De-Intensification from Basal-Bolus Insulin Therapy to Liraglutide in Type 2 Diabetes: Predictive Value of Mean Glycaemia during Fasting Test.

BACKGROUND: Successful conversion from insulin therapy to glucagon-like peptide 1 receptor agonist (GLP-1RA) with basal insulin in well-controlled patients has already been demonstrated. However, the data concerning individuals with poor glycaemic control are scarce. The aim of this work was to assess the success rate of insulin therapy to liraglutide transition in poorly controlled diabetes in a real-world clinical setting and to define predictors of success. We are the first to present the method of a fasting test as a way to identify the patients at higher risk of failure after treatment de-intensification. METHODS: The retrospective observational study analyzed data of 62 poorly controlled obese diabetic patients on high-dose insulin therapy, who were subjected to a 72 h fasting test during hospitalization and subsequently switched to liraglutide ± basal insulin therapy. During the fasting, all antidiabetic treatment was discontinued. Patients were classified as responders if they remained on GLP-1RA treatment after 12 months. Non-responders restarted the basal-bolus insulin (BBI) regimen. Development of glycated hemoglobin (HbA1c) and body weight in both groups, alongside with parameters associated with the higher risk of return to the BBI regimen, were analyzed. RESULTS: A total of 71% of patients were switched successfully (=responders). Responders had more significant improvement in HbA1c (-6.4 ± 19.7 vs. -3.4 ± 22.9 mmol/mol) and weight loss (-4.6 ± 7.1 vs. -2.5 ± 4.0). Statistically significant difference between groups was found in initial HbA1c (75.6 ± 17.9 vs. 90.5 ± 23.6; p = 0.04), total daily dose of insulin (67.6 ± 36.4 vs. 90.8 ± 32.4; p = 0.02), and mean glycaemia during the fasting test (6.9 ± 1.7 vs. 8.6 ± 2.2 mmol/L; p < 0.01). CONCLUSIONS: This study confirms that therapy de-intensification in poorly controlled patients with a BBI regimen is possible. Higher baseline HbA1c, total daily insulin dose, and mean glucose during fasting test are negative predictive factors of successful therapy de-escalation.

A Federated Learning-Inspired Evolutionary Algorithm: Application to Glucose Prediction.

In this paper, we propose an innovative Federated Learning-inspired evolutionary framework. Its main novelty is that this is the first time that an Evolutionary Algorithm is employed on its own to directly perform Federated Learning activity. A further novelty resides in the fact that, differently from the other Federated Learning frameworks in the literature, ours can efficiently deal at the same time with two relevant issues in Machine Learning, i.e., data privacy and interpretability of the solutions. Our framework consists of a master/slave approach in which each slave contains local data, protecting sensible private data, and exploits an evolutionary algorithm to generate prediction models. The master shares through the slaves the locally learned models that emerge on each slave. Sharing these local models results in global models. Being that data privacy and interpretability are very significant in the medical domain, the algorithm is tested to forecast future glucose values for diabetic patients by exploiting a Grammatical Evolution algorithm. The effectiveness of this knowledge-sharing process is assessed experimentally by comparing the proposed framework with another where no exchange of local models occurs. The results show that the performance of the proposed approach is better and demonstrate the validity of its sharing process for the emergence of local models for personal diabetes management, usable as efficient global models. When further subjects not involved in the learning process are considered, the models discovered by our framework show higher generalization capability than those achieved without knowledge sharing: the improvement provided by knowledge sharing is equal to about 3.03% for precision, 1.56% for recall, 3.17% for F1, and 1.56% for accuracy. Moreover, statistical analysis reveals the statistical superiority of model exchange with respect to the case of no exchange taking place.

Comparison of Insulin Dose Adjustments Made by Artificial Intelligence-Based Decision Support Systems and by Physicians in People with Type 1 Diabetes Using Multiple Daily Injections Therapy.

Objective: Artificial intelligence-based decision support systems (DSS) need to provide decisions that are not inferior to those given by experts in the field. Recommended insulin dose adjustments on the same individual data set were compared among multinational physicians, and with recommendations made by automated Endo.Digital DSS (ED-DSS). Research Design and Methods: This was a noninterventional study surveying 20 physicians from multinational academic centers. The survey included 17 data cases of individuals with type 1 diabetes who are treated with multiple daily insulin injections. Participating physicians were asked to recommend insulin dose adjustments based on glucose and insulin data. Insulin dose adjustments recommendations were compared among physicians and with the automated ED-DSS. The primary endpoints were the percentage of comparison points for which there was agreement on the trend of insulin dose adjustments. Results: The proportion of agreement and disagreement in the direction of insulin dose adjustment among physicians was statistically noninferior to the proportion of agreement and disagreement observed between ED-DSS and physicians for basal rate, carbohydrate-to insulin ratio, and correction factor (P < 0.001 and P ≤ 0.004 for all three parameters for agreement and disagreement, respectively). The ED-DSS magnitude of insulin dose change was consistently lower than that proposed by the physicians. Conclusions: Recommendations for insulin dose adjustments made by automatization did not differ significantly from recommendations given by expert physicians regarding the direction of change. These results highlight the potential utilization of ED-DSS as a useful clinical tool to manage insulin titration and dose adjustments.

Adjustment of Insulin Pump Settings in Type 1 Diabetes Management: Advisor Pro Device Compared to Physicians' Recommendations.

AIMS: To compare insulin dose adjustments made by physicians to those made by an artificial intelligence-based decision support system, the Advisor Pro, in people with type 1 diabetes (T1D) using an insulin pump and self-monitoring blood glucose (SMBG). METHODS: This was a multinational, non-interventional study surveying 17 physicians from 11 countries. Each physician was asked to provide insulin dose adjustments for the settings of the pump including basal rate, carbohydrate-to-insulin ratios (CRs), and correction factors (CFs) for 15 data sets of pumps and SMBG of people with T1D (mean age 18.4 ± 4.8 years; eight females; mean glycated hemoglobin 8.2% ± 1.4% [66 ± 11mmol/mol]). The recommendations were compared among the physicians and between the physicians and the Advisor Pro. The study endpoint was the percentage of comparison points for which there was an agreement on the direction of insulin dose adjustments. RESULTS: The percentage (mean ± SD) of agreement among the physicians on the direction of insulin pump dose adjustments was 51.8% ± 9.2%, 54.2% ± 6.4%, and 49.8% ± 11.6% for the basal, CR, and CF, respectively. The automated recommendations of the Advisor Pro on the direction of insulin dose adjustments were comparable )49.5% ± 6.4%, 55.3% ± 8.7%, and 47.6% ± 14.4% for the basal rate, CR, and CF, respectively( and noninferior to those provided by physicians. The mean absolute difference in magnitude of change between physicians was 17.1% ± 13.1%, 14.6% ± 8.4%, and 23.9% ± 18.6% for the basal, CR, and CF, respectively, and comparable to the Advisor Pro 11.7% ± 9.7%, 10.1% ± 4.5%, and 25.5% ± 19.5%, respectively, significant for basal and CR. CONCLUSIONS: Considerable differences in the recommendations for changes in insulin dosing were observed among physicians. Since automated recommendations by the Advisor Pro were similar to those given by physicians, it could be considered a useful tool to manage T1D.

Pituitary apoplexy without chiasm compression: A case report.

The present report presents a rare case in which a patient with pituitary apoplexy (PA) without compression of the optic chiasm experienced diagnosable visual impairment in the ensuing months. Endocrinologically, the condition was a prolactinoma followed by bleeding into the pituitary gland. Due to the unexplained functional changes in the patient, an electrophysiological examination (pattern electroretinogram and pattern visual evoked potentials) was performed, which verified a bilateral non-inflammatory neurogenic lesion. This finding was confirmed by functional magnetic resonance imaging (fMRI) examination. Structural MRI did not reveal chiasm compression in the time sequence or alteration of the optic nerves (the diameter of the optic nerve at different distances from the eye and the diameter of the optic nerve sheath at different distances from the eye). Similarly, neither the retinal nerve fiber layer (RNFL) nor the vessel density was altered. The present report suggests that changes in visual fields may be due to ischemia in the area of the chiasm and optic nerves, similar to PA.

Inoperable CASTLE of the thyroid gland treated with radical radiotherapy with complete remission.

Carcinoma showing thymus-like elements (CASTLE) is an extremely rare malignant tumor of the thyroid gland and soft tissues of the neck with favorable prognosis. Histological features of the CASTLE are similar to thymic carcinoma, and it is assumed that it arises from the ectopic thymic tissue or the remnants of branchial pouches. The optimal treatment strategy is still uncertain because of the rarity of the tumor. The mainstay of treatment is surgery. The role of other modalities is unclear. We present a case report of a patient with locally advanced CASTLE of the thyroid gland who was not suitable for surgery and underwent radical radiotherapy with subsequent achievement of complete remission. We also present a literature review.

Characterization of esophageal motor activity, gastroesophageal reflux, and evaluation of prokinetic effectiveness in mechanically ventilated critically ill patients: a high-resolution impedance manometry study.

BACKGROUND: Motility disorders of upper gastrointestinal tract are common in critical illness and associated with significant clinical consequences. However, detailed quantitative and qualitative analyses of esophageal motor functions are lacking. Therefore, we aimed to characterize the key features of esophageal motility functions using high-resolution impedance manometry (HRIM) and to evaluate an objective link between esophageal motor patterns, gastric emptying, and gastroesophageal reflux. We also studied the prokinetic effects of metoclopramide. METHODS: We prospectively performed HRIM for 16 critically ill hemodynamically stable patients. Patients were included if they had low gastric volume (LGV; < 100 mL/24 h, n = 8) or high gastric volume (HGV; > 500 mL/24 h, n = 8). The HRIM data were collected for 5 h with intravenous metoclopramide administration (10 mg) after the first 2 h. RESULTS: The findings were grossly abnormal for all critically ill patients. The esophageal contraction vigor was markedly increased, indicating prevailing hypercontractile esophagus. Ineffective propulsive force was observed for 73% of esophageal activities. Panesophageal pressurization was the most common pressurization pattern (64%). Gastroesophageal reflux predominantly occurred with transient lower esophageal sphincter relaxation. The common features of the LGV group were a hyperreactive pattern, esophagogastric outflow obstruction, and frequent reflux. Ineffective motility with reduced lower esophageal sphincter tone, and paradoxically fewer reflux episodes, was common in the HGV group. Metoclopramide administration reduced the number of esophageal activities but did not affect the number of reflux episodes in either group. CONCLUSION: All critically ill patients had major esophageal motility abnormalities, and motility patterns varied according to gastric emptying status. Well-preserved gastric emptying and maintained esophagogastric barrier functions did not eliminate reflux. Metoclopramide failed to reduce the number of reflux episodes regardless of gastric emptying status. Trial registration ISRCTN, ISRCTN14399966. Registered 3.9.2020, retrospectively registered. https://www.isrctn.com/ISRCTN14399966 .

Predictive and prognostic significance of tumour subtype, SSTR1-5 and e-cadherin expression in a well-defined cohort of patients with acromegaly.

In somatotroph pituitary tumours, somatostatin analogue (SSA) therapy outcomes vary throughout the studies. We performed an analysis of cohort of patients with acromegaly from the Czech registry to identify new prognostic and predictive factors. Clinical data of patients were collected, and complex immunohistochemical assessment of tumour samples was performed (SSTR1-5, dopamine D2 receptor, E-cadherin, AIP). The study included 110 patients. In 31, SSA treatment outcome was evaluated. Sparsely granulated tumours (SGST) differed from the other subtypes in expression of SSTR2A, SSTR3, SSTR5 and E-cadherin and occurred more often in young. No other clinical differences were observed. Trouillas grading system showed association with age, tumour size and SSTR2A expression. Factors significantly associated with SSA treatment outcome included age, IGF1 levels, tumour size and expression of E-cadherin and SSTR2A. In the group of SGST, poor SSA response was observed in younger patients with larger tumours, lower levels of SSTR2A and higher Ki67. We observed no relationship with expression of other proteins including AIP. No predictive value of E-cadherin was observed when tumour subtype was considered. Multiple additional factors apart from SSTR2A expression can predict treatment outcome in patients with acromegaly.

The influence of cardiovascular autonomic neuropathy on mortality in type 1 diabetic patients; 10-year follow-up.

AIM: The aim of our retrospective study was to answer the question if the presence of cardiovascular autonomic neuropathy (CAN) affects mortality in type 1 diabetic patients during a 10-year follow-up. METHODS: Patients with type 1 diabetes mellitus examined for CAN in 2003 were enrolled in this retrospective study. A total of 278 patients were included and divided into two groups according to the presence or absence of CAN (111 CAN+, 167 CAN-). The group characteristics and outcomes were compared at baseline and after ten years (in 2013). RESULTS: In the follow-up period, a total of 18 patients died; CAN+ (14/111; 12.6%) and CAN- (4/167; 2.4%) (P < 0.001). At baseline, the CAN+ patients were older (47 vs. 33 years; P < 0.001), had longer duration of diabetes (20 vs. 12 years; P < 0.05), had worse glycemic control assessed by HbA1c (73 vs. 68 mmol/mol; P < 0.05), higher systolic (130 vs. 120 mmHg; P < 0.001) and diastolic (80 vs. 70 mmHg; P < 0.01) blood pressure and had more diabetic complications. In our analysis we found the strongest predictor of mortality to be the presence of CAN (P < 0.01) and the blood pressure value at baseline (P < 0.05). Other baseline characteristics, including the duration of diabetes, age and the presence of micro- and macrovascular complications were not significant. The statistical analysis was performed using logistic regression step-wise analysis. CONCLUSIONS: During the 10-year follow-up, CAN+ patients had a 5-fold higher mortality rate than CAN- patients. The strongest predictor of mortality was the presence of CAN.

[Has the pregnancy outcome of women with pregestational diabetes mellitus improved in ten years?]. / Zlepsil se osud gravidit zen s pregestacním diabetes mellitus za deset let?

INTRODUCTION: In spite of progress in medicine, studies from a number of countries indicate steadily increased risk of perinatal morbidity and mortality in the offspring of diabetic mothers. No data regarding the pregnancy outcome in women with diabetes mellitus type 1 and 2 (pregestational DM) have been published in the Czech Republic. The aim of the study was to evaluate the pregnancy course of women with pregestational DM and outcome of their offspring and to assess whether it has improved in ten years. METHODS: A retrospective evaluation of pregnancy outcome of pregestational DM women followed up in the University Hospital Pilsen in years 2000-2009 (Group A, n = 107) and comparison with the period 1990-1997 (Group B, n = 39) were performed. Wilcoxon non-paired test, contingency tables, step-wise logistic regression and step-wise linear multiple regression methods were used for statistical analyses. RESULTS: Data is presented as median (interquartile range). Women from the Group A were older 28 (25, 31) vs 25 (22, 27) years, p = 0.01. Otherwise, the groups did not statistically significantly differ in diabetes duration, BMI, and representation of women with type 2 diabetes. A better glycemic control (HbA1c, mmol/mol) was achieved in the Group A in all trimesters - 1st trimester: 59 (47, 67) vs 66 (56, 76), 2nd trimester: 46 (40, 52) vs 54 (48, 59) and 3rd trimester: 46 (40, 51) vs 53 (47, 60), p = 0.01. The caesarean section rate decreased (65.2 % vs 87.5 %, p < 0.05). The incidence of the respiratory distress syndrome after adjustment for age and diabetes duration also decreased (8.9 % vs 18.2 %, p < 0.05). A decreasing trend in the rate of premature delivery before 34th week of gestation (1.1 % vs 6.3 %) and neonatal mortality (1.1 % vs 2.9 %) was observed, however, the differences were not statistically significant. CONCLUSION: The achieved improved glycemic control led to only a partial improvement in the course of pregnancy and outcome of the offspring of diabetic mothers.

Arteriovenous malformation of the thyroid gland as a very rare cause of mechanical neck syndrome: a case report.

INTRODUCTION: Vascular malformations of the thyroid gland represent a very rare, often accidentally diagnosed, disease that in the case of eufunctional goitre may be the cause of mechanical neck syndrome. The authors present here the complex differential-diagnosis and treatment approach and stress the importance of histopathology for determining the final diagnosis. CASE PRESENTATION: Using various imaging methods (ultrasound, multidetector computed tomography of the neck), the cause of breathing difficulties in a 64-year-old old man from the Czech Republic with normal thyroid gland function was found to be an arteriovenous malformation of the left lobe of his thyroid gland, 80 × 70 × 55 mm in size, reaching retrosternally between the major arteries branching from his aortic arch and displacing his trachea 10mm to the right. In preparation for surgery, he underwent a radio-interventional procedure with embolisation of the arteries supplying the left lobe. This was followed by a lobectomy on the left via a partial sternotomy. The definitive histology result confirmed that the arteriovenous malformation was the benign cause of the mechanical neck syndrome. CONCLUSIONS: The case report presented here extends the differential diagnostic options in cases of mechanical neck syndrome. It describes a very rare disease of the thyroid gland, which prior to surgery may arouse suspicion of malignancy. It stresses the importance of close team cooperation between the endocrinologist, interventional radiologist and surgeon within the framework of preoperative diagnosis as well as preparation for surgery. Determination of the definitive histopathological diagnosis requires a pathologist experienced in such issues.

Clostridium difficile infection in hospitalized patients at a Czech tertiary center: analysis of epidemiology, clinical features, and risk factors of fulminant course.

OBJECTIVE: Clostridium difficile infection (CDI) has been increasing in incidence, with significant morbidity and mortality, and is subject to geographical and institutional variability. We aimed to characterize epidemiology and clinical manifestations of CDI in a Czech tertiary care center and to identify risk factors of fulminant course. METHODS: All adult patients hospitalized with primary CDI in a 3-year period were retrospectively identified. Epidemiological and clinically descriptive data were extracted from medical records. Multivariate analysis was used to identify the risk factors of fulminant course. The relationship between incidence of CDI and antibiotic consumption was evaluated. RESULTS: Overall, 183 CDI patients, median age 67 years, were enrolled. Hospital-acquired CDI was present in 85% of cases. The incidence of CDI was 1/10,000 patient-days. Hospital-acquired CDI hospital mortality was 22.4%. Severe CDI (SCDI) was identified in 15.8% of patients, with 62% mortality. SCDI patients had longer onset of symptoms to diagnosis interval compared with mild CDI (P=0.05). Multivariate analysis showed that SCDI patients were older (P=0.018), and more frequently had abnormal abdominal physical findings (P=0.001), higher inflammatory markers (P<0.001), higher creatinine (P=0.002), and lower albumin (P<0.001) than patients with mild CDI. Analysis of antibiotic consumption at departments with the highest incidence of CDI showed a trend toward higher incidence of CDI associated with penicillin use (P=0.08) and a negative correlation of CDI incidence with nitroimidazoles consumption (P=0.03). CONCLUSION: CDI is less frequent in the conditions studied compared with literary data; however, the fulminant form has a very high mortality. Delayed recognition and treatment is a crucial determinant of the severity of CDI. The association between CDI and antibiotic consumption is less clear.

Comparison of glucose variability assessed by a continuous glucose-monitoring system in patients with type 2 diabetes mellitus switched from NPH insulin to insulin glargine: the COBIN2 study.

BACKGROUND: Glucose variability combined with glycosylated hemoglobin (HbA1c) assessments more reliably represents the level of glycemic control. The study was aimed to compare blood glucose variability with insulin glargine vs. neutral protamine Hagedorn (NPH) in patients with type 2 diabetes mellitus using a continuous glucose-monitoring system (CGMS), in patients treated with basal insulin using stable dose of oral antidiabetic agents and HbA1c in the range of 4.5-8.0 % International Federation of Clinical Chemistry (IFCC) units. [6.2-9.4 % Diabetes Control and Complications Trial (DCCT) units]. METHODS: This was a multicenter, prospective, open-label, single-arm study in patients (N = 116) treated for ≥ 2 months with NPH and metformin combined with sulfonylurea or glinide. Glucose variability was measured after a 4-week NPH treatment phase and after a subsequent 12-week glargine treatment phase using CGMS. Based on 72-hour CGMS, glucose variability was assessed by area under the curve [AUC (mmol/L · h)]. Differences (glargine-NPH) in AUC within 24 h in the glucose ranges of ≤ 3.3, ≤ 3.9, 7.5-3.9 (margins excluding), ≥ 7.5, ≥ 10, and ≥ 15 mmol/L were evaluated. Circadian fluctuation of glucose was assessed by M-value (log-transformation of the deviation from an arbitrary standard). RESULTS: AUCs of glucose in the lowest ranges (≤ 3.3 and ≤ 3.9 mmol/L) did not change significantly after treatment with glargine. Those in the higher ranges (≥ 7.5, ≥ 10, and ≥ 15 mmol/L) were significantly lower (p < 0.001 for all ranges), whereas AUC of glucose in the normal range (3.9-7.5 mmol/L) was significantly higher (p < 0.001) at the end of glargine treatment phase. Circadian fluctuation of glucose assessed by M-value showed a significant decrease after glargine treatment (p < 0.003). No significant differences in hypoglycemia confirmed by glucose value ≤ 3.3 mmol/L were found between treatment phases. This trial is registered at ClinicalTrials.gov, NCT00659477. CONCLUSIONS: As monitored by CGMS, switching from NPH to glargine with active titration shifted glucose from abnormally high to normal levels with reduced fluctuation and without increased risk of hypoglycemia.

Laparoendoscopic single-site surgery adrenalectomy - own experience and matched case-control study with standard laparoscopic adrenalectomy.

INTRODUCTION: At our institution, laparoendoscopic single-site surgery (LESS) has been established as a technique for laparoscopic nephrectomy since 2011, and since 2012 in selected cases for adrenalectomy (AE) as well. AIM: To compare LESS AE with standard laparoscopic AE (SLAE). MATERIAL AND METHODS: Between 3/2012 and 7/2014, 35 adrenalectomies were performed. In 18 (51.4%), a LESS approach was chosen. Indications were strictly non-complicated cases (body mass index (BMI) < 34 kg/m(2), tumour ≤ 7 cm, non-malignant aetiology, no previous surgery). All LESS procedures were done by one surgeon. Standard equipment was a 10 mm rigid 0° camera, Triport+, one pre-bent grasper, and a sealing instrument. The approach was pararectal in all cases except one (transumbilical in a slim man). Three patients with LESS were excluded (2 partial AEs only, one adrenal cancer converted to SLAE and then to open surgery). These 15 LESS AE procedures were compared to 15 SLAEs with similar characteristics chosen among 54 SLAEs performed in the period 1/2008-2/2012. RESULTS: In 8 cases (53.3%) of LESS AE, a 3 mm port was added to elevate the liver/spleen. Mean parameters of LESS AE vs. SLAE (Wilcoxon test): maximal tumour diameter 43.7 mm vs. 36.1 mm (p = 0.28), time of surgery 63.3 min vs. 55.3 min (p = 0.22), blood loss 38.0 ml vs. 38.0 ml (p = 0.38), BMI 26.9 kg/m(2) vs. 28.5 kg/m(2) (p = 0.13), discharge from hospital 5.4 days vs. 3.9 days (p = 0.038). There were no complications in either group. CONCLUSIONS: The LESS AE is feasible in selected cases, especially small left-sided tumours in thin patients with no history of previous abdominal operations, but requires an additional port in half of the cases.

Diagnosing celiac disease in patients with a history of lymphoma: factors that matter.

OBJECTIVE: The aim of this study was to identify pitfalls in establishing the diagnosis of celiac disease (CD) in patients with a history of lymphoma. METHODS: A total of 103 patients with a history of lymphoma had anti-tissue transglutaminase antibodies (atTGA) and their class A, G, and M immunoglobulin (IgA, IgG) levels determined. Patients with atTGA positivity underwent enterobiopsy and CD-associated HLA locus testing. RESULTS: The mean age of patients was 55 ( ± 13.5) years. The predominant lymphoma types included B-type non-Hodgkin's lymphoma (B-NHL, 66 %), T-type NHL (8 %), and Hodgkin's lymphoma (26 %). Serological positivity was documented in 3.9 % of cases; one patient had the diagnosis of CD confirmed by enterobiopsy. In 11 patients (10.7 %), IgA levels were decreased to a various extent; of these patients, 10 were shown to have also their IgG levels decreased. The median time from follow-up to blood collection was 58 (32-104) months. The decrease in immunoglobulin levels correlated with a more advanced stage of the tumor (Ann Arbor III-IV) at the time of diagnosis [1.4 (0.9-2.0) g/l versus 2.4 (1.5-3.0) g/l for IgA, p = 0.0001; and 9.4 (7.2-11.5) g/l versus 11.2 (10.3-12.3) g/l for IgG, p = 0.001] and older age [65 (54-72) years versus 55 (44-61) years for IgA, p = 0.04; and 69 (59-74) years versus 53 (43-61) years for IgG, p = 0.0001]. Rituximab therapy in B-NHL patients had no effect on the subsequent incidence of decreased IgA levels. CONCLUSION: Reduced IgA and IgG levels represent important factors contributing to the low detection rate of serological screening for CD in patients with a history of lymphoma.

Influence of physiological and supraphysiological hyperinsulinemia on skin microcirculation in healthy volunteers.

AIM: To examine skin perfusion in dependency on insulinemia in healthy subjects. METHODS: All volunteers were informed in detail about the procedures and signed informed consent. The protocol of this study was approved by the ethical committee. In our study, a two stage hyperinsulinemic euglycemic clamp was performed, with insulinemia 100 and 250 mIU/mL and glycemia 5.0 mmol/L (3% standard deviation). Before the clamp and in steady states, microcirculation was measured by laser Doppler flowmetry and transcutaneous oximetry and energy expenditure was measured by indirect calorimetry. Results (average and standard deviation) were evaluated with paired t-test. RESULTS: Physiological (50 mIU/L) insulinemia led to higher perfusion in both tests; hyperemia after heating to 44%-1848% (984-2046) vs 1599% (801-1836), P < 0.05, half time of reaching peak perfusion after occlusion release 1.2 s (0.9-2.6) vs 4.9 s (1.8-11.4), P < 0.05. Supraphysiological (150 mIU/L) insulinemia led to even higher perfusion in both tests; hyperemia after heating to 44%-1937% (1177-2488) vs 1599% (801-1836), P < 0.005, half time to reach peak perfusion after occlusion release 1.0 s (0.7-1.1) vs 4.9 s (1.8-11.4), P < 0.005. A statistically significant increase occurred in tissue oxygenation in both insulinemia. The difference in perfusion and oxygenation between physiological and supraphysiological hyperinsulinemia was not statistically significant. CONCLUSION: The post occlusive hyperemia test in accordance with heating test showed significantly increasing skin perfusion in the course of artificial hyperinsulinemia. This effect rises non-linearly with increasing insulinemia. Dependency on the dose was not statistically significant.

Influence of physical activity on metabolic state within a 3-h interruption of continuous subcutaneous insulin infusion in patients with type 1 diabetes.

BACKGROUND: The aim of this study was to evaluate the influence of physical activity on blood glucose, insulinemia, and ketone bodies level during interruption of insulin delivery. METHODS: We enrolled 12 patients with type 1 diabetes (men with an average age of 33.4±8.66 years, body mass index of 25.7±3.75 mg/m(2), and glycated hemoglobin of 8.4±0.95%). The test was performed after overnight fasting at the usual insulin dosage. The delivery of insulin by the pump was stopped for 3 h, and blood samples were obtained in 30-min intervals for determination of blood glucose, insulinemia, ß-hydroxybutyrate, non-esterified fatty acids, and acid-base balance parameters. A test with (EXE) or without (CON) physical exercise (moderate aerobic exercise) was performed in each patient at random in the course of 2 weeks. Results are presented as median (first quartile; third quartile). RESULTS: Groups CON and EXE did not differ in blood levels of insulin during the test. Regarding time course of glycemia, we found differences only in min 270 for CON versus EXE of 15.2 (13.6; 16.7) and 13.9 (9.1;16.5) mmol/L, respectively (P=0.038). Concerning blood levels of ß-hydroxybutyrate, we found significant differences in min 180-300 of the test: CON of 419 (354; 541), 485 (344; 580), and 107 (63; 156) µmol/L versus EXE of 690 (631; 723), 703 (562; 871), and 241 (113; 507) µmol/L (P<0.01). Comparable results were found in values of total ketone bodies and free fatty acids. CONCLUSIONS: The influence of physical activity during a 3-h interruption of insulin pump treatment is evident, especially in the increase in plasma levels of non-esterified fatty acids and ketone bodies. Correction bolus leads to a rapid increase in insulinemia; however, normalization of blood glucose and ketone bodies is achieved within another 90 min.

The influence of insulin pump treatment on metabolic syndrome parameters in type 2 diabetes mellitus.

INTRODUCTION: The aim of our study was to evaluate the influence of long-term insulin pump treatment (CSII) on the parameters of metabolic syndrome in insulin-resistant patients with poorly controlled type 2 diabetes mellitus. PATIENTS AND METHODS: Thirteen obese (BMI>30) patients (8 women, 5 men), average age 58.8+/-9.06 years, treated with an intensified insulin regimen with high doses of insulin (>0.8 IU/kg per 24 h) for at least 12 months were enrolled in the study. Prior to CSII treatment, all patients were reeducated regarding diabetes treatment and metabolic syndrome, and glycemic control parameters were assessed. Insulin resistance was evaluated with the hyperinsulinemic euglycemic clamp test. All tests were repeated after six months of CSII treatment. The Wilcoxon matched-pairs signed-rank test and Spearman's rank correlation coefficient were used for statistical evaluation. Results are presented as median (1st quartile; 3rd quartile). RESULTS: There were no changes in long-term glycemic control during the course of CSII treatment: HbA1c prior to CSII 9.60 (8.95; 10.60) vs. after 6 months 9.80 (9.50; 10.20) %, BMI 33.0 (32.1; 34.2) vs. 32.9 (32.0; 34.5), total daily insulin dose 69.0 (65.0; 94.0) vs. 68.0 (58.9; 92.4) IU/24 h in observed patients. There was a statistically significant improvement in insulin resistance: M value 2.55 (1.92; 3.15) vs. 3.32 (2.23; 4.49) mg/kg per min (P<0.01), and improvement in atherosclerosis risk factors (blood coagulation and endothelial dysfunction): fibrinogen 3.44 (3.13; 3.86) vs. 3.24 (2.77; 3.38) g/l, factor VII 115 (101; 128) vs. 109 (93; 119)%, factor VIII 230 (148; 260) vs. 188 (126; 225)%, vWF:RiCo 162 (141; 193) vs. 128 (100; 132)%, PAI-1 39 (30; 44) vs. 30 (25; 36) AU/ml, thrombomodulin Ag 4.1 (3.7; 4.4) vs. 3.7 (3.45; 4.05) ng/ml (P<0.01). CONCLUSIONS: Six months of CSII treatment led to decrease in insulin resistance and improvement in parameters of lipid metabolism, blood coagulation and endothelial dysfunction independently of glycemic control and weight.

Influence of cardiovascular autonomic neuropathy on atherogenesis and heart function in patients with type 1 diabetes.

AIM: Cardiovascular autonomic neuropathy (CAN) increases mortality of patients with type 1 diabetes (Type 1 DM). We set out to find out whether the presence of CAN in asymptomatic, normotensive Type 1 DM affects endothelial function (marker of atherogenesis) and left ventricle function (marker of cardiomyopathy). METHODS: Twenty-one Type 1 DM with CAN (Group A) and 35 Type 1 DM without CAN (Group B) were enrolled in the study. None of them suffered from any cardiovascular disease nor advanced chronic complications of diabetes. Both groups were comparable in age, glycemic control, BMI, and blood pressure. Markers of endothelial dysfunction and chronic inflammation were used as indicators of incipient atherogenesis. Left ventricle function was evaluated using echocardiography. RESULTS: Both groups did not differ in any parameter of atherogenesis. However we found a statistically significant difference in values characterizing systolic and diastolic left ventricle functions between the groups. CONCLUSIONS: CAN is not associated with elevation of markers of endothelial dysfunction and chronic inflammation in normotensive asymptomatic Type 1 DM. However CAN is associated with the impairment of systolic and diastolic left ventricle function and can thus be regarded as one of the risk factors of diabetic cardiomyopathy.