Serum Levels of Incretin Hormones - GLP-1 and GIP in Patients with Type 1 Diabetes Mellitus.

BACKGROUND: The glucagon-like peptide-1 (GLP-1) and the glucose- dependent Insulinotropic peptide (GIP) are natural incretin hormones, which are secreted respectively by the L- and K-cells of the intestinal mucosa in response to the physiological gastrointestinal glucose absorption. In patients with type 2 diabetes mellitus, the incretin effect is reduced, whereas the results in type 1 diabetes mellitus (T1DM) are heterogeneous, in some patients normal incretin response is observed. AIM: Comparative analysis of the basal serum levels of the incretin hormones GLP-1 and GIP in patients with type 1 DM and in individuals without carbohydrate disorders. MATERIALS AND METHODS: The study included 27 patients with diagnosed T1DM and a control group of 39 individuals without carbohydrate disorders. All participants in the study were subjected to the following clinical measurements and laboratory tests - height, weight, bioimpedance analysis of body composition, fasting blood sugar (BS 0'), postprandial blood sugar (PPBS), glycated haemoglobin (HbA1c) in T1DM patients, total cholesterol (TC), HDL cholesterol (HDL chol), triglycerides (TG), transaminase (AST and ALT), basal serum levels of GLP-1 and GIP. RESULTS: The serum levels of GIP in the patients with type T1DM were significantly higher, compared to the individuals without carbohydrate disorders (P<0.05), while there was no statistically significant difference in the GLP-1 levels. CONCLUSION: The significantly higher GIP levels and the similar GLP-1 levels in our patients with type 1 DM, compared to the individuals without carbohydrate disorders, support the hypothesis of intact incretin effect in this type of diabetes mellitus Key Words: Glucagon-like peptide-1, Glucose-dependent insulinotropic peptide, Type 1 diabetes mellitus.

Cortisol Correlates with Structural Magnetic Resonance Imaging Parameters in Middle Aged Bulgarian Patients with Metabolic Syndrome: A Pilot Study.

BACKGROUND: There is a dose-dependent relationship between chronically increased cortisol levels and the number of metabolic syndrome (MetS) components. Both cortisol and MetS are linked to various brain abnormalities. AIM: To investigate an association of MetS components and salivary cortisol levels with cortical thickness in middle-aged Bulgarian patients with MetS. MATERIALS AND METHODS: We examined 26 healthy volunteers (mean age 50, 16±3.1 yrs) divided into two groups depending on whether or not they were diagnosed with MetS. Salivary cortisol was sampled and tested at two time points -morning and evening. Cortical thickness measures were obtained from structural T1-images using FreeSurfer software. We performed vertex-wise analysis across entire cortex and for preselected brain regions in frontal, temporal and cingulate cortex partial correlation analysis, accounting for gender. RESULTS: The control group consisted of 12 women; in the MetS group there were 6 men and 8 women. The whole brain analysis showed that waist circumference (WC) was negatively correlated with cortical thickness in rostro-lateral area in left frontal lobe and the right lateral orbito-frontal cortex. Morning cortisol levels, accounting for sex and WC, correlated negatively with thickness in left superior temporal area (r = -0.477, p = 0.039) and entorhinal area (r = -0.465, p = 0.045) and left mediotemporal cortex (r = -0.477, p = 0.038). CONCLUSION: Our pilot study confirmed that WC is associated with brain atrophic changes mainly in the frontal lobe. Our finding that cortisol levels negatively correlate with thinning of the cortex in temporal lobe should be further explored in subsequent study.

Effect of Training at Lactate Threshold Intensity on Maximal Time to Exhaustion, Depression and Anxiety Behaviour of Spontaneously Hypertensive Rats after Kainate-Induced Status Epilepticus.

AIM: The objective of the present study was to investigate the effect of treadmill training at lactate threshold intensity on maximum time to exhaustion (MTE) and heart rate (HR) as well as behavioral changes after kainate (KA)-induced status epilepticus (SE) of spontaneously hypertensive rats (SHRs). MATERIALS AND METHODS: Male SHRs were divided in four groups: two sedentary (vehicle- and KA-treated) and two exercised (vehicle- and KA-treated), respectively. The exercised rats were trained on a treadmill at a speed of 20 m.min-1 and 0° elevation for 40 min.d-1, for 4 wk. Maximal time to exhaustion and HR was measured at the beginning and at the end of the training period. Status epilepticus was evoked in half of the sedentary and trained rats by a repetitive intraperitoneal injection of KA in low subconvulsive doses. The other half of the groups received saline. Sucrose preference test (SPT) for depression-like behavior and hole board test (HBT) for impulsivity were performed a month after KA/veh injection. RESULTS: The maximum time of exhaustion was elongated in the SHRs at the end of the training period in comparison with the beginning. However, no effect on HR was detected in trained rats. Kainate treatment after one month of training alleviated the SE-induced anhedonia in SPT and stereotyped behavior in HBT, respectively. CONCLUSIONS: Taken together, these results demonstrate that exercise exerts a beneficial influence on physical working capacity, depression and impulsive behavior in a co-morbid model of essential hypertension and SE.

The effect of flutamide on the physical working capacity and activity of some of the key enzymes for the energy supply in adult rats.

The aim of the study was to assess the effects of androgen receptor antagonists on the physical working capacity and activity of some of the key muscle enzymes for the energy supply in rats. Young adult male Wistar rats were divided into two groups. One group received 15 mg kg-1 of flutamide daily for 6 days a week and the other group served as control for 8 weeks. At the beginning and at the end of the experiment, all rats were subjected to submaximal running endurance (SRE), maximum time to exhaustion (MTE), and maximal sprinting speed (MSS) tests. At the end of the trial, maximum oxygen consumption (VO2max) test was performed and the levels of testosterone, erythrocytes, hemoglobin as well as enzyme activity of succinate dehydrogenase (SDH), lactate dehydrogenase (LDH), and NAD.H2-cytochrome-c reductase (NAD.H2) of the gastrocnemius muscle were measured. Serum testosterone of the flutamide-treated rats was higher than that of the controls, which verifies the effectiveness of the dose chosen. MTE and SRE of the anti-androgen-treated group were lower compared with the initial values. Flutamide treatment decreased the activity of SDH and NAD.H2 compared with the controls. We found no effect of the anti-androgen treatment on MSS, VO2max, running economy, LDH activity, and hematological variables. Our findings indicate that the maintenance of the submaximal and maximal running endurance as well as the activity of some of the key enzymes associated with muscle oxidative capacity is connected with androgen effects mediated by androgen receptors.

Serum melatonin in women with polycystic ovary syndrome.

UNLABELLED: There has been a surge of interest in recent years in studying the changes of serum melatonin concentrations in disorders that are associated with insulin resistance such as diabetes mellitus type 2 and polycystic ovary syndrome (PCOS). AIM: The present study was designed to investigate the day-time and night-time levels of serum melatonin and the cortisol rhythm in women with PCOS and compare them with those of healthy women. PATIENTS AND METHODS: This is a case-control study which included 30 women with PCOS and 25 healthy women. All hormonal measurements in both the study group and controls were carried out between days 3 and 5 counted from the beginning of the last regular menstrual cycle; they included serum levels of melatonin and cortisol at 03:00 a.m and 08:00 a.m, total testosterone (T), dehydroepiandrosterone sulfate (DHEA-S), luteinizing hormone (LH), follicle stimulating hormone (FSH), and immunoreactive insulin at 08:00 a.m. RESULTS: Women with PCOS were found to have a significantly higher melatonin level at 08:00 a.m. and smaller mean night-day difference in the concentrations of melatonin in comparison with those of healthy women (natural log (Ln) night-day difference 0.60 +/- 0.10 pg/ml versus 1.15 +/- 0.14, p < 0.002). Melatonin to cortisol ratios at 03:00 a.m. and 08:00 a.m. showed no statistically significant differences between the two groups (Ln melatonin/cortisol 03:00 a.m., 1.01 +/- 0.06 versus 1.05 +/- 0.05; Ln melatonin/cortisol at 08:00 a.m., 0.62 +/- 0.01 versus 0.56 +/- 0.03, p > 0.05). CONCLUSION: The results we obtained about the changes of melatonin in women with PCOS could help in elucidating the complex pathophysiological pattern of this disease.

Prevalence of cytomegalovirus infection in hospitalized infants.

UNLABELLED: Data on cytomegalovirus infection (CMV) prevalence and course in hospitalized infants are rather scarce, obsolete and considerably inconsistent. AIM: to determine the prevalence, rate of clinical manifestations, risk factors and predictive capacity of clinical manifestations of CMV infection in hospitalized infants during their first year of life. PATIENTS AND METHODS: All 163 infants hospitalized in the Pediatric Ward for Nonrespiratory Pathology in a tertiary hospital were serologically screened for cytomegalovirus infection for 10 months. In infants up to 6 months old that were CMV IgG (+) and CMV IgM (-) we followed up the CMV IgG concentration or compared it with that of their mothers. RESULTS: The CMV prevalence for the entire study sample was 33.1 +/- 3.7% (54 seropositive out of 163 examined infants); in newborns it was 19.4 +/- 6.7% (7 of 36), in infants aged 1-3 months--23.8 +/- 5.4% (15 of 63), in 4-6-month olds--28.1 +/- 8.1% (9 of 32), and in 7-12-month old--71.9 +/- 8.1% (23 of 32). The rates of clinically apparent infections in the respective groups was 33.3 +/- 6.5%, 57.01 +/- 20.2%, 53.3 +/- 13.3%, 33.3 +/- 16.6%, and 13.0 +/- 7.17%. The overall rate of clinically apparent CMV infection in all 163 children was between 11.0 +/- 2.5% and 17.2 +/- 2.9%. The probability of CMV infection increased with age and duration of breastfeeding. Hepatitis, cerebral vasculopathy and pneumonia (alone or combined) turned out to be predictors of CMV infection, but none of these symptoms had a frequency greater than 22%. CONCLUSIONS: We found a high rate of cytomegalovirus infections in hospitalized infants less than one year of age. This infection is the reason why at least 10% of the newborns and 12% of the children aged 1 to 3 months were hospitalised. The course was clinically apparent in over half of the infected children of up to 3 months of age.

Melatonin reference limits at 3:00 AM and 8:00 AM in healthy adults.

We determined melatonin reference limits in blood serum of 129 healthy volunteers, aged 21 to 70 years, using enzyme-linked immunosorbent assay (IBL ELISA kit, Hamburg, Germany). At 3:00 AM, in almost full dark, the reference limits were found to be 18.3-134 pg/ml in males, 19.0-197 pg/ml in females and 18.5-180 pg/ml in the whole group. At 8:00 AM, they were statistically lower (5.63-61.8, 3.30-93.2 and 3.83-80.4 pg/ml respectively) possibly due to the light.

Early hypothyroidism after subtotal thyroidectomy in patients with Graves' disease--the role of the preoperative conservative treatment and hormonal status.

AIM: The aim of the present study was to evaluate the role of the preoperative antithyroid drug treatment and hormonal status in the development of early postoperative hypothyroidism after subtotal thyroidectomy in patients with Graves' disease. MATERIAL AND METHODS: Eighty-five patients with Graves' disease (males : females ratio 1:5.54, age range 19 to 64, 37.52 +/- 1.09 yrs) who had previously undergone surgical treatment were enrolled in the study. All patients underwent bilateral subtotal thyroidectomy with the amount of remnant tissue of 2-3 g for each lobe (total 4-6 g). Development of early (within one year after the operation) postoperative hypothyroidism was analyzed regarding the type of the antithyroid drug, preoperative dose, duration of the preoperative medical treatment, FT3, FT4, FT3/FT4 and hTSH. RESULTS: Forty six percent of all examined patients (54.12%) were euthyroid and 39 (45.88%/)--hypothyroid. Postoperative hypothyroidism was developed by 33.33% of the patients that had received preoperatively propylthiouracil compared with 50.82% of those treated with methymazol (p > 0.05). The duration of the preoperative treatment was 38.36 +/- 3.53 months for the hypothyroid patients and 30.11 +/- 2.34 months for the euthyroid patients (p < 0.05). Postoperative hypothyroidism developed in 58.70% of the patients with preoperatively suppressed thyroid-stimulating hormone (hTSH) and in 33.33% of those with normalized values of hTSH (p < 0.05). No statistically significant between-group difference was found in the preoperative dose of antithyroid agent, mean values of free triiodothyronine (FT3), free thyroxine (FT4), FT3/FT4, thyrotropic hormone (TSH). CONCLUSIONS: Longer preoperative antithyroid drug treatment and suppression of hTSH in the preoperative period correlated with higher risk of hypothyroidism after subtotal thyroidectomy. The type and the preoperative dose of the antithyroid agent, as well as the mean values of thyroid hormones before the operation have no prognostic significance for postoperative thyroid hypofunction.

Interleukin-6, interleukin-8, interleukin-10, and C-reactive protein in febrile neutropenia in children with malignant diseases.

AIM: To compare serum levels of interleukin-6, interleukin-8 and interleukin-10 in bacteremic and non-bacteremic episodes of febrile neutropenia in children with malignant diseases, and determine their changes and correlation with C-reactive protein (CRP). MATERIAL AND METHODS: Between January 2003 and June 2004, we examined 41 episodes of febrile neutropenia in 24 children with malignant diseases who were receiving polychemotherapy. C-reactive protein was measured at the onset of febrile episodes and on days 3 and 5 from beginning of therapy. The soluble interleukins-6, -8, and -10 were determined in the serum using enzyme bound immunosorbent analysis at the onset of fever and at 24 and 72 hours after initiation of an empiric antibiotic therapy. RESULTS: The CRP baseline levels differentiated the patients with unexplained fever from those with local infection but did not differentiate them from those with bacteremia. Interleukin-8 at 24 hours differentiated bacteremic from non-bacteremic episodes (P < 0.05) and at a cut-off value of 130 pg/ml it had a sensitivity of 72% and a specificity of 84% to differentiate bacteremia. Interleukin-10 at 24 hours yielded higher values in Gram (-) bacteremia in comparison with the non-bacteremic episodes (P < 0.001) and Gram (+) bacteremia (P < 0.05). Interleukin-6 at 24 hours had significantly higher values in febrile episodes of more than 3 days duration (P < 0.05). CONCLUSIONS: Interleukin-8 could differentiate in the first 24 hours bacteremic from non-bacteremic episodes in febrile neutropenia, while interleukin-10 is perhaps a more accurate marker for Gram (-) bacteremia.

Effect of chromium on the insulin resistance in patients with type II diabetes mellitus.

INTRODUCTION: Chromium deficiency in diabetic patients is a debatable problem. The prevailing opinion suggests the presence of low serum concentrations in such patients and therefore an early, long-term addition of chromium to the standard therapy is recommended. PURPOSE: The aim of the present study was to evaluate the effect of chromium on the insulin resistance in diabetic patients with type II diabetes mellitus. MATERIAL AND METHODS: We have studied a total of 34 overweight patients with type II diabetes mellitus, who were distributed in two study sub-groups--patients with very good metabolic control and patients with bad control. For sixty days the patients of both groups received 30 microg of chromium picolinate as food additive. We measured the serum concentration of chromium (using atom-absorption methods), immune-reactive insulin and the insulin resistance index at baseline and at the end of the two-month period. RESULTS: The serum concentrations of chromium was significantly lower in diabetic patients than in the healthy individuals used as controls (2.18 +/- 0.87 nmol/l versus 4.03 +/- 0.96 nmol/l; p < 0.001). We found a significant decrease of the immune-reactive insulin and the insulin resistance index after a two-month application of chromium 30 microg daily (1 tablet of chrome picolinate). The effects of this trace element are analysed in the light of an improved first phase of secretion of insulin or facilitated post-receptor insulin sensibility as a way of potentiating the insulin action. CONCLUSION: Chromium included early in the complex therapy of diabetes is beneficial in the reduction of the degree of insulin resistance.