Acute glycemic changes in brain and subcutaneous tissue measured by continuous glucose monitoring system in hereditary hypertriglyceridemic rat.

Parallel glucose measurements in blood and other different tissues give us knowledge about dynamics of glycemia changes, which depend on vascularization, distribution space and local utilization by tissues. Such information is important for the understanding of glucose homeostasis and regulation. The aim of our study was to determine the time-lag between blood, brain, and adipose tissue during rapid glucose changes in a male hHTG rat (n=15). The CGMS sensor Guardian RT (Minimed/Medtronic, USA) was inserted into the brain and into the abdominal subcutaneous tissue. Fixed insulin and variable rate of glucose infusion was used to maintain euglycemia during sensor calibration period. At 0 min, 0.5 g/kg of bolus of glucose was administered, and at 50 min, 5 IU/kg of bolus of insulin was administered. Further glucose and insulin infusion was stopped at this time. The experiment was finished at 130 min and animals were euthanized. The time-shift between glycemia changes in blood, brain, and subcutaneous tissue was calculated by identification of the ideal correlation function. Moreover, the time to achieve 90 % of the maximum glucose excursion after intervention (T90) was measured to compare our data with the literature. The time-lag blood vs. brain and blood vs. subcutaneous tissue was 10 (10; 15) min and 15 (15; 25) min, respectively. The difference was statistically significant (P=0.01). T90 after glucose bolus in brain and subcutaneous tissue was 10 min (8.75; 15) and 15 min (13.75; 21.25), respectively. T90 after insulin bolus in brain and subcutaneous tissue was 10 min (10; 15) and 20 min (20; 27.5), respectively. To the contrary, with literature, our results showed earlier glucose level changes in brain in comparison with subcutaneous tissue after glucose and insulin boluses. Our results suggest that glucose dynamics is different within monitored tissues under rapid changing glucose level and we can expect similar behavior in humans. Improved knowledge about glucose distribution and dynamics is important for avoiding hypoglycemia.

[Does physical activity produce clinically significant changes during discontinuation of insulin pump in type 1 diabetic patients?]. / Vede fyzická aktivita pri prerusení dodávky inzulinu inzulinovou pumpou u pacientu s diabetem 1. typu ke klinicky významným zmenám?

INTRODUCTION: Discontinuation of insulin pump treatment (CSII) before, during and after physical activity is a common practice among a number of patients. The aim of the study was to evaluate the course of insulinemia during a 3- hour insulin pump suspension and after consecutive insulin bolus administration, and additionally, to assess the effect of physical activity (mid intensity aerobic exercise). PATIENT AND METHODS: We enrolled 12 patients with diabetes mellitus type 1 in the study (men, mean age 33.4 ± 8.66 years, diabetes duration 16.3 ± 8.76 years, CSII treatment duration 6.9 ± 4.60 years, BMI 25.7 ± 3.75 mg/ m2, HbA1c 8.4 ± 0.95%, total insulin dose 50.3 ± 12.50 IU/ day). The tests were performed after night fasting at usual insulin doses, without serving breakfast and morning bolus dose. In the course of the test, insulin administration by a pump was suspended for 3 hours. Blood for assessment of blood glucose and insulinemia was taken in 30- minute intervals during the test. A test with or without physical exercise on bicycle ergometer was performed in each patient 2 weeks later. RESULTS: We did not prove any influence of physical exercise on insulinemia during suspended insulin deli-very by an insulin pump. Insulinemia of approximately 50% of the original value persisted for another 90 minutes following insulin pump suspension. A rapid increase in insulinemia occurred after bolus administration in the 180th minute of the test. However, the decrease in blood glucose level did not occur until after another 90 minutes. CONCLUSION: When modifying CSII treatment by reduction or suspension of insulin delivery it is essential to bear in mind the gradual decrease in insulinemia as well as the delay in insulin action following bolus administration.

[Spondylodiscitis and epidural empyema as a complication of diabetic foot]. / Spondylodiscitida, epidurální empyém jako komplikace syndromu diabetické nohy.

UNLABELLED: Spinal column infection (vertebral osteomyelitis, discitis, epidural empyema/ abscess) is a rare condition, albeit its incidence has been increasing in recent years. Staphylococcus aureus is the most frequent pathogen. The routes of infection are predominantly hematogenous. Any delay in making correct diagnosis increases risk of adverse outcome of the patient. The authors present 3 case reports of patients with diabetic foot syndrome, who were diagnosed with spondylodicitis in the period of 2009- 2012, two patients had associated epidural empyema. Apart of a chronic neuropathic foot wound, the patients reported severe or deteriorated dorsal pain (2 in the lumbal region, one in thoracic spine), had no new neurologic lesion in the beginning, some had fever, but all had high laboratory parameters of inflammation that did not correlate with local finding on the foot. Methicillin sensitive Staphylococcus aureus cultured from the foot defect in all cases, in two patients from blood cultures and from epidural empyema. They were patients with recurrent local infectious complications of diabetic foot ulcers. Two patients had a concomitant diabetic nephropathy, classified into stages 3- 4/ 5 according to K/ DOQI. Glycemic control (Type 1, Type 2 and secondary DM) ranged from excellent to unsatisfactory (HbA1c 43- 100 mmol/ mol). Apart of patient history and clinical examination, the magnetic resonance imaging of the spine was essential for the diagnosis of spondylodiscitis, or epidural empyema. The treatment was founded on longterm (initially parenteral) antibiotic treatment, bed rest, then mobilization with orthosis. Neurosurgical procedure was necessary in the patients with epidural empyema. All patients were mobile following a varied time period of convalescence and rehabilitation. CONCLUSION: Dorsal pain and degenerative changes of the spinal column belong to common findings in our population. When searching for the origin of an infection in patients with elevated inflammatory parameters (inadequate finding for a diabetic ulcer), the history of dorsal pain suddenly becomes the fundamental clue for diagnosis of spondylodiscitis with or without epidural empyema.

Analysis of continuous patient data from the Czech National Register of patients with type 1 and type 2 diabetes using insulin pump therapy.

AIM: Patient data from the Czech National Register of patients treated with Continuous Subcutaneous Insulin Infusion (CSII) were evaluated to compare treatment indication, efficacy and safety with specific regard to the type of diabetes (T1 vs. T2). METHODS: Evaluation was done on complete data sets of at least 3 years from patients with either T1 diabetes (n=730, 93.1%) or T2 diabetes (n=54, 6.9%) between 1995 and 2006. RESULTS: HbA(1c) decreased from 9.65 (+/-0.07) and 9.66 (+/-0.05) for T1 and T2 respectively to 8.24 (+/-0.07) for T1 and 8.52 (+/-0.27) for T2 after 1 year of treatment, 8.34 (+/-0.07) and 8.54 (+/-0.26) after 2 years and 8.44 (+/-0.07) and 8.71 (+/-0.25) after 3 years (adjusted mean values, +/-SEM). This reduction is significant for both diabetes types. Results gathered from the safety analysis revealed almost comparable results for both patient groups (rates of adverse events of 42.5 and 34.8 for T1 and T2, per 100 patients and year). CONCLUSION: Both patient groups achieved substantial reduction of HbA(1c). Safety evaluation showed that fewer patients with T2 diabetes were affected by adverse events. According to that CSII treatment for patients with T2 diabetes is similarly effective with a slightly better safety profile.

[Bioelectical impedance analysis for comparison of the body composition in type 1 diabetes patients, obese patients and healthy volunteers]. / Srovnání telesného slození diabetiku 1. typu, obézních jedincu a zdravých dobrovolníku metodou bioelektrické impedancní analýzy.

BACKGROUND: Effects ofglycaemic control and insulin treatment on body composition in type 1 diabetes patients have not been clearly proven yet. AIM: Comparison of the body composition in type 1 diabetes patients, obese patients and healthy volunteers using multifrequency bioelectrical impedance analysis. METHODS: Multifrequency bioelectrical impedance measurements were performed on 153 type 1 diabetes patients, 176 obese patients and on 159 healthy controls of the same age and gender. HbA1c level, duration of disease and daily dose of insulin were measured in diabetes patients. RESULTS: Significant differences were observed in body composition between obese patients and both type 1 diabetes patients and healthy controls. Higher fat mass (FM) and body cell mass (BCM) and lower lean body mass (LBM) were observed in obese patients. Only a higher reactance by the healthy controls (56.75 Omega +/- 11.22 vs 53.27 Omega +/- 7.97, p < 0.05) was observed between type 1 diabetes patients and healthy controls. No significant differences were observed in other parameters of body composition between these two groups. HbA1c level negatively correlated with LBM in the diabetes patients. The duration of disease negatively correlated with BCM. And a negative correlation was also found between daily dose of insulin (IU/kg) and weight and LBM. CONCLUSIONS: The treated type 1 diabetes does not influence the body composition. We found a negative correlation between HbA1c level and LBM, between duration ofdisease and BCM and between daily dose ofinsulin and weight and LBM. Higher FM and BCM was observed in obese patients, lower LBM is due to the abnormally high level in diabetes patients and healthy controls.

Effect of mild increase of physical activity on microvasculary reactivity in obese subjects with diabetes mellitus type 2.

UNLABELLED: Microangiopathy, well known in diabetic patients as a cause of late complications, develops mainly due to chronic exposition to elevated glucose and triglyceride level. Physical training acts as a protective factor even if no changes in metabolic parameters are observed. It's supposed, that lifestyle modification leads to the improvement of endothelial dysfunction and microvasculary reactivity, in healthy subjects it has already been proven experimentally. AIM: Determine if mild, short time and metabolically indifferent increase of physical activity changes microvasculary reactivity in obese diabetic patients and how long these findings persist after return to habitual lifestyle. In 8 patients with type 2 diabetes mellitus was measured microvasculary reactivity and perfusion of skin in lower limbs by laser-doppler flowmetry and transcutaneous oximetry. First before the study, second after 3-week's period of habitual physical activity, third after 3-week's period of mild increased physical activity and finally after next 3-week's period of habitual activity. Training intensity was objectified (non sport-practiced subjects) by pedometers. Results were evaluated by Friedman and pair Wilcoxon test. After mild aerobic activity (walk about 800 [560-1400] meters/day) microvasculary reactivity was increased in both tests (increase after heating from 4,9x [4,4 D 5,4] to 6,1x [5,7 D 6,8], p<0.01, shorten half time to reach maximum perfusion from 4,1 [2,7 D 5,4] s to 3,1 [2,4 D 4,0] s, p<0.05. The increased perfusion lasted after following four weeks of habitual activity in smaller extent (microvascular reactivity increase after heating 5.2 [4.8 D 6.1] s, half time to reach maximum perfusion 3.8 [2.7 D 5.0], this increase was not significant in comparison with habitual activity in the first period). Metabolic and anthropometric parameters and transcutaneous oxygen tension didn't change significantly.

[Glycated haemoglobin--is it its exclusive position in diabetology under threat?]. / Glykovaný hemoglobin. Je ohrozeno jeho výsostné postavení v diabetologii?

Hyperglycaemia is the common characteristic for diabetes patients. Prolonged hyperglycaemia due to absolute or relative lack of insulin is the cause of microangiopathy. Glucose reacts with both blood vessel wall proteins and plasmatic proteins and erythrocyte haemoglobin. This characteristic of glucose is used to monitor the level of diabetes compensation. The level of glycated haemoglobin reflects glycaemia for the last 2 to 3 months. It began to be used in diabetology in the 1980's. This outline paper deals with some of the pitfalls with which glycated haemoglobin has been recently associated. The first part is dedicated to factors influencing haemoglobin glycation. The second, methodological part focuses on factors influencing its assessment and interpretation. The third part concentrates on the options for the substitution ofglycated haemoglobin by other diabetes compensation markers.

The relationship between glycemia, insulin and oxidative stress in hereditary hypertriglyceridemic rat.

The aim of this study was to determine the effects of insulin infusion on oxidative stress induced by acute changes in glycemia in non-stressed hereditary hypertriglyceridemic rats (hHTG) and Wistar (control) rats. Rats were treated with glucose and either insulin or normal saline infusion for 3 hours followed by 90 min of hyperglycemic (12 mmol/l) and 90 min of euglycemic (6 mmol/l) clamp. Levels of total glutathione (GSH), oxidized glutathione (GSSG) and total antioxidant capacity (AOC) were determined to assess oxidative stress. In steady states of each clamp, glucose infusion rate (GIR) was calculated for evaluation of insulin sensitivity. GIR (mg.kg(-1).min(-1)) was significantly lower in hHTG in comparison with Wistar rats; 25.46 (23.41 - 28.45) vs. 36.30 (27.49 - 50.42) on glycemia 6 mmol/l and 57.18 (50.78 - 60.63) vs. 68.00 (63.61 - 85.92) on glycemia 12 mmol/l. GSH/GSSG ratios were significantly higher in hHTG rats at basal conditions. Further results showed that, unlike in Wistar rats, insulin infusion significantly increases GSH/GSSG ratios in hHTG rats: 10.02 (9.90 - 11.42) vs. 6.01 (5.83 - 6.43) on glycemia 6 mmol/l and 7.42 (7.15 - 7.89) vs. 6.16 (5.74 - 7.05) on glycemia 12 mmol/l. Insulin infusion thus positively influences GSH/GSSG ratio and that way reduces intracellular oxidative stress in insulin-resistant animals.

[Clinical experience in treatment with the long-term insulin analogue glargin in a diabetes centre]. / Klinické zkusenosti s lécbou diouhodobým inzulinovým analogem glargin v diabetologickém centru.

OBJECTIVE: To assess the experience obtained by a diabetes centre in the treatment of patients with type 1 diabetes with the long-term insulin analogue glargin. PATIENT SAMPLE AND METHOD: 136 patients with type 1 diabetes mellitus (DM) were evaluated on a retrospective basis for the period from March 2004 to march 2005. We monitored HbA(1c) before the treatment with glargin, after 3 months, again after 6 months, and finally after 1 year of therapy. We evaluated the effectiveness of treatment with glargin insulin based upon diabetes compensation at the start of treatment. We also compared glycaemia variability in the 6 months prior to treatment initiation and the 6 months after the application of glargin insulin, this was done using the standard glycaemia deviation obtained from the patients' glucometers. In addition we evaluated the changes in total, basal and bolus daily dose of insulin after the change in therapy. RESULTS: The results were evaluated in the form of a median and the percentile of 25 and 75. Before the glargin therapy started, HbA(1c) was 7.4 (6.5-8.5)%. It decreased dramatically to 7.0 (6.2-8.1)% after 3 months of therapy (p < 0.01), to 7.2 (6.3-8.2)% after 6 months of therapy (p < 0.05), and reached the level of 7.1 (6.1-8.2)% after one year (p < 0.01). Analysis of glycemic profiles during the 6 months before and 6 months after transfer to glargin insulin therapy showed a significant decrease in the variability as evaluated by the decrease in standard deviations from the original 4.9 (4.3-5.6) mmol/l to 4.5 (3.9-5.1) mmol/l (p < 0.001). The total daily dose of insulin prior to treatment and after 6 months of therapy with glargin decreased from 44 (35-56) IU/day to 42 (34-53) IU/day (p = 0.01). There was no change in the basal dose of insulin after the change in therapy--it remained at 20 (12-28), (16-26) IU/day. The dose of bolus administered insulin decreased from 24 (18-32) to 21 (17-29) IU/day (p < 0.01). CONCLUSION: A dramatic improvement in HbA(lC) and a dramatic decrease in glycaemia variability are associated with glargin insulin treatment. The dose ofglargin insulin does not differ from that of NPH.

[Effects of insulin on glucose metabolism in sepsis]. / Metabolizmus glukózy a ucinky inzulinu v sepsi.

The study surveys potential effects of hyperglycemia on prognosis, complications and mortality of critical patients. Normalization of glycemia seems to be an effective therapeutic approach that influences morbidity and mortality of critical patients. Although insulin therapy has many positive effects, it is rather a way how to achieve normoglycemia. Authors present their own research of the impact of plasmatic insulin levels on glucose metabolism. It seems that the ability of critical patients to utilise and store glucose is significantly decreased due to their insulin resistance. Glucose oxidation is decreased only slightly. Glucose utilisation and oxidation in sepsis can be enhanced by administration of insulin.

[Economic aspects of the diabetic foot syndrome]. / Ekonomický pohled na syndrom diabetické nohy.

UNLABELLED: The diabetic foot is one of the most expensive complications of diabetes mellitus. AIMS: To determine the direct costs of both inpatient and outpatient care of diabetic foot provided in Diabetic Centre University Hospital in Plzen. METHODS: 42 patients with diabetic ulcers (45% neuropathic, 26% ischaemic and 29% mixed) who have attended the podiatric surgery from January to June 2000 were randomly selected. SUBJECT CHARACTERISTICS: 4 patients with type 1 diabetes, 38 patients with type 2 diabetes, mean of age 63 years (37-81), mean of duration of diabetes 17 years (1-31), mean of duration of diabetic ulcers 37 months (1-168) ulcers. Patients visited Diabetic Centre 9 times (5-13). 23 hospitalizations occurred in 17 patients (40%) with mean of 14 days duration (3-42). The AP-DRG (all patients diagnosis related groups) model was used to determine the hospital direct costs. The ambulatory costs included the reimbursed care, drugs (local treatment, antibiotics and antiagregans), bandages, patient transport and home care. Antidiabetic drugs and insulin or antihypertensive drugs were not included. RESULTS: Total direct costs of diabetic foot care 42 patients were 1,440.600.-CK, 34.500.-CK (6.300.-CK-190.200.-CK)/patient in Diabetic Centre Plzen during 6 months. 37% of total costs (533.000.-CK), resp. 12.500.-CK (5.900.-CK -45.700.-CK)/patient represented ambulatory and 63% of total cost (907 600.-CK), resp. 53.700.-CK (18.000.CK-180.600.-CK)/patient hospital care.

[Autonomic neuropathy in diabetics, treatment possibilities]. / Autonomní neuropatie u diabetiku, lécebné moznosti.

Diabetic neuropathy is a chronic complication of diabetes. It involves non-inflammatory damage of the function and structure of peripheral nerves by metabolic vascular pathogenic processes. In case of affection of vegetative nerves (small non-myelinated C fibres) autonomic neuropathy develops. It is a relatively frequent form of neuropathy which remains for a long time without clinical symptoms and therefore is rarely diagnosed and treated. Manifestations of the affection are encountered in all organs which are supplied by vegetative nerves. The presence of this complication of diabetes is signalized by tachycardia at rest, deterioration of gastric evacuation, diabetic diarrhoea or constipation, erectile dysfunction, impaired function of the sweat glans or impaired pupillary reaction. The advanced form involves the danger of latent myocardial ischaemia, serious postural hypotension and sudden death. It increases significantly the mortality of the affected patients. Similarly as the treatment of other complication of diabetes, treatment of autonomic neuropathy is difficult. The objective of the present paper is to review contemporary therapeutic possibilities. An essential prerequisite remain efforts to achieve optimal compensation. The authors draw attention to the effect of alpha-lipoic acid which exerts a positive effect not only on subjective symptoms but also on the objective finding. The other mentioned drugs are used either only experimentally or for purely symptomatic treatment.

[Effect of composition of enteral nutrition on energy expenditure and CO2 production during periods of average and excessive energy intake]. / Vliv slození enterální výzivy na energetický výdej a produkci CO2 v období primereného a nadmerného prívodu energie.

UNLABELLED: The objective of the presented work is to evaluate to what extent the CO2 production and O2 utilization and energy metabolism at rest (REE) are influenced by an excessive nutrient intake and to what extent by the composition of enteral nutrition. REE, CO2 production and O2 utilization were investigated in 9 patients on complete enteral nutrition by indirect calorimetry in four modifications: I--nutrition with 40% kJ fat in a ration 1.2x the energy output at rest at the onset of the trial; II--40% kJ and high energy intake (2.4x energy output at rest; III--60% kJ fat in ration of 1.2x energy output at rest; IV--60% kJ fat and energy intake 2.4x energy output at rest. At 40% (I) and 60% (III) fat content in a caloriocally adequate diet the energy output at rest, the CO2 production and O2 utilization did not differ (mean +/- SD: 1438 +/- 264.1 kcal/24 h, 179 +/- 31.6 nl/min, 209 +/- 38.1 ml/min vs. 1431 +/- 342.7, 190 +/- 54.2, 207 +/- 46.5). Comparison of modifications II and IV revealed a significant (p < 0.05) increase of CO2 production on a diet rich in carbohydrates (218 +/- 52.0 vs. 202 +/- 42.3). The energy output at rest (1674 +/- 389.6 vs. 1661 +/- 378.7), nor O2 production (240 +/- 54.5 vs. 242 +/- 55.4) changed. Overfeeding with 40% fat (II) as compared with (I) led to a rise of the energy output at rest (p < 0.05), O2 utilization (p < 0.05) and CO2 production (p < 0.01). Overfeeding with lipids (IV) led as compared with III to a rise of the energy output at rest and O2 utilization; CO2 production did not change. CONCLUSION: The composition of enteral nutrition according to the described modification does not influences the energy output at rest, O2 utilization and CO2 production under conditions of an adequate energy intake. In case of an excessive nutrient intake nutrition with 60% fat does not lead to an increase of CO2 production.

Hyperinsulinemia and oxidative stress.

The aim of the study was to compare the effect of short-term hyperglycemia and short-term hyperinsulinemia on parameters of oxidative stress in Wistar rats. Twenty male rats (aged 3 months, average weight 325 g) were tested by hyperinsulinemic clamp (100 IU/l) at two different glycemia levels (6 and 12 mmol/l). Further 20 rats were used as a control group infused with normal saline (instead of insulin) and 30 % glucose simultaneously. Measured parameters of oxidative stress were malondialdehyd (MDA), reduced glutathion (GSH) and total antioxidant capacity (AOC). AOC remained unchanged during hyperglycemia and hyperinsulinemia. Malondialdehyde (as a marker of lipid peroxidation) decreased significantly (p<0.05) during the euglycemic hyperinsulinemic clamp, and increased significantly during isolated hyperglycemia without hyperinsulinemia. Reduced glutathion decreased significantly (p<0.05) during hyperglycemia without hyperinsulinemia. These results suggest that the short-term exogenous hyperinsulinemia reduced the production of reactive oxygen species (ROS) during hyperglycemia in an animal model compared with the control group.