Publications by authors named "Yavor Assyov"

23 Publications

  • Page 1 of 1

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

Targeting Inflammatory Cytokines to Improve Type 2 Diabetes Control.

Biomed Res Int 2021 13;2021:7297419. Epub 2021 Sep 13.

Clinic of Rheumatology, University Hospital "St. Marina, " First Department of Internal Medicine, Medical Faculty, Medical University-Varna, Varna 9010, Bulgaria.

Type 2 diabetes (T2D) is one of the most common chronic metabolic disorders in adulthood worldwide, whose pathophysiology includes an abnormal immune response accompanied by cytokine dysregulation and inflammation. As the T2D-related inflammation and its progression were associated with the balance between pro and anti-inflammatory cytokines, anticytokine treatments might represent an additional therapeutic option for T2D patients. This review focuses on existing evidence for antihyperglycemic properties of disease-modifying antirheumatic drugs (DMARDs) and anticytokine agents (anti-TNF-, anti-interleukin-(IL-) 6, -IL-1, -IL-17, -IL-23, etc.). Emphasis is placed on their molecular mechanisms and on the biological rationale for clinical use. Finally, we briefly summarize the results from experimental model studies and promising clinical trials about the potential of anticytokine therapies in T2D, discussing the effects of these drugs on systemic and islet inflammation, beta-cell function, insulin secretion, and insulin sensitivity.
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http://dx.doi.org/10.1155/2021/7297419DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8455209PMC
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

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

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

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

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

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

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

Classical (adiponectin, leptin, resistin) and new (chemerin, vaspin, omentin) adipocytokines in patients with prediabetes.

Horm Mol Biol Clin Investig 2018 Jan 15;34(1). Epub 2018 Jan 15.

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

Background In the last decade, there has been an increased interest toward fat tissue as an endocrine organ that secretes many cytokines and bioactive mediators that play a role in insulin sensitivity, inflammation, coagulation and the pathogenesis of atherosclerosis. The aim of this study was to investigate classical (adiponectin, leptin, resistin) and new (chemerin, vaspin, omentin) adipocytokine levels in subjects with prediabetes [impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT)] and obese subjects with normoglycemia. Methods In this study, 80 patients with a mean age of 50.4 ± 10.6 years were recruited, divided into two groups with similar age and body mass index (BMI) - with obesity and normoglycemia (n = 41) and with obesity and prediabetes (n = 39). Results Serum adiponectin levels were significantly higher in subjects with normoglycemia compared to patients with prediabetes. Adiponectin has a good discriminating power to distinguish between patients with and without insulin resistance in our study population [area under the curve (AUC) = 0.728, p = 0.002]. Other adipocytokine levels were not significantly different between the two groups. The patients with metabolic syndrome (MetS) had significantly lower levels of leptin compared to those without MetS (33.03 ± 14.94 vs. 40.24 ± 12.23 ng/mL) and this difference persisted after adjustment for weight and BMI. Receiver operating characteristic (ROC) analysis showed that low serum leptin can predict the presence of MetS (p = 0.03), AUC = 0.645. Conclusion Serum adiponectin is statistically higher in patients with normoglycemia compared to those with prediabetes and has a predictive value for distinguishing between patients with and without insulin resistance in the studied population. Serum leptin has a good predictive value for distinguishing between patients with and without MetS in the studied population.
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http://dx.doi.org/10.1515/hmbci-2017-0031DOI Listing
January 2018

Irisin and Testosterone in Men with Metabolic Syndrome.

Horm Metab Res 2017 Oct 31;49(10):755-759. Epub 2017 Jul 31.

Central Clinical Laboratory, University Hospital Alexandrovska, Medical University, Sofia, Bulgaria.

The beneficial effects of testosterone on the metabolism and body composition of men are well established but the exact mechanisms of these effects are not clearly understood. A potential explanation might lie in the hormones, secreted from skeletal muscles, named "myokines". One such myokine, irisin, has been shown to also have potential beneficial metabolic effects. The aim of this pilot study was to evaluate the association of serum testosterone with circulating serum irisin levels in men with metabolic syndrome. A total 128 men with metabolic syndrome (MS) based on the IDF criteria participated in the study. Irisin serum concentration was determined by means of ELISA. Mean age±SD of the study participants was 51.8±8.3 years. Seventy percent of the subjects had type 2 diabetes mellitus. Circulating irisin was inversely associated with serum testosterone (r=-0.279, p<0.01) and was significantly higher in subjects with hypogonadism - mean±SD 252.0±147.1 vs.172.9±92.2 ng/ml (p=0.002). ROC analysis of serum irisin value was determined for distinguishing subjects with hypogonadism (AUC=0.670). In a multiple linear regression model with BMI, FPG, age, and irisin, only BMI (β=-0.228, p=0.004) and irisin (β=-0.170, p=0.045) were variables independently associated with testosterone concentrations. Irisin is negatively associated with serum testosterone in our population sample of men with MS. This might suggest a possible involvement of myokines and testosterone with regards to the human metabolism. As no such data on this association has been reported in the literature thus far, further prospective studies are required to elucidate this correlation.
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http://dx.doi.org/10.1055/s-0043-115227DOI Listing
October 2017

Increased kallistatin levels in patients with obesity and prediabetes compared to normal glucose tolerance.

Endocr Res 2017 May 16;42(2):163-168. Epub 2017 Feb 16.

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

Purpose: Kallistatin is a member of serine protease inhibitors (SERPIN) family, which has various functions such as regulation of cardiovascular function and blood vessels development. Its levels are elevated in patients with type 1 and type 2 diabetes with chronic diabetic complications. The aim of the present study was to compare serum kallistatin levels between obese subjects with prediabetes and with normal glucose tolerance.

Methods: In this study we included 80 subjects at mean age of 50.4 ± 10.6 years, divided into two 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 with measurement of immunoreactive insulin was performed in all participants and levels of kallistatin were measured using ELISA method.

Results: We found significantly higher levels of kallistatin in patients with prediabetes compared to controls (data are presented as median (min; max) because data were not normally distributed) (6.3 (4.4; 9.0) vs. 5.6 (3.1; 8.7) ng/ml; p = 0.022) and in patients with metabolic syndrome compared to those without (6.0 (4.9; 9.0) vs. 5.5 (3.1; 7.7); p = 0.006), but the levels were similar in patients with and without insulin resistance.

Conclusions: The levels of kallistatin are higher in individuals with prediabetes, but are similar in subjects with and without insulin resistance, which indicates that the main factor for its increased levels may be hyperglycemia and not insulin sensitivity state.
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http://dx.doi.org/10.1080/07435800.2017.1286671DOI Listing
May 2017

Myostatin and carbohydrate disturbances.

Endocr Res 2017 May 29;42(2):102-109. Epub 2016 Jun 29.

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

Purpose/aim of the study: Myostatin is a myokine that has been shown to inhibit muscle growth and to have potentially deleterious effects on metabolism. The aim of the current study was to compare its circulating serum levels in subjects from the whole spectrum of carbohydrate disturbances leading to diabetes.

Materials And Methods: A total of 159 age-, sex-, and BMI-matched subjects participated in the study - 50 had normal glucose tolerance (NGT), 60 had prediabetes (PreDM), and 49 had type 2 diabetes mellitus (T2D). Oral glucose tolerance testing was used to determine glucose tolerance. Serum myostatin was quantified by means of ELISA.

Results: Circulating serum myostatin levels were highest in patients with T2D, lower in subjects with prediabetes, and lowest in subjects with normoglycemia (all p < 0.05). Myostatin was shown to be positively associated with fasting plasma glucose, HOMA-IR, hepatic enzymes, uric acid, and FINDRISC questionnaire scores in both sexes. ROC analyses determined circulating myostatin levels to be of value for differentiating subjects with T2D (AUC = 0.72, p = 0.002 in men; AUC = 0.70, p = 0.004 in women) in the study population. After adjustment for potential confounders, in a multiple binary logistic regression model, serum myostatin added further information to traditional risk estimates in distinguishing subjects with T2D.

Conclusions: Serum myostatin levels are higher with deterioration of carbohydrate tolerance. Furthermore, circulating myostatin is positively associated with traditional biochemical estimates of poor metabolic health. These data add to evidence of the involvement of this myokine in the pathogenesis of T2D.
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http://dx.doi.org/10.1080/07435800.2016.1198802DOI Listing
May 2017

Increased peroxiredoxin 4 levels in patients with prediabetes compared to normal glucose tolerance subjects.

Clin Endocrinol (Oxf) 2016 Oct 18;85(4):551-5. Epub 2016 Jul 18.

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

Background: Peroxiredoxin 4 is a part of endogen antioxidant system and its levels are elevated in oxidative stress conditions. Its levels are positively associated with cardiovascular risk. The aim of this study was to compare serum peroxiredoxin 4 levels between obese subjects with prediabetes and with normal glucose tolerance.

Methods: In this study, we included 80 patients with mean age 50·4 ± 10·6 years and divided them into two age and BMI-matched groups - group 1 with obesity without glycaemic disturbances (n = 41) and group 2 with obesity and prediabetes (n = 39). Oral glucose tolerance test with measurement of immunoreactive insulin was performed in all participants, and the levels of peroxiredoxin 4 were measured using ELISA method.

Results: We found significantly higher levels of peroxiredoxin 4 in patients with prediabetes compared to controls (2851·2 ± 4576·6 pg/ml vs 1088·0 ± 753·3 pg/ml; P = 0·022). There was a mild but statistically significant correlation between peroxiredoxin 4 and weight (r = 0·232; P = 0·038), waist circumference (r = 0·239; P = 0·044), creatinine (r = 0·264; P = 0·019), liver enzymes (ASAT - r = 0·289; P = 0·019 and ALAT - r = 0·305; P = 0·07) and white blood cells count (r = 0·317; P = 0·005). There was no difference in peroxiredoxin 4 levels in patients with and without insulin resistance, as well as with and without metabolic syndrome (MetS), although the levels of peroxiredoxin 4 increased with the number of components of MetS.

Conclusions: The levels of peroxiredoxin 4 are higher in patients with prediabetes, but are similar in subjects with and without insulin resistance, which suggests that the main factor for its increased levels is hyperglycaemia and not insulin sensitivity state.
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http://dx.doi.org/10.1111/cen.13135DOI Listing
October 2016

Concomitant insulinoma and type 2 diabetes mellitus diagnoses: a case report.

J Diabetes 2016 Sep 1;8(5):740-2. Epub 2016 Jul 1.

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

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http://dx.doi.org/10.1111/1753-0407.12409DOI Listing
September 2016

A comparison of the clinical usefulness of neck circumference and waist circumference in individuals with severe obesity.

Endocr Res 2017 Feb 6;42(1):6-14. Epub 2016 Apr 6.

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

Purpose/Aim: Neck circumference (NC) is an emerging anthropometric parameter that has been proposed to reflect metabolic health. The aim of the current study was to compare its clinical usefulness to waist circumference (WC) in the assessment of individuals with severe obesity.

Materials And Methods: A total of 255 subjects participated in the study. All anthropometric measurements were done by a single medical professional. Biochemical measurements included oral glucose-tolerance tests (OGTTs), fasting insulin, lipids, and hepatic enzymes.

Results: The mean age of the participants was 49 ± 12 years with the mean body mass index (BMI) of 36.9 ± 6.2 kg/m. Correlation analyses revealed that while WC was better associated with adiposity parameters, it was of little use in comparison to NC with regard to metabolic outcomes. In men, NC was positively associated with fasting plasma glucose, fasting insulin, FINDRISC scores. ROC analyses showed NC was better in distinguishing type 2 diabetes (AUC = 0.758; p < 0.001), insulin resistance (AUC = 0.757; p = 0.001), metabolic syndrome (AUC = 0.724; p < 0.001), and hypertension (AUC = 0.763; p = 0.001). Similar correlations were observed in women. Using binary logistic regression, we determined that a NC of ≥35 cm in women and ≥38 cm in men are valuable cut-off values to use in the everyday practice.

Conclusion: In individuals with severe obesity, NC performs better than WC in the assessment of metabolic health.
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http://dx.doi.org/10.3109/07435800.2016.1155598DOI Listing
February 2017

Soluble CD40L is associated with insulin resistance, but not with glucose tolerance in obese nondiabetic patients.

Arch Physiol Biochem 2016 Jul 29;122(3):161-5. Epub 2016 Mar 29.

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

Objective: The soluble platelet secreted ligand CD40 (sCD40L) has a role in atherosclerosis progression. The aim of the present study was to investigate the link between the levels of sCD40L and some classical cardiovascular risk factors in obese nondiabetic patients.

Methods: In the present cross-sectional study, we included76 patients with mean age of 50.7 ± 10.7 years. Oral glucose tolerance test (OGTT) was performed in all participants and levels of sCD40L were measured using enzyme-linked immunosorbent assay (ELISA) method.

Results: We found significantly higher levels in patients with insulin resistance compared to those without (6.4 ± 3.7 vs. 4.1 ± 2.4 ng/ml, р = 0.025) and only a tendency toward higher levels in prediabetes compared to normoglycemic patients (5.9 ± 3.6 vs. 5.3 ± 3.4 ng/ml). There was no correlation between sCD40L and platelet count, systolic and diastolic blood pressure and lipid profile.

Conclusions: The main factor for increased sCD40L plasma levels was the presence of insulin resistance and not the state of glucose tolerance.
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http://dx.doi.org/10.3109/13813455.2016.1160934DOI Listing
July 2016

Acne vulgaris is associated with intensive pubertal development and altitude of residence--a cross-sectional population-based study on 6,200 boys.

Eur J Pediatr 2013 Apr 18;172(4):465-71. Epub 2012 Dec 18.

Clinical Center of Endocrinology and Gerontology, Medical University of Sofia, Faculty of Medicine, 2, Zdrave Str., 1431 Sofia, Bulgaria.

Unlabelled: Acne vulgaris is a chronic inflammatory disease with a complex pathogenesis that affects predominantly adolescents. The aim of the study was to investigate the interrelations between the presence of acne and several variables associated with somatic growth, pubertal maturation, and environmental conditions (altitude and regions of residence). A population sample of 6,200 clinically healthy boys (0-19 years) was examined and the presence of acne was determined. Height, weight, testicular volumes, penile length and circumference, as well as pubic hair were also measured. The prevalence of moderate and severe acne in the whole group was 7.74 %, while in the age group 12-19 years, it was 19.31 %. Twelve-15-year-old boys with acne were taller and heavier than the ones without. They also had increased penile length and circumference as well as larger testicular volumes. Somatometric and pubertal characteristics of 17-19-year-old boys with and without acne were similar. The prevalence of the disease did not differ between the rural and urban inhabitants. However, the acne frequency decreased with the increasing of the altitude where the boys lived.

Conclusions: Our results showed that the development of acne vulgaris in male adolescents was associated with an intensive growth and pubertal maturation, while obesity per se did not play an important role. Of particular interest was the association between the prevalence of acne and the altitude of residence.
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http://dx.doi.org/10.1007/s00431-012-1907-1DOI Listing
April 2013
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