Department of Internal Medicine, Clinic of Endocrinology, University Hospital "Alexandrovska", Medical University Sofia, Sofia, Bulgaria.

In the last years there is an increasing interest towards the bone as an endocrine organ and the role of bone and calcium-phosphate metabolism markers in a range of metabolic disturbances. The aim of the present study is to assess the changes of calcium phosphate metabolism markers in patients with prediabetes compared to normogycemic controls and their link to glucose disturbances and cardiovascular risk factors. In this study, 80 patients with mean age 50.4±10.6 years were included, divided into 2 age- and BMI-matched groups - group 1 with obesity without glycemic disturbances (n=41) and group 2 with obesity and prediabetes (n=39). Oral glucose tolerance test (OGTT) with measurement of immunoreactive insulin was performed in all participants and levels of PTH, 25(OH)D, FGF23, and Klotho were measured. We found significantly higher levels of FGF23 in patients with prediabetes compared to normal glucose tolerance subjects (10.4±10.7 vs. 5.8±7.3 pg/ml; p=0.03). FGF23 showed a weak positive correlation to fasting blood glucose (r=0.224; p=0.048) but not to blood glucose on the first and second hour of oral glucose tolerance test or insulin levels. There was extremely high prevalence of vitamin D deficiency in both groups. Lower levels of 25(OH)D were observed in prediabetes group, although without statistical significance (p=0.57). Patients with prediabetes have higher FGF23 levels and higher prevalence of vitamin D deficiency compared to normal glucose tolerance subjects. Elevated FGF23 levels seem to be correlated more to elevated fasting blood glucose levels than to insulin resistance state of the patients.
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http://dx.doi.org/10.1055/a-0813-3164DOI Listing
February 2019

Endothelial dysfunction and intima media thickness are selectively related to the different carbohydrate disturbances across the glucose continuum.

Arch Physiol Biochem 2019 Dec 8;125(5):430-434. Epub 2018 Jun 8.

Clinic of Endocrinology, University Hospital "Alexandrovska" Medical University-Sofia , Sofia , Bulgaria.

The aim of the present study was to investigate the prevalence of macrovascular complications across different carbohydrate disturbances. In the study, we included 167 patients, divided them into three age and BMI matched groups - group 1 with obesity without carbohydrate disturbances ( = 66), group 2 with prediabetes ( = 68) and group 3 with newly diagnosed type 2 diabetes ( = 33). Endothelial function was evaluated using EndoPAT, intima media thickness (IMT) was measured on the common carotid artery and ankle-brachial index (ABI) was calculated. The patients with T2D had significantly higher mean IMT than the other two groups. The best predictors of increased IMT were fasting blood glucose followed by age and SBP. ROC-analysis showed that blood glucose on 60 min of OGTT had a very good predictive value for endothelial dysfunction. Patients with newly diagnosed diabetes have increased IMT and a tendency towards higher ABI compared to normoglycemic and prediabetic subjects.
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http://dx.doi.org/10.1080/13813455.2018.1479762DOI Listing
December 2019
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