Cardiovascular Biomarkers and Calculated Cardiovascular Risk in Orally Treated Type 2 Diabetes Patients: Is There a Link?

The aim of the study was to test the correlation of serum levels of asymmetric dimethylarginine (ADMA), endothelin 1 (ET-1), N-terminal brain natriuretic pro-peptide (NT-proBNP), and placental growth factor (PIGF-1) with estimated cardiovascular (CV) risk. The study group was composed of 102 women and 67 men with type 2 diabetes, having their glycemic and metabolic parameters assessed. All were on oral antidiabetic drugs. Serum levels of NT-proBNP and PIGF-1 were measured by electro-hemi-luminescence on an Elecsys 2010 analyzer. Enzymatic immunoassays were used for ADMA and ET-1. The Framingham Risk Score (FRS), the UKPDS 2.0 and the ADVANCE risk engines were used to calculate cardiovascular risks while statistical analysis was performed on SPSS. Levels of PIGF-1 showed no correlation with the calculated CV risks. The same was true for ADMA, except for a weak correlation with the UKPDS-based 10-year risk for stroke (Pearsons's R=0.167, p=0.039). Plasma levels of ET-1 were correlated with the UKPDS-based 10-year risk for stroke (R=0.184, p=0.032) and fatal stroke (R=0.215, p=0.012) only. NT-proBNP was significantly correlated with all CV risk calculations: ADVANCE-based 4-yr risk (Spearman's Rho=0.521, p<0.001); UKPDS-based 10-year risk for: CHD (Rho=0.209, p=0.01), fatal CHD (Rho=0.282, p<0.001), stroke (Rho=0.482, p<0.001), fatal stroke (Rho=0.505, p<0.001); and 10-year FRS risk (Rho=0.246, p=0.002). In conclusion, ADMA and PIGF-1 did not seem useful in stratifying CV risk while ET-1 is linked to the risk of stroke, and NT-proBNP to all CV risk estimations.

Bone Health Index and bone turnover in pediatric patients with type 1 diabetes mellitus and poor metabolic control.

BACKGROUND: There is a need for a non-invasive, affordable, and reliable method for bone health screening in pediatric patients at risk. OBJECTIVE: To assess Bone Health Index (BHI) in pediatric patients with type 1 diabetes (T1D) and its relation to bone metabolism, age at onset, duration, control, and insulin dose. SUBJECTS AND METHODS: Left-hand radiographs were obtained from 65 patients with T1D, mean age 11.23 ± 3.89 years, mean disease duration 5.23 ± 3.76 years and mean glycosylated hemoglobin (HbA1c)-83 mmol/mol (9.7%). Blood and 24 hours urine samples were collected for bone and mineral metabolism assessment. BoneXpert was used to determine BHI, Bone Health Index standard deviation score (BHI SDS), and bone age. RESULTS: Mean BHI SDS was -1.15 ± 1.19 (n = 54). In 20.37% (n = 11) BHI SDS was < -2SD with mean value -2.82 ± 0. 69, P < .001. These patients had lower levels of beta cross laps (0.77 ± 0.33 ng/mL vs 1.17 ± 0.47 ng/mL), osteocalcin (47.20 ± 14.07 ng/mL vs 75.91 ± 32.08 ng/mL), serum magnesium (0.79 ± 0.05 mmol/L vs 0.83 ± 0.06 mmol/L) and phosphorus (1.48 ± 0.29 mmol/L vs 1.71 ± 0.28 mmol/L) but higher ionized calcium (1.29 ± 0.04 mmol/L vs 1.26 ± 0.05 mmol/L), P < .05, compared to patients with BHI SDS in the normal range. We found a positive correlation between BHI SDS and age at manifestation (r = 0.307, P = 0.024) and a negative one with disease duration (r = -0.284, P = .038). No correlations were found with HbA1c, insulin dose, height, weight, BMI. CONCLUSIONS: To the best of our knowledge, this is the first study to assess bone health in pediatric patients with T1D using BHI. We found significantly decreased cortical bone density and bone turnover in 20.37%. Earlier age at onset and diabetes duration may have a negative impact on cortical bone density in patients with poor control. Longitudinal studies are needed to follow changes or to assess future interventions.

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

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 (n = 40); Obese PCOS (n = 20) and Obese control group (n = 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; p = .023) and lower of 25(OH)D (35.8 ± 21.4 vs 47.8 ± 26.5 nmol/l; p = .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; p = .031) and decreased levels of 25(OH)D (31.9 ± 16.8 vs. 47.1 vs 28.4 nmol/l; p = .017) compared to those not at risk. There was no correlation between bone markers and blood glucose levels, insulin resistance or hormonal levels.

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

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.

Interleukin-18 and testosterone levels in men with metabolic syndrome.

OBJECTIVE: Interleukin 18 (IL-18) is an adipokine associated with obesity. Data about the relationship of IL-18 to the metabolic syndrome (MS) are still scarce. Low testosterone (T) levels are common in men with MS, but we did not find data about the levels of IL-18 in men with low T. The aim of this study was to determine the levels of IL-18 in men with MS with or without low T. PATIENTS AND METHODS: A total of 251 men were included in the study. Of them 218 had MS (IDF 2005) and they were divided according to their morning total testosterone (TT) level (cutoff 10.4 nmol/l) into two groups: MS-low T (N = 84) and MS-normal T (N = 134). The control group consisted of 33 men without MS and low T. IL-18 was determined in serum using enzyme-linked immunosorbent assay. A small group of eight men with MS and low T levels received testosterone therapy for three months and physical and laboratory parameters were monitored at the end of that period. RESULTS: MS men were at mean age (±SD) = 53.77 ± 9.59 years; body mass index (BMI) = 34.0 ± 6.3 kg/m2; and TT = 12.59 ± 5.66 nmol/l. The control group was at age = 52.12 ± 5.2 years (NS); BMI = 25.6 ± 2.4 kg/m2 (p < .001); and TT = 17.8 ± 5.68 nmol/l (p < .001), respectively. The levels of IL-18 were higher in the MS group - 345 pg/ml compared to the control one - 264 pg/ml (p < .01). There was no significant difference between MS-low T (330.6 pg/ml) and MS-normal T (350.2 pg/ml) subgroups. The MS-normal T differed more significantly from the control group (p < .001). Significant correlation of testosterone with IL-18 levels was not found. IL-18 correlated with parameters of obesity, lipids, fasting blood sugar (p < .05) and the number of criteria for MS (p < .001). Three months on T treatment showed improvement in obesity parameters and only in one patient IL-18 had clear reduction while the rest showed no change. CONCLUSIONS: In this study, higher IL-18 levels were found in the presence of MS compared to healthy men, but they did not differ between men having MS with or without LOH.

Irisin and Testosterone in Men with Metabolic Syndrome.

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 (ß=-0.228, p=0.004) and irisin (ß=-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.

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

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/m2. 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.

Diabetes Mellitus Type 2 in Hospitalized COPD Patients: Impact on Quality of Life and Lung Function.

INTRODUCTION: Diabetes mellitus (DM) is estimated to affect 2-37% of COPD patients, results varying widely between studies. DM may also correlate with quality of life and lung function. AIM: To examine correlations between DM and quality of life and lung function in COPD patients admitted to hospital with exacerbation of COPD. PATIENTS AND METHODS: A hundred and fifty-two patients were included in the study. They were all examined for diabetes mellitus. All patients completed CAT and mMRC questionnaires and underwent spirometry. RESULTS: 13.2% (20/152) of patients received medications for DM. 21.7% (33/152) had newly diagnosed DM and 30.9% (47/152) had prediabetes. DM is not associated with reduced quality of life and worse pulmonary function. However, untreated DM is associated with both reduced quality of life and worse pulmonary function. HbA1c is negatively correlated with FVC and positively correlated with CAT score. CONCLUSIONS: COPD patients hospitalized for exacerbation are at high risk for impaired glucose metabolism. Untreated DM is associated with worse lung function and lower quality of life, which stresses the importance of screening for the disease. The patients may benefit from optimizing blood glucose level.

25(OH) vitamin D levels in premenopausal women with polycystic ovary syndrome and/or obesity.

BACKGROUND: Insulin resistance, hyperinsulinemia, and obesity play an important role in development of polycystic ovary syndrome (PCOS). Current evidence suggests that vitamin D (VitD) deficiency may contribute to the disturbance in insulin metabolism and the development of the metabolic syndrome. The aim of this study was to investigate VitD levels, measured as 25(OH)D, in Bulgarian women with PCOS and/or obesity. MATERIALS AND METHODS: The study included 103 women, divided into three groups - group 1 Obese (n = 33); group 2 Nonobese PCOS (n = 50), and group 3 Obese PCOS (n = 20). 25(OH)D levels were measured by electrochemiluminescence immunoassay. RESULTS: Almost 2/3 of the women with PCOS and/or obesity appeared to be VitD-deficient. Women with obesity, especially visceral (with or without PCOS), had significantly lower levels of 25(OH)D compared to lean PCOS subjects. Women with and without metabolic syndrome however did not differ significantly in 25(OH)D levels. Women with normal body mass index (BMI) had higher 25(OH)D levels compared to overweight and obese (p = 0.028). There was no correlation between 25(OH)D levels and indices of glucose metabolism - fasting blood glucose and immunoreactive insulin (IRI) and after OGTT and HOMA index.

Total Testosterone as a Specific Marker of Acute Kidney Injury in Male Patients With Myocardial Infarction.

Aim The aim of the present study was to assess the significance of total testosterone (T) as a marker of acute kidney injury (AKI) in patients with acute myocardial infarction (MI). Patients and methods The study was a retrospective, single-center cohort study that included 55 consecutive male patients diagnosed with acute MI who were admitted to the Cardiology Clinic of Alexandrovska University Hospital (Sofia, Bulgaria) between July 2011 and December 2013. The plasma total T levels, measured at admission, the peak levels of myocardial necrosis markers, high-sensitive C-reactive protein (hsCRP), and the left ventricular ejection fraction (LVEF) were analyzed in relation to the incidence of AKI. Results The occurrence of AKI was positively predicted by reduced EF (OR=0.825; CI=0.724-0.942; P=0.004), advanced age (OR=1.077; CI=1.038-1.151; P=0.029), and low levels of total T (OR=0.837; CI=0.707-0.990; P=0.037). Reduced systolic function (OR=0.861; 95% CI=0.758-0.978; P=0.022 for EF) and marginally age (OR=1.094; 95% CI=1.000-1.197; P=0.051) contributed to the incidence of AKI in a multivariate model. Total T was not an independent factor (OR=0.841; 95% CI=0.669-1.058; P=0.139) for AKI. The total T levels were significantly inversely correlated with the peak of hsCRP (r= -0.153; P=0.009) and showed a tendency to inverse relation with the SYNTAX score (r= -0.235; P=0.083). Conclusion The total T levels are significantly inversely related to the peak of hsCRP and as a tendency to the SYNTAX score in male patients with acute MI. A low level of plasma total T is not an independent marker of AKI in acute MI. Advanced age and low EF are independent factors for AKI discrimination in a small cohort of patients with acute MI.

Diaphragmatic Movement at Rest and After Exertion: A Non-Invasive and Easy to Obtain Prognostic Marker in COPD.

Introduction: Diaphragmatic dysfunction is common in patients with chronic obstructive pulmonary disease (COPD). This study aimed to assess the prognostic significance of impaired diaphragmatic movement at rest and after exercise. Methods: This was a prospective study of patients with stable COPD. Diaphragmatic movements were examined at rest and after a 6-minute walking test (6MWT) with a convex transducer with a frequency of 3.5-5-7.5 MHz. Maximal movement of the diaphragm was measured in both right and left diaphragm, and the side with higher amplitude was selected for further analysis. Measurements obtained were evaluated for their prognostic value for a composite endpoint of moderate and severe COPD exacerbations and death in 1 year time period was assessed. In addition, postbronchodilator spirometry, symptoms, quality of life, and demographic and clinical information were collected. Results: A total of 96 patients were analyzed (62.5% male, mean age 65.1 years (standard deviation (SD): 8.1), mean FEV1 (% predicted): 55.8%, SD: 18.3%, mean CAT: 15.6 units, SD: 9.2). Sixty-four patients (67%) presented the composite endpoint. In the multivariate Cox analysis, FVC (HR = 0.944, p = 0.005), CAT score (HR = 1.133, p = 0.011), previous severe exacerbations (HR = 5.446, p = 0.004) and diaphragmatic movement at rest (HR = 0.932, p = 0.033) were found to be predictors of the composite endpoint. This model correctly classified 86.5% (83/96) of the patients. Conclusion: Non-invasive assessment of diaphragmatic movement by ultrasound measurement both at rest and after exercise could contribute to the assessment of disease severity and prognosis of COPD.

Body Composition Indices and Cardiovascular Risk in Type 2 Diabetes. CV Biomarkers are not Related to Body Composition.

BACKGROUND: This study aims to explore the correlations of body mass index (BMI), waist circumference (WC), waist-to-height ratio (WHtR), waist-to-hip ratio (WHR) and body composition with levels of asymmetric dimethylarginine (ADMA), endothelin 1(ET-1), N-terminal brain natriuretic pro-peptide (NT-proBNP) and calculated cardiovascular risks. METHODS: 102 women and 67 men with type 2 diabetes participated. Serum levels of NT-proBNP were measured by electro-hemi-luminescence while ELISA were used for ADMA and ET-1. Cardiovascular risks were calculated using the Framingham Risk Score (FRS), the UKPDS 2.0 and the ADVANCE risk engines. Statistical analysis was performed on an IBM SPSS 19.0. RESULTS: The BMI outperformed all other indices of obesity (WC, WHtR, WHR), as well as body composition parameters (body fat%, fat mass, fat free mass and total body water) in relation to the estimated risks for coronary heart disease and stroke, based on different calculators. The correlations of the obesity indices with the serum cardiovascular biomarkers were not significant except for BMI and fat mass versus ET-1, and for fat free mass and total body water versus ADMA. CONCLUSIONS: The WC, WHR, WHtR, BF%, FM and FFM apparently do not add significant information related to the levels of cardiovascular biomarkers or the calculated CV-risks.

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

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 ±â€¯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.

Reduced soluble Toll-like receptors 2 in type 2 diabetes.

BACKGROUND: Soluble forms of Toll-like receptors (sTLR) 2 and 4 exert negative regulatory control on membrane-bound receptor activation. The study estimates the sTLR2 and sTLR4's serum levels in type 2 diabetes (T2D) and evaluates their relationship with metabolic and inflammatory parameters. SUBJECTS AND METHODS: Sixty three patients with T2D and 25 controls were enrolled. sTLR were assayed through ELISA. Inflammatory markers included Interleukin 6 (IL-6), high sensitivity C-reactive protein (hs-CRP) and tumour necrosis factor α. RESULTS: Analysis demonstrated lower sTLR2 level in T2D than in control subjects (1.15 ± 0.65 versus 1.44 ± 0.60 ng/ml, p = .019) while sTLR4 level remained similar (0.09 ± 0.16 versus 0.07 ± 0.12 ng/ml, p > .05) despite higher IL-6 (2.65 ± 2.46 versus 1.44 ± 0.22 pg/ml, p = .005) and hs-CRP (2.79 ± 2.89 versus 0.70 ± 0.89 mg/l, p < .001) concentrations. Neither sTLR correlated with BMI, HbA1c, plasma glucose and analysed cytokines (p > .05). CONCLUSION: The sTLR2 serum level in T2D patients was reduced despite elevated inflammatory parameters.

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

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.

Interleukin-18 serum level is elevated in type 2 diabetes and latent autoimmune diabetes.

BACKGROUND: Interleukin-18 (IL-18) is an inflammatory cytokine found to be elevated in obesity, metabolic syndrome and type 2 diabetes (T2D) as a part of the chronic low-grade inflammatory process in these states. The aim of the study was to evaluate the interleukin level in patients with latent autoimmune diabetes of the adults (LADA) in comparison to that in T2D subjects. MATERIALS AND METHODS: IL-18 was analyzed through enzyme-linked immunosorbent assay in 76 participants with T2D and 24 with LADA and 14 control subjects. Evaluation was also carried out in body mass index (BMI)- and glycemic control-matched diabetic patients. RESULTS: The serum concentration of IL-18 was higher in patients with T2D (389.04 ± 203.44 pg/mL) and LADA (327.04 ± 144.48 pg/mL) than that in control subjects (219.88 ± 91.03 pg/mL), P < 0.05. However, it was not significantly different between both diabetic groups (P = 0.255) despite higher IL-6 (4.78 ± 5.84 vs 1.79 ± 0.96 pg/mL, P < 0.001) and hs-CRP (2.60 ± 1.70 vs 1.29 ± 1.20 mg/L, P = 0.002) level in T2D patients. The results were persistent in BMI-matched subjects with diabetes (IL-18 = 403.48 ± 226.32 vs 329.30 ± 146.30 pg/mL, respectively for T2D and LADA, P = 0.391). The correlations in T2D group concerning HDL cholesterol (r = -0.377, P = 0.001), postprandial glucose (r = 0.244, P = 0.043), IL-6 (r = 0.398, P < 0.001) and hs-CRP (r = 0.427, P = 0.001) were not confirmed in LADA and control subjects. CONCLUSION: The IL-18 serum level was higher in T2D and LADA than that in control subjects, but did not differ between both diabetic groups, even when they were BMI matched. Correlations with lipid, glycemic and inflammatory parameters were present in T2D only.

Prevalence of Positive Diabetes-Associated Autoantibodies among Type 2 Diabetes and Related Metabolic and Inflammatory Differences in a Sample of the Bulgarian Population.

BACKGROUND: The study aimed to estimate the prevalence of unrecognized cases with positive autoantibodies among type 2 diabetes (T2D) in a sample of the Bulgarian population and to compare some metabolic and inflammatory markers to those of patients having negative autoantibodies and subjects with latent autoimmune diabetes (LADA). METHODS: Patients with T2D, patients with LADA, and control participants were enrolled. Antiglutamic acid decarboxylase, anti-insulinoma-associated 2, and antizinc transporter 8 autoantibodies were assayed through ELISA. C-reactive protein and interleukin 6 (IL-6) and tumor necrosis factor alpha were assessed. RESULTS: Ten percent of patients with T2D had positive autoantibodies. They had lower body mass index (p = 0.014), worse glycemic control (HbA1c, p = 0.033), and better HDL cholesterol (p = 0.026) than those in negative autoantibodies cases. Compared to LADA, glycemia and anthropometric data did not differ significantly but metabolic syndrome was more prevalent among newly found cases with positive autoantibodies (p = 0.046). Their level of inflammatory markers was similar to that of patients having negative autoantibodies (p > 0.05), but IL-6 was higher when compared to LADA (p = 0.002). CONCLUSION: Prevalence of patients having positive autoantibodies within T2D in the analyzed sample of the Bulgarian population was 10%. They shared common metabolic features with subjects with LADA, but inflammatory phenotype was closer to that of T2D.

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

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.

One-year mortality after severe COPD exacerbation in Bulgaria.

INTRODUCTION: One-year mortality in COPD patients is reported to be between 4% and 43%, depending on the group examined. AIM: To examine the one-year mortality in COPD patients after severe exacerbation and the correlation between mortality and patients' characteristics and comorbidities. METHODS: A total of 152 COPD patients hospitalized for severe exacerbation were assessed for vitamin D status, diabetes mellitus (DM), arterial hypertension (AH), and metabolic syndrome (MS). Data were gathered about smoking status and number of exacerbations in previous year. CAT and mMRC questionnaires were completed by all patients. Pre- and post-bronchodilatory spirometry was performed. One-year mortality was established from national death register. RESULTS: One-year mortality is 7.2%. DM, MS, and VD are not predictors for one-year mortality. However there is a trend for increased mortality in patients with AH (9.5% vs. 2.1%, p = 0.107). There is increased mortality in patients with mMRC > 2 (11.1 vs. 0%, p = 0.013). The presence of severe exacerbation in the previous year is a risk factor for mortality (12.5% vs. 1.4%, p = 0.009). There is a trend for increased mortality in the group with FEV1 < 50% (11.5 vs. 4.4%, p = 0.094). Cox regression shows 3.7% increase in mortality rate for 1% decrease in FEV1, 5.2% for 1% decrease in PEF, 7.8% for one year age increase and 8.1% for 1 CAT point increase (all p < 0.05). CONCLUSIONS: This study finds relatively low one-year mortality in COPD patients after surviving severe exacerbation. Grade C and FEV1 > 80% may be factors for good prognosis. Risk factors for increased mortality are age, FEV1 value, severe exacerbation in previous year and reduced quality of life.

Vitamin D Deficiency and Insufficiency in Hospitalized COPD Patients.

INTRODUCTION: 31-77% of patients with COPD have vitamin D deficiency and insufficiency, with results being highly variable between studies. Vitamin D may also correlate with disease characteristics. AIM: To find out the prevalence of vitamin D deficiency and insufficiency in patients with COPD admitted for exacerbation and a risk factors for lower vitamin D levels among comorbidities and COPD characteristics. METHODS: 152 patients were studied for vitamin D serum levels (25(OH)D). All of them were also assessed for diabetes mellitus (DM) and metabolic syndrome (MS). Data were gathered also for smoking status and exacerbations in last year. All patients completed CAT and mMRC questionnaires and underwent spirometry. RESULTS: A total of 83,6% of patients have reduced levels of vitamin D. 42,8% (65/152) have vitamin D insufficiency (defined as 25-50 nmol/L) and 40,8% (62/152) have vitamin D deficiency (<25 nmol/L). The mean level of 25(OH)D for all patients is 31,97 nmol/L (95%CI 29,12-34,68). Vitamin D deficiency and insufficiency are more prevalent in females vs. males (97,7 vs 77,8%; p = 0.003). The prevalence and severity of vitamin D deficiency and insufficiency in this study is significantly higher when compared to an unselected Bulgarian population (prevalence 75,8%; mean level 38,75 nmol/L). Vitamin D levels correlate with quality of life (measured by the mMRC scale) and lung function (FVC, FEV1, FEV6, FEF2575, FEV3, but not with FEV1/FVC ratio and PEF), it does not correlate with the presence of arterial hypertension, DM, MS and number of moderate, severe and total exacerbations. Vitamin D deficiency is a risk factor for longer hospital stay. CONCLUSIONS: The patients with COPD admitted for exacerbation are a risk group for vitamin D deficiency and insufficiency, which is associated with worse disease characteristics.