Retinal oxygen saturation is associated with HbA1c but not with short-term diabetes control, internal environment, smoking and mild retinopathy - ROXINEGLYD study.

PURPOSE: Purpose of this prospective uncontrolled single-centre pilot study was to find an association of retinal oxygen saturation (SatO2 ) with acid-base balance (ABB), carboxyhaemoglobin concentration, current plasma glucose concentration (PG), mean PG and PG variability over the last 72 hr, haemoglobin A1c (HbA1c), and other conditions. METHODS: Forty-one adults (17 men) with type 1 (N = 14) or type 2 (N = 27) diabetes mellitus, age 48.6 ± 13.5 years, diabetes duration 9 (0.1-36) years, BMI 29.4 ± 6.3 kg/m2 , and HbA1c 52 ± 12.7 mmol/mol completed the study. The 4-day study comprised two visits (Day l, Day 4) including 72 hr of continuous glucose monitoring (CGM) by iPro® 2 Professional CGM (Medtronic, MiniMed, Inc., Northridge, CA, USA). Retinal oximeter Oxymap T1 (Oxymap ehf., Reykjavik, Iceland) was used to assess SatO2 . RESULTS: Wilcoxon signed-rank test showed no SatO2 difference between eyes and visits. Spearman's correlation analysis revealed a significant correlation between arterial SatO2 and PG variability in type 2 diabetes mellitus, a positive correlation of venous SatO2 with HbA1c and with finger pulse oximetry. However, no correlation of SatO2 with ABB, carboxyhaemoglobin, current PG, mean PG over the 72 hr, age, diabetes duration, BMI, lipoproteinaemia, body temperature, systolic and diastolic blood pressure, heart rate, central retinal thickness and retinal nerve fibre layer thickness was found. CONCLUSION: This study confirmed the association of venous SatO2 with long-term but not with short-term diabetes control, ABB and other conditions. The increased SatO2 and questionable impact of PG variability on retinal SatO2 is a research challenge.

Complex Assessment of Metabolic Effectiveness of Insulin Pump Therapy in Patients with Type 2 Diabetes Beyond HbA1c Reduction.

BACKGROUND: This prospective single-center study recruited insulin-resistant continuous subcutaneous insulin infusion (CSII) therapy-naive patients with type 2 diabetes (T2D) using insulin analog-based multiple daily injections (MDI) therapy and metformin. METHODS: A total of 23 individuals with T2D (70% male), aged a mean ± standard deviation 57.2 ± 8.03 years, with body mass index of 36.2 ± 7.02 kg/m2, diabetes duration of 13.3 ± 4.64 years, and HbA1c of 10.0% ± 1.05% were randomly assigned to a CSII arm or an MDI continuation arm to explore glucose control, weight loss, total daily insulin dose (TDD), and insulin resistance. Insulin dosing was optimized over a 2-month run-in period. RESULTS: At 6 months, patients assigned to the CSII arm achieved a significant mean HbA1c reduction of -0.9% (95% confidence interval [CI] = -1.6, -0.1), while reducing their TDD by -29.8 ± 28.41 U/day (33% of baseline [92.1 ± 20.35 U/day]) and achieving body mass (BM) reduction of -0.8 ± 5.61 kg (0.98% of baseline [104.8 ± 16.15 kg]). MDI patients demonstrated a nonsignificant HbA1c reduction of -0.3% (95% CI = -0.8, 0.1) with a TDD reduction of 5% from baseline (99.0 ± 25.25 U/day to 94.3 ± 21.25 U/day), and a BM reduction of -1.0 ± 2.03 kg (0.99% of baseline [108.9 ± 20.55 kg]). After 6 months, the MDI arm crossed over to CSII therapy. At 12 months, patients continuing CSII demonstrated an additional mean 0.7% HbA1c reduction with 54.6% achieving HbA1c<8%. The final TDD reduction was -9.7 U/day in comparison to baseline; BM increased by 1.1 ± 6.5 kg from baseline. The MDI patients that crossed to CSII showed an HbA1c reduction of -0.5% ± 1.04%, HbA1c response rate of 27.3%, a TDD reduction of -17.4 ± 21.06 U/day, and a BM reduction of -0.3 ± 3.39 kg. Diabetic ketoacidosis or severe hypoglycemia did not occur in either arm. CONCLUSION: CSII therapy safely and significantly improved metabolic control with less insulin usage, with no sustainable reduction of BM, blood pressure, and lipid profile, in insulin-resistant T2D patients. Treatment adherence and satisfaction in these patients were excellent.

Glucose concentrations in blood and tissue - a pilot study on variable time lag.

AIM: The aim of this pilot study was to acquire insight into the parameters of glycaemic control, especially, (1) the time delay (lag phase) between plasma and tissue glucose concentrations in relation to rise and fall in glucose levels and (2) the rate of glucose increase and decrease. METHODS: Four healthy people (HP), 4 people with type 1diabetes (DM1) and 4 with type 2 diabetes (DM2) underwent concurrent glucose measurements by means of (1) the continuous glucose monitoring system (CGMS-Medtronic), Medtronic-Minimed, CA, USA, calibrated by the glucometer Calla, Wellion, Austria, and, (2) the Beckman II analyser to measure glucose concentrations in venous plasma. Samples were taken on 4 consecutive days in the fasting state and 4 times after consumption of 50 g glucose. Carelink Personal, MS Excel, Maple and Mat lab were applied to plot the evolution of glucose concentration and analyse the results. The time difference between increase and decrease was calculated for HP, DM 1 and DM 2. RESULTS: In DM1and DM2, glucose tolerance testing (GTT) resulted in slower transport of glucose into subcutaneous tissue than in HP where the lag phase lasted up to 12 min. The maximum increase/decrease rates in DM1 and DM2 vs HP were 0.25 vs < 0.1 mmol/L/min. CONCLUSION: CGMS is shown to provide reliable plasma glucose concentrations provided the system is calibrated during a steady state. The analysis of glucose change rates improves understanding of metabolic processes better than standard GTT.

Glucose sensing module - is it time to integrate it into real-time perioperative monitoring? An observational pilot study with subcutaneous sensors.

AIMS: To explore the feasibility of subcutaneous continuous glucose monitoring (CGM) in perioperative settings and to evaluate the perioperative development of glycaemia in persons with diabetes mellitus or impaired glucose tolerance by means of CGM. METHODS: Monitoring by means of Guardian REAL-Time CGMS (Medtronic, Nortridge, USA) in 20 perioperative periods. Sensor was inserted on the day before surgery and continued for 3 days with some exceptions. RESULTS: Full implementation of the method was successful in the intensive care unit setting only. No electromagnetic interference and no side effects were found. The Wilcoxon signed-rank test revealed no significant difference between sensor and laboratory analyser values. Pearson's correlation coefficients of the values obtained by sensor and the Wellion Linus glucometer were 0.875 for the whole perioperative period, 0.866 for the intraoperative period and 0.903 for the first perioperative day. A decline in sensor accuracy on the 6(th) day was registered in one case. 16 monitored cases (80%) did not meet the criteria for safe plasma glucose range. Hypoglycaemia was found in 4 (20%) cases. There was an association between grade of the perioperative dysglycaemia and need for reoperation within the next 3 months. The most frequent perioperative glycaemic patterns are demonstrated. CONCLUSION: Subcutaneous CGM is safe offering detailed insight into glucose homeostasis in the dynamic perioperative period. Laboratory confirmation of sensor plasma glucose concentration by approved laboratory analyser is still necessary. The potentional benefits of maintaining patients within a safe glucose range should be comfirmed by future studies.

Wavesense technology glucometer Linus for routine self-monitoring and clinical practice.

Conventional glucometer systems for plasma/blood glucose monitoring are based on colorimetry or static electrochemistry using a fixed input signal. The recent glucometer Linus, Wellion, Agamatrix, USA, based on wavesense dynamic electrochemistry, uses a time-varying input signal to give a more accurate glucose reading. The purpose of this study was to compare the plasma glucose (PG) readings obtained by nursing staff from glucometer Linus and PG values estimated on an approved analyzer Daytona™, Randox, Global Medical Instrumentation, Inc., MN, USA. In the course of 5 weeks, 221 fingerprick capillary blood samples were taken from persons with diabetes at different times and investigated using glucometer Linus. Within two following minutes, blood from the same fingerprick was also collected in a tube and centrifuged; the plasma was analyzed on the Daytona™ analyzer. Statistical analysis was performed using the software SPSS v. 15.0, SPSS Inc., Chicago, IL, USA. A total of 221 paired PG values were plotted on the error grid diagram indicating that 218 values (98.6%) of the glucose readings (Linus vs. Daytona) were within the clinically accurate zone A (maximum difference ±20%) and 3 values (1.4%) within the acceptable zone B. Daytona showed 4 PG values <4.2 mmol/l (75 mg/dl) and their difference of respective Linus readings was always <0.83 mmol/l (15 mg/dl). Correlation of results was strong (r = 0.992). Glucometer Linus readings correspond to the ISO and FDA standards. So, Linus appears to be an accurate device for PG-self-monitoring and clinical practice.

Influence of oral antidiabetic drugs on hyperglycemic response to foods in persons with type 2 diabetes mellitus as assessed by continuous glucose monitoring system: a pilot study.

BACKGROUND: The purpose of this prospective open-label trial was (1) to assess the influence of oral antidiabetic drugs (OAD) on the glycemic index (GI), glucose response curves (GRCs), daily mean plasma glucose (MPG) and (2) to compare the GI of foods in persons with OAD-treated type 2 diabetes mellitus (T2DM) with the respective GI in healthy persons (HP). METHODS: Tested foods containing 50 g of carbohydrates were eaten for breakfast and dinner after 10 and 4 h of fasting, respectively. Glycemic index, GRC, and MPG were obtained using the CGMS System Gold (CGMS). In T2DM patients [n = 16; age (mean +/- standard error) 56.0 +/- 2.25 years], foods were tested four times: tests 1, 2, and 3 were performed within one week in which placebo was introduced on day 2, and test 4 was carried out five weeks after reintroduction of OAD. Glycemic indexes, GRC, and MPG from tests 1, 2, 3, and 4 were compared. In a control group of 20 HP (age 24.4 +/- 0.71 years), the mean GIs were calculated as the mean from 20 subject-related GIs. RESULTS: In T2DM patients, subject-related assessment of GIs, GRC, and MPG distinguished persons with and without OAD effect. Nevertheless, the group-related GIs and the MPG on days 2, 8, and 39 showed no significant difference. There was no significant difference between the GIs in OAD-treated T2DM patients (test 4) versus HP (except in apple baby food). Glucose response curves were significantly larger in T2DM patients (test 4) versus HP. CONCLUSIONS: Determination of GRC and subject-related GI using the CGMS appears to be a potential means for the evaluation of efficacy of OAD treatment. Further studies are underway.

Extended prandial glycemic profiles of foods as assessed using continuous glucose monitoring enhance the power of the 120-minute glycemic index.

BACKGROUND: The glycemic index (GI) is routinely measured 120 minutes after food intake (GI120). The purpose of this prospective open label study was to assess (1) the dynamics of glycemia over the 210 minutes following food consumption and (2) the evolution of GIs based on 120-, 150-, 180-, and 210-minute glycemic profiles. METHOD: Twenty healthy subjects (mean +/- SE; 21.9 +/- 1.39 years of age; body mass index 23.6 +/- 0.63 kg/m(2); 7 men and 13 women) completed the study. Each subject consumed 10 different foods with known GI120 on three separate occasions at four different times of day according to a defined meal plan over a 9-day period; 32 meals were evaluated. The GIs for intervals of 120, 150, 180 and 210 minutes after food consumption were determined using a continuous glucose monitoring system (CGMS) to measure glycemia. The Wilcoxon signed-rank test was applied to compare the GIs. RESULTS: Glycemia returned to baseline within 120 minutes for honey and tomato soup; within 210 minutes for white bread, choco-rice cookies, fish and potatoes, wafers, and meat ravioli with cheese; and later for dark chocolate, apricot dumplings, and choco-wheat cookies. The extended GIs were higher than the respective GI120s in eight of the foods. CONCLUSIONS: The 120-minute glycemic index fails to fully account for changes in glycemia after ingestion of a mixed meal because glycemia remains above baseline for a longer period. The CGMS is a convenient method to determine the glucose response/GIs over intervals extended up to 210 minutes, which is adequate time for the absorption of most foods.

Impact of buccal glucose spray, liquid sugars and dextrose tablets on the evolution of plasma glucose concentration in healthy persons.

OBJECTIVES: The purpose of this prospective controlled trial was to assess the efficacy of three commercially available glucose products, (1) buccal glucose spray, (2) liquid sugars, and (3) dextrose tablet, on the evolution of plasma glucose concentration (PG). METHODS: Sixteen healthy volunteers aged 21.8 +/- 0.78 y (mean +/- SE), BMI 23.5 +/- 0.84 kg/m(2), tested their PG over the course of 3 sets of 4 sessions (S) each: S(0)-control fasting, S(1)-buccal administration of 10 glucose spray-doses (0.84 g of glucose) without swallowing; S(2-) consumption of 1 sachet (13 ml) of liquid sugar (ca. 5.2 g glucose, 5.2 g fructose, 5.2 g sucrose); S(3-) consumption of one dextrose tablet (6 g). PG was tested in finger-prick capillary blood using a personal glucometer Linus at the start, and at 5, 10, 15, 20 and 30 min. The means of 3 respective sessions for each of the 16 subjects were analyzed. RESULTS: The Wilcoxon signed rank test revealed no significant differences between changes in the mean PG at the start vs. 5-minute interval either in control, or any intervention sessions. Analysis of regression coefficients after 30 min compared to the control session, demonstrated an increase in PG with the sachet of liquid sugars (0.068 mmol/l/min, p = 0.001) which was greater than a single dextrose tablet (0.052 mmol/l/min, p = 0.002), but no significant PG increase was found after buccal glucose spray. CONCLUSION: Liquid sugars or dextrose tablets, but not the buccal glucose spray, are effective means to increase PG within 10 minutes after ingestion.

Benefits of three-month continuous glucose monitoring for persons with diabetes using insulin pumps and sensors.

BACKGROUND: The latest Paradigm 722 insulin pump, Medtronic MiniMed, USA, enables daily reading of 288 interstitial fluid glucose concentrations determined by a sensor inserted into subcutaneous tissue; the sensor signals are transmitted into the insulin pump, enabling the patient to see real-time glucose concentration on the display and adapt further treatment. AIMS: To assess the evolution of HbA1c over the course of a 3-month period in two cohorts of persons with type 1 (n=39) or type 2 (n=3) diabetes (PWD): 1) PWD on Paradigm 722 using sensors for continuous glucose monitoring (CGM group), 2) PWD on other types of insulin pumps performing intensive self-monitoring as before (3 to 6 times/d) on glucometer Linus, Wellion, Agamatrix (control group). METHODS: Compliant PWDs using insulin pump with insulin aspart for several previous months were included in the study. Seventeen were put on Paradigm 722 with CGM and 25 were included in the control group. Paired t-test and the statistical program SPSS v.15.0 were used to analyze the data. RESULTS: There was no significant difference in age between the two groups (P=0.996), in diabetes duration (P=0.482) or in daily insulin dose (P=0.469). In the CGM group (but not in the control group) HbA1c/IFCC dropped from 6.98+/-0.43 % to 5.98+/-0.36 % (P=0.006) within 1 month and remained reduced. CONCLUSION: The use of the Paradigm 722 insulin pump with CGM resulted in significant improvement in HbA1c which appeared within one month and remained throughout the whole 3-month study period. No significant improvement in HbA1c was seen in the control group.

Improved glycemic control through continuous glucose sensor-augmented insulin pump therapy: prospective results from a community and academic practice patient registry.

BACKGROUND: Conducted by highly experienced investigators with abundant time and resources, phase III studies of continuous glucose sensing (CGS) may lack generalizability to everyday clinical practice. METHOD: Community or academic practices in six Central and Eastern European or Mediterranean countries prospectively established an anonymized registry of consecutive patients with type 1 insulin-dependent diabetes mellitus starting CGS-augmented insulin pump therapy with the Paradigm X22 (Medtronic MiniMed, Northridge, CA) under everyday conditions, without prior CGS with another device. We compared glycosylated hemoglobin (GHb) values before and after 3 months of CGS and assessed relationships between insulin therapy variables and glycemia-related variables at weeks 1, 4, and 12 of CGS. RESULTS: Of 102 enrolled patients, 85 (83%) with complete weeks 1, 4, and 12 sensor data and baseline/3-month GHb data were evaluable. Evaluable patients were approximately 54% male and approximately 75% adult (mean age, 33.2 +/- 16.9 years) with longstanding diabetes and high personal/family education levels. Mean GHb declined significantly after 3 months of CGS (7.55 +/- 1.33% at baseline to 6.81 +/- 1.08% after 12 weeks, 0.74% absolute decrease, P < 0.001). The absolute GHb reduction correlated significantly (P < 0.0005) with baseline GHb: larger absolute reductions tended to occur when baseline levels were higher. An increased basal insulin dose as a percentage of the total daily insulin dose and a decreased daily bolus count from week 1 to week 12 of CGS predicted GHb improvement from baseline to week 12. CONCLUSIONS: CGS-augmented insulin pump therapy appears to improve glycemic control in type 1 diabetes in varied everyday practice settings.

Automated computation of glycemic index for foodstuffs using continuous glucose monitoring.

BACKGROUND: The glycemic index (GI) is a measure of the ability of a food to raise glucose levels after it is eaten. Continuous glucose monitoring (CGM) has been shown to give identical values of GI when compared to traditional methods. However, there has been no standardized protocol for measuring GI that takes into account interindividual variability and chronophysiological glycemic response to food. Our aim was (1) to create and describe software based on a Microsoft Excel 2000 spreadsheet to facilitate rapid, automated, accurate, and standardized processing of data obtained using recent CGM methodology to measure GI and its variability and (2) to assess the benefits of this new approach. METHOD: Twenty healthy subjects consumed 50 grams of glucose or four alternative foodstuffs (chocolate, apple baby food, rice squares, or yogurt) at breakfast and dinner during 1 week, resulting in 300 CGMS glucose profiles; 92% of meal tests were satisfactory for evaluation. Application and functions of the software DegifXL are described. RESULTS: Using the new spreadsheet software DegifXL, time required for data processing for the 15 data sets for each subject was reduced from 2000 to 160 minutes relative to previously used manual methods. We characterized the GI for four foodstuffs with three replicate measurements in each of 20 subjects and evaluated between person, between time period, and between replicate GI variabilities. CONCLUSION: DegifXL, combined with CGM, was an efficient and effective tool for routine measurement of group- and subject-related GI.

Benefits of complementary therapy with insulin aspart versus human regular insulin in persons with type 2 diabetes mellitus.

BACKGROUND: Absorption rates of the phosphate-buffered insulin analogs aspart, lispro, and glulisine prevail over that of regular human insulin. The aim of this prospective observational open-label controlled study was to compare the effects of aspart and human regular insulin resulting from their sequential long-lasting routine administration in small preprandial boluses to individuals with type 2 diabetes according to identical algorithms. METHODS: Fifty-seven individuals with type 2 diabetes 64.0 +/- 1.29 (mean +/- SE) years old with diabetes' duration of 12.4 +/- 1.06 years, treated with human regular insulin for 5.2 +/- 0.44 years, and a serum C-peptide level of 1.1 +/- 0.10 nmol/L were enrolled into the study. Following two checkups performed in the course of the 364 +/- 17.9-day baseline period, human regular insulin was replaced with aspart in equivalent boluses, and two checkups in the course of 330 +/- 11.1-day sequential period were performed. The control group consisted of 17 individuals with type 2 diabetes 68.4 +/- 2.36 years old with diabetes' duration of 9.9 +/- 1.57 years, treated with insulin for 4.2 +/- 0.57 years, and a C-peptide level of 1.1 +/- 0.11 nmol/L. Data were analyzed using the statistical program SPSS version 10.1. (SPSS, Inc., Chicago, IL). RESULTS: Following the switch from human regular insulin to aspart, hemoglobin A1c (HbA1c) decreased from 8.4 +/- 0.23% at baseline to 7.9 +/- 0.17% (P = 0.031), and thereafter to 7.5 +/- 0.20% (P < 0.001), while plasma glucose concentrations in 10-point profiles, daily insulin dose (37.1 +/- 1.39 IU/day), body mass index (BMI) (30.5 +/- 0.82 kg/m(2)), and frequency of hypo- and hyperglycemic episodes did not change (P > 0.05). Patients quote satisfaction was good. No adverse events were recorded. In the control group, no significant change of baseline HbA1c (8.4 +/- 0.54%), insulin dose (33.1 +/- 3.17 IU/day), and BMI (32.1 +/- 1.12 kg/m(2)) was found. CONCLUSION: Aspart appears to be more effective than human regular insulin for complementary insulin treatment in individuals with type 2 diabetes.

Function and accuracy of glucose sensors beyond their stated expiry date.

BACKGROUND: The sensor of the Continuous Glucose Monitoring System (CGMS, Medtronic Minimed, Northridge, CA) is labeled to expire 6 months following its production and to measure the glucose concentration in interstitial fluid up to 3 days after insertion. The purpose of this study was to demonstrate potential possibilities of sensors when used beyond their expiry date. METHODS: Twenty sensors, each between 3 to 18 months after the expiry date, were assessed in a 7-day period after insertion. Twenty healthy volunteers 23.4 +/- 2.92 (mean +/- SD) years old were trained in handling the CGMS and the Hypoguard (Woodbridge, UK) Advance glucometer system to measure their capillary plasma glucose concentration 18 times a day. Sensor function was estimated according to the number of readings per day, the accuracy according to the mean absolute difference (MAD), and correlation coefficient (r) between glucometer and sensor resulting from paired values. RESULTS: Uninterrupted sensor function was found in 117 of 140 sensor-days (83.6%). A reduction of readings in 23 sensor-days (16.4%) was caused by user error (5 sensor-days, 3.6%), connecting cable (7 sensor-days, 5%), sensor failure (8 sensor-days, 5.7%), or uncertain factors (3 sensor-days, 2.1%). MAD was always < 28%, and r = 0.79. CONCLUSIONS: Neither the expiry date nor the 3-day period of use limits the reliable function of a CGMS sensor. Sensors were found to function as long as 18 months after the expiry date, mostly for at least 7 days. There were no serious local adverse reactions. Prolongation of shelflife label and insertion time appears to be reasonable. Further studies are in progress.

Serum leptin in the development of insulin resistance and other disorders in the metabolic syndrome.

The metabolic syndrome mostly represented by obesity and hyperinsulinaemia connected with insulin resistance, presents the main mechanism in the pathogenesis of cardiovascular disease. The aim of this study was to analyze the interrelations between several metabolic variables (including leptin) and factors related to insulin resistance in groups of both normal and non-diabetic hyperlipemic postmenopausal women and men of appropriate age, and to attempt to elucidate the gender differences. Two groups of patients (20 men, 20 women) with hypertriglyceridemia were compared with 30 individuals (10 men, 20 women) with normal serum triacylglycerols. Fasting serum leptin concentration, lipid parameters (triacylglycerols, HDL cholesterol, LDL cholesterol) and BMI were measured and compared with changes in insulin parameters influencing insulin resistance (HOMA IR, insulin, intact proinsulin, C-peptide). Statistical analysis was performed using SAS/STAT software including unpaired Student's t-test, Kolmogorov-Smirnov's test, Spearman's rank-order correlation and multiple regression analysis. In men, the insulin sensitivity correlates with leptin only. In women insulin sensitivity is markedly influenced by a complex of factors: leptin and lipid parameters. Increased insulin resistance in men is followed mainly by the increased correlations between leptin, HOMA IR and insulin parameters. In women correlations between leptin, HOMA IR and insulin parameters were smaller, but the inverse correlation with HDL cholesterol was stronger. In postmenopausal women and also in men, serum leptin concentration contributes to insulin resistance. However in women the effect of increase in serum triacylglycerols in contribution of insulin resistance seems to be more dominant.

TNF-alpha in the development of insulin resistance and other disorders in metabolic syndrome.

Insulin resistance and obesity are very frequent disorders and are described as the dominant risk factors for cardiovascular disease. The aim of this study was to analyze the interrelations between several metabolic variables (including TNF-alpha) and factors related to insulin resistance in groups of both normal and hyperlipidemic postmenopausal women and men of appropriate age, and to attempt to elucidate the gender differences. The study was carried out on 70 out-patients of the Metabolic Center. From these, 40 patients (20 men and 20 women) were selected with mild hyperlipidemia. Two other groups (10 men and 20 women) with approximately normal serum lipids parameters were taken as "controls". In hyperlipidemic women the mean serum concentration of the TNF-alpha was no different from that in the control group in spite of the fact that values of HOMA IR, insulin, proinsulin and lipid parameters increased significantly. In hyperlipidemic men we have found the decrease in TNF-alpha in comparison with the control group. In all four groups the statistical analysis showed correlations between metabolic parameters (including TNF-alpha) and parameters related to insulin resistance. Also differences in relation to the gender have been found. Multiple regression analysis demonstrated the important role of TNF-alpha in the regulation of both the insulin resistance and in the secretion of insulin in women. In men, BMI and HDL-cholesterol played a dominant role, while the role of TNF-alpha seemed to be minimal.

Results of selfmonitoring on glucometer systems Advance and Optium in daily routine.

The aim of this prospective clinical study was to compare the results of B-glucose estimations performed simultaneously on glucometer Advance (with Micro-draw strips) and Optium (G3 strips) by lay healthy volunteers under non-standardized conditions of everyday life, to assess the difficulties dealing with lay-handling of these systems and to demonstrate the possibilities of the software Glucobalance (Hypoguard) and PC-Link (Medisense/Abbott) for the analysis of selfmonitoring. In the course of 5 days, a total of 721 pairs of measurements were carried out on 10 pairs of glucometer Advance and Optium by 10 healthy volunteers aged 16-40 years. The data transfer of all values into computer from glucometer Advance using the Glucobalance software and from glucometer Optium using the PC-Link was carried out to determine the results. The correlation of B-glucose measured on the glucometer Advance and Optium was strong (r = 0.73). Glucometer Advance brings values about 0.21 +/- 0.06 mmol/l lower than glucometer Optium. The average difference found within each pairs of glucometers Advance - Optium varied. Nevertheless, these differences are acceptable for routine selfmonitoring. The handling of glucometer Advance is not difficult for lay persons. The Glucobalance software simplifies the result evaluation by each tested person. Even though there are some advantages in comparison with the PC-Link, it should be further developed.

Determination of the glycaemic index of selected foods (white bread and cereal bars) in healthy persons.

UNLABELLED: The glycaemic index (GI) is a measure of the food power to raise blood glucose (B-glucose) concentration after a meal. For healthy eating, foods with low GI are recommended. However, for many foods in the European Union the GI has not been defined yet. The aims of this prospective open-label study were: (1) to determine the GI of white bread and juicy cereal bars FIT (Usovsko, Czech Republic) by means of the glucometer Optium (Abbott/Medisense); (2) to compare the GI of tested foods determined in the morning and in the evening hours; (3) to compare the GI of tested foods in men and women and (4) to assess the variability of the GI. METHODS: To determine the GI, measured portions of food containing 50 g of carbohydrates were eaten by 11 healthy volunteers. B-glucose curves were constructed from B-glucose values at time 0, 15, 30, 45, 60, 60, 120 min after the meal. The GI was calculated by dividing the incremental area under the curve (IAUC) for the tested food by that for the standard food (IAUCS). In each volunteer each food was tested 5 times so that 5 GI's was obtained and the average was calculated. The GI for each tested food was calculated as the mean from the respective average GI's of the 11 volunteers. MS Excel and the statistical program SPSS v. 10.1 were used to analyze the data. RESULTS: (1) The mean values of the GI for white bread was 70.3 % and for juicy cereal bars was 101.0 %, as determined in a total of 139 tests in the whole group of 11 volunteers. There was a difference when comparing white bread vs. glucose (p = 0.012) and white bread vs. cereal bars (p = 0.026) but no difference between glucose and cereal bars. (2) There was no significant difference between the GI determined in the morning and in the evening hours either for the total of 139 tests or for the individual tested foods. (3) No significant difference could be seen between the GI in men and women when comparing glucose, cereal bars and white bread. (4) There was a wide variability of GI in all tested foods: the standard deviation of GI for white bread was 30.7 %, for juicy cereal bars 38.0 %. CONCLUSIONS: The GI's for white bread and juicy cereal bars were determined. There was no difference either between the GI values determined in the morning vs. the evening hours or between the values in men vs. women. The results show wide variability. An accurate standard method for the determination of GI needs to be defined, carefully used and re-evaluated to enable a comparison of the results with various methods of other working groups.

Benefits of insulin aspart vs phosphate-buffered human regular insulin in persons with type 1 Diabetes treated by means of an insulin pump.

UNLABELLED: Absorption rates of phosphate buffered insulin analogs aspart and lispro prevail over regular human insulin. However, insulin aspart has not been widely used. The aim of this open controlled clinical study is to compare the metabolic effects of insulin aspart and phosphate buffered insulin when both are used in insulin pumps according to the identical algorithms. METHODS: Twenty one persons aged 39.9 +/- 2.89 (mean +/- SE) years (y) with type 1 diabetes mellitus duration of 17.9 +/- 2.21 y treated by an insulin pump for 4.3 +/- 0.53 y (at least 3 months), educated in self monitoring, entered the study. Mean plasma glucose, rates of hypo- and hyperglycaemias from the glucometer memory and other data from the first 256 +/- 19.97 days period with regular human insulin (check-up 1 and 2) and consequent 364 +/- 8.78 days long period with insulin aspart (check-up 3 and 4) were compared (paired t-test). Replacement of human regular insulin with insulin aspart after two check-ups was the only change in the treatment of diabetes. No special therapeutic education or training was made during the study. RESULTS: In persons with type 1 diabetes treated by an insulin pump with insulin aspart, despite the lower daily dose of insulin aspart vs human regular insulin, the HbA1c decreased; the frequency of hypo- and hyperglycaemias and the BMI did not change. CONCLUSIONS: Insulin analog aspart appears to be more effective for continuous subcutaneous insulin infusion than regular human insulin.

A Continuous Glucose Monitoring System (CGMS) - a promising approach for improving metabolic control in persons with type 1 Diabetes mellitus treated by insulin pumps.

This pilot study deals with the possibilities of a Continuous Glucose Monitoring System (CGMS, Minimed- Medtronic) to optimize insulin substitution. Ten persons with type 1 diabetes mellitus treated by means of an insulin pump entered the study and eight of them completed the protocol. CGMS was introduced for a period of 5 days. The standard dinner (60 g of carbohydrates) and overnight fasting were designed to ensure standard night conditions in all persons in the study while maintaining their usual daily eating routine, physical exercise and assessment of prandial insulin boluses. The only adaptation of basal rates of insulin pump was performed on day 3. Comparison of the mean plasma glucose concentration (0:00-24:00 hrs) between day 2 (before adaptation) and day 4 (following adaptation) was made. An independent comparison of the mean plasma glucose concentration between the night from day 2 till day 3 (22:00-6:00 hrs) and the night from day 4 till day 5 (22:00-6:00 hrs) was performed. The mean plasma glucose investigated by means of CGMS improved in the 24-hour period in 5 out of 8 persons and in the night fasting period (22:00 to 6 hrs) in 6 out of 8 persons. The CGMS is a useful means for assessment of the effectiveness of basal rate and prandial insulin doses in persons with type 1 diabetes treated by means of an insulin pump. However, further studies are necessary to improve the algorithm for insulin substitution.

Methods for retrospective assessment of an unusual behavior of a person with diabetes: ebrietas alcoholica and/or hypoglycaemia?

Drunkenness and/or hypoglycaemia are possible causes of unusual behavior in a person with diabetes. The aim of this study was to demonstrate different methods which were used in two contradictory reviews of experts for retrospective assessment of a patient's condition in the course of a car crash: An insulin-treated driver caused a car accident resulting in injuries to two men. He was accused of the crime of damage to health as well as of driving under the influence of an addictive drug. One expert, having seen the police and medical reports, concluded the driver was influenced by alcohol at the time of the accident. The contradictory argument of another expert, based on his own thorough investigation including self monitoring and completed by a model experiment, resulted in the conclusion that the driver was probably influenced by hypoglycaemia. Thus, the methods of the second expert seem to be useful reasonable tools to assess the unusual behavior of a person with diabetes.