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L Heinemann

Publications and source records attributed to L Heinemann.

At least 19 recordsLinked to original sources
PubMed2006

Non-invasive glucose monitoring in patients with diabetes: a novel system based on impedance spectroscopy.

The aim of this work was to evaluate the performance of a novel non-invasive continuous glucose-monitoring system based on impedance spectroscopy (IS) in patients with diabetes. Ten patients with type 1 diabetes (mean+/-S.D., age 28+/-8 years, BMI 24.2+/-3.2 kg/m(2) and HbA(1C) 7.3+/-1.6%) and five with type 2 diabetes (age 61+/-8 years, BMI 27.5+/-3.2 kg/m(2) and HbA(1C) 8.3+/-1.8%) took part in this study, which comprised a glucose clamp experiment followed by a 7-day outpatient evaluation. The measurements obtained by the NI-CGMD and the reference blood glucose-measuring techniques were evaluated using retrospective data evaluation procedures. Under less controlled outpatient conditions a correlation coefficient of r=0.640 and a standard error of prediction (SEP) of 45 mg dl(-1) with a total of 590 paired glucose measurements was found (versus r=0.926 and a SEP of 26 mg dl(-1) under controlled conditions). Clark error grid analyses (EGA) showed 56% of all values in zone A, 37% in B and 7% in C-E. In conclusion, these results indicate that IS in the used technical setting allows retrospective, continuous and truly non-invasive glucose monitoring under defined conditions for patients with diabetes. Technical advances and developments are needed to expand on this concept to bring the results from the outpatient study closer to those in the experimental section of the study. Further studies will not only help to evaluate the performance and limitations of using such a technique for non non-invasive glucose monitoring but also help to verify technical extensions towards a IS-based concept that offers improved performance under real life operating conditions.

Adult↗
PubMed2006

[Interactive thresholded volumetry of abdominal fat using breath-hold t1-weighted magnetic resonance imaging].

PURPOSE: Development of a feasible and reliable method for determining abdominal fat using breath-hold T1-weighted magnetic resonance imaging. MATERIALS AND METHODS: The high image contrast of T1-weighted gradient echo MR sequences makes it possible to differentiate between abdominal fat and non-fat tissue. To obtain a high signal-to-noise ratio, the measurements are usually performed using phased array surface coils. Inhomogeneity of the coil sensitivity leads to inhomogeneity of the image intensities. Therefore, to examine the volume of abdominal fat, an automatic algorithm for intensity correction must be implemented. The analysis of the image histogram results in a threshold to separate fat from other tissue. Automatic segmentation using this threshold results directly in the fat volumes. The separation of intraabdominal and subcutaneous fat is performed by interactive selection in a last step. RESULTS: The described correction of inhomogeneity allows for the segmentation of the images using a global threshold. The use of semiautomatic interactive volumetry makes the analysis more subjective. The variance of volumetry between observers was 4.6 %. The mean time for image analysis of a T1-weighted investigation lasted less than 6 minutes. CONCLUSION: The described method facilitates reliable determination of abdominal fat within a reasonable period of time. Using breath-hold MR sequences, the time of examination is less than 5 minutes per patient.

Abdomen↗
PubMed2006

Time-action profile of insulin detemir and NPH insulin in patients with type 2 diabetes from different ethnic groups.

AIM: To evaluate the time-action profiles and the dose-response relationship of the long-acting insulin analogues insulin detemir (IDet) and NPH insulin (NPH) in type 2 diabetic patients belonging to different ethnic groups. METHODS: Forty-eight type 2 diabetic patients belonging to different ethnic groups (three groups of 16 African Americans (AA), 16 Hispanics/Latinos (HL) and 16 Caucasians) participated in this double-blind crossover trial. Each patient took part in six 16-h isoglycaemic glucose clamps (clamp target 7.2 mmol/l) and was randomly allocated to three doses (0.3, 0.6 and 1.2 (I)U/kg) of IDet and NPH, respectively. RESULTS: IDet and NPH showed comparable pharmacodynamic effects [the area under the glucose infusion rate curve (AUC(GIR 0-16 h)) (mg/kg)] in the investigated dose range: IDet, 0.3 U/kg, 207 AA, 535 HL, 285 Caucasians; 0.6 U/kg, 1203 AA, 824 HL and 1126 Caucasians; 1.2 U/kg, 1502 AA, 1977 HL and 2269 Caucasians; NPH, 0.3 IU/kg, 733 AA, 1148 HL and 1148 Caucasians; 0.6 IU/kg, 1395 AA, 1976 HL and 1077 Caucasians; 1.2 IU/kg, 2452 AA, 3296 HL and 2455 Caucasians. Both IDet and NPH showed a linear dose-response relationship in all three groups (p = 0.31), without any significant differences in slope (p = 0.71) or intercept (p = 0.51). Comparable results were obtained for pharmacokinetics. CONCLUSIONS: These results confirm a linear dose-response relationship of IDet, without any relevant differences between ethnic groups. This suggests that similar dosing recommendation can be used for IDet in type 2 diabetic patients belonging to different ethnic group.

Adult↗
PubMed2006

Inhaled insulin as adjunctive therapy in subjects with type 2 diabetes failing oral agents: a controlled proof-of-concept study.

AIM: This controlled proof-of-concept study investigated inhaled insulin (INH) as adjunctive therapy to existing oral antidiabetic agents in subjects with type 2 diabetes. METHODS: Twenty-four subjects with type 2 diabetes [19 men and 5 women, 56.1 +/- 6.6 years, body mass index 32.7 +/- 4.2 kg/m(2), glycosylated haemoglobin (HbA1c) 8.4 +/- 0.8% (mean +/- s.d.)] inadequately controlled by metformin and/or sulfonylureas were randomized to receive additional therapy with either INH administered preprandially using a metered-dose inhaler (MDI), or insulin glargine (GLA) injected subcutaneously at bedtime for 4 weeks. Both inhaled and injected insulin doses were titrated to predefined blood glucose (BG) targets. RESULTS: INH and GLA improved metabolic control to a similar extent. Mean daily BG decreased by 2.8 mmol/l in the INH group (p < 0.001) and by 2.4 mmol/l in the GLA group (p < 0.001). Accordingly, fasting BG (-2.7 vs. -3.6 mmol/l for INH vs. GLA), preprandial- and 2-h postprandial BG, HbA1c (-1.23 vs. -1.05%), body weight (-1.9 vs. -2.3 kg) and serum fructosamine were similarly and significantly reduced in both groups (p < 0.05). Triglycerides decreased significantly with INH (-1.15 micromol/l; p < 0.001) but not with GLA [-0.52 micromol/l; not significant (NS)]. Incidence rates of adverse events did not differ significantly, and there were no indications of respiratory tract irritation. CONCLUSIONS: In subjects with type 2 diabetes inadequately controlled by oral agents, preprandial administration of INH delivered by a MDI provided a comparable metabolic control to bedtime GLA and did not show any safety concerns during a 4-week treatment. These results warrant a more extensive investigation of preprandial treatment with INH in longer term studies.

Administration, Inhalation↗
PubMed2005

Self-monitoring of blood glucose in type 2 diabetes and long-term outcome: an epidemiological cohort study.

AIMS/HYPOTHESIS: The aim of this study was to obtain epidemiological data on self-monitoring of blood glucose (SMBG) in type 2 diabetes and to investigate the relationship of SMBG with disease-related morbidity and mortality. METHODS: The German multicentre Retrolective Study 'Self-monitoring of Blood Glucose and Outcome in Patients with Type 2 Diabetes' (ROSSO) followed 3,268 patients from diagnosis of type 2 diabetes between 1995 and 1999 until the end of 2003. Endpoints were diabetes-related morbidity (non-fatal myocardial infarction, stroke, foot amputation, blindness or haemodialysis) and all-cause mortality. SMBG was defined as self-measurement of blood glucose for at least 1 year. RESULTS: During a mean follow-up period of 6.5 years, 1,479 patients (45.3%) began SMBG prior to an endpoint and an additional 64 patients started SMBG after a non-fatal endpoint. Interestingly, many patients used SMBG while being treated with diet or oral hypoglycaemic drugs (808 of 2,515, 32%). At baseline, the SMBG cohort had higher mean fasting blood glucose levels than the non-SMBG cohort (p<0.001), suggesting that insufficient metabolic control was one reason for initiating SMBG. This was associated with a higher rate of microvascular endpoints. However, the total rate of non-fatal events, micro- and macrovascular, was lower in the SMBG group than in the non-SMBG group (7.2 vs 10.4%, p=0.002). A similar difference was found for the rate of fatal events (2.7 vs 4.6%, p=0.004). Cox regression analysis identified SMBG as an independent predictor of morbidity and mortality, with adjusted hazard ratios of 0.68 (95% CI 0.51-0.91, p=0.009) and 0.49 (95% CI 0.31-0.78, p=0.003), respectively. A better outcome for both endpoints was also observed in the SMBG cohort when only those patients who were not receiving insulin were analysed. CONCLUSIONS/INTERPRETATION: SMBG was associated with decreased diabetes-related morbidity and all-cause mortality in type 2 diabetes, and this association remained in a subgroup of patients who were not receiving insulin therapy. SMBG may be associated with a healthier lifestyle and/or better disease management.

Aged↗
PubMed2005

The pharmacokinetic and pharmacodynamic properties of biphasic insulin Aspart 70 (BIAsp 70) are significantly different from those of biphasic insulin Aspart 30 (BIAsp 30).

AIMS: To evaluate the pharmacokinetic and pharmacodynamic properties of two different formulations of premixed analogue (mixed biphasic insulin aspart [BIAsp]), BIAsp 30 (30 % soluble insulin aspart [IAsp] and 70 % protaminated IAsp) and BIAsp 70 (70 % soluble IAsp and 30 % protaminated IAsp), in patients with type 1 diabetes using a 12-hour euglycaemic clamp technique. METHODS: In this randomised, double-blind, two-period crossover trial, 27 patients with type 1 diabetes received 7 days of treatment with BIAsp 30 three times daily (TID) and 7 days of treatment with BIAsp 70 TID, with a 2 - 6 week washout period between treatment periods. At the start (day 1) and end (day 8) of each treatment period, 12-hour serum IAsp profiles and glucose infusion rate (GIR) profiles were determined during an overnight euglycaemic clamp following subcutaneous (sc) administration of a single 0.3 U/kg dose of trial insulin. All pharmacokinetic and pharmacodynamic endpoints were derived from individual serum IAsp and GIR profiles. RESULTS: The larger fraction of soluble IAsp in BIAsp 70 compared with BIAsp 30 resulted in greater metabolic effect during the initial post-dosing phase (0 - 6 hours) and decreased activity during the late phase (6 - 12 hours). On day 8, AUC (GIR 0 - 6 hours) was 16 % greater for BIAsp 70 than for BIAsp 30 (p = 0.016) and AUC (GIR 6 - 12 hours) was 90 % (p < 0.001) greater for BIAsp 30 relative to BIAsp 70, reflecting the increased proportion of intermediate-acting (protamine co-crystallised) IAsp in BIAsp 30. Overall metabolic effect (AUC (GIR 0 - 12 hours)) was similar for both insulin formulations on day 8 (Ratio, BIAsp 30:BIAsp 70 = 1.04, p = 0.538). Likewise, the larger fraction of soluble IAsp in BIAsp 70 compared with BIAsp 30 resulted in greater exposure to IAsp during the initial post-dosing phase (0 - 6 hours) and a smaller exposure to IAsp during the late phase (6 - 12 hours). On day 8, AUC (IAsp 0 - 6 hours) was 59 % (p < 0.001) greater for BIAsp 70 than for BIAsp 30, and AUC (IAsp 6 - 12 hours) was 61 % (p < 0.001) greater for BIAsp 30 than for BIAsp 70, reflecting the increased proportion of intermediate-acting (protamine co-crystallised) IAsp in BIAsp 30. However, the overall IAsp exposure (AUC 0 - 12 hours) on day 8 was significantly greater for BIAsp 70 than for BIAsp 30 (Ratio, BIAsp 30:BIAsp 70 = 0.73, p < 0.001). The GIR profiles on day 8 were similar to those on day 1. Serum IAsp profiles on day 8 showed a slight increase compared with day 1. CONCLUSIONS: The different proportions of soluble and protaminated IAsp result in differences in the pharmacokinetic and pharmacodynamic properties of BIAsp 30 and BIAsp 70. The pharmacokinetic and pharmacodynamic differences observed may allow for flexibility and individualised treatment regimens in patients with diabetes, while maintaining a limited number of daily injections.

Adult↗
PubMed2004

Dependency of the metabolic effect of sc-injected human regular insulin on intra-abdominal fat in patients with type 2 diabetes.

Ten patients with type 2 diabetes were enrolled in an isoglycemic glucose clamp study to determine the impact of intra-abdominal fat, subcutaneous abdominal fat and total abdominal fat on the metabolic effect of a single bolus (0.2 IU/kg) of sc-injected human regular insulin. The maximum metabolic effect associated highly and negatively with intra-abdominal fat (r = - 0.72, p < 0.02) and with the homeostasis model assessment insulin resistance score (HOMA, r = - 0.71, p < 0.03). Likewise, the total metabolic effect of sc-injected insulin correlated strongly and negatively with intra-abdominal fat (r = - 0.77, p < 0.01), HOMA (r = - 0.74, p < 0.02) and HbA (1c) (r = - 0.70, p < 0.03). Stepwise multiple regression analyses showed that the highest metabolic effect was only significantly predicted by intra-abdominal fat, indicating a high negative correlation with the maximum effect (beta = - 0.72) whereas time to maximum metabolic effect showed a strong (beta = 0.72) and positive correlation with HOMA. In combination with the HOMA, it is intra-abdominal fat, and not subcutaneous abdominal fat, which explains 50 - 75 % of the variability of the effect of sc human regular insulin in patients with type 2 diabetes.

Abdomen↗
PubMed2004

Inhaled micronized crystalline human insulin using a dry powder inhaler: dose-response and time-action profiles.

AIM: The aim of this euglycaemic glucose clamp study was to investigate the pharmacokinetics, glucodynamics, safety and tolerability of micronized crystalline human insulin inhalation powder delivered by a Spiros dry powder inhaler system in healthy volunteers. METHODS: Thirteen healthy, non-smoking, male and female volunteers [age 30 +/- 7 years; BMI 23.5 +/- 2.7 kg/m(2); (mean +/- sd)] with normal pulmonary function participated in an open-label, randomised, 6-period crossover trial. Each volunteer received four single doses of inhaled insulin (60, 90, 120, 150 U) on separate occasions. For comparison, each volunteer also received two of three possible doses of subcutaneous (s.c.) injected regular human insulin (8, 14, or 20 U). RESULTS: Serum immunoreactive insulin following inhalation of insulin peaked an average of 60 min earlier compared with s.c. injected insulin (P < 0.0001). Following inhalation, the time to maximum glucose infusion rate occurred an average of 70 min earlier than with s.c. insulin: 187, 129, 161 and 162 min vs. 227, 241 and 241 min (P < 0.0001). The dose-response relationships for serum insulin pharmacokinetics and glucodynamics were linear for both inhaled and s.c. insulin. Relative bioavailability (based on serum insulin levels) ranged from 11.5 to 12.2% for the four doses of inhaled insulin and relative biopotency (based on glucose infusion rates) was 10.0 to 16.5%, respectively. Dosing was well tolerated by all volunteers. CONCLUSION: This study demonstrates that inhalation of human insulin via a dry powder inhaler system provides a promising alternative route for administration of insulin.

Administration, Inhalation↗
PubMed2004

Overcoming obstacles: new management options.

The outlook for patients with type 2 diabetes looks set to improve with the availability of new diabetes management options that provide more comprehensive control of blood glucose levels and/or encourage better patient compliance than previous alternatives. New insulin analogues, such as insulin lispro, aspart and glargine, allow more physiological insulin replacement and greater freedom in the timing and content of meals, compared with regular insulin preparations. The development of novel non-invasive routes of insulin administration promises to further improve diabetes management. Many barriers to initiating insulin relate to the need for frequent insulin injections, fears that insulin injections will be painful and difficult to administer, and concerns about hypoglycaemia and weight gain. Thus, each measure that reduces these barriers will help to prevent inappropriate delays in starting insulin therapy as well as to promote better compliance with therapy. The output from continuous glucose monitoring devices will assist accurate insulin replacement, which is difficult using point-estimates of blood glucose. Such devices will hopefully also circumvent the need for finger stick tests. There are several novel therapies in development that will further expand the portfolio of treatment options for patients with type 2 diabetes. Improved quality and choice of diabetes management options will provide doctors with the tools they require to develop tailored treatment plans, increase the probability that treatment goals are achieved and thereby reduce the risk of patients developing late-stage diabetes-related complications.

Blood Glucose Self-Monitoring↗
PubMed2003

First human experiments with a novel non-invasive, non-optical continuous glucose monitoring system.

This paper describes a non-invasive continuous glucose monitoring system based on impedance spectroscopy. Changes in the glucose concentrations can be monitored by varying the frequency in the radio band over a range, optimised to measure the impact of glucose on the impedance pattern. A number of clinical-experimental studies (hyperglycaemic excursions) were performed with healthy subjects in order to prove the applicability of this approach. The sensor used in these experiments is the size of a wristwatch and holds an open resonant circuit coupled to the skin and a circuit, performing an impedance measurement. In most cases, the experiments showed a good correlation between changes in blood glucose and the sensor recordings. A detailed description of the trials is presented. The results of this first series of experiments can be considered as a proof of concept for this novel non-invasive monitoring approach. Nevertheless, partly due to the indirect measurement, a considerable number of questions remain to be clarified.

Blood Glucose↗
PubMed2002

Quantification of total abdominal fat volumes using magnetic resonance imaging.

The purpose of this study was to develop a rapid and reliable method for the measurement of total abdominal fat volumes in diabetic patients using magnetic resonance imaging (MRI). Total volume coverage of the abdomen was obtained using T1-weighted images in 37 diabetic patients (age 48 +/- 13 y mean +/-SD). Quantification of intraabdominal (IAF), subcutaneous (SCF), and total abdominal fat volumes (TAF) was performed using a semiautomated computer assisted analysis. The variability of image analysis for fat measurements between two observers and within observers was assessed. Mean volumes (+/- SD) for IAF, SCF and TAF were 10.5 l (+/- 5.0 l), 15.1 l (+/-7.3 l) and 25.7 l (+/-11.5 l), respectively. Reliability of measurements was excellent for both observers (observer I: intraobserver reliability IAF, SCF and TAF: r = 0.999, r = 0.999 r = 1.0, observer II: r = 0.999, r = 0.999 and r = 1.0), as well as between both observers (interobserver reliability IAF, SCF, and TAF: r = 0.999, r = 0.999, r = 1.0). A single computer analysis required about 9 min in addition to 7 min scan time. The developed analysis method of MR images allows a rapid and reliable determination of total intraabdominal, subcutaneous and total fat volumes. This method has the potential to be very valuable in respective studies in patients with diabetes.

Abdomen↗
PubMed2002

No evidence for accumulation of insulin glargine (LANTUS): a multiple injection study in patients with Type 1 diabetes.

AIMS: Insulin glargine is a long-acting insulin analogue that is metabolically active for at least 24 h. We investigated the multiple-dose pharmacokinetic properties of insulin glargine to determine whether daily injections lead to the accumulation of circulating insulin levels and a corresponding decrease in blood glucose levels in patients with Type 1 diabetes. METHODS: Fifteen patients using preprandial insulin lispro (mean age 36 +/- 9 years, body mass index 24.6 +/- 2.2 kg/m(2)) completed the study. Each patient's optimal insulin glargine dose was determined during a dose-finding phase. After a washout period, patients were treated over 12 days with a constant daily dose of insulin glargine injected in the abdominal subcutaneous adipose tissue at 22:00 h, and with preprandial insulin lispro. Free serum insulin (FSI) and blood glucose concentrations were assessed hourly after the first, fourth, and eleventh injection, after which patients fasted for 24 h and did not use any other insulin preparation. RESULTS: There were no changes in daily insulin doses during the dose-finding phase (insulin glargine: initial dose 24 +/- 6 IU, mean change 0 +/- 3 IU; insulin lispro: 18 +/- 9 IU, 0 +/- 7 IU). The time course of FSI was comparable on the three pharmacokinetic study days. Notably, the trough FSI at the end of the sampling periods was almost identical (day 1, 79 +/- 56 pmol/l, day 4, 77 +/- 56 pmol/l, day 11, 86 +/- 60 pmol/l). No changes occurred in any of the pharmacokinetic parameters studied. CONCLUSIONS: There is no evidence that insulin glargine accumulates after multiple injections over 12 days. These results indicate that the predetermined dose of insulin glargine will not need to be reduced after commencing treatment because of a risk of accumulation.

C-Peptide↗
PubMed2002

Technosphere/Insulin--proof of concept study with a new insulin formulation for pulmonary delivery.

Summary.Technosphere/Insulin (TI) is a formulation of regular human insulin and Technosphere, a new drug delivery system for pulmonary administration. The formulation is designed for efficient transport of insulin across the intact respiratory epithelium into the systemic circulation. We have investigated the pharmacodynamic and pharmacokinetic properties of Technosphere/Insulin in five healthy, non-smoking volunteers. In an open, randomized, three-way crossover study, subjects received 5 IU regular human insulin (HI) intravenously, 10 IU HI subcutaneously; and 100 IU TI via inhalation using a small commercially available asthma inhaler. The time action profiles of all three insulin formulations were assessed by the euglycemic glucose clamp technique on three different study days. Glucose infusion rates were monitored from 2 h before until 6 h after insulin administration. Other study measures were serum insulin, serum C-peptide concentrations, and safety parameters. The inhalation of TI was well tolerated. The time to peak action was significantly shorter with both i.v. injection and inhalation, as compared to s.c. (14 +/- 6 min and 39 +/- 36 min vs. 163 +/- 25 min; p < 0.0002 and p < 0.007 (mean +/- SD)). The metabolic effect during the first 3 h after insulin administration was higher with inhaled TI than with HI s.c. (AUC0-180 for glucose infusion rate: 1.94 +/- 0.77 mg/kg * min vs. 1.15 +/- 0.50 mg/kg * min; p < 0.04). Relative and absolute bioavailability for the first 3 h were 26 +/- 12% and 15 +/- 5% respectively (6 h: 16 +/- 8 and 16 +/- 6%). We conclude that inhalation of TI leads to a rapid onset of metabolic action resembling the effect observed with i.v. administration of regular HI. Despite the use of a common asthma inhaler, bioavailability over the three hour prandial period was substantially greater than with other reported pulmonary systems. Therefore, inhalation of Technosphere/Insulin may become a suitable and attractive alternative for prandial insulin delivery, especially for patients with type 2 diabetes mellitus.

Adult↗